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3478.                        Abbadi S.  Rashed HG.  Morlock GP.  Woodley CL.  El Shanawy O.  Cooksey RC. Characterization of IS6110 restriction fragment length polymorphism patterns and mechanisms of antimicrobial resistance for multidrug-resistant isolates of Mycobacterium tuberculosis from a major reference hospital in Assiut, Egypt. Journal of Clinical Microbiology.  39(6):2330-4, 2001 Jun.


We evaluated 25 Mycobacterium tuberculosis isolates from patients at a major Egyptian reference hospital in Assiut, Egypt, who had been treated for at least 1 year for tuberculosis. Typing patterns (IS6110) were diverse, and multidrug resistance was found among 11 (44%) of the isolates. Mutations associated with antimicrobial drug resistance were found in rpoB, katG, rpsL, and embB in the resistant isolates.

3479.                        Abe C.  Hirano K.  Wada M.  Aoyagi T. Resistance of Mycobacterium tuberculosis to four first-line anti-tuberculosis drugs in Japan, 1997. International Journal of Tuberculosis & Lung Disease.  5(1):46-52, 2001 Jan.


SETTING: Five years after the last survey of drug-resistant tuberculosis in Japan, a nationwide survey was conducted by the Tuberculosis Research Committee. OBJECTIVE: To determine the prevalence of and risk factors for resistance to four first-line anti-tuberculosis drugs. DESIGN: Cultures were obtained from patients hospitalized at 78 hospitals in different districts of Japan throughout a 6-month period, 1 June-30 November 1997. Drug susceptibility testing was carried out at the Research Institute of Tuberculosis, Tokyo, one of the supranational reference laboratories of the WHO/IUATLD global project. RESULTS AND CONCLUSION: Among patients with no prior treatment, resistance to any of the four drugs was found in 10.3%, and the prevalence of primary multidrug resistance (MDR) was 0.8%. The prevalence of acquired resistance was 42.4% for any of the four drugs and 19.7% for MDR, indicating a high prevalence rate compared with those reported in the WHO/IUATLD global project. About 73% of resistant isolates from new cases were resistant to one drug, while 64.3% of resistant isolates from the re-treatment cases were resistant to two or more drugs (P < 0.0001). No significant differences in resistance rates by sex, age group, nationality, district, and/or accompanying diseases were observed in any of the new or re-treatment cases. Other factors associated with the high prevalence in re-treatment cases remain to be determined.

3480.                        Agger EM.  Andersen P. Tuberculosis subunit vaccine development: on the role of interferon-gamma.  Vaccine.  19(17-19):2298-302, 2001 Mar 21.


  Tuberculosis (TB) remains a major global health problem and subunit vaccines for the control of the disease are presently under development. This vaccine strategy requires an in vitro correlate of protection for the identification of relevant vaccine candidate antigens and for monitoring the induction of a protective cell-mediated immune response after vaccination. New studies of experimental vaccines in the mouse model of TB support interferon-gamma as a relevant marker for the induction of a protective immune response. In contrast, searching for immunodominant antigens capable of inducing strong interferon-gamma responses in PPD positive healthy or TB infected individuals may not identify all relevant candidate antigens for inclusion in a novel TB subunit vaccine.


3481.                        Agrawal S.  Thomas NS.  Dhanikula AB.  Kaul CL.  Panchagnula R. Antituberculosis drugs and new drug development. [Review] [31 refs] Current Opinion in Pulmonary Medicine.  7(3):142-7, 2001 May.


  Tuberculosis affects more than 8 million people and has serious repercussions on economic, psychologic, and social status. Since its declaration as a global emergency in 1993 by the World Health Organization, significant development in the treatment and control of tuberculosis has been the implementation of the short-course directly observed treatment along with fixed dose combinations of existing drugs. However, the currently available therapeutic regimens have inherent disadvantages of long treatment duration, patient noncompliance, and risk of drug resistance. Hence, new antituberculosis drugs that are potent, are active against resistant strains and latent forms, and reduce the treatment period are needed to combat this disease. In this review, the authors discuss new chemical entities that in their opinion have a potential to become new antituberculosis drugs. This article emphasizes the role of biopharmaceutics and pharmacokinetics as an indispensable part in the development of new antituberculosis drugs to overcome the common hurdles such as exorbitant cost, time, and attrition rate involved in the process. [References: 31]


3482.                        Ahmed A.  Pereira SP.  Steger A.  Starke I. Abdominal tuberculosis: the great mimic. [see comments]. Hospital Medicine (London).  62(6):368-9, 2001 Jun.

3483.                        Ahuja A.  Ying M.  Yuen YH.  Metreweli C. Power Doppler sonography to differentiate tuberculous cervical lymphadenopathy from nasopharyngeal carcinoma. Ajnr: American Journal of Neuroradiology.  22(4):735-40, 2001 Apr.


  BACKGROUND AND PURPOSE: Tuberculous lymphadenitis and metastatic nodes from nasopharyngeal carcinoma are common in Asians and are often indistinguishable clinically. Because their treatment depends on prompt diagnosis, we undertook this study to evaluate if power Doppler sonography could distinguish these two pathologic abnormalities. The intranodal vascular appearances of tuberculous neck nodes are compared with benign reactive neck nodes and metastatic nodes from nasopharyngeal carcinoma. METHODS: The appearances of power Doppler sonograms of 42 tuberculous nodes were compared with 28 metastatic nodes from nasopharyngeal carcinoma and 27 benign reactive nodes. The intranodal distribution of vessels and the intranodal vascular resistance of vessels were compared among these three groups. All examinations were performed by the same sonologist (A.A.), who had more than 3 years' scanning experience, and all data analysis was performed by the same investigator (M.Y.). RESULTS: The intranodal vascular distribution in tuberculous nodes was varied and simulated both benign and malignant disease. Avascularity of nodes and displacement of hilar vascularity were frequent in tuberculous nodes. Metastatic nodes from nasopharyngeal carcinoma (resistive index [RI], 0.81+/-0.09; pulsatile index [PI], 1.91+/-0.81) had a higher vascular resistance than did tuberculous nodes (RI, 0.71+/-0.11; PI, 1.34+/-0.55). Tuberculous nodes had a higher vascular resistance than did reactive nodes (RI, 0.66+/-0.09; PI, 1.10+/-0.26). CONCLUSION: Avascularity, displaced hilar vessels, and low intranodal vascular resistance are clues that may suggest the tuberculous nature of neck nodes. However, there is overlap of appearance between tuberculous nodes, benign reactive neck nodes, and metastatic nodes. Thus, histologic analysis is often required for a definitive diagnosis.


3484.                        Akpede GO.  Akenzua GI. Management of children with prolonged fever of unknown origin and difficulties in the management of fever of unknown origin in children in developing countries. [Review] [90 refs] Paediatric Drugs.  3(4):247-62, 2001.


  This is Part II of a 2-part paper on fever of unknown origin (FUO) in children. It examines the aetiology and management of prolonged FUO in children and the difficulties in the management of FUO in children in developing countries. Part I of this paper discussed acute FUO in children and was published in the March 2001 issue of Paediatric Drugs. Prolonged FUO is documented fever of more than 7 to 10 days which has no apparent source and no apparent diagnosis after 1 week of clinical investigations. About 34% of cases of prolonged FUO are caused by infections, with bacterial meningitis and urinary tract infection accounting for about 6.5 and 11.4%, respectively, of cases attributable to infections. Chronic infections, particularly tuberculosis and 'old' disorders such as Kawasaki disease, cat-scratch disease and Epstein-Barr virus infection presenting with 'new' manifestations, collagen-vascular diseases and neoplastic disorders are the other issues of major concern in prolonged FUO. Overall, however, there is a trend towards an increased number of undiagnosed cases. This is due to advancements in diagnostic techniques, such that illnesses which were previously common among the causes of prolonged FUO are now diagnosed earlier, before the presentation becomes that of prolonged FUO. Clinical examination supplemented with laboratory tests to screen for serious bacterial infections should be the mainstay of initial evaluation of children with prolonged FUO. Use of scanning techniques (such as computerised tomography and ultrasound) as additional supplements to this clinical examination may allow for the earlier diagnosis of causes of prolonged FUO in children such as 'occult' abdominal tumours. A common error in management of children with prolonged FUO is the failure to perform a complete history and physical examination; repeated clinical examination and continued observation are of paramount importance in the diagnosis of difficult cases. Major difficulties in the management of FUO in children in developing countries include constraints in the availability and reliability of laboratory tests, cost, misuse of antibiotics and difficulties encountered in the diagnosis of malaria and typhoid fever. Malaria and typhoid fever are major aetiological considerations in both acute and prolonged FUO in children in developing countries. The newer quinolones may hold great promise for the treatment of serious bacterial infections, including meningitis, which are associated with prolonged FUO in developing countries. [References: 90]

3485.                         Al-Serhani AM.  Al-Mazrou K. Pharyngeal tuberculosis. American Journal of Otolaryngology.  22(4):236-40, 2001 Jul-Aug.


  PURPOSE: To increase awareness of tuberculosis (TB) as an important differential diagnosis of lesions in the pharynx and discuss its presentation. PATIENTS AND METHODS: The study included nine patients (2 males and 7 females); each with a diagnosis of primary pharyngeal tuberculosis (PTB). Of these, 3 had nasopharyngeal TB, 5 had tonsillar TB, and 1 had hypopharyngeal TB. The diagnostic criteria were either positive culture, positive smear, or histopathologic features of caseating granuloma consistent with TB in the biopsy specimen and a response to treatment. RESULTS: All patients had primary infection. The main presenting symptom in all nasopharyngeal TB was neck mass, whereas tonsillar TB patients presented with sore throats or discomfort. Dysphagia was the presenting symptom in hypopharyngeal TB. Six patients (3 with nasopharyngeal TB and 3 with tonsillar TB) had cervical adenopathy. The smear for acid-fast bacillus was positive in 4 patients (44.4%); culture was positive in 2 patients (22.2%). Histopathologic features of caseating granuloma, consistent with TB, were positive in all patients who received antituberculous medications. CONCLUSION: Otolaryngologists should consider pharyngeal TB as one of the differential diagnosis of lesions of the pharynx especially in those countries where TB is endemic.

3486.                         Altare F.  Ensser A.  Breiman A.  Reichenbach J.  Baghdadi JE.  Fischer A.  Emile JF.  Gaillard JL.  Meinl E.  Casanova JL. Interleukin-12 receptor beta1 deficiency in a patient with abdominal tuberculosis.  Journal of Infectious Diseases.  184(2):231-6, 2001 Jul 15.


  Two siblings with interleukin-12 receptor beta1 (IL-12Rbeta1) deficiency but different clinical phenotypes were studied. Both are homozygous for an IL12RB1 missense mutation that prevents receptor expression and abolishes cellular responses to IL-12. Transfection of the patients' T cells with wild-type IL12RB1 restored IL-12Rbeta1 expression and function. One patient had the expected phenotype of disseminated bacille Calmette-Guérin (BCG) infection in early childhood, whereas the other did not develop BCG infection, despite 3 inoculations with live BCG. Abdominal tuberculosis was diagnosed in this second patient at age 18 years. To date, neither of them has had clinical disease caused by environmental mycobacteria. These observations show unexpected interfamilial and intrafamilial heterogeneity of the clinical phenotype associated with IL-12Rbeta1 deficiency. The patients may be resistant to BCG but remain vulnerable to Mycobacterium tuberculosis. A diagnosis of IL-12Rbeta1 deficiency should therefore be considered in selected patients with severe tuberculosis, despite their resistance to BCG and a lack of atypical mycobacteriosis.

3487.                         Antinori S.  Galimberti L.  Parente F. Intestinal tuberculosis as a cause of chronic diarrhoea among patients with human immunodeficiency virus infection: report of two cases. Digestive & Liver Disease.  33(1):63-7, 2001 Jan-Feb.


  In Western countries human immunodeficiency virus infection is considered the main risk factor of tuberculous disease, its incidence being 500 times higher in HIV-infected patients than in the general population. Despite the disease frequently present in these patients with extraintestinal manifestations, intestinal localization is rarely observed and often as a consequence of complications such as acute gastrointestinal bleeding or perforation. The diagnosis of intestinal tuberculosis is difficult and is often delayed due to the lack of specific signs and symptoms as well as the low sensitivity of routine methods. A review of the literature is made and personal experience in the diagnosis of two cases is reported.

3488.                        Asai S.  Miyachi H.  Suzuki K.  Shimamura K.  Ando Y. Ultrasonographic differentiation between tuberculous lymphadenitis and malignant lymph nodes. Journal of Ultrasound in Medicine.  20(5):533-8, 2001 May.


  OBJECTIVE: To assess the usefulness of ultrasonography in the differential diagnosis of cervical tuberculous lymphadenitis versus malignant lymph nodes. METHODS: Ultrasonography of cervical lymph nodes was performed with a real-time linear scanner using a 7.5- or 11-MHz probe or both. Ultrasonographic findings were retrospectively reviewed in 73 patients: 49 with malignant lymphoma, 15 with tuberculous lymphadenitis, and 9 with metastatic lymph nodes. RESULTS: Ultrasonographic features specific to cervical tuberculous lymphadenitis were strong echoes (33.3%) and an echogenic thin layer (86.7%). When the lymph nodes had at least 1 of these 2 features, tuberculous lymphadenitis was diagnosed with a sensitivity of 100% and a specificity of 100%. CONCLUSIONS: Ultrasonographic evaluation of cervical lymph nodes can be useful in the diagnosis of cervical tuberculous lymphadenitis.

3489.                        Ashford DA.  Whitney E.  Raghunathan P.  Cosivi O. Epidemiology of selected mycobacteria that infect humans and other animals. [Review] [156 refs] Revue Scientifique et Technique.  20(1):325-37, 2001 Apr.


  This paper provides a summary of salient clinical and epidemiological features of selected mycobacterial diseases that are common to humans and other animals. Clinical and diagnostic issues are discussed and related to estimates of the incidence and prevalence of these diseases among humans. Source of infection, route of transmission and control measures are also presented. The mycobacteria discussed in this paper are Mycobacterium bovis, M. ulcerans, M. leprae and M. avium complex, although this is by no means a complete list of the mycobacteria common to humans and other animals. Certain generalities can be made regarding these species of mycobacteria and their occurrence in humans and other animals; firstly, current understanding of the epidemiology and control of many of the resultant diseases is incomplete; secondly, environmental sources other than animal reservoirs may play a role in transmission (with M. leprae perhaps being the exception); and thirdly, the incidence and prevalence of these diseases in many countries of the world are unclear, principally because of the complexity of diagnosis and lack of reporting systems. [References: 156]


3490.                         Bedwell J.  Kairo SK.  Behr MA.  Bygraves JA. Identification of substrains of BCG vaccine using multiplex PCR. Vaccine.  19(15-16):2146-51, 2001 Feb 28.


Current methods for determining the identity of substrains of Mycobacterium bovis BCG (BCG) vaccine are labour intensive, or provide only limited substrain differentiation. In this paper we describe a multiplex PCR that distinguishes between M. tuberculosis (TB) and M. bovis and the non-pathogenic BCG strain, and also subdivides the BCG vaccine substrains investigated into seven distinct fingerprints based on six target regions in the DNA. This test is specific, rapid, reproducible and portable and is proposed as a novel test for BCG vaccine control. It offers substantial advantages over the methods currently in use. Using this test we have characterised a number of commercial BCG vaccines.


3491.                        Behr MA. Comparative genomics of BCG vaccines. [Review] [30 refs] Tuberculosis.  81(1-2):165-8, 2001.


  Bacille Calmette-Guérin (BCG) vaccines have been given to more people than any other vaccine. They have also probably resulted in as much controversy as any other vaccine. In clinical trials, the efficacy of BCG vaccination against pulmonary TB has been widely variable. At the same time, a number of investigators have observed phenotypic differences between BCG daughter strains, raising the possibility that differences between BCG products may in some way translate into different outcomes. With recent genomic analysis of BCG strains, it has become possible to piece together the molecular events that have resulted in current BCG vaccines. Between the derivation of BCG in 1921 and the lyophilization of BCG Pasteur 1173 in 1961, there have been at least seven genetic events, including deletions, duplications and a single nucleotide polymorphism. The phenotypic relevance of these changes in BCG vaccines remains to be explored. Copyright 2001 Harcourt Publishers Ltd. [References: 30]

3492.                         Bhat S, Singal N, Aggrawal C S, Jain R C. Knowledge, attitudes and practices of newly diagnosed sputum positive cases of pulmonary tuberculosis. J Commun Dis. 31(4):247-52, 1999. No Abstract.

3493.                        Boudiaf M.  Soyer P.  Terem C.  Pelage JP.  Maissiat E.  Rymer R. Ct evaluation of small bowel obstruction. [Review] [36 refs]  Radiographics.  21(3):613-24, 2001 May-Jun.


  Although small bowel obstruction is a common occurrence, it is essential that this clinical condition be treated properly, that the site, level, and cause of obstruction be determined accurately, and that a tentative prognosis be formulated prior to surgery. The diagnosis of small bowel obstruction is based on a comprehensive approach that includes clinical background, patient history, and results of physical examination and laboratory tests. A variety of radiologic procedures are available to aid in the diagnosis of small bowel obstruction. Recent studies have demonstrated the superiority of CT in revealing the site, level, and cause of obstruction and in demonstrating threatening signs of bowel inviability. CT has proved useful in characterizing small bowel obstruction from extrinsic causes (adhesions, closed loop, strangulation, hernia, extrinsic masses), intrinsic causes (adenocarcinoma, Crohn disease, tuberculosis, radiation enteropathy, intramural hemorrhage, intussusception), intraluminal causes (eg, bezoars), or intestinal malrotation. Conventional radiography was the modality of choice for many years and should remain the initial imaging method in patients with suspected small bowel obstruction. However, the unique capabilities of CT in this setting make this modality an important additional diagnostic tool when specific disease management issues must be addressed. [References: 36]

3494.                        Brock I.  Munk ME.  Kok-Jensen A.  Andersen P. Performance of whole blood IFN-gamma test for tuberculosis diagnosis based on PPD or the specific antigens ESAT-6 and CFP-10. International Journal of Tuberculosis & Lung Disease.  5(5):462-7, 2001 May.


  OBJECTIVE: To evaluate the QuantiFERON-TB test in BCG-vaccinated, non-BCG-vaccinated and tuberculosis (TB) patient donor groups, and to compare its diagnostic performance with that of a blood test based on the Mycobacterium tuberculosis specific antigens ESAT-6 and CFP-10. DESIGN: Analysis of the IFN-gamma responses of whole blood cells from BCG-vaccinated or non-BCG-vaccinated donors or patients with tuberculosis, stimulated with PPD, ESAT-6 or CFP-10 antigens, and evaluation of the specificity and sensitivity of the test. RESULTS: None of the non-vaccinated donors showed positive responses to M. tuberculosis-PPD, ESAT-6 or CFP-10. In BCG-vaccinated donors, 9/19 (47%) donors responded to the QuantiFERON-TB test based on M. tuberculosis-PPD, whereas 2/19 (10.5%) responded to either ESAT-6 or CFP-10. Comparable levels of sensitivity were obtained with the QuantiFERON-TB test based on M. tuberculosis-PPD (79%) and ESAT-6 or CFP-10 antigens (72%). CONCLUSION: Our results demonstrate that the whole blood test based on M. tuberculosis-PPD did not efficiently distinguish BCG-vaccinated donors from individuals with disease due to M. tuberculosis. The introduction of new recombinant antigens specific for M. tuberculosis, such as ESAT-6 or CFP-10, should increase the specificity of the whole blood test and enable discrimination between TB infection, atypical mycobacterial reactivity and reactivity due to BCG vaccination. Such a test would provide a quantum improvement over the current practice of using the tuberculin skin test for TB control and elimination.

3495.                        Burgess LJ.  Swanepoel CG.  Taljaard JJ. The use of adenosine deaminase as a diagnostic tool for peritoneal tuberculosis. Tuberculosis.  81(3):243-8, 2001.


  SETTING: Tygerberg Hospital, an academic hospital in the Western Cape, South Africa.Objective: To determine the diagnostic utility of ascitic fluid adenosine deaminase (ADA) in the diagnosis of tuberculous peritonitis. DESIGN: A prospective study, carried out from February 1995 to February 1998, resulted in 178 paired ascites and serum specimens being collected from adult patients. Specimens were evaluated for biochemistry, ADA, microbiology and cytology; further investigations were done at the treating clinician's discretion. Diagnoses were made according the pre-determined criteria. RESULTS: The median (range) ADA activity in the tuberculous group was 61.6 (17.5--115.0) U/L and was significantly higher than in any other diagnostic group (p<0.05). Using ROC curves, a cut-off level of 30 U/L for the diagnosis of tuberculous peritonitis was found to yield the best results; corresponding sensitivity and specificity was 94% and 92%, respectively. No statistically significant difference in ADA activity was observed when tuberculous ascites occurred in the absence or presence of cirrhosis. CONCLUSIONS: Ascitic fluid ADA activity is useful in identifying those patients in whom the diagnosis of tuberculous peritonitis should be actively pursued to justify its routine use, at least in areas such as South Africa where TB is endemic. The presence or absence of underlying cirrhosis does not appear to distract from its diagnostic utility. Copyright 2001 Harcourt Publishers Ltd.

3496.                        Cayli SR.  Onal C.  Kocak A.  Onmus SH.  Tekiner A. An unusual presentation of neurotuberculosis: subdural empyema. Case report. Journal of Neurosurgery.  94(6):988-91, 2001 Jun.


  Tuberculosis continues to be a major public health concern, especially in developing countries. Many types of neurotuberculosis have been described, but there is only one previously reported case of subdural empyema caused by tuberculous bacilli. A 1-year-old boy who had been treated for pulmonary tuberculosis was referred to the authors' institution with a diagnosis of right frontoparietal extraaxial abscess formation. Computerized tomography and magnetic resonance imaging revealed an extraaxial abscess with no evidence of calvarial infection. A craniotomy was performed to drain the pus, which was located subdurally. A polymerase chain reaction test yielded positive results, and histopathological examination revealed caseation. Antituberculous treatment was started after a diagnosis of subdural empyema with related neurotuberculosis had been made. At the end of a 12-month course of medical therapy, the patient was well with no evidence of tuberculosis.

3497.                         Cheng WF.  Hung CF.  Chai CY.  Hsu KF.  He L.  Rice CM.  Ling M.  Wu TC. Enhancement of Sindbis virus self-replicating RNA vaccine potency by linkage of Mycobacterium tuberculosis heat shock protein 70 gene to an antigen gene. Journal of Immunology.  166(10):6218-26, 2001 May 15.


  Recently, self-replicating RNA vaccines (RNA replicons) have emerged as an effective strategy for nucleic acid vaccine development. Unlike naked DNA vaccines, RNA replicons eventually cause lysis of transfected cells and therefore do not raise the concern of integration into the host genome. We evaluated the effect of linking human papillomavirus type 16 E7 as a model Ag to Mycobacterium tuberculosis heat shock protein 70 (HSP70) on the potency of Ag-specific immunity generated by a Sindbis virus self-replicating RNA vector, SINrep5. Our results indicated that this RNA replicon vaccine containing an E7/HSP70 fusion gene generated significantly higher E7-specific T cell-mediated immune responses in vaccinated mice than did vaccines containing the wild-type E7 gene. Furthermore, our in vitro studies demonstrated that E7 Ag from E7/HSP70 RNA replicon-transfected cells can be processed by bone marrow-derived dendritic cells and presented more efficiently through the MHC class I pathway than can wild-type E7 RNA replicon-transfected cells. More importantly, the fusion of HSP70 to E7 converted a less effective vaccine into one with significant potency against E7-expressing tumors. This antitumor effect was dependent on NK cells and CD8(+) T cells. These results indicated that fusion of HSP70 to an Ag gene may greatly enhance the potency of self-replicating RNA vaccines.

3498.                        Chiang CY.  Yu MC.  Bai KJ.  Suo J.  Lin TP.  Lee YC. Pulmonary resection in the treatment of patients with pulmonary multidrug-resistant tuberculosis in Taiwan.  International Journal of Tuberculosis & Lung Disease.  5(3):272-7, 2001 Mar.


  SETTING: Chronic Disease Control Bureau, Department of Health, Taiwan. OBJECTIVE: To evaluate the role of pulmonary resection in the treatment of pulmonary tuberculosis resistant to isoniazid and rifampin (MDR-TB). DESIGN: In a retrospective cohort study, 27 MDR-TB patients who underwent pulmonary resection between December 1990 and March 1999 were reviewed. Individually-tailored treatment regimens were selected at a once-weekly staff conference following review of the patient's case history and drug susceptibility results. Surgery was performed for selected patients, essentially those: 1) whose medical treatment had failed, or for whom treatment failure seemed highly likely, or for whom post-treatment relapse seemed likely, 2) with predominantly localised disease, 3) with adequate cardiopulmonary reserve, and 4) whose treatment regimen had been composed of at least two effective drugs to diminish the mycobacterial burden. RESULTS: There was no surgical mortality apart from one peri-operative death (4%). Three patients (11%) developed complications, and 24 (92%) patients demonstrated sputum conversion and/or remained negative after surgery. Twenty-three patients have already completed treatment, and during a mean of 42 +/- 18 follow-up months (range 15-80 months), one patient relapsed. This patient was disease-free after another course of treatment. CONCLUSION: For selected patients, pulmonary resection may improve the outcome of pulmonary MDR-TB.

3499.                        Cho SN.  Choi BW.  Ra SY.  Hong YK.  Park JS.  Kim SC.  Kim JD.  Choe KO. Prevalence of antibodies to PPD and lipoarabinomannan of Mycobacterium tuberculosis among patients with an indication of fine needle aspiration biopsy. Yonsei Medical Journal.  42(3):324-32, 2001 Jun.


  Recent increase in the incidence of lung cancer often makes it difficult to differentiate between lung cancer and tuberculosis (TB), due to their radiologic similarities. Fine needle aspiration biopsy (FNAB) has been widely employed for the diagnosis of lung cancer and TB, but the diagnostic accuracy of TB is not high enough. As a rapid screening test for tuberculosis, we evaluated serological tests using Mycobacterium tuberculosis PPD and lipoarabinomannan (LAM) antigens. A total of 95 patients with indication of FNAB cytology from initial CT findings were enrolled. 25 patients had TB, 76 thoracic malignancy, and six (7.9%) of the lung cancer patients also had TB, indicating much higher prevalence of TB in thoracic tumor patients. Antibodies to PPD were elevated in 18 (72.0%) of 25 TB patients and in 22 (31.4%) of 70 patients with thoracic malignancy. In contrast, only 3 (4.7%) of 64 healthy controls aged 40 or above were seropositive to PPD antigen. The prevalence of anti-PPD antibodies in thoracic tumor patients was therefore significantly greater than that amongst the healthy controls (p<0.001, chi-square test). However, no significant difference in the prevalence of anti-LAM antibodies was found between study subjects and controls. This study demonstrates that thoracic tumor patients have significantly elevated antibodies to PPD; therefore, high anti-PPD seroreactivity in thoracic tumor patients should be cautiously interpreted. A longitudinal investigation on seropositive thoracic tumor patients is required to determine the role of the serological test for TB in lung cancer patients.

3500.                        Chowdhury A.  Santra A.  Kundu S.  Mukherjee A.  Pandit A.  Chaudhuri S.  Dhali GK. Induction of oxidative stress in antitubercular drug-induced hepatotoxicity. Indian Journal of Gastroenterology.  20(3):97-100, 2001 May-Jun.


  BACKGROUND AND AIM: Oxidative stress could play a role in the pathogenesis of antitubercular drug (ATD)-induced hepatotoxicity. We therefore studied the plasma level of reduced glutathione (GSH) and malondialdehyde (MDA) in patients with ATD-induced hepatotoxicity (cases), ATD-treated controls (disease controls) and in healthy volunteers. METHODS: This study was carried out in a case-control design. Twenty-one cases, 21 age- and sex-matched disease controls, and 10 healthy volunteers were enrolled. Plasma levels of GSH and MDA were measured. RESULTS: Plasma levels of GSH (median [range] 11.5 [6.2-21.2] mmol/dL) and MDA (1390 [560-2310] nmol/dL) of cases were significantly different (p<0.01) from GSH (18.4 [10.5-24.4]) and MDA (290 [240-550]) of disease controls. Further, plasma GSH and MDA levels of both the ATD-treated groups were different from those in healthy controls. CONCLUSION: Lower levels of plasma GSH and higher levels of MDA may be due to oxidative stress resulting from ATD therapy.

3501.                        Chugh K. Clinical approach to a patient with cough.  Indian Journal of Pediatrics.  68  Suppl 2:S11-9, 2001 Apr.


  A number of disorders of the respiratory tract and some even outside the respiratory tract can cause cough. A systematic approach towards a patient of chronic cough consisting of detailed history, physical examination of upper as well as lower respiratory tract, complete blood counts, tuberculin test, chest X-ray, and peak flow rate testing will give the diagnosis in majority of children. Pulmonary tuberculosis and asthma are the two commonest conditions diagnosed. If the initial work up is inconclusive, further laboratory testing and imaging studies should be considered. Thus, radiolabelled milk scan, barium swallow and 24-hour pH monitoring would diagnose gastroesophageal reflux. Spirometry, methacholine/exercise challenge test or a therapeutic trial may be required for confirming bronchial asthma. Flexible bronchoscopy is useful for evaluation for suspected aspiration syndromes and any anatomical or dynamic problem of the airway (e.g. tracheomalacia). Spiral and high resolution computed tomography (HRCT) along with magnetic resonance imaging are the modern day imaging techniques used for studying mediastinal masses, airway obstruction and even lung parenchyma (HRCT). Sputum examination for type of cells and bacteria can be useful, especially if pseudomonas or acid-fast bacilli are identified. Pseudomonas suggests cystic fibrosis (an uncommon disease in India) which can be confirmed by sweat chloride test and gene mutation studies.


3502.                        Colaco C. Stressed bacteria and TB vaccines. Trends in Immunology.  22(8):418, 2001 Aug.

3503.                        Dabiri S.  Meymandi SS.  Nadji M.  Kharazmi A. A description of parasite-harbouring cells in localized lymphadenitis in dry type cutaneous leishmaniasis.  Acta Tropica.  79(2):129-33, 2001 May 25.


  Lymphadenitis with or without dry-type cutaneous leishmaniasis is rare. The lesion might self heal or show excellent response to antimonial therapy. Routine histopathological changes of localized leishmaniasis lymphadenitis are non-caseating to suppurative granulomata mostly in paracortical areas, some with extension to germinal centres, medullary cords and/or pericapsular spaces which have to be distinguished from other causes of lymphadenitis such as tuberculosis, cat-scratch disease and toxoplasmosis. Dense lymphoplasmocytic infiltrate was observed surrounding the necrotizing granuloma together with dense capsular fibrosis with multiple granulomata in subcapsular and pericapsular areas. Immunostaining of lymph nodes showed that a few macrophages were harbouring Leishman bodies. Dispersed Langerhans cells were also harbouring Leishman bodies in the parasitophorous vacuoles between their cytoplasmic pseudopods. In conclusion multiple noncaseating to suppurative granulomata with dense pericapsular and capsular granulomo-sclerotic changes should be considered in the differential diagnosis of leishmaniasis lymphadenitis.

3504.                         Dannenberg AM Jr.  Collins FM. Progressive pulmonary tuberculosis is not due to increasing numbers of viable bacilli in rabbits, mice and guinea pigs, but is due to a continuous host response to mycobacterial products. [Review] [107 refs] Tuberculosis.  81(3):229-42, 2001.


  Tuberculosis (TB) kills more people in the world today than any other infectious disease. A better vaccine to prevent clinical tuberculosis is greatly needed. Candidate vaccines are often evaluated by infecting rabbits, mice and guinea pigs by an aerosol of virulent tubercle bacilli and culturing their lungs for viable bacilli at various times thereafter. In all three species, however, the number of viable bacilli usually does not continuously increase until the host succumbs. The number of viable bacilli increases logarithmically for only about 3 weeks. Then, the host develops delayed-type hypersensitivity (DTH) and cell-mediated immunity (CMI), which keep the number of viable bacilli rather constant during the subsequent weeks. In the immunized host, DTH and CMI stop the logarithmic increase sooner than in the unimmunized controls, so that the stationary bacillary levels that follow are lower. This review analyzes host-parasite interactions in the lungs of rabbits, mice and guinea pigs. All three species cannot prevent inhaled fully virulent tubercle bacilli from establishing an infection, but they differ markedly in the type of the disease produced once it is established. Copyright 2001 Harcourt Publishers Ltd. [References: 107]

3505.                        Dannenberg AM Jr.  Pathogenesis of pulmonary Mycobacterium bovis infection: basic principles established by the rabbit model. [Review] [39 refs] Tuberculosis.  81(1-2):87-96, 2001.

3506.                         de Lisle GW.  Mackintosh CG.  Bengis RG.  Mycobacterium bovis in free-living and captive wildlife, including farmed deer. [Review] [151 refs] Revue Scientifique et Technique.  20(1):86-111, 2001 Apr.


  Mycobacterium bovis has been isolated from a wide range of wildlife species, in addition to domestic animals. This review examines the role played by various species in the maintenance of M. bovis in wildlife communities and the spread to domestic animals. Badgers (Meles meles), brushtail possums (Trichosurus vulpecula), deer (Odocoileus virginianus), bison (Bison bison) and African buffalo (Syncerus caffer) are examples of wildlife that are maintenance hosts of M. bovis. The importance of these hosts has been highlighted by the growing realisation that these animals can represent the principal source of infection for both domestic animals and protected wildlife species. The range of methods for controlling M. bovis in wildlife is limited. While population control has been used in some countries, this approach is not applicable in many situations where protected wildlife species are concerned. Vaccination is a potential alternative control method, although as yet, no practical, effective system has been developed for vaccinating wildlife against bovine tuberculosis. Tuberculosis caused by M. bovis has also been a problem in captive wildlife and in recently domesticated animals such as farmed deer. Control of M. bovis in this group of animals is dependent on the judicious use of diagnostic tests and the application of sound disease control principles. The advances in the development of bovine tuberculosis vaccines for cattle and farmed deer may offer valuable insights into the use of vaccination for the control of tuberculosis in a range of captive wildlife species. [References: 151]

3507.                         Delogu G.  Brennan MJ. Comparative immune response to PE and PE_PGRS antigens of Mycobacterium tuberculosis. Infection & Immunity.  69(9):5606-11, 2001 Sep.


3508.                         Desarkar S, Chaudhiri T K, Datta K B. Certain facts and findings about immunodiagnostics of human pulmonary tuberculosis. Perspective Cytol Genet.(10):95-101, 2001. No Abstract.


3509.                         Dixit R, Gupta R.C, Gupta M.L, Gupta N: Asmptomatic duodenal tuberculosis in HIV positive patient. Cure med Trends 4(3):729-4,2000.  No Abstract.


  Sequencing of the entire genome of Mycobacterium tuberculosis identified a novel multigene family composed of two closely related subfamilies designated PE and PE_PGRS. The major difference between these two families is the presence of a domain containing numerous Gly-Ala repeats extending to the C terminus of the PE_PGRS genes. We have used a representative PE_PGRS gene from M. tuberculosis, Rv1818c (1818PE_PGRS), and its amino-terminal PE region (1818PE), to investigate the immunological response to these proteins during experimental tuberculosis and following immunization with DNA constructs. During infection of mice with M. tuberculosis, a significant humoral immune response was observed against recombinant 1818PE_PGRS but not toward the 1818PE protein. Similarly, immunization with a 1818PE_PGRS DNA construct induced antibodies directed against 1818PE_PGRS but not against 1818PE proteins, and no humoral response was induced by 1818PE DNA. These results suggest that certain PE_PGRS genes are expressed during infection of the host with M. tuberculosis and that an antibody response is directed solely against the Gly-Ala-rich PGRS domain. Conversely, splenocytes from 1818PE-vaccinated mice but not mice immunized with 1818PE_PGRS secreted gamma interferon following in vitro restimulation and demonstrated protection in the mouse tuberculosis challenge model. These results suggest that the PE vaccine can elicit an effective cellular immune response and that immune recognition of the PE antigen is influenced by the Gly-Ala-rich PGRS domain.


3510.                         Dowdy L.  Ramgopal M.  Hoffman T.  Ciancio G.  Burke G.  Roth D.  Mies C.  Jones B.  Miller J. Genitourinary tuberculosis after renal transplantation: report of 3 cases and review. [Review] [8 refs] Clinical Infectious Diseases.  32(4):662-6, 2001 Feb 15.


  Mycobacterium tuberculosis infection of the genitourinary tract is an uncommon disease in renal transplant recipients and presentation is atypical. Genitourinary tuberculosis is associated with graft rejection, and this diagnosis should be considered for renal transplant recipients with unexplained fever and constitutional symptoms. [References: 8]


3511.                         No Abstract.

3512.                         No Abstract.


3513.                         E Raji Nair, S Banerjee, MVR Reddy, S Kumar & BC Harinath. Isolation of Mycobacterium tuberculosis 31 kDa antigen protein of diagnostic interest from culture filtrate using anti ES-31 antibody by affinity chromatography. Ind. J. Clin. Biochem. 2001; 16: 132-135.


Proteins secreted into the culture medium by Mycobacterium tuberculosis are shown to be source of antigens of immunodiagnostic interest. An in vitro released 31 kDa antigen ESAS-7F isolated from M.tb H37Ra culture filtrate by salt precipitation, SDS-PAGE and cation exchange fast protein liquid chromatography (FPLC) was shown earlier to be a diagnostically important antigen fraction. In this report, we describe the isolation of ESAS-7F antigen using monospecific antibody coupled to sepharose CL-4B column.The percentage recovery of ESAS-7F antigen using affinity chromatography was approximately 8% of the total ES antigen proteins compared to 0.05% obtained by conventional purification steps using salt precipitation, SDS-PAGE and FPLC. Similar seroreactivity was observed by the antigen isolated by both the methods in indirect ELISA. Affinity chromatography helped in an increased recovery of ESAS-7F antigen and obviates the need for time consuming conventional purification steps .

3514.                         E Raji Nair, Swati Banerjee,  Satish Kumar, MVR Reddy & BC Harinath. Purification and characterization of a 31 kDa mycobacterial excretory-secretory antigenic protein with a diagnostic potential in pulmonary tuberculosis. Indian J Chest Dis Allied Sci 2001; 43:81-90.

3515.                        Eastwood JB.  Corbishley CM.  Grange JM. Tuberculosis and the kidney. [Review] [49 refs] Journal of the American Society of Nephrology.  12(6):1307-14, 2001 Jun.

3516.                        Emler S.  Feldmann K.  Giacuzzo V.  Hewitt PL.  Klapper PE.  Lagrange PH.  Wilkins EW.  Young KK.  Herrmann JL. Multicenter evaluation of a pathogenic mycobacterium screening probe. Journal of Clinical Microbiology.  39(7):2687-9, 2001 Jul.


  The introduction of nucleic acid amplification assays into the clinical laboratory has reduced the time needed to diagnose diseases caused by members of the Mycobacterium tuberculosis complex (MTBC). However, several mycobacterial species other than those of the MTBC are known to cause disease, especially in immunocompromised individuals. A screening assay has been developed for the detection of the major pathogenic mycobacterial species. The assay utilizes pan-genus primers to amplify mycobacterial DNA and a screening probe (KY493) that detects all major pathogenic mycobacteria. A multicenter European study was conducted to assess the performance of the screening probe in the clinical laboratory. The screening probe was evaluated against individual probes specific for M. tuberculosis, M. avium, and M. intracellulare, a genus-specific probe with broader species coverage, and culture. The screening probe had a sensitivity equivalent to that of the species-specific probes; all specimens positive with any of the species-specific probes were also positive with the screening probes. Compared to culture, the sensitivity of the screening probe was 89% (154 of 173) for all culture-positive specimens tested. This value was 89.6% for the genus-specific probe. The screening probe was more specific than the genus-specific probe. Specificity was 93.9% (661 of 704) compared to culture results alone. The comparable specificity value for the genus-specific probe was 84.8%. When clinical data were taken into consideration, the sensitivity of the screening assay was similar to that of culture (81% versus 76.2%) but the positive predictive value of the test was lower (76.2% versus 100% for culture). However, the screening probe was more sensitive than smear and may be a useful tool in the rapid diagnosis of mycobacterial disease.


3517.                        Enserink M.  Driving a stake into resurgent TB. Science.  293(5528):234-5, 2001 Jul 13.

3518.                        Farrington DM.  Melini de Paz F.  Moral Pinteno JC. Slipped capital femoral epiphysis associated with peripheral osteoarticular tuberculosis. Journal of Pediatric Orthopaedics. Part B.  10(2):96-100, 2001 Apr.


  We report a case of slipped capital femoral epiphysis that developed associated with a peripheral osteoarticular tuberculosis lesion located at the proximal metaphysis of the femur in contact with the growth plate in a 12-year-old boy. Multiple factors have been involved in slipped capital femoral epiphysis pathogenesis, but we believe an osteoarticular tuberculosis lesion is not a common finding as a possible etiological factor causing weakness of the growth plate and, therefore, the femoral head displacement.

3519.                        Fietta A.  Morosini M.  Cascina A. Effects of continuous or pulsed exposure to rifabutin and sparfloxacin on the intracellular growth of Staphylococcus aureus and Mycobacterium tuberculosis.  Journal of Chemotherapy.  13(2):167-75, 2001 Apr.


  The time-kinetics of the intracellular bioactivity and intracellular post-antibiotic effect (PAE) of rifabutin and sparfloxacin against Staphylococcus aureus and Mycobacterium tuberculosis, grown in human monocytes, were evaluated. Intracellular bactericidal activity against staphylococci was shown in the presence of extracellular drug concentrations equal or superior to 1/10 plasma Cmax. The bactericidal activity of rifabutin was dependent on both its extracellular concentrations and the exposure time. In contrast, the pattern of the intracellular activity of sparfloxacin was characterized by a minimal concentration dependent killing. Both antibiotics (from 1/10 to the expected lung Cmax) showed intracellular bioactivity against M. tuberculosis H37Ra and H37Rv strains. A long intracellular PAE on staphylococci (>4 hours) was demonstrated when drugs were removed from the infected monocytes after 1 h treatment. Our findings suggest that rifabutin and sparfloxacin may be useful in the treatment of lower respiratory tract infections due to intracellular pathogens.


3520.                        Fine PE. BCG: the challenge continues. [Review] [16 refs] Scandinavian Journal of Infectious Diseases.  33(4):243-5, 2001.


  It is widely recognized that BCG provides inconsistent and often inadequate protection against tuberculosis; however, simple estimates of efficacy fail to reflect the complexity of protection within, let alone between, populations. A decline in protection with an increase in age at vaccination has been seen in many studies. This may reflect 2 things: (i) that as people age they are exposed to a variety of mycobacterial challenges which may interfere with, or mask, the protection of BCG; and/or (ii) that the vaccine is better at protecting against primary disease than against either reactivation- or reinfection-type disease. These factors need to be taken into consideration when interpreting the results obtained with screening vaccines in animal models, as most of these models mimic acute primary-type disease. In addition, we have no evidence that the protection induced by BCG lasts for > 15 y, in any population. Recent data from South India indicate a complex interaction of age and time effects: BCG imparted consistent protection in children, but no protection for subjects > 15 y old, and may even have imparted negative protection among these older individuals. If true, these findings have important implications for efforts to develop a vaccine against adult pulmonary tuberculosis. [References: 16]

3521.                        Floros J.  Wang G. A point of view: quantitative and qualitative imbalance in disease pathogenesis; pulmonary surfactant protein A genetic variants as a model. [Review] [62 refs] Comparative Biochemistry & Physiology. Part A, Molecular & Integrative Physiology.  129(1):295-303, 2001 May.


  The high degree of similarity at the molecular level, between humans and other species, has provided the rationale for the use of a variety of species as model systems in research, resulting in enormous advances in biological sciences and medicine. In contrast, the individual variability observed among humans, for example, in external physique, organ functionality and others, is accounted for, by only a fraction of 1% of differences at the DNA level. These small differences, which are essential for understanding disease pathogenesis, have posed enormous challenges in medicine, as we try to understand why patients may respond differently to drugs or why one patient has complications and another does not. Differences in outcome are most likely the result of interactions among genetic components themselves and/or the environment at the molecular, cellular, organ, or organismal level, or the macroenvironment. In this paper: (1) we consider some issues for multifactorial disease pathogenesis; (2) we provide a review of human SP-A and how the knowledge gained and the characteristics of the hSP-A system may serve as a model in the study of disease with multifactorial etiology; and (3) we describe examples where hSP-A has been used in the study of disease. [References: 62]


3522.                        Freeman R.  Magee J.  Barrett A. Identifying sputum specimens of high priority for examination by enhanced mycobacterial detection, identification, and susceptibility systems (EMDISS) to promote the rapid diagnosis of infectious pulmonary tuberculosis. Journal of Clinical Pathology.  54(8):613-6, 2001 Aug.


  AIMS: To compare clinical information and sputum microscopy as methods for the selection of samples for enhanced mycobacterial detection, identification, and susceptibility systems (EMDISS) to promote the rapid diagnosis of patients with infectious pulmonary tuberculosis. METHODS: Two thousand, two hundred and sixty four specimen request forms were examined for clinical details, which were then used to identify specimens likely to yield Mycobacterium tuberculosis on culture. These results were compared with the results of sputum microscopy for acid fast bacilli (AFB). Both methods were assessed against the results of culture using a combination of continuous automated mycobacterial liquid culture (CAMLiC) and conventional solid culture. RESULTS: Classification based on clinical details was an inefficient method of identifying high priority specimens for EMDISS. Although, when given, clinical details were often consistent, a substantial proportion of specimens arrived with no details. This approach would result in the referral of at least 16% of the workload but lead to the detection by culture of only 46% of the M tuberculosis present within it. In contrast, microscopy for AFB defined a much smaller number of specimens (4.8% of the total), which contained 90% of the M tuberculosis isolates. CONCLUSIONS: Microscopy for AFB is the most efficient method for defining sputum specimens suitable for referral for enhanced mycobacteriological techniques. However, it is essential that the methods used for smear preparation and microscopy are of the highest possible standard, otherwise some patients with infectious pulmonary tuberculosis will be denied, unnecessarily, the benefits of important advances in mycobacteriology.

3523.                        Garg P.  Godara R.  Karwasra RK.  Jain R.  Yadav V. A palpably enlarged hard gall bladder can be tubercular. Indian Journal of Gastroenterology.  20(3):120, 2001 May-Jun.

3524.                        Gennaro MC.  Calvino R.  Abrigo C. Ion interaction reagent reversed-phase high-performance liquid chromatography determination of anti-tuberculosis drugs and metabolites in biological fluids. Journal of Chromatography. B, Biomedical Sciences & Applications.  754(2):477-86, 2001 Apr 25.


  New methods of ion interaction reagent (IIR) RP-HPLC are presented for the determination of anti-tuberculosis drugs and their metabolites, singly or in multi-component mixtures, in biological fluids. The following analytes are considered: isoniazid, ethionamide, pyrazinamide, morphazinamide, p-aminosalicylic acid, nicotinic and isonicotinic acids. Aqueous solutions of three different ion interaction reagents are alternatively or comparatively used as the mobile phases, namely: (A) 5.00 mM octylamine at pH 3.00 for o-phosphoric acid, (B) 5.00 mM octylamine at pH 8.00 for o-phosphoric acid, and (C) 5.00 mM 1,6 diaminohexane at pH 6.00 for o-phosphoric acid. The response linearity between peak area and analyte concentration is verified for all the analytes in the concentration range within the determination limits and 2.00 mg/l. Detection limits are always lower than 82 microg/l for standard solutions; in the analysis of samples of rat serum, rat plasma and human serum, the matrix effect is negligible, the detection limits are always lower than 94 microg/l and the average recovery yield is always greater than 96%.


3525.                         Gladych E.  Goland S.  Attali M.  Somin M.  Malnick SD. Cardiac tamponade as a manifestation of tuberculosis. [Review] [29 refs] Southern Medical Journal.  94(5):525-8, 2001 May.


  Tuberculosis has been increasing in incidence in recent years. Pericardial involvement and pericardial effusions are well-documented and may result in pericardial tamponade. Despite this, large pericardial effusions are uncommon, and manifestation as cardiac tamponade is rare. We report two cases of tuberculous pericarditis in which the initial feature was tamponade. Since the diagnosis of tuberculosis may be delayed due to the slow-growing nature of the bacterium, physicians need to be aware of this possibility and consider the use of modern diagnostic techniques that may permit an earlier diagnosis. [References: 29]

3526.                         Goloubeva V.  Lecocq M.  Lassowsky P.  Matthys F.  Portaels F.  Bastian I. Evaluation of mycobacteria growth indicator tube for direct and indirect drug susceptibility testing of Mycobacterium tuberculosis from respiratory specimens in a Siberian prison hospital. Journal of Clinical Microbiology.  39(4):1501-5, 2001 Apr.


  The manual Mycobacteria Growth Indicator Tube (MGIT) method was evaluated for performing direct and indirect drug susceptibility testing (DST) of Mycobacterium tuberculosis for isoniazid and rifampin on 101 strongly smear-positive sputum specimens in a Siberian prison hospital. Using the indirect method of proportion (MOP) as the "gold standard," the accuracies of isoniazid and rifampin susceptibility testing by the direct MGIT system were 97.0 and 94.1%, respectively. The accuracy of the indirect MGIT system was 98.0% for both drugs. The turnaround times from specimen processing to reporting of the DST results ranged between 4 and 23 (mean, 9.2) days by the direct MGIT method, 9 and 30 (mean, 15.3) days by the indirect MGIT method, and 26 and 101 (mean, 59.6) days by the indirect MOP. MGIT appears to be a reliable, rapid, and convenient method for performing direct and indirect DSTs in low-resource settings, but further studies are required to refine the direct DST protocol. Cost is the only factor prohibiting widespread implementation of MGIT.

3527.                         Govender S.  Parbhoo AH.  Kumar KP.  Annamalai K. Anterior spinal decompression in HIV-positive patients with tuberculosis.  A prospective study. Journal of Bone & Joint Surgery - British Volume.  83(6):864-7, 2001 Aug.


  total of 39 HIV-infected adults with spinal tuberculosis underwent anterior spinal decompression for neurological deficit. Fresh-frozen allografts were used in 38 patients. Antituberculous drugs were prescribed for 18 months, but antiretroviral therapy was not used. Six patients died within two years of surgery. Neurological recovery and allograft incorporation were observed at follow-up at a mean of 38 months, although the CD4/CD8 ratios were reversed in all patients. Adequate preoperative nutritional support and compliance with antituberculous treatment are essential in ensuring a satisfactory outcome.

3528.                         Graham SM.  Coulter JB.  Gilks CF. Pulmonary disease in HIV-infected African children. [Review] [93 refs] International Journal of Tuberculosis & Lung Disease.  5(1):12-23, 2001 Jan.


  Childhood human immunodeficiency virus (HIV) infection is common in most regions of sub-Saharan Africa. Acute and chronic respiratory diseases are major causes of morbidity and mortality in HIV-infected children. They represent a significant added burden in a region where diagnostic capabilities are limited and management decisions are often made on the basis of clinical guidelines alone. Pneumocystis carinii pneumonia is now recognised as an important cause of acute severe pneumonia and death in HIV-infected infants. However, there are few data on incidence and aetiology for more treatable conditions such as bacterial pneumonia. The association of pulmonary tuberculosis and HIV infection is uncertain, and the diagnosis is further confused by the presence of lymphoid interstitial pneumonitis and other chronic HIV-related pulmonary disease. This article reviews the literature and highlights the urgent need for further research in order to improve clinical management and appropriate interventions. [References: 93]

3529.                        No Abstract.

3530.                        No Abstract.


3531.                        Gupta R.  Kim JY.  Espinal MA.  Caudron JM.  Pecoul B.  Farmer PE.  Raviglione MC. Public health. Responding to market failures in tuberculosis control. Science.  293(5532):1049-51, 2001 Aug 10.

3532.                        No Abstract.

3533.                        No Abstract.

3534.                        Hawken MP.  Muhindi DW.  Chakaya JM.  Bhatt SM.  Ng'ang'a LW.  Porter JD. Under-diagnosis of smear-positive pulmonary tuberculosis in Nairobi, Kenya. International Journal of Tuberculosis & Lung Disease.  5(4):360-3, 2001 Apr.


  SETTING: Nairobi City Council Chest Clinic, Nairobi, Kenya. OBJECTIVE: To determine if under-reading of sputum smears is a contributing factor in the disproportionate increase in smear-negative tuberculosis in Nairobi, Kenya. METHODOLOGY: Between October 1997 and November 1998, patients fulfilling the local programme definition of smear-negative presumed pulmonary tuberculosis were enrolled in the study. Two further sputum specimens were collected for examination in a research laboratory by fluorescence microscopy. RESULTS: Of 163 adult subjects enrolled, 55% were seropositive for the human immunodeficiency virus type 1 (HIV-1). One hundred subjects had had two pre-study sputum smears assessed before recruitment and produced two further sputum specimens for re-examination in the research laboratory; of these 19 (19%) were sputum smear-positive on re-examination and a further seven (7%) became smear-positive on second re-examination. CONCLUSIONS: Of those patients with smear-negative presumed pulmonary tuberculosis by the local programme definition, 26% were smear-positive when reexamined carefully with two repeat sputum smears. This suggests that the high rates of smear-negative tuberculosis being seen may in part be due to under-reading. This is probably as a result of the overwhelming burden of tuberculosis leading to over rapid and inaccurate sputum examination. Retraining of existing technicians and training of more technicians is likely to reduce underreading and increase the yield of smear-positive tuberculosis. This finding also stresses the need for regular quality assurance.

3535.                        Hodsdon WS.  Luzze H.  Hurst TJ.  Quigley MA.  Kyosiimire J.  Namujju PB.  Johnson JL.  Kaleebu P.  Okwera A.  Elliott AM. HIV-1-related pleural tuberculosis: elevated production of IFN-gamma, but failure of immunity to Mycobacterium tuberculosis. AIDS.  15(4):467-75, 2001 Mar 9.


  BACKGROUND: Pleural tuberculosis can resolve spontaneously, suggesting that the inflammatory process may represent a protective immune response. However, pleural tuberculosis is strongly associated with HIV infection. It has been suggested that cell-mediated immune responses may be reduced, and direct bacterial invasion may have a role in pathogenesis, in HIV-positive cases. To test this hypothesis, we compared production of the pro-inflammatory cytokines, interferon (IFN)-gamma and tumour necrosis factor(TNF)-alpha, production of the immunosuppressive cytokine, interleukin (IL)-10, and mycobacterial culture positivity, in HIV-negative and HIV-positive patients with pleural tuberculosis. METHODS: Cytokine levels were measured in serum and pleural fluid, and in supernatants of blood and pleural fluid stimulated in vitro using mycobacterial antigens. Intracellular IFN-gamma and TNF-alpha production was measured after stimulation with phorbol myristate acetate and ionomycin in vitro. RESULTS: IFN-gamma was strikingly elevated in serum and pleural fluid in HIV-positive, compared to HIV-negative subjects (P < or = 0.02). TNF-alpha was elevated, but this was not statistically significant. IL-10 levels were higher in serum (P < 0.001), but similar in pleural fluid. IFN-gamma responses to soluble mycobacterial antigen in vitro were reduced in peripheral blood (P = 0.006), but not pleural fluid, of HIV-positive subjects. Intracellular cytokine staining suggested that CD8+ T cells were a major source of IFN-gamma in HIV-positive subjects. The proportion of subjects with a positive culture for Mycobacterium tuberculosis from pleural fluid was higher in the HIV-positive group. CONCLUSIONS: HIV-positive patients with pleural tuberculosis show elevated production of IFN-gamma, for which CD8+ T cells may be a major source. Mycobacterium tuberculosis can proliferate despite high levels of pro-inflammatory cytokines.

3536.                         Hup AK.  Haitjema T.  de Kuijper G. Primary nasal tuberculosis. Rhinology.  39(1):47-8, 2001 Mar.


  We present a case of a patient with primary nasal tuberculosis. Although this is a rare finding, it should be considered when a patient presents with a nasal obstruction. Smears for acid fast bacilli and cultures tend to be negative in nasal tuberculosis. Diagnosis is often based on histo- pathologic findings. Nasal TB is known to respond well to the regular treatment for (pulmonary) tuberculosis.


3537.                         Jaruratanasirikul S.  Sriwiriyajan S. Effect of indinavir on the pharmacokinetics of rifampicin in HIV-infected patients. Journal of Pharmacy & Pharmacology.  53(3):409-12, 2001 Mar.


  Indinavir, an antiretroviral agent, has an influence on the pharmacokinetics of other drugs by acting as an inhibitor of cytochrome P450-mediated drug metabolism. The incidence of tuberculosis has increased dramatically in the past decade because of an epidemic of HIV infection. Rifampicin is still one of the most valuable drugs for the standard treatment of tuberculosis. The objective of this study was to investigate the effects of indinavir on the pharmacokinetics of rifampicin in man. Our study was conducted in eleven HIV-infected patients. All patients received a 600-mg single dose of oral rifampicin on day 1 and 15- and 800-mg oral indinavir three times a day from day 2 to day 15. Rifampicin pharmacokinetic studies were carried out on day 1 and day 15. The results showed that rifampicin concentrations were higher when it was administered with indinavir than when it was administered alone. With concomitant indinavir medication, the mean AUC0-24 of rifampicin was increased by 73%. Therefore, we conclude that indinavir has an inhibitory effect on the metabolism of rifampicin.

3538.                         Jensen-Cain DM.  Quinn FD.  Differential expression of sigE by Mycobacterium tuberculosis during intracellular growth. Microbial Pathogenesis.  30(5):271-8, 2001 May.


  The Mycobacterium tuberculosis sigE gene encodes a sigma factor that is a member of the extracytoplasmic function subfamily of sigma factors. Using RT-PCR we demonstrated that sigE is expressed in M. tuberculosis bacilli during growth in human macrophages beginning after 30 min but before 6 h after infection through at least 5 days after infection, but that sigE is not expressed by M. tuberculosis bacteria during growth in Middlebrook 7H9 broth medium. However, sigE expression can be induced by treatment of broth cultures with hydrogen peroxide. Further, sigE is not expressed by M. tuberculosis bacilli during attachment or growth in type II pneumocytes. Using a green fluorescent protein (GFP) reporter gene fused to the sigE promoter, we observed induction of GFP expression following macrophage infection. Western blotting confirmed that sigE protein expression correlated with mRNA expression in induced systems. Analysis of the region of the M. tuberculosis genome encoding sigE suggested it is part of an operon consisting of sigE-orf1-htrA-orf2. The data presented in this report showed that sigE is differentially expressed by M. tuberculosis bacilli in macrophages and might play a role in the pathogenesis of this organism. Copyright 2001 Crown Copyright.


3539.                        Jepson A.  Fowler A.  Banya W.  Singh M.  Bennett S.  Whittle H.  Hill AV. Genetic regulation of acquired immune responses to antigens of Mycobacterium tuberculosis: a study of twins in West Africa.  Infection & Immunity.  69(6):3989-94, 2001 Jun.


  The role of genetic factors in clinical tuberculosis is increasingly recognized; how such factors regulate the immune response to Mycobacterium tuberculosis in healthy individuals is unclear. In this study of 255 adult twin pairs residing in The Gambia, West Africa, it is apparent that memory T-cell responses to secreted mycobacterial antigens (85-kDa antigen complex, "short-term culture filtrate," and peptides from the ESAT-6 protein), as well as to the 65-kDa heat shock protein, are subject to effective genetic regulation. The delayed hypersensitivity response to intradermal tuberculin also demonstrates significant genetic variance, while quantitative T-cell and antibody responses to the 38-kDa cell membrane protein appear to be determined largely by environmental factors. Such findings have implications for vaccine development.


3540.                         John MA.  Coovadia YM. Shortfalls in the use of adenosine deaminase in tuberculous meningitis.  Tropical Doctor.  31(3):138-9, 2001 Jul.


3541.                         Jungblut PR.  Muller EC.  Mattow J.  Kaufmann SH. Proteomics reveals open reading frames in Mycobacterium tuberculosis H37Rv not predicted by genomics. Infection & Immunity.  69(9):5905-7, 2001 Sep.


  Genomics revealed the sequence of 3924 genes of the H37Rv strain of Mycobacterium tuberculosis. Proteomics complements genomics in showing which genes are really expressed, and here we show the expression of six genes not predicted by genomics, as proved by two-dimensional electrophoresis and matrix-assisted laser desorption ionization and nano-electrospray mass spectrometry.

3542.                        No Abstract.

3543.                        No Abstract.

3544.                         Karcic AA.  Maudar V.  Karcic E. An elderly woman with chronic knee pain and abnormal chest radiography. Postgraduate Medical Journal.  77(911):600, 606-7, 2001 Sep.

3545.                         No Abstract.

3546.                         Kataria YP.  Khurshid I. Adenosine deaminase in the diagnosis of tuberculous pleural effusion. [letter; comment]. Chest.  120(2):334-6, 2001 Aug.


3547.                         Kaul KL. Molecular detection of Mycobacterium tuberculosis: impact on patient care. Clinical Chemistry.  47(8):1553-8, 2001 Aug.


  BACKGROUND: Nucleic acid amplification technologies such as PCR are revolutionizing the detection of infectious pathogens such as tuberculosis (TB). Amplification technology offers the potential for the diagnosis of TB in a few hours with a high degree of sensitivity and specificity. However, molecular assays neither replace nor reduce the need for conventional smear and culture, speciation, and antibiotic sensitivity assays. METHODS: We undertook prospective studies of sputum samples to assess the performance of two PCR-based assays for the detection of TB as well as the impact of more rapid availability of test results on patient care. RESULTS: The sensitivity of both the in-house and Amplicor PCR assays was 100% for smear-positive sputa. For smear-negative sputa (two sputum samples collected during the first 24 h of hospitalization), the sensitivity was 85% for our in-house PCR assay and 74% for the Roche PCR assay. Approximately 10% of the smear- and culture-negative sputa yielded positive PCR results; however, more than one-half of these were positive with both the in-house and Amplicor assays, suggesting the presence of TB DNA or organisms. Several of these came from patients whose other samples grew Mycobacterium tuberculosis during the same admission, and others came from patients who had previously treated TB. Overall, the specificities of the in-house and Amplicor PCR assays in smear-negative patients were 86% and 93%, respectively. CONCLUSIONS: Molecular detection of slow-growing pathogens such as M. tuberculosis have the potential to improve clinical care through a dramatic reduction in the time required for detection and may provide substantial savings in the overall cost of care of a patient compared with conventional smear, culture, and speciation alone, despite the fact that conventional assays must still be performed for speciation of nontuberculous mycobacteria and for full assessment of antibiotic sensitivity.

3548.                         Khan MY.  Kinsara AJ.  Osoba AO.  Wali S.  Samman Y.  Memish Z. Increasing resistance of M. tuberculosis to anti-TB drugs in Saudi Arabia. International Journal of Antimicrobial Agents.  17(5):415-8, 2001 May.


  The incidence of drug resistance in Mycobacterium tuberculosis (MTB) isolated from our hospital between April 1996 and March 1998 was compared with an earlier study (1993-1995). Thirty (29.7%) of 101 MTB isolates were resistant to one or more anti-TB drugs and 21 (20%) of 101 were multi-drug resistant M. tuberculosis (MDR-TB). Resistance was most common to isoniazid (28.7%), followed by streptomycin (22.8%) and rifampicin (20.8%). Resistance to pyrazinamide and ethambutol was 7.9 and 6.9%, respectively. There was a three-fold increase in resistance compared with the earlier study.

3549.                         Kindler T.  Schindel C.  Brass U.  Fischer T.  Fatal sepsis due to mycobacterium tuberculosis after allogeneic bone marrow transplantation. Bone Marrow Transplantation.  27(2):217-8, 2001 Jan.


  Mycobacterium tuberculosis is a serious, but rare infectious complication after allogeneic bone marrow transplantation. We describe a case of fatal sepsis due to Mycobacterium tuberculosis after allogeneic bone marrow transplantation for Philadelphia chromosome-positive ALL. The diagnosis was made after BAL. Although broad-spectrum antituberculous therapy was started immediately after diagnosis, blood cultures became positive for Mycobacterium tuberculosis. The patient developed severe pyrexias and finally died of multi-organ failure. Rapid progression of mycobacterial infection should be considered in patients post BMT with unexplained fever, particularly in patients from endemic areas.



3550.                         Kotnis R.  Simo R. Tuberculous meningitis presenting as sensorineural hearing loss. Journal of Laryngology & Otology.  115(6):491-2, 2001 Jun.


  We report a 60-year-old male who presented to the Otorhinolaryngology department with an acute unilateral sensorineural hearing loss associated with fever and night sweats. The diagnosis of tuberculous meningitis was made. Unilateral sensorineural hearing loss as a presenting symptom of tuberculous meningitis has not been previously reported.

3551.                         Krayem AB.  Abdullah LS.  Raweily EA.  Wali SO.  Rawas MM.  Samman YS.  Batouk AA. The diagnostic challenge of pulmonary Kaposi's sarcoma with pulmonary tuberculosis in a renal transplant recipient: a case report. Transplantation.  71(10):1488-91, 2001 May 27.


  We report a case of a 39-year-old, HIV-negative, post renal transplant patient who developed mucocutaneous Kaposi's sarcoma with lung parenchymal involvement and concurrently culture proven pulmonary tuberculosis. To the best of our knowledge, this is the first case report of this combination, which presented with cavitating lung nodules and responded well to withdrawal of immunosuppressive drugs beside antituberculous treatment.


3552.                         No Abstract.

3553.                        Kuo PH.  Yang PC.  Kuo SS.  Luh KT. Severe immune hemolytic anemia in disseminated tuberculosis with response to antituberculosis therapy. Chest.  119(6):1961-3, 2001 Jun.


  Severe hemolytic anemia in patients with disseminated tuberculosis is exceedingly rare. We report an episode of Coombs'-positive hemolytic anemia in a previously healthy young man with miliary tuberculosis, resulting in a hemoglobin level of 5 g/dL and an undetectable haptoglobin level. The patient responded well to treatment with antituberculosis drugs, and the results of the direct Coombs' test became negative without the need of blood transfusion or steroid therapy.

3554.                         Lalvani A.  Pathan AA.  Durkan H.  Wilkinson KA.  Whelan A.  Deeks JJ.  Reece WH.  Latif M.  Pasvol G.  Hill AV. Enhanced contact tracing and spatial tracking of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells. Lancet.  357(9273):2017-21, 2001 Jun 23.


  BACKGROUND: Identification of individuals latently infected with Mycobacterium tuberculosis is an important part of tuberculosis control. The current method, the tuberculin skin test (TST), has poor specificity because of the antigenic cross-reactivity of purified protein derivative (PPD) with M bovis BCG vaccine and environmental mycobacteria. ESAT-6 is a secreted antigen that is highly specific for M tuberculosis complex, but is absent from M bovis BCG. With an enzyme-linked immunospot (ELISPOT) assay for interferon gamma, we have identified ESAT-6-specific T cells as an accurate marker of M tuberculosis infection. METHODS: We did a prospective, masked study of 50 healthy contacts, with varying but well defined degrees of exposure to M tuberculosis, who attended an urban contact-tracing clinic. We assessed and compared the efficacy of our assay and TST for detection of symptomless infected individuals by correlation of test results with the degree of exposure to an infectious index case. FINDINGS: The ESAT-6 ELISPOT assay results had a strong positive relation with increasing intensity of exposure (odds ratio=9.0 per unit increase in level of exposure [95% CI 2.6--31.6], p=0.001), whereas TST results had a weaker relation with exposure (1.9 [1.0--3.5], p=0.05). By contrast, ELISPOT results were not correlated with BCG vaccination status (p=0.7), whereas TST results were significantly more likely to be positive in BCG-vaccinated contacts (12.1 [1.3--115.7], p=0.03). INTERPRETATION: This new antigen-specific T cell-based assay could allow more accurate identification of symptom-free individuals recently exposed to M tuberculosis, and thereby help to improve tuberculosis control.


3555.                        Landowski CP.  Godfrey HP.  Bentley-Hibbert SI.  Liu X.  Huang Z.  Sepulveda R.  Huygen K.  Gennaro ML.  Moy FH.  Lesley SA.  Haak-Frendscho M. Combinatorial use of antibodies to secreted mycobacterial proteins in a host immune system-independent test for tuberculosis. Journal of Clinical Microbiology.  39(7):2418-24, 2001 Jul.


  Laboratory diagnosis of tuberculosis is often difficult. Immunodetection of circulating Mycobacterium tuberculosis proteins shed during active infection would not depend on an intact host immune response and could take advantage of the speed and low costs afforded by antibody-based assays. We previously showed that patients with active tuberculosis had increased levels of circulating antigen 85 (Ag85) proteins independent of their tuberculin skin test status (S. I. Bentley-Hibbert, X. Quan, T. Newman, K. Huygen, and H. P. Godfrey, Infect. Immun. 67:581-588, 1999). To extend these observations to a Mycobacterium bovis BCG-vaccinated population and to another secreted mycobacterial protein, Ag85 and PstS-1 (protein antigen B, p38 antigen) were quantified in sera from 97 Chilean tuberculosis patients and healthy controls (many of whom had received BCG as children) using dot immunobinding, mouse monoclonal anti-BCG Ag85 complex antibody, and chicken antipeptide antibodies reactive with M. tuberculosis Ag85B and PstS-1. The latter antibodies had been raised to peptide-derived immunogens expressed on a novel proprietary protein carrier in Escherichia coli. Median serum Ag85 levels measured by using either anti-Ag85 antibody were significantly higher in patients with active tuberculosis than in healthy controls (P, <0.001 to 0.01); the median serum PstS-1 levels were similar in patients and controls. The sensitivity of significantly elevated circulating Ag85 levels in patients with pulmonary tuberculosis measured by anti-Ag85 complex or anti-Ag85B antibodies was 60 and 55%, respectively, but increased to 77% when results obtained with both anti-Ag85 antibodies were considered jointly (P < 0.02). The corresponding specificities for individual and joint consideration were 95, 85, and 80%, respectively. These results indicate that elevated Ag85 levels can be detected in patients with active tuberculosis even after BCG vaccination and suggest that combinatorial use of antibodies directed at different epitopes of this protein could provide a viable strategy for developing new host immune response-independent diagnostic tests for tuberculosis.

3556.                         Laserson KF.  Kenyon AS.  Kenyon TA.  Layloff T.  Binkin NJ. Substandard tuberculosis drugs on the global market and their simple detection. International Journal of Tuberculosis & Lung Disease.  5(5):448-54, 2001 May.


  SETTING: The prevalence of substandard anti-tuberculosis drugs is unknown. To maximize the effectiveness of tuberculosis (TB) control efforts, simple, inexpensive drug quality screening methods are needed. DESIGN: Isoniazid (INH) and rifampin (RMP) single- and fixed-dose combination (FDC) formulations were collected from selected TB programs and pharmacies in Colombia, Estonia, India, Latvia, Russia and Vietnam. Samples were screened using a recently developed thin-layer chromatography (TLC) kit. All abnormal samples and a 40% random sample of normal formulations were further analyzed using confirmatory techniques. Samples outside of 85% to 115% of stated content, and/or containing compounds other than the stated drug, were defined as being substandard. RESULTS: Overall, 10% (4/40) of all samples, including 13% (4/30) RMP samples, contained <85% of stated content. More FDCs (5/24, 21%) than single-drug samples (2/16, 13%) were substandard. A comparison of TLC with the confirmatory analysis for RMP analysis showed a sensitivity of 100% (4/4), a specificity of 92% (24/26), a positive predictive value (PPV) of 67% (4/6), and a negative predictive value (NPV) of 100% (24/24). An analysis of INH showed a specificity of 90% (9/10). However, sensitivity, PPV, and NVP could not be determined. CONCLUSION: A substantial number of anti-tuberculosis drugs from several countries, in particular FDCs, were found to be substandard. Such drugs may contribute to the creation of drug-resistant TB. TLC is an effective, convenient, and inexpensive method for the detection of substandard drugs.

3557.                         Lawn SD.  Griffin GE. The irreversible cost of delayed diagnosis of tuberculosis in HIV co-infected persons in sub-Saharan Africa. International Journal of Tuberculosis & Lung Disease.  5(2):200-1, 2001 Feb. 

3558.                         Lee DG.  Choi JH.  Kim YJ.  Lee S.  Min CK.  Kim DW.  Lee JW.  Min WS.  Shin WS.  Kim CC. Hepatosplenic tuberculosis mimicking disseminated candidiasis in patients with acute leukemia. International Journal of Hematology.  73(1):119-21, 2001 Jan.


  Two cases of hepatosplenic tuberculosis in patients with acute leukemia during or after chemotherapy following prolonged neutropenia are presented. Tuberculosis should be considered as one cause of hepatosplenic abscesses during prolonged neutropenia, especially in countries where the disease is endemic.

3559.                         Lee YC.  Rogers JT.  Rodriguez RM.  Miller  KD.  Light RW. Adenosine deaminase levels in nontuberculous lymphocytic pleural effusions. [see comments]. Chest.  120(2):356-61, 2001 Aug.


  OBJECTIVES: Adenosine deaminase (ADA) can aid in the diagnosis of tuberculous pleural effusions, but false-positive findings from lymphocytic effusions have been reported. We studied the ADA levels in a variety of nontuberculous lymphocytic effusions and analyzed the relationships between ADA and conventional hematologic and biochemical parameters. METHODS: One hundred six lymphocytic pleural fluid samples (lymphocyte count > 50%) were analyzed. These included post-coronary artery bypass grafting (CABG) effusions (n = 45), malignant effusions (n = 27), miscellaneous exudative effusions (n = 10), and transudative effusions (n = 24). ADA levels were determined using the Giusti method. In 22 randomly selected cases, ADA was measured again on the same sample 6 weeks later. RESULTS: The ADA level reached the diagnostic cutoff for tuberculosis (40 U/L) in only three cases (2.8%): two lymphomas and one complicated parapneumonic effusion. There was no significant correlation between effusion ADA levels and the total leukocyte (r = 0.08), differential lymphocyte (r = 0.18) or monocyte (r = - 0.18) counts. ADA levels were significantly lower in the transudative effusions (7.2 +/- 3.5 U/L) than in post-CABG (16.6 +/- 7.2 U/L), malignant (15.3 +/- 11.2 U/L), and other exudative (15.4 +/- 13.1 U/L) effusions (p < 0.001). ADA measurements were consistent when assayed 6 weeks apart (r = 0.95; p < 0.00001; coefficient of variation, 14%). CONCLUSIONS: ADA levels in nontuberculous lymphocytic effusions seldom exceeded the diagnostic cutoff for TB. Effusion ADA levels cannot be predicted from total or differential leukocyte counts. Post-CABG pleural fluids had ADA levels similar to other nontuberculous lymphocytic effusions. ADA is stable in effusion fluids, and its measurement is reproducible.


3560.                         Lodes MJ.  Dillon DC.  Mohamath R.  Day CH.  Benson DR.  Reynolds LD.  McNeill P.  Sampaio DP.  Skeiky YA.  Badaro R.  Persing DH.  Reed SG.  Houghton RL. Serological expression cloning and immunological evaluation of MTB48, a novel Mycobacterium tuberculosis antigen. Journal of Clinical Microbiology.  39(7):2485-93, 2001 Jul.


  Improved diagnostics are needed for the detection of Mycobacterium tuberculosis, especially for patients with smear-negative disease. To address this problem, we have screened M. tuberculosis (H37Rv and Erdman strains) genomic expression libraries with pooled sera from patients with extrapulmonary disease and with sera from patients with elevated reactivity with M. tuberculosis lysate. Both serum pools were reactive with clones expressing a recombinant protein referred to here as MTB48. The genomic sequence of the resulting clones was identical to that of the M. tuberculosis H37Rv isolate and showed 99% identity to the Mycobacterium bovis and M. bovis BCG isolate sequences. The genomic location of this sequence is 826 bp upstream of a region containing the esat-6 gene that is deleted in the M. bovis BCG isolate. The mtb48 1,380-bp open reading frame encodes a predicted 47.6-kDa polypeptide with no known function. Southern and Western blot analyses indicate that this sequence is present in a single copy and is conserved in the M. tuberculosis and M. bovis isolates tested but not in other mycobacterial species tested, including Mycobacterium leprae and Mycobacterium avium. In addition, the native protein was detected in the cytoplasm, as was a processed form that was also shed into the medium during culture. Serological analysis of recombinant MTB48 and the M. tuberculosis 38-kDa antigen with a panel of patient and control sera indicates that the inclusion of recombinant MTB48 in a prototype serodiagnostic test increases assay sensitivity for M. tuberculosis infection when it is combined with other known immunodominant antigens, such as the 38-kDa antigen.

3561.                         Manji KP.  Msemo G.  Tamim B.  Thomas E. Tuberculosis (presumed congenital) in a neonatal unit in Dar-es-Salaam, Tanzania. Journal of Tropical Pediatrics.  47(3):153-5, 2001 Jun.


  This is the first report of congenital tuberculosis from Tanzania. It discusses the problems of diagnosis in a typical neonatal unit in a developing country. Three cases are reported within 1 year. Failure to thrive was the most common symptom. We speculate that congenital tuberculosis is not rare and carries a high mortality. There is need to have a high index of suspicion especially where maternal HIV and tuberculosis are highly prevalent.

3562.                         No Abstract.

3563.                        Mathai A.  Radhakrishnan VV.  George SM.  Sarada C. A newer approach for the laboratory diagnosis of tuberculous meningitis. Diagnostic Microbiology & Infectious Disease.  39(4):225-8, 2001 Apr.


  In this prospective study, a simple method was standardized for measuring circulating mycobacterial antigen in the cerebrospinal fluid (CSF) for the laboratory diagnosis of tuberculous meningitis (TBM). The heat-inactivated CSF specimens from tuberculous and non-tuberculous patients were subjected to sodium dodecyl sulfate (SDS) - polyacrylamide gel electrophoresis (PAGE) (SDS-PAGE) and they were subsequently transferred onto nitrocellulose membrane (NCM) Using a rabbit polyvalent antibody to M tuberculosis, a heat stable 82 kDa mycobacterial antigen was demonstrated in the CSFs of patients with TBM. This antigen was conspicuous by its absence in the CSFs of non-tuberculous subjects. Due to inactivation of CSF specimens, there is a minimal risk of handling of infectious material in the laboratory. Besides, this newer approach is simple, inexpensive and can be readily applied in any routine clinical laboratory and it is particularly suited to developing countries.

3564.                        Mazade MA.  Evans EM.  Starke JR.  Correa AG. Congenital tuberculosis presenting as sepsis syndrome: case report and review of the literature. [Review] [19 refs] Pediatric Infectious Disease Journal.  20(4):439-42, 2001 Apr.


  We report an infant with congenital tuberculosis who presented with fulminant septic shock, disseminated intravascular coagulation and respiratory failure. Aggressive resuscitation and supportive care and prompt initiation of antituberculosis medications led to resolution of the shock state. We reviewed six other cases with a similar presentation. Congenital tuberculosis should be in the differential of the infant presenting acutely with sepsis syndrome. [References: 19]

3565.                        McMurray DN. A coordinated strategy for evaluating new vaccines for human and animal tuberculosis. [Review] [37 refs] Tuberculosis.  81(1-2):141-6, 2001.


  There is a remarkable convergence in the current efforts to develop and evaluate new tuberculosis (TB) vaccine candidates for use in humans, domestic animals, and wild animal reservoirs. It is quite likely that similar vaccination strategies will prove useful in these diverse host species. Many TB vaccine candidates are being screened for protective efficacy in conventional laboratory animals (e.g. mouse, guinea pig), in captive wild species under laboratory conditions (e.g. brushtail possum), and in the target hosts (e.g. cattle, deer). These systems share some important features, e.g. direct challenge infection of the lung by intratracheal or aerosol exposure, and the use of bacterial enumeration, and gross and microscopic histopathology, as the readouts. Some TB vaccine candidates have been tested in many models, yielding important insights into common mechanisms of resistance to Mycobacterium tuberculosis and M. bovis, and providing evidence of the vaccine's ability to induce protection under widely different circumstances. Coordination of this global search for better TB vaccines, irrespective of target species, would facilitate the rapid application of new technologies and maximize the sharing of materials and experiences between human and veterinary TB researchers. The creation of liaisons between TB vaccine research efforts of government-sponsored medical and agricultural research programs, international bodies such as the World Health Organization (WHO) and the European Community (EC), private foundations and the vaccine industry, will yield a high return. Copyright 2001 Harcourt Publishers Ltd. [References: 37]

3566.                         Mehra V.  Khanna H.  Chandra R.  Singh Y. Anthrax-toxin-mediated delivery of a 19 kDa antigen of Mycobacterium tuberculosis into the cytosol of mammalian cells. Biotechnology & Applied Biochemistry.  33(Pt 2):71-4, 2001 Apr.


  PA63, the proteolytically activated 63 kDa fragment of protective antigen (PA, 83 kDa), mediates translocation of lethal factor (LF) and oedema factor into the cytosol. The N-terminal 254 amino acids of LF (LFn) are required for binding to PA63 and mediating translocation of active ligands fused to either the N- or C-terminus. Here we report translocation of a 19 kDa antigen of Mycobacterium tuberculosis into the cytosol of mammalian cells when fused to the C-terminus of LFn (LFn-19kDa). The fusion protein was non-toxic to J774A.1 macrophage cells in combination with PA and retained the ability to bind to PA63 when incubated with Chinese hamster ovary K1 cells. The data show the efficacy of anthrax toxin to mediate translocation of M. tuberculosis antigens into the cytosol of mammalian cells and may prove useful in delivering proteins and peptides carrying immunodominant mycobacterial antigens into the cytosol.

3567.                         Merino JM.  Alvarez T.  Marrero M.  Anso S.  Elvira A.  Iglesias G.  Gonzalez JB. Microbiology of pediatric primary pulmonary tuberculosis. Chest.  119(5):1434-8, 2001 May.


  OBJECTIVE: To determine the sensitivity of bacteriologic studies in pediatric pulmonary tuberculosis. PATIENTS AND METHODS: Between January 1988 and December 1996, 104 consecutive patients aged 0 to 18 years received a diagnosis of primary pulmonary tuberculosis at our institution. Demographic, clinical, laboratory, and bacteriologic data were collected. Clinical specimens were studied for acid-fast bacilli detection by Ziehl-Neelsen stain and cultured for Mycobacterium recovery by Lowenstein-Jensen culture medium. Statistical analysis was performed utilizing chi(2), t tests, and multivariate logistic regression analysis. RESULTS: Bacteriologic results were available for 57 patients (54.8%). A positive smear or culture result for Mycobacterium tuberculosis was obtained in 9 of 54 patients (16.6%) and 25 of 50 patients (50%), respectively. Confirmation of M tuberculosis disease was achieved in 28 patients (49.1%). Ziehl-Neelsen stain and Lowenstein-Jensen culture recovery rates were 10.3% (14 of 135) and 52% (48 of 92) of specimens studied, respectively. Sputum, pleural fluid, and biopsy material cultures yielded M tuberculosis in 55%, 75%, and 63% of patients, respectively. Mean +/- SD age (13.7 +/- 4.5 years vs 9.6 +/- 4.5 years) and number of samples submitted for culture (1.93 +/- 0.94 vs 1.31 +/- 0.97) were significantly higher in the confirmed tuberculosis disease group (p < 0.05). The presence of a pleural effusion was also more commonly found in the confirmed tuberculosis disease group (p < 0.05). CONCLUSION: The sensitivity of bacteriologic studies in pediatric pulmonary tuberculosis disease was 49.1%. Age is the main factor associated with the positivity of culture results.

3568.                         Milburn HJ. Primary tuberculosis. [Review] [52 refs] Current Opinion in Pulmonary Medicine.  7(3):133-41, 2001 May.


  The natural history of tuberculosis is complex. Primary infection, the initial phase, occurs in people without specific immunity, generally normal children and young adults who have not previously been exposed to Mycobacterium tuberculosis. The initial infection can occur at any time during childhood, but adolescence is the peak time of risk. Primary disease develops within 5 years of the initial infection, which stimulates specific immunity, demonstrated by the development of a positive skin response to purified protein derivative of tuberculin. Although symptoms of primary disease may be few, early detection and treatment are important for both preventing the development of immediate complications, which carry a high risk of morbidity and mortality, and preventing spread of infection following later reactivation of disease. Our understanding of the host's immune response to the primary infection is increasing, and it is hoped this will lead to improved possibilities for vaccines in the future. [References: 52]

3569.                        Mohapatra PR. Direct observation of tuberculosis treatment. Lancet.  357(9269):1708, 2001 May 26.

3570.                         Montali RJ.  Mikota SK.  Cheng LI. Mycobacterium tuberculosis in zoo and wildlife species. [Review] [78 refs] Revue Scientifique et Technique.  20(1):291-303, 2001 Apr.


  Tuberculosis caused by Mycobacterium tuberculosis and M. tuberculosis-like organisms has been identified in a wide range of species, including non-human primates, elephants and other exotic ungulates, carnivores, marine mammals and psittacine birds. Disease associated with M. tuberculosis has occurred mostly within captive settings and does not appear to occur naturally in free-living mammals. Mycobacterium tuberculosis probably originated as an infection of humans, but from the zoonotic standpoint, non-human primates, Asian elephants and psittacine birds have the potential to transmit this disease to humans. However, the overall prevalence of disease in these susceptible species is low and documented transmissions of M. tuberculosis between animals and humans are uncommon. Mycobacterium tuberculosis causes progressive pulmonary disease in mammals and a muco-cutaneous disease in parrots. In all cases, the disease can disseminate and be shed into the environment. Diagnosis in living animals is based on intradermal tuberculin testing in non-human primates, culturing trunk secretions in elephants, and biopsy and culture of external lesions in parrots. Ancillary testing with deoxyribonucleic acid probes and nucleic acid amplification, and enzyme-linked immunosorbent assays have been adapted to some of these species with promising results. Additionally, new guidelines for controlling tuberculosis in elephants in the United States of America, and programmes for tuberculosis prevention in animal handlers have been established. [References: 78]


3571.                         Moran AJ.  Treit JD.  Whitney JL.  Abomoelak B.  Houghton R.  Skeiky YA.  Sampaio DP.  Badaro R.  Nano FE.  Assessment of the serodiagnostic potential of nine novel proteins from Mycobacterium tuberculosis. FEMS Microbiology Letters.  198(1):31-6, 2001 Apr 20.


  To identify antigens that would improve the accuracy of serological diagnosis of active tuberculosis, we cloned the genes encoding nine potentially immunogenic secreted or surface-associated proteins of Mycobacterium tuberculosis. Recombinant proteins were reacted with sera from HIV-negative individuals with extrapulmonary tuberculosis (EP-TB) or HIV-positive individuals with pulmonary tuberculosis (TBH). Specific and high level antibody responses were obtained for four recombinant proteins, of which antigen GST-822 was recognized by 60% of EP-TB and 42% of TBH and antigen MBP-506 was recognized by 45% of EP-TB and 61% of TBH. These results suggest that these proteins are strong candidates as subunits in a polyvalent serodiagnostic test.


3572.                         No Abstract.

3573.                        Murthy KJ.  Frieden TR.  Yazdani A.  Hreshikesh P. Public-private partnership in tuberculosis control: experience in Hyderabad, India. International Journal of Tuberculosis & Lung Disease.  5(4):354-9, 2001 Apr.


  SETTING: Hyderabad, India. OBJECTIVE: To determine whether private practitioners and the government can collaborate with a nongovernmental intermediary to implement DOTS effectively. DESIGN: A non-profit hospital provided DOTS services to a population of 100000 for 3 years, then expanded coverage to 500000 in October 1998. A hospital physician visited all private practitioners, encouraged them to refer patients, and gave feedback on each patient referred. After diagnosis, patients received directly observed treatment free of charge at the trust hospital or at 30 conveniently located small hospitals operated by local private practitioners. No financial incentives were used to encourage physicians to refer patients or to provide treatment observation. Diagnosis, treatment, and case and outcome definitions were performed as per DOTS policies; medicines and laboratory reagents were provided by the government. RESULTS: All 244 allopathic and 114 non-allopathic physicians practising in the area agreed to participate; 59% referred at least one patient. Of 2244 persons referred, 969 (43%) had tuberculosis. Physicians had obtained chest radiographs on 80% of patients before referral for sputum microscopy. The detection rate increased from 50 to 200/100000 over the first 2-3 years of the project, and has increased gradually since expansion; 90% of new smear-positive patients and 77% of re-treatment patients were successfully treated. Compared with those treated at a neighbouring government DOTS centre, patients in this project paid less for diagnosis ($5 vs. $20) and treatment ($1 vs. $11), largely due to lower transport costs. CONCLUSIONS: Collaborative efforts between private practitioners and the government can achieve moderate-high rates of case detection and high rates of treatment success. Public-private services appeared to be more convenient to patients, who paid less for care and were less likely to miss work in order to participate in DOTS. Clearly defined roles and expectations and frequent communication are essential to success. An institution such as a non-profit hospital can serve as an effective intermediary between the government DOTS programme and private practitioners.

3574.                        Naga MI.  Okasha HH.  Ismail Z.  El-Fatatry M.  Hassan S.  Monir BE. Endoscopic diagnosis of colonic tuberculosis. Gastrointestinal Endoscopy.  53(7):789-93, 2001 Jun.


  BACKGROUND: GI tuberculosis is a diagnostic challenge, particularly in the absence of evidence of pulmonary infection. It may mimic many other abdominal diseases such as other infectious processes, tumors, and Crohn's disease. In the absence of positive laboratory and radiologic tests, the diagnosis is often established definitively by obtaining a surgical specimen. Colonoscopy, however, has been used successfully to diagnose the disease and thus avoid the morbidity and mortality associated with exploratory laparotomy. METHODS: An evaluation was conducted of colonoscopic features in 10 patients with colonic tuberculosis. OBSERVATIONS: In all cases there was ileocecal involvement; total colonic involvement was found in only 1 case. The colonoscopic appearance included the following: ulcerated lesions, sessile firm polyps, masses, and small diverticula, ranging from 3 to 5 mm in diameter. In 5 of our patients the diagnosis was confirmed bacteriologically, in 3 with endoscopic biopsy material, and in 2 by sputum examination. In all cases antituberculous therapy produced remarkable symptom and endoscopic improvement. CONCLUSION: This report highlights the importance of colonoscopy in the diagnosis of tuberculous involvement of the GI tract.

3575.                        Nagesh BS.  Sehgal S.  Jindal SK.  Arora SK. Evaluation of polymerase chain reaction for detection of Mycobacterium tuberculosis in pleural fluid. Chest.  119(6):1737-41, 2001 Jun.


  OBJECTIVES: Tuberculosis, a reemergent killer, is threatening to assume serious proportions all over the world, particularly in view of the AIDS pandemic. The detection of mycobacterial DNA by polymerase chain reaction (PCR) in clinical samples is a promising approach for the rapid diagnosis of tuberculous infections. The aims of this study were to evaluate PCR for detection of Mycobacterium tuberculosis in pleural fluids and to correlate the results with adenosine deaminase activity (ADA) estimation and acid-fast bacilli (AFB) screening. METHODS: The sensitivity and specificity of PCR in detection of mycobacterial DNA in 20 samples of tuberculous pleural effusion were evaluated using 40 samples of nontubercular pleural effusion as controls. The results were correlated with the ADA in all 60 pleural fluids. In addition, AFB detection by Ziehl-Neelsen staining on cytospin smears of all pleural fluids was also compared. RESULTS: Of the 20 samples of tuberculous pleural effusion, mycobacterium could be detected by AFB staining in 4 samples. Fourteen samples were PCR positive. None of the samples from the control group were AFB or PCR positive. The sensitivity of PCR, therefore, was 70.0% with specificity of 100% (positive predictive value, 100%; negative predictive value, 86.95%). The sensitivity of AFB screening was at best 20%. The mean of ADA values in tubercular pleural effusions was 63.21 U/L (SD, 33.01), and the mean in the control samples was 51.1 U/L (SD, 29.71). Taking a cut-off value of 50 U/L, both the sensitivity and specificity of ADA estimation in diagnosing tuberculosis were only 55%. CONCLUSION: PCR represents a rapid and sensitive method for the detection of mycobacterial DNA in tuberculous pleural effusions. AFB screening has low sensitivity, and ADA estimation has both low sensitivity and specificity. Therefore, when the clinical suspicion is high and smear result is negative, but the signs and symptoms of M tuberculosis are apparent, PCR is the method of choice for identifying the infection.

3576.                         Nair ER.  Banerjee S.  Kumar S.  Reddy MV.  Harinath BC. Purification and characterization of a 31 kDa mycobacterial excretory-secretory antigenic protein with a diagnostic potential in pulmonary tuberculosis. Indian Journal of Chest Diseases & Allied Sciences.  43(2):81-90, 2001 Apr-Jun.

3577.                        No Abstract.

3578.                        No Abstract.

3579.                        Odunukwe NN.  Tuberculosis masquerading as 'constant malaria'. West African Journal of Medicine.  20(1):22-7, 2001 Jan-Mar.


  Four hundred adults aged 20-60 years, (200 females and 200 males) were studied. All the subjects were residing in the urban areas of Lagos, Nigeria. Thirteen percent claimed they were having "constant malaria" (> 8 times per year), 5% (20) claimed to have cough mostly during the cold period, 2.5% (10) produced mucoid sputum, 2.5% unproductive cough, 13% were AFB smear positive, 1.5% had positive chest X-ray for pulmonary Tuberculosis (PTB), 1.5% were HIV positive and 50% were mantoux positive (> 10 mm induration). All who complained of "constant malaria" were AFB positive. Malaria parasite density was lower in those who complained of "constant malaria" than those who did not complain (P = 0.003). The complaint of frequent malaria attack decreased after Antituberculosis therapy for 6 months. This study revealed that in a malaria and tuberculosis endemic region, early stage of tuberculosis can masquerade as "constant malaria". Therefore any such complaint should be fully investigated.

3580.                        Oh EJ.  Park YJ.  Chang CL.  Kim BK.  Kim SM. Improved detection and differentiation of mycobacteria with combination of Mycobacterium Growth Indicator Tube and Roche COBAS AMPLICOR System in conjunction with Duplex PCR. Journal of Microbiological Methods.  46(1):29-36, 2001 Jul 30.


  In this study, a combination of liquid and solid media (current "gold standard" for culture) with combinations of liquid media (Mycobacteria Growth Indicator Tube (MGIT)) plus a commercial amplification system (Roche COBAS AMPLICOR System (CAS)), and solid media (Ogawa) plus CAS for detection of Mycobacterium tuberculosis were compared. In addition, the ability of the MGIT to recover mycobacteria from various clinical samples was compared with the abilities of egg-based Ogawa medium using equal volume of samples and a high concentration (6%) of NaOH for decontamination. A total of 705 specimens (395 respiratory and 310 extrapulmonary) that were collected from 554 patients were tested in parallel with three assays. The results of MGIT and Ogawa were evaluated with the "gold standard" (combination of culture and clinical data) and those of CAS were evaluated with extended gold standard including treated tuberculosis. A total of 130 mycobacterial infections (M. tuberculosis, n=122; mycobacterium other than tuberculosis (MOTT), n=8) were detected. The differentiation of M. tuberculosis and MOTT was successfully accomplished using duplex PCR. The overall sensitivity of the MGIT, Ogawa, and CAS for M. tuberculosis was 89.9%, 73.9%, and 79.9%, respectively. For the MOTT, the corresponding values for the MGIT and Ogawa medium were 100% and 12.5%, respectively. The mean detection time for M. tuberculosis was 22 days using MGIT and 32 days when using the Ogawa medium. The specificity of CAS was 98.4%, with an inhibition rate of 1.4%. A combination of MGIT plus CAS detected 97.5% of all M. tuberculosis infections (compared with MGIT plus Ogawa, 91.8%, P<0.05; compared with Ogawa plus CAS, 87.7%. P<0.01). Our results indicate that a combination of MGIT plus a Roche CAS in conjunction with duplex PCR, would be quite useful in clinical laboratories for both rapid detection and differentiation of M. tuberculosis and MOTT.

3581.                        Orme IM. The search for new vaccines against tuberculosis. [Review] [106 refs] Journal of Leukocyte Biology.  70(1):1-10, 2001 Jul.


  The failure of the BCG vaccine for tuberculosis in large, controlled clinical trials, coupled with the gradual consensus that it is mostly ineffective in preventing adult pulmonary disease in endemic areas, has led to a concerted effort to develop a new generation of vaccines. This work is ongoing in a variety of areas, including DNA vaccines, subunit vaccines, recombinant vaccines, and auxotrophic vaccines. Several such candidates are giving promising results in mouse and guinea pig, aerosol-challenge infection models and should move to clinical trials in the near future. [References: 106]

3582.                        Packham S. Tuberculosis in the elderly. [Review] [24 refs] Gerontology.  47(4):175-9, 2001 Jul-Aug.


  Tuberculosis is still a major cause of morbidity and mortality worldwide. Recent studies have suggested that even in the developed world its incidence in the elderly is increasing. Symptoms of active tuberculosis are non-specific and less pronounced in the elderly. Radiological features are more likely to be 'atypical' in the older subject and skin tests more frequently negative. This results in delay in diagnosis and higher mortality from tuberculosis in the aged population. A high degree of clinical suspicion is therefore required to ensure the diagnosis is not missed and appropriate treatment instigated. Copyright 2001 S. Karger AG, Basel [References: 24]

3583.                         Prasad A.  Pandey KK. Tuberculous biliary strictures: uncommon cause of obstructive jaundice. Australasian Radiology.  45(3):365-8, 2001 Aug.


  Tuberculous biliary stricture is a very rare cause of obstructive jaundice. A case of a man who had had pulmonary tuberculosis 20 years ago is reported. He now presented with obstructive jaundice due to multiple strictures just below the confluence of the hepatic ducts and in the right hepatic duct. At surgery these turned out to be tuberculous in origin. There was also tuberculous involvement of the gall bladder and cystic duct. The commonest differential diagnosis in such cases is cholangiocarcinoma (as in the present case). Imaging helps in defining the extent of bile duct obstruction. Suspicion of the disease and establishing a tissue diagnosis is very important in treating this potentially curable condition, especially with the worldwide resurgence of tuberculosis.

3584.                         Preston I.  O'Brien A. Clues to an elusive effusion. Postpericardiotomy syndrome. Postgraduate Medicine.  109(5):131-2, 2001 May.

3585.                         Rahmatulla RH.  al-Mofleh IA.  al-Rashed RS.  al-Hedaithy MA.  Mayet IY.  Tuberculous liver abscess: a case report and review of literature. [Review] [11 refs] European Journal of Gastroenterology & Hepatology.  13(4):437-40, 2001 Apr.


  Tuberculous liver abscess is rare worldwide. We report a 45-year-old man who presented with abdominal pain, fever and weight loss. Ultrasound and computed tomography of the abdomen showed multiple cystic lesions in the liver. Ultrasound guided needle aspiration revealed yellowish brownish aspirate, which was flooded with acid-fast bacilli. The abscess was drained under ultrasound guidance. Subsequent abdominal ultrasound a few days later showed resolution of the abscess cavity. He was concomitantly started on systemic antituberculous therapy. A tuberculous liver abscess has to be thought of in the differential diagnosis of liver abscesses and to consider the role of percutaneous drainage along with systemic antituberculous chemotherapy as an alternative to surgery in the management. A greater awareness of this clinical entity is required for successful treatment. [References: 11]


3586.                         Rastogi N.  Legrand E.  Sola C. The mycobacteria: an introduction to nomenclature and pathogenesis. [Review] [192 refs] Revue Scientifique et Technique.  20(1):21-54, 2001 Apr.


  Tuberculosis, caused by Mycobacterium tuberculosis, and leprosy, caused by M. leprae, are diseases known since antiquity. In developing countries, tuberculosis is still the leading cause of mortality due to an infectious disease. Taxonomically, mycobacteria belong to the genus Mycobacterium, which is the single genus within the family of Mycobacteriaceae, in the order Actinomycetales. Actinomycetales include diverse micro-organisms, but mycobacteria and allied taxa are easily distinguished on the basis of the ability to synthesise mycolic acids. Mycobacterial species are traditionally differentiated on the basis of phenotypic characteristics, and the authors provide an updated list of the biochemical tests currently employed and the culture properties that help to discriminate among various species of mycobacteria. However, as the phenotypic characteristics do not allow precise identification of all species, recent molecular taxonomical approaches for mycobacterial classification and phylogeny are also described. Mycobacteria are also a leading cause of infection in various domesticated animals and wildlife. The authors briefly describe the mycobacteria involved in animal infections, the wildlife reservoirs and strategies to control bovine tuberculosis, and the use of molecular tools for diagnostics and epidemiology of mycobacterial infections in animals. The characteristic of intracellular parasitism is discussed, in addition to the fate of pathogenic mycobacteria that have the ability to grow inside phagosomes and phagolysosomes of infected host macrophages. The mycobacterial cell envelope, which is a complex tripartite structure containing a high proportion of lipids (approximately 30% to 40% of the total weight) could play a crucial role in the adaptation of mycobacteria to intracellular growth and survival, immune modulation and drug resistance. [References: 192]

3587.                         Ray G.  Banerjee PK.  Ghoshal UC.  Dhar K.  Pal BB.  Biswas AD.  Das U.  Saha ML.  Acharya AN.  Majumdar S. Etiology and management of obscure gastrointestinal bleed--an appraisal from eastern India. Indian Journal of Gastroenterology.  20(3):90-3, 2001 May-Jun.


  OBJECTIVES AND METHOD: Forty patients (mean age 45 years; 24 men) attending a tertiary care hospital in eastern India during the period 1996-2000 were investigated to evaluate the etiology and clinical spectrum of obscure gastrointestinal bleed. RESULTS: The patients presented to hospital after mean symptom duration of 2.5 years. They had received an average of 15 units of blood transfusion. Most patients presented with recurrent melena (85%); all had iron-deficiency anemia. A total of 230 investigations (89 gastroscopies, 54 colonoscopies, 25 double-contrast meal and follow-through studies, 14 small bowel enemas, 24 radionuclide scans, 16 mesenteric angiographies and 8 intraoperative endoscopies) yielded positive diagnosis in 87.5% of cases. The diseases encountered were small bowel and colonic angiodysplasias (32.5%), ileal Crohn's disease (20%), intestinal tuberculosis (10%), intestinal tumors (10%), nonspecific small bowel ulcers and strictures (7.5%), Meckel's diverticulum (5%) and hemobilia (2.5%). The etiology remained obscure in 5 (12.5%) cases. Overall success of surgery was 63%; in-hospital mortality was 7.5%. CONCLUSION: Though obscure gastrointestinal bleed is commonly caused by angiodysplasias, it can be an atypical presentation of Crohn's disease.

3588.                         Redha S.  Suresh RL.  Subramaniam J.  Merican I. Pancreatic tuberculosis presenting with recurrent acute pancreatitis. Medical Journal of Malaysia.  56(1):95-7, 2001 Mar.


  Tuberculosis, in its extrapulmonary form, though emerging as a common clinical problem, rarely affects the pancreas. Its indolent course, vague symptomatology along with its non-specific laboratory and radiographic findings call for greater vigilance. We report a case of pancreatic tuberculosis, previously managed as recurrent alcohol related pancreatitis which showed symptomatic improvement following commencement of antituberculosis drugs. The diagnosis of pancreatic tuberculosis in this case was based on the abdominal CT scan findings, response to anti-tubeculous chemotherapy and overall laboratory and radiological work-up.

3589.                         Robinson AJ.  Horne CA.  Weaver A. Coexistence of axillary tuberculous lymphadenitis with lymph node metastases from a breast carcinoma. Clinical Oncology (Royal College of Radiologists).  13(2):144, 2001.

3590.                         Rook GA.  Zumla A. Advances in the immunopathogenesis of pulmonary tuberculosis. [Review] [68 refs]  Current Opinion in Pulmonary Medicine.  7(3):116-23, 2001 May.


  Tuberculosis remains a global emergency because of our lack of understanding of the details of its pathogenesis. In the last 12 months there have been striking advances in the molecular genetics of the organism. Mutated strains of Mycobacterium tuberculosis have been used to study the genetic requirements for virulence and establishment of latency, and the biology of the interaction with host cells. Genes involved in lipid metabolism seem particularly important. The probable sites of latency within the host lungs have been identified by in situ polymerase chain reaction. The complex control by M. tuberculosis of apoptosis of T cells and macrophages has been somewhat clarified, and the data may suggest that M. tuberculosis causes death of a subset of T cells, while preserving some macrophages as hiding places with reduced microbicidal and antigen-presenting function. Similarly the demonstration of a very large relative increase in interleukin (IL)-4 and IL-13 expression, (together with IL-4delta2, the IL-4 splice variant), that correlates with lung damage, has been supported by data from flow cytometry and in situ hybridization, and indicates that a subversive T helper-2 (Th2) component in the response to M. tuberculosis may undermine the efficacy of immunity and contribute to immunopathology. Recently defined changes in metabolism of cortisol within the lesions may contribute to the development of the Th2 component. These findings underline the need to start testing vaccine candidates in models that mimic the situations in which bacille Calmette-Guerin fails, such as in the presence of latent infection, pre-existing Th2 responses to cross-reactive organisms, and stress. [References: 68]

3591.                         Russell DG.  Mycobacterium tuberculosis: here today, and here tomorrow. [Review] [70 refs] Nature Reviews Molecular Cell Biology.  2(8):569-77, 2001 Aug.


  Mycobacterium tuberculosis is a highly successful pathogen that parasitizes the macrophages of its host. Its success can be attributed directly to its ability to manipulate the phagosome that it resides in and to prevent the normal maturation of this organelle into an acidic, hydrolytic compartment. As the macrophage is key to clearing the infection, the interplay between the pathogen and its host cell reflects a constant battle for control. [References: 70]

3592.                         Saczek KB.  Schaaf HS.  Voss M.  Cotton MF.  Moore SW. Diagnostic dilemmas in abdominal tuberculosis in children. Pediatric Surgery International.  17(2-3):111-5, 2001 Mar.


  The authors review 45 pediatric patients with intra-abdominal tuberculosis (ATB) treated between May 1990 and April 1998. The diagnosis was confirmed histologically or by positive culture for Mycobacterium tuberculosis. Clinical presentation was with an abdominal mass (12), subacute obstruction (11), ascites (5), mass and ascites (4), peritonitis (4), and 9 unusual presentations. Mantoux tests were positive in 68% of patients tested. There were radiologic features suggestive of pulmonary TB in 29 patients (64%); abnormal abdominal radiographs were recorded in 21 (47%). Lymphadenopathy was noted on abdominal ultrasound in 23 of 30 patients (77%) and on computed tomography scan in a further 3 of 8 patients investigated. Ascitic fluid adenosine deaminase (ADA) levels were greater than 30 IU/l in 3 of 4 patients (75%), suggesting ATB. All 28 patients screened for human immunodeficiency virus were negative. A surgical procedure was performed in 39 patients. 29 (74%) had an elective diagnostic laparotomy for tissue diagnosis. One (3.4%) developed a postoperative intra-abdominal abscess. Ten (26%) presented with complications requiring surgical intervention including perforated viscus, segmental bowel resection, strictureplasty, adhesiolysis, or ileostomy. One of the latter died due to sepsis after having complications of persistent intestinal obstruction and cecal perforation. The authors recommend an aggressive approach to patients with suspected ATB in order to obtain an early definitive diagnosis, prevent complications, and reduce morbidity and mortality. They emphasize the importance of tissue diagnosis and confirmation by culture.

3593.                         Samanich K.  Belisle JT.  Laal S. Homogeneity of antibody responses in tuberculosis patients.  Infection & Immunity.  69(7):4600-9, 2001 Jul.


  The goals of the present study were twofold: (i) to compare the repertoires of antigens in culture filtrates of in vitro-grown Mycobacterium tuberculosis that are recognized by antibodies from noncavitary and cavitary tuberculosis (TB) patients and (ii) to determine the extent of variation that exists between the antigen profiles recognized by individual TB patients. Lipoarabinomannan-free culture filtrate proteins of M. tuberculosis were fractionated by one-dimensional (1-D) and 2-D polyacrylamide gel electrophoresis, and the Western blots were probed with sera from non-human immunodeficiency virus (non-HIV)-infected cavitary and noncavitary TB patients and from HIV-infected, noncavitary TB patients. In contrast to earlier studies based on recombinant antigens of M. tuberculosis which suggested that antibody responses in TB patients were heterogeneous (K. Lyashchenko et al., 1998, Infect. Immun. 66:3936-3940, 1998), our studies with native culture filtrate proteins show that the antibody responses in TB patients show significant homogeneity in being directed against a well-defined subset of antigens. Thus, there is a well-defined subset of culture filtrate antigens that elicits antibodies during noncavitary and cavitary disease. In addition, another set of antigens is recognized primarily by cavitary TB patients. The mapping with individual patient sera presented here suggests that serodiagnostic tests based on the subset of antigens recognized during both noncavitary and cavitary TB will enhance the sensitivity of antibody detection in TB patients, especially in difficult-to-diagnose, smear-negative, noncavitary TB patients.

3594.                         Sanchez-Perez H.  Flores-Hernandez J.  Jansa J.  Cayla J.  Martin-Mateo M. Pulmonary tuberculosis and associated factors in areas of high levels of poverty in Chiapas, Mexico. [see comments]. International Journal of Epidemiology.  30(2):386-93, 2001 Apr.


  OBJECTIVES: To estimate the prevalence of pulmonary tuberculosis (PTB) and factors associated with PTB in areas of high levels of poverty in Chiapas, Mexico. METHODS: In 1998 active case-finding was carried out among those aged over 14 years who had a cough of > or =15 days duration, in a convenience sample of 1894 households in 32 communities selected at random based on the level of poverty and on the level of access to health services, measured by travelling time (<1 hour, > or =1 hour) from the community to the nearest health care unit. Of the 277 identified with a productive cough, we obtained sputum samples from 228 for the purposes of detecting PTB through acid-fast smears and cultures. Mycobacteria characterization was carried out using the BACTEC method. The identification of factors associated with PTB was performed using bivariate analysis and via logistic regression models. RESULTS: A PTB rate of 276.9 per 100 000 persons aged > or =15 years was found (95% CI : 161-443). Blood in sputum was the only factor associated with PTB (none of the demographic or socioeconomic characteristics were). Of 16 positive cultures, 14 became contaminated. The two cultures characterized were Mycobacterium tuberculosis (one being multiresistant). CONCLUSION: The high prevalence of PTB detected indicates the need, both in the area studied and in others with similar conditions, to develop PTB control programmes which give priority to early diagnosis and to the provision of adequate treatment.


3595.                        No Abstract.

3596.                        No Abstract.

3597.                        No Abstract.

3598.                        No Abstract.

3599.                        Sharma SK.  Suresh V.  Mohan A.  Kaur P.  Saha P.  Kumar A.  Pande JN. A prospective study of sensitivity and specificity of adenosine deaminase estimation in the diagnosis of tuberculosis pleural effusion. Indian Journal of Chest Diseases & Allied Sciences.  43(3):149-55, 2001 Jul-Sep.


  We prospectively evaluated the usefulness of adenosine deaminase [ADA] estimation in the diagnosis of tuberculosis [TB] pleural effusion. Seventy five subjects with pleural effusion were studied. Forty eight of them had TB pleural effusion [M:F: 37:11; mean age 33 +/- 14.4 years range 17-76] and the remaining 27 had pleural effusion due to causes other than TB [non-TB group] [M:F: 19:8; mean age 47.3 +/- 16.5 years; range 17-75]. Pleural fluid [PF] ADA levels were significantly higher in TB (n=48; mean 95.8 +/- 57.5 IU/L) compared with non-TB group (n=27; mean 30.7 +/- 27.2 IU/L) [p<0.001]. Serum ADA [S-ADA] levels were also significantly higher in TB (n=45; mean 39.6 +/- 18.3 IU/L) compared with non-TB group (n=26; mean 18.0 +/- 13.7 IU/L) [p<0.001]. PF-ADA levels were higher compared to S-SDA in TB (p <0.001) and non-TB groups [p<0.01]. Using a cut off of 35 IU/L, the sensitivity and specificity of PF-ADA in the diagnosis of TB was computed to be 83.3% and 66.6% respectively. At a cut-off level of 100 IU/L, PF-ADA was found to have a sensitivity 40% and specificity 100%. From this study it is concluded that, using 100 IU/L as the cut-off, it is possible to avoid pleural biopsy to ascertain the diagnosis of TB in as much as 40% of the patients.

3600.                        Sheu SJ.  Shyu JS.  Chen LM.  Chen YY.  Chirn SC.  Wang JS. Ocular manifestations of tuberculosis. Ophthalmology.  108(9):1580-5, 2001 Sep.


  OBJECTIVE: To present the clinical and histopathologic findings in five cases of tuberculosis (TB) with various ocular manifestations. DESIGN: Observational case series. METHODS: Retrospective review of clinical findings, course, and treatment of five patients. Diagnostic techniques, including biomicroscopic, histopathologic, and molecular biologic test results, are presented. MAIN OUTCOME MEASURES: Visual acuity, slit-lamp biomicroscopy, indirect ophthalmoscopy, and fluorescein angiography results. RESULTS: The ocular manifestations of TB in our patients included panophthalmitis, endophthalmitis, posterior uveitis with choroidal tubercles, keratitis, and a lid mass. Mycobacterium tuberculosis was identified in four cases in ocular specimens using acid-fast bacilli microscopy and in three cases by culture. Rapid diagnosis using polymerase chain reaction was obtained in one case. Extraocular foci of TB were identified in three cases with an intraocular infection at presentation. No patients had the human immunodeficiency virus (HIV) and none were immunocompromised. Two eyes could not be saved using antituberculous treatment because of delayed diagnosis and treatment. CONCLUSIONS: In this age of the HIV pandemic, TB is becoming more common. Because it is curable, heightened awareness and better understanding of the disease's ocular manifestations should be of concern to all ophthalmologists.

3601.                        Shimouchi A. Tuberculosis problems in the Asia-Pacific region. Respirology.  6(1):75-8, 2001 Mar.


  Tuberculosis (TB) is the top killer of the productive age group in developing countries. More than half of cases in the world occur in Asia-Pacific region. The number of cases will increase in the next decades due to increase in urban poor population and HIV incidence, and poor access to health services and poor TB programme. The mainstay of effective strategy is to promote DOTS. DOTS population coverage is high, 58% in the Western Pacific Region but low; 29% in the southeast Asia region. Even among intermediate TB-burden countries in Asia, reduction of incidence has stagnated in recent years because of aging population, health problems in the urban poor population and influx of populations from high endemic areas. Indicators of successful TB programmes are high cure rate and low drug resistance rate. There is a strong correlation between the overall quality of TB control in the past and the current primary drug-resistant rate. To solve these problems, priority should be given to nationwide implementation of DOTS in high TB-burden countries with emphasis on ensuring availability of free anti-TB drugs and strengthening primary health care. General hospitals and private sector should be involved in control programmes to prevent drug resistant cases.

3602.                        Singh KK.  Zhang X.  Patibandla AS.  Chien P Jr.  Laal S. Antigens of Mycobacterium tuberculosis expressed during preclinical tuberculosis: serological immunodominance of proteins with repetitive amino acid sequences. Infection & Immunity.  69(6):4185-91, 2001 Jun.


  Four antigens of Mycobacterium tuberculosis that are expressed in vivo after aerosol infection but prior to the development of clinical tuberculosis (TB) in rabbits were identified by immunoscreening of an expression library of M. tuberculosis genomic DNA with sera obtained 5 weeks postinfection. Three of the proteins identified, PirG (Rv3810), polymorphic GC-repetitive sequence (PE-PGRS; Rv3367), and proline-threonine repetitive protein (PTRP) (Rv0538), have multiple tandem repeats of unique amino acid sequences and have characteristics of surface or secreted proteins. The fourth protein, MtrA (Rv3246c), is a response regulator of a putative two-component signal transduction system, mtrA-mtrB, of M. tuberculosis. All four antigens were recognized by pooled sera from TB patients and not from healthy controls, confirming their in vivo expression during active infection in humans. Three of the antigens (PE-PGRS, PTRP, and MtrA) were also recognized by retrospective preclinical TB sera obtained, prior to the clinical manifestation of TB, from human immunodeficiency virus-TB patients, suggesting that they are potential candidates for devising diagnostic tests for active, preclinical TB.

3603.                        No Abstract.

3604.                         Stanford JL.  Stanford CA.  Grange JM.  Lan NN.  Etemadi A. Does immunotherapy with heat-killed Mycobacterium vaccae offer hope for the treatment of multi-drug-resistant pulmonary tuberculosis? [see comments]. Respiratory Medicine.  95(6):444-7, 2001 Jun.


  A patient is described with the tubulointerstitial nephritis with uveitis syndrome. The diagnosis can be difficult since it has to be differentiated from sarcoidosis, or infections like tuberculosis and toxoplasmosis. Our patient showed prompt recovery of fever, ocular symptoms and renal function after starting corticosteroids.


3605.                        Su WJ.  Huang CY.  Huang CY.  Perng RP. Utility of PCR assays for rapid diagnosis of BCG infection in children. International Journal of Tuberculosis & Lung Disease.  5(4):380-4, 2001 Apr.


  We report Mycobacterium bovis BCG infection in two children vaccinated with BCG (Tokyo strain) on the first day of life. Their diagnoses were made by biopsy of skin lesions and pus from an anterior chest wall abscess, respectively, yielding a positive culture of mycobacteria fully susceptible to rifampicin, isoniazid and ethambutol, but resistant to pyrazinamide. M. bovis BCG was identified by a negative niacin test, absence of nitrate reductase and resistance to pyrazinamide and cycloserine. The diagnoses were further confirmed by a combination of an allele-specific polymerase chain reaction ated strain of Mycobacterium bovis, is the only available vaccine for the prevention of tuberculosis. Although complications are rare after BCG vaccination and the outcome is usually favourable, serious BCG infections can occur. We report two cases of M. bovis BCG infection in children, a 4-year-old immunocompetent girl and an 8-month-old immunodeficient boy. To our knowledge, this is the first report of BCG complications in children in which two recently developed polymerase chain reaction (PCR) based methods were used for rapid identification of M. bovis BCG infection. (PCR) and a multiplex PCR method. Based on the drug susceptibility results, treatment with rifampicin, isoniazid and ethambutol was instituted. One patient (Case 1) improved clinically and is well after treatment. However, the other patient with severe combined immunodeficiency died of disseminated BCG infection in spite of intensive anti-tuberculosis therapy. Although BCG is considered to be a safe vaccine, it should be kept in mind that complications related to BCG do occur.


3606.                         Swati Banerjee, E Raji Nair, Satish Kumar, MVR Reddy & BC Harinath. Assay of tubercular antibody, circulating free and immune complexed antigen in the diagnosis of pulmonary tuberculosis. Indian J Clin Biochem 2001;16(2):203-206.

3607.                         Tahaoglu K.  Atac G.  Sevim T.  Tarun T.  Yazicioglu O.  Horzum G.  Gemci I.  Ongel A.  Kapakli N.  Aksoy E. The management of anti-tuberculosis drug-induced hepatotoxicity. International Journal of Tuberculosis & Lung Disease.  5(1):65-9, 2001 Jan.


  SETTING: A tuberculosis ward in a chest disease teaching hospital. OBJECTIVE: To compare the efficacy of two different retreatment protocols on hepatotoxicity recurrence in tuberculosis treatment. DESIGN: In a prospective, randomised study, 45 patients with new tuberculosis developed hepatotoxicity after anti-tuberculosis treatment. Patients in Group I (n = 20) were retreated with a drug regimen consisting of isoniazid, rifampicin, ethambutol and streptomycin administered by gradually increasing the number and dosage of the drugs. Patients in Group II (n = 25) were retreated with the same regimen (isoniazid, rifampicin, pyrazinamide and ethambutol) in the same dosages throughout. RESULTS: Hepatotoxicity recurred in respectively zero and six (24%) patients in Groups I and II (P = 0.021). Of the six patients with recurrence of hepatitis, one could not be followed up. The other five received the same retreatment protocol as Group I. By the end of retreatment, all patients were cured. CONCLUSION: The recurrence rate of hepatotoxicity in the retreatment of tuberculosis is higher in the reintroduction of a full-dose regimen including pyrazinamide, which causes more hepatotoxicity than gradual reintroduction of a regimen without pyrazinamide.


3608.                         Tang XN.  Chu KA.  Lu JY.  Ting YM.  Lin CH. Multiple pleural nodules without effusion--a rare presentation of tuberculous pleurisy. Chung Hua i Hsueh Tsa Chih - Chinese Medical Journal.  64(3):187-90, 2001 Mar.


  We report a rare case of tuberculous pleurisy presenting with multiple pleural nodules without associated effusion or parenchymal lung lesions. A 62-year-old man had multiple discrete pleural nodules in the right hemithorax on chest radiography without any clinical symptoms. Thoracoscopic biopsy of the pleural nodules revealed a caseous granuloma with acid-fast bacilli. The patient received antituberculous therapy, with resolution of tuberculomas on chest film within 2 months. To our knowledge, only two similar cases have been previously reported in the English literature, and our observation should lead to broadening of the spectrum of the differential diagnosis of multiple pleural nodules.


3609.                        van Gorkom J.  van Cleeff M.  Becx-Bleumink M.  Veen J.  Short-course instead of long-course chemotherapy for smear-negative patients in sub-Saharan Africa. International Journal of Tuberculosis & Lung Disease.  5(1):4-11, 2001 Jan.


  The use of short-course chemotherapy (SCC) in directly-observed treatment, short-course (DOTS) programmes in sub-Saharan Africa was often restricted to patients with infectious and serious forms of tuberculosis, because of high costs of such regimens. With reduced drug prices and wide-scale substitution of thiacetazone by ethambutol in the continuation phase of treatment, various short-course regimens are now available at the same or even lower costs than long-course regimens. Several DOTS programmes are considering extending access to short-course chemotherapy to non-infectious patients, or have done so already. The authors provide an overview of the issues regarding the debate on the introduction of universal SCC in national tuberculosis control programmes in low-income countries in sub-Saharan Africa. They advise on a low-risk strategy to avoid the emergence of rifampicin resistance as a consequence of the wide availability of rifampicin associated with universal short-course, and strengthening of the health system to maintain high performance levels in diagnosis and treatment.

3610.                         Verver S.  Bwire R.  Borgdorff MW. Screening for pulmonary tuberculosis among immigrants: estimated effect on severity of disease and duration of infectiousness. International Journal of Tuberculosis & Lung Disease.  5(5):419-25, 2001 May.


  OBJECTIVE: To estimate the effect of tuberculosis screening among recent immigrants on the severity of disease at diagnosis and on the duration of the infectious period. DESIGN: Comparison of pulmonary tuberculosis cases among immigrants detected through screening with those detected passively, using information from the Netherlands Tuberculosis Register. PARTICIPANTS: Immigrants from highly endemic countries diagnosed with culture-positive pulmonary tuberculosis within 30 months after arrival in The Netherlands, 1993 through 1998. OUTCOME MEASURES: Severity of disease (smear-positive disease, hospitalisation, case fatality) and duration of symptomatic period. RESULTS: A total of 882 bacteriologically confirmed tuberculosis patients from highly endemic countries had been in The Netherlands less than 30 months, and were detected through screening (454), or passively (368). Compared with patients detected passively, patients found through screening were less often sputum smear-positive (OR 0.5, 95%CI 0.3-0.8) and less often hospitalised (OR 0.2, 95%CI 0.1-0.2). Those detected through screening had a shorter symptomatic period. Screening is estimated to have reduced the infectious period by approximately 33%. CONCLUSION: The screening programme detected cases earlier, resulting in fewer hospital admissions, shorter duration of symptoms and therefore probably reduced tuberculosis transmission.

3611.                        Von Arx DP.  Husain A. Oral tuberculosis. British Dental Journal.  190(8):420-2, 2001 Apr 28.


  Although rare, doctors and dentists should be aware of the possible occurrence of oral lesions of tuberculosis and consider them in the differential diagnosis of suspicious oral ulcers.


3612.                        Wallis RS.  Johnson JL. Adult tuberculosis in the 21st century: pathogenesis, clinical features, and management. [Review] [89 refs] Current Opinion in Pulmonary Medicine.  7(3):124-32, 2001 May.


  This article reviews the significant advances in the past year in the basic and clinical aspects of adult tuberculosis (TB). Further research has deepened our understanding of host susceptibility and resistance mechanisms, including cytotoxicity, apoptosis, and antimicrobial polypeptides such as granulysin. Studies have confirmed the effects of HIV infection on risk of disease and disease manifestations, and have defined the effects of HIV on TB transmission. Recent studies also indicate a possible role for extended treatment of active disease and latent infection in HIV-1 infected individuals. Multidrug-resistant disease has been reported on every continent; rapid molecular approaches to the simultaneous diagnosis of TB and detection of rifampin resistance may facilitate prompt initiation of treatment. TB remains one of the major problems in global health. [References: 89]

3613.                        Wang CH.  Lin HC.  Liu CY.  Huang KH.  Huang TT.  Yu CT.  Kuo HP. Upregulation of inducible nitric oxide synthase and cytokine secretion in peripheral blood monocytes from pulmonary tuberculosis patients. International Journal of Tuberculosis & Lung Disease.  5(3):283-91, 2001 Mar.


  SETTING: Peripheral blood monocytes (PBM) are the main source of alveolar macrophages, which have an upregulation of inducible nitric oxide synthase (iNOS) in pulmonary tuberculosis (TB). TNF-alpha and IL-1 beta are thought to be involved in the immune response to mycobacterial infection. OBJECTIVE: To identify whether iNOS expression and cytokine release of PBM are upregulated and have a connection in TB infection. DESIGN: The expression of iNOS immunoreactivity on PBM from TB patients and normal subjects was measured by loading with anti-macrophage iNOS polyclonal primary antibody analyzed by flow cytometry. Expression of iNOS mRNA in PBM was detected by RT-PCR. The spontaneous generation of nitrite and cytokines (IL-1 beta and TNF-alpha) by cultured monocytes was also determined. RESULTS: Compared to normal subjects, iNOS immuno-reactivity, the capacity for spontaneous nitrite generation and the level of TNF-alpha or IL-1 beta secretion of PBM were significantly higher in TB patients. The amount of nitrite, TNF-alpha and IL-1 beta released from PBM of TB patients was inhibited by NG-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of NOS. The level of iNOS immunoreactivity on PBM was highly correlated with nitrite generation both in all the subjects studied and in TB patients alone. Spontaneous TNF-alpha production showed a stronger correlation with nitrite production than with IL-1 beta. CONCLUSION: The NO and cytokine synthase activities of monocytes appear to be concomitantly upregulated in response to mycobacterial infection. The enhanced NO generation by monocytes in TB patients may play an autoregulatory role in amplifying the synthesis of pro-inflammatory cytokines.

3614.                         Wendel KA.  Alwood KS.  Gachuhi R.  Chaisson RE.  Bishai WR.  Sterling TR. Paradoxical worsening of tuberculosis in HIV-infected persons. Chest.  120(1):193-7, 2001 Jul.


  OBJECTIVE: To determine the incidence of paradoxical worsening of tuberculosis (TB) in HIV-infected persons. DESIGN: Observational cohort study. SETTING: Public, urban TB clinic. PATIENTS: HIV-infected persons treated for TB between January 1, 1996, and December 31, 1999, and followed through June 30, 2000. INTERVENTION: Patients received standard anti-TB therapy. Antiretroviral therapy was provided by primary medical providers. Patients receiving antiretroviral therapy were given nucleoside reverse transcriptase inhibitors alone or highly active antiretroviral therapy (HAART; nucleoside reverse transcriptase inhibitors in combination with a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor). Main outcome measure: Paradoxical worsening of TB. RESULTS: There were 82 TB cases in 76 patients. Paradoxical worsening was identified in 6 of 82 cases (7%; 95% confidence interval, 3 to 15%). Paradoxical worsening occurred in 3 of 28 cases (11%) in patients receiving HAART and in 3 of 44 cases (7%) in patients not receiving antiretroviral therapy (p = 0.67). Cases complicated by paradoxical worsening were more likely to have both pulmonary and extrapulmonary disease at initial diagnosis than cases without paradoxical worsening (83% vs 24%; p = 0.006). TB relapse occurred in 2 of 6 cases (33%) in patients with paradoxical worsening and in 4 of 76 cases (5%) in patients without paradoxical worsening (p = 0.06). CONCLUSIONS: Paradoxical worsening of TB occurred less frequently than in previous reports and was not associated with HAART. Paradoxical worsening also appeared to be associated with an increased risk of TB relapse. Further studies are warranted to better characterize the risk factors for paradoxical worsening and the appropriate duration of anti-TB therapy in patients in whom it occurs.

3615.                         Wheeler C.  Berkley S. Initial lessons from public-private partnerships in drug and vaccine development. Bulletin of the World Health Organization.  79(8):728-34, 2001.


  In recent years, venture capital approaches have delivered impressive results in identifying and funding promising health discoveries and bringing them to market. This success has inspired public sector experiments with "social venture capital" approaches to address the dearth of affordable treatment and prevention for diseases of the developing world. Employing the same focus on well-defined and measurable objectives, and the same type of connections to pool and deploy resources as their for-profit counterparts, social venture capitalists seek to use the tools and incentives of capitalism to solve one of its biggest failures: the lack of drugs and vaccines for diseases endemic to low-income populations. As part of a larger trend of partnerships emerging in health product donation and distribution, public-private partnerships for pharmaceutical development have led research and development (R&D) efforts to generate more accessible and efficacious products for diseases such as malaria, tuberculosis, and AIDS. In this article, three R&D-focused partnerships are explored: the International AIDS Vaccine Initiative; the Medicines for Malaria Venture; and the newly formed Global Alliance for TB Drug Development. The article highlights key elements essential to the success of these ventures.



3616.                         Wilkinson RJ.  DesJardin LE.  Islam N.  Gibson BM.  Kanost RA.  Wilkinson KA.  Poelman D.  Eisenach KD.  Toossi Z. An increase in expression of a Mycobacterium tuberculosis mycolyl transferase gene (fbpB) occurs early after infection of human monocytes. Molecular Microbiology.  39(3):813-21, 2001 Feb.


  Changes in the mRNA levels of two Mycobacterium tuberculosis genes (fbpB known as antigen 85B, and hspX known as Acr) were studied in infected human monocytes. Antigen 85B is an enzyme involved in cell wall biosynthesis and is also a major target of the immune response. Acr is a stress protein believed to be involved in the bacillary response to adverse conditions and in non-replicating persistence. During the first 24 h of intracellular infection, the intramonocyte 85B mRNA level increased 54-fold (P = 0.00001) and 14.6 times in comparison with the 16S ribosomal rRNA. In contrast, the Acr mRNA fell 14.3 times. Although monocyte cytokine production was very variable, the 24 h secretion of tumour necrosis factor (TNF)-alpha correlated with the 85B-16S RNA ratio at 24 h (r = 0.77, Pcorr < 0.01). Furthermore, the addition of exogenous TNF-alpha to cultures was associated with a twofold increase in the 85B-16S ratio and, conversely, neutralization of endogenous TNF-alpha reduced the ratio. As antigen 85B also induces TNF-alpha, the positive feedback implied by our findings suggests a previously unsuspected role for this protein in the immunopathogenesis of tuberculosis.

3617.                         Yamada Y.  Nakamura A.  Hosoda M.  Kato T.  Asano T.  Tonegawa K.  Itoh M. Cytokines in pleural liquid for diagnosis of tuberculous pleurisy. Respiratory Medicine.  95(7):577-81, 2001 Jul.


  An elevated level of adenosine deaminase (ADA) in pleural liquid has been considered as a supplemental diagnostic marker for tuberculous pleurisy. However, this is complicated by false-positives and -negatives. Recently, it has been revealed that various cytokines are intimately involved in the pathognomonic physiology of tuberculosis. In this study, interleukin-8 (IL-8), tumour necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma) were compared with ADA in pleural liquid of patients with inflammatory (21 cases), malignant (28 cases) and tuberculous (21 cases) disease. The pleural ADA, IL-8, TNFalpha and IFNgamma levels in the tuberculous group were higher than in the other three groups. Analysis of receiver operating characteristic (ROC) curves, to evaluate the utility of the various parameters, demonstrates values for the area under the curve (AUC) of 0.770, 0.875, 0.892 and 0.987, respectively for IL-8, TNFalpha, ADA and IFNgamma. No false-positives were encountered with IFNgamma and only one case with a small volume of pleural liquid was a false-negative. This indicates that IFNgamma is a very reliable marker of tuberculous pleurisy.

3618.                         Yuen MC.  Tung WK.  An uncommon cause of foot ulcer: tuberculosis osteomyelitis. Emerg Med J.  18(2):140-1, 2001 Mar.


  Tuberculous osteomyelitis is an uncommon infection that usually involves the vertebrae. An otherwise healthy young man with a chronic discharging sinus on his right foot caused by tuberculous osteomyelitis is described. The risk factors, clinical features, radiological findings, and investigations of tuberculous osteomyelitis are briefly reviewed. Tuberculous osteomyelitis usually runs an insidious course; emergency physicians should be aware of the possibility of tuberculous osteomyelitis especially when patients present with chronic unexplained musculoskeletal symptoms.

3619.                        Zissin R.  Gayer G.  Chowers M.  Shapiro-Feinberg M.  Kots E.  Hertz M. Computerized tomography findings of abdominal tuberculosis: report of 19 cases. Israel Medical Association Journal: Imaj.  3(6):414-8, 2001 Jun.


  BACKGROUND: Abdominal tuberculosis usually presents with general symptoms and obscure abdominal complaints for which computerized tomography is often the first imaging study. OBJECTIVE: To evaluate the CT findings of abdominal tuberculosis. METHODS: The CT scans of 19 patients (10 men and 9 women aged 20-85 years) with proven abdominal tuberculosis were retrospectively reviewed to define the location and extent of the disease. The patients were referred for the study mainly with general systemic symptoms. Additional abdominal complaints were present in four, including acute abdomen in one. Two had symptoms deriving from the urinary tract. Nine patients had recently arrived from high prevalence countries; five of them and two others were positive for human immunodeficiency virus. Three patients had a family history of tuberculosis; one had previously been treated for tuberculosis and four others had an underlying chronic disease. The diagnosis of tuberculosis was established by standard microbiological and histological techniques. RESULTS: We divided the disease manifestations into intraperitoneal (n = 13) and genitourinary involvement (n = 6). Peritoneal tuberculosis was fairly common, characterized by ascites, omental and mesenteric infiltration, and smooth thickening of the parietal peritoneum. One oncology patient had a false positive Tc-99m CEA isotope scanning, suggesting tumor recurrence. Genitourinary disease manifested mainly as hydronephrosis and calcifications. Three patients had pulmonary tuberculosis as well. CONCLUSION: The CT findings of abdominal tuberculosis may mimic various diseases, mainly diffuse peritoneal malignancy. We emphasize the need to consider tuberculosis in the differential diagnosis in patients with obscure abdominal symptoms, especially with multi-organ involvement. A high degree of clinical suspicion and familiarity with the abdominal CT manifestations allow early diagnosis of this treatable disease.

Apr 02


4281.                  Aggarwal AN, Dhammi IK, Jain AK. Multifocal skeletal  tuberculosis. Trop Doct  2001 Oct;31(4):219-20


Multifocal skeletal tuberculosis is an uncommonly reported entity. The article presents a series of 18 cases encountered in our institution. There clinical characteristics are analysed and compared with available international literature.

4282.                  Amaral L, Viveiros M, Kristiansen JE. Phenothiazines: potential alternatives for the management of antibiotic resistant infections of tuberculosis and malaria in developing countries. Trop Med Int Health  2001 Dec;6(12):1016-22


The in vitro and in vivo activity of phenothiazines against antibiotic susceptible and antibiotic resistant Mycobacterium tuberculosis and malaria-causing Plasmodia is reviewed. Given the facts that pulmonary tuberculosis and malaria are the major causes of death in developing countries, that both of these infections continue to escalate in their resistance to antibiotics, that the cost for the management of these infections is beyond that afforded by most developing nations, and lastly, that new and effective agents are not forthcoming from the pharmaceutical industry, the scientific rationale for the potential use of select phenothiazines for the management of these infections is presented.

4283.                  Andersen P, McAdam KP, Marchant A. Tuberculosis contacts but not patients have higher gamma interferon responses to ESAT-6 than do community controls in The Gambia. Infect Immun  2001 Oct;69(10):6554-7


The Mycobacterium tuberculosis antigen ESAT-6 has been proposed for tuberculosis immunodiagnosis. In The Gambia, 30% of community controls produced gamma interferon (IFN-gamma) in response to ESAT-6. Increased proportions of responders and intensities of responses were found in household contacts. Responses that were initially low in tuberculosis patients increased after treatment. An ESAT-6 IFN-gamma assay will be of limited use in the diagnosis of tuberculosis in countries where tuberculosis is endemic. Its role in contact tracing should be evaluated further.

4284.                  Antoun MD, Ramos Z, Vazques J, Oquendo I, Proctor GR, Gerena L, Franzblau SG. Evaluation of the flora of Puerto Rico for in vitro antiplasmodial and antimycobacterial activities. Phytother Res  2001 Nov;15(7):638-42


The emergence of resistant strains of Plasmodium falciparum and Mycobacterium tuberculosis underscores the need for novel drugs that are effective against these microorganisms. As part of our screening programme of the flora of Puerto Rico, we tested a number of ethanol extracts of higher plants for antiplasmodial and antimycobacterial activities. A total of 40 extracts belonging to 23 plant families and 37 species were tested for antiplasmodial activity. Five extracts demonstrated activity against Plasmodium falciparum in vitro (50%-100% parasite suppression at 5 microg/mL). Another 63 extracts belonging to 30 plant families and 50 species were tested in vitro against Mycobacterium tuberculosis. Two extracts were found to be active, Ficus citrifolia and Pisonia borinquena (85% or more inhibition of microbial growth at 100 microg/mL of extract). Copyright 2001 John Wiley & Sons, Ltd.

4285.                  Anupam Prakash, Hira H S: Tuberculous osteomyelitis of sternum in adiabetic. Indian J Tuberc 2001, 48(1), 35-6.(014224). July 16, 2001.

Middle-aged diabetic woman who presented with a painless swelling of upper middle part of anterior chest was diagnosed to be suffering from the comparatively rare tuberculosis sternum. Pertinent literature is reviewed along with the case report.

4286.                  Basta M, Lydakis C, Daskalogiannaki M, Schiza S, Siafakas NM. Multi-focal tuberculosis with multiple intracranial tuberculomas in a non-immunocompromised patient. Respir Med  2001 Oct;95(10):841-3 No abstract.

4287.                  Berker M, Atalay B, Soylemezoglu F, Ariogul S, Palaoglu S. Cervical tuberculous spondylitis associated with systemic lupus erythematosus. Spinal Cord  2001 Oct;39(10):549-53


STUDY DESIGN: A case report of cervical tuberculous spondylitis associated with systemic lupus erythematosus (SLE). Infection is a frequent problem in SLE, especially in patients hospitalised with the complications of the disease. Tuberculous spondylitis very rarely occurs in SLE patients, and cervical involvement has not been previously reported. CASE REPORT: A 54-year-old female patient was admitted to our hospital with a complaint of neck pain radiating to her shoulder of 2 months' duration. The neurological examination was completely normal and radiological investigations revealed narrowing, angulation and destruction of the end plates of the 5th and 6th cervical vertebrae. She has received corticosteroid and colchicine treatment for the diagnosis of SLE during the last 10 years. The anterior cervical approach was used and pyogenic material was debrided from the C5-6 intervertebral space, and an otogenous bone graft with a Smith Robinson type fusion was performed. CONCLUSION: High doses of corticosteroids are implicated as a risk factor for infection in SLE patients. Early diagnosis and appropriate medical and surgical treatment, as well as increased awareness of higher susceptibility to opportunistic infections, such as tuberculous spondylitis, are keystones for decreasing morbidity and mortality in patients with SLE.

4288.                  Bewes P. Spinal  tuberculosis. Trop Doct  2001 Oct;31(4):237-40


Spinal tuberculosis is an important and potentially crippling disease, but if recognized early and treated energetically it can be brought under control, often with very gratifying results. Knowledge of the exact bacteriology and sensitivity pattern of the organisms involved can be very helpful indeed, and should be sought where possible.

4289.                  Boddinghaus B, Wichelhaus TA, Brade V, Bittner T. Removal of PCR inhibitors by silica membranes: evaluating the Amplicor Mycobacterium tuberculosis kit. J Clin Microbiol  2001 Oct;39(10):3750-2


The effectiveness of PCR inhibitor removal by silica membranes in combination with the Amplicor Mycobacterium tuberculosis kit was analyzed for 655 respiratory and nonrespiratory specimens. The overall inhibition rate was reduced from 12.5%, when applying the Amplicor kit alone, to 1.1% with the addition of silica membrane DNA purification.

4290.                  Bretsche PA, Ismail N, Menon JN, Power CA, Uzonna J, Wei G. Vaccination against and treatment of tuberculosis, the leishmaniases and AIDS: perspectives from basic immunology and immunity to chronic intracellular infections. Cell Mol Life Sci  2001 Nov;58(12-13):1879-96


The occurrence of infectious disease represents a failure of the immune system, a failure that must be prevented by effective vaccination or remedied by treatment. Vaccination against acute diseases such as smallpox and polio are very effective, due to the rapid and increased immune response of vaccinated individuals upon natural infection. In contrast, effective vaccination against intracellular pathogens that cause chronic diseases, such as the leishmaniases, tuberculosis and AIDS, has not been achieved. Clinical observations suggest cell-mediated, Th1 responses, exclusive of antibody production and the generation of Th2 cells, are optimally protective against these intracellular pathogens. Effective vaccination must ensure the generation of such a protective response. We explore here whether understanding very broad features of the regulation of the immune response can accommodate modern findings on the immunological features of these diseases, and provide a perspective within which strategies for effective vaccination and treatment can be developed.

4291.                  Brown HM, Abbitt PL, Wilkinson EJ. Diagnosis of clinically unsuspected extrapulmonary tuberculosis by fine needle aspiration: a case report. Acta Cytol  2001 Nov-Dec;45(6):1032-6


BACKGROUND: Mycobacterium tuberculosis (MTb) infection remains the cause of higher morbidity and mortality than any other infectious disease in the world. Intact cellular immunity is necessary to resist the disease, and therefore the AIDS epidemic has greatly contributed to the resurgence of MTb. Depending on the degree of immunosuppression, the presentation of MTb in patients with AIDS can be atypical and difficult to diagnose as compared to the classical presentation of MTb in the nonimmunocompromised population. CASE: A patient who was not known to be HIV positive had a clinical picture of extensive abdominal and pelvic lymphadenopathy without chest radiographic abnormalities. The diagnosis of MTb was made by fine needle aspiration (FNA) of a pelvic lymph node. CONCLUSION: Miliary tuberculosis associated with AIDS may have an unusual clinical presentation and unusual cytologic features on ENA.

4292.                  Carricajo A, Fonsale N, Vautrin AC, Aubert G. Evaluation of BacT/Alert 3D liquid culture system for recovery of mycobacteria from clinical specimens using sodium dodecyl (lauryl) sulfate-NaOH decontamination. J Clin Microbiol  2001 Oct;39(10):3799-800


A total of 52 mycobacterial isolates were recovered from 1,197 clinical specimens decontaminated by a sodium dodecyl (lauryl) sulfate (SDS) NaOH protocol. Of these, 94% were recovered with the BacT/Alert 3D system (Organon Teknika, Durham, N.C.) and 79% were recovered on Lowenstein-Jensen (LJ) medium. Mean times to detection of organisms of the Mycobacterium tuberculosis complex (n = 47) were 22.8 days with LJ medium and 16.2 days with the system. The BacT/Alert 3D system is a rapid and efficient detection system which can be used with an SDS-NaOH decontamination procedure.

4293.                  Caws M, Drobniewski FA. Molecular techniques in the diagnosis of Mycobacterium tuberculosis and the detection of drug resistance. Ann N Y Acad Sci  2001 Dec;953:138-45


Early diagnosis of Mycobacterium tuberculosis disease is crucial in initiating treatment and interrupting the train of transmission. The increasing incidence of MDR TB worldwide has also placed emphasis on the need for early detection of drug resistance, particularly to isoniazid and rifampicin. Molecular diagnostic techniques and automated culture systems have reduced turnaround times in the modern mycobacteriology laboratory, and the continuing evaluation and development of such techniques is increasing the use of molecular technology in developed nations. Simple phenotypic methods for the detection of resistance to first-line drugs and genotypic kit-form assays for detection of rifampicin resistance have been developed that have become key tools in the containment of MDR TB.

4294.                  Chan ED, Chan J, Schluger NW. What is the role of nitric oxide in murine and human host defense against tuberculosis?Current knowledge. Am J Respir Cell Mol Biol  2001 Nov;25(5):606-12


The production of reactive oxygen intermediates and reactive nitrogen intermediates by innate immune cells is considered to be an effective host-defense mechanism against microbial pathogens. In the murine model of tuberculosis (TB), nitric oxide (NO) plays an essential role in the killing of Mycobacterium tuberculosis by mononuclear phagocytes. For example, in the mouse strain with a genetic disruption for inducible NO synthase (iNOS-/-), infection with M. tuberculosis is associated with a significantly higher risk of dissemination and mortality. Although more controversial in humans, there is a growing body of evidence that NO produced by TB-infected macrophages and by epithelial cells also has antimycobacterial effects against M. tuberculosis. The precise mechanism(s) by which NO and other reactive nitrogen species antagonize M. tuberculosis is not known, but may involve disruption of bacterial DNA, proteins, signaling, and/or induction of apoptosis of macrophages that harbor mycobacteria. In addition to cytokines such as tumor necrosis factor-alpha and interleukin 1-beta, mycobacterial cell wall components such as lipoarabinomannan and 19 kD lipoprotein, along with the T-cell-derived interferon-gamma, may also induce NO expression. In a Darwinian fashion, it also appears that certain strains of M. tuberculosis have evolved strategies to combat the toxic effects of NO.


4295.                  Chen YC, Hsu SW. Tuberculous arthritis mimic arthritis of the Sjogren's syndrome: findings from sonography, computed tomography and magnetic resonance images. Eur J Radiol  2001 Dec;40(3):232-5


A patient with a history of Sjogren's syndrome developed chronic arthritis of left ankle. It was diagnosed as arthritis of the Sjogren's syndrome initially. However, joint pain persisted despite corticosteroid therapy. Sonography disclosed a multiloculated cystic lesion with peripheral hyperechoic enhancement around left ankle and extended to Achilles tendon and subcutaneous region. Computed tomography (CT) confirmed the findings. Magnetic resonance imaging (MRI) revealed increased signal intensity of the lesion after gadonillium enhancement on T1-weighted images. These abnormalities showed inhomogenous high signal intensities on T2-weighted images. Tuberculous arthritis was diagnosed by positive synovial tuberculous culture. Sonography is a valuable tool that offers significant advantages for the initial evaluation of arthritis of the Sjogren's syndrome and help early suspicious of tuberculous arthritis, because of its cost-effectiveness, superior differentiation between the cyst and solid lesions, convenience for guiding biopsy and drainage.

4296.                  Chierakul N, Damrongchokpipat P, Chaiprasert A, Arjratanakul W. Antibody detection for the diagnosis of tuberculous  pleuritis. Int J Tuberc Lung Dis  2001 Oct;5(10):968-72


SETTING: University Hospital, Bangkok, Thailand. OBJECTIVE: To evaluate the diagnostic value of antibody detection in serum and in pleural effusion as a marker of tuberculous pleuritis (TBP). DESIGN: Cross-sectional study. MATERIALS AND METHODS: One hundred and fifty-five patients with pleural effusion who underwent diagnostic evaluation at Siriraj Hospital between March 1999 and May 2000 were recruited. Samples of pleural fluid were examined biochemically, cytologically and microbiologically. Pathological examination of pleural tissue was also performed. The diagnosis of TBP or other diagnosis was made by either pathological finding or culture result. Immunochromatographic tuberculosis (ICT-TB) tests for antibody detection were then performed using the stored serum samples and effusions from those patients with a final definite diagnosis. This test detects antibodies to five secreted antigens of Mycobacterium tuberculosis, including the 38 kDa antigen. RESULTS: We investigated 67 patients with TBP, 44 with malignant pleural effusions, seven with transudates and one with cryptococcal pleuritis. The combined ICT-TB serum and effusion tests were positive in 34/67 TBP and 22/52 non-TBP patients. The sensitivity, specificity, positive predictive value and negative predictive value of the ICT-TB test were 50.7, 57.7, 60.7 and 47.6%, respectively. In 11 TBP patients with human immunodeficiency virus (HIV) co-infection, the sensitivity of the ICT-TB test was 45.6%. There was no correlation between the test positivity and culture result or duration of disease. CONCLUSIONS: The diagnostic value of antibody detection in TBP is modest in an area with intermediate prevalence of tuberculosis, independently of HIV serological status.

4297.                  Choi H, Lee CJ, Lee KJ, Moon KD. Primary tubercolous osteomyelitis of the  sternum. J Cardiovasc Surg (Torino)  2001 Dec;42(6):841-3


We present an 82-year-old woman with anterior sternal pain diagnosed as primary mycobacterial osteomyelitis of the sternum. She was treated with simultaneous wide resection and reconstruction of the chest wall. On admission, computed tomographic scan showed a sclerotic sternal mass with soft tissue reaction. Mycobacterium tuberculosis was grown in initial culture. First-line antituberculous medication and local debridement failed. The successful result was achieved by extensive sternal and chondral resection followed by simultaneous bilateral pectoralis major muscle flap positioning.


4298.                  Collins J. CT signs and patterns  of lung disease. Radiol Clin North Am  2001 Nov;39(6):1115-35


The ground-glass pattern is a common but nonspecific finding on CT. In certain clinical circumstances, it can suggest a specific diagnosis, indicate a potentially treatable disease, and guide a clinician to an appropriate area for biopsy. A pattern of centrilobular ground-glass nodules is fairly specific for the diagnosis of hypersensitivity pneumonitis with the appropriate clinical history. The tree-in-bud pattern indicates disease affecting the small airways. The differential diagnosis is lengthy; however, the most common process leading to this CT appearance is infection. Although commonly associated with M. tuberculosis, many infectious organisms can produce this pattern. When honeycombing is seen on HRCT, a confident diagnosis of lung fibrosis can be made. The most common causes of interlobular septal thickening on HRCT are pulmonary edema, pulmonary hemorrhage, and lymphangitic spread of cancer, and smooth thickening is characteristic of all three. Diffuse lung cysts in patients who are not immunocompromised generally signify Langerhans' cell histiocytosis, lymphangioleiomyomatosis, or centrilobular emphysema. Centrilobular emphysema can be diagnosed when the centrilobular artery is seen as a small nodular opacity in the center of the cyst. Langerhans' cell histiocytosis is often associated with parenchymal nodules, helping to distinguish it from lymphangioleiomyomatosis. When a nodular pattern is seen on HRCT, the differential diagnosis is very long, but can be narrowed by noting whether the nodules are random, centrilobular, or perilymphatic in distribution. A mosaic pattern of lung attenuation can represent an infiltrative, small airway, or vascular process. The distinction can often be made by noting the size of the pulmonary vessels in the abnormal areas of lung, and whether air trapping is present on expiratory scanning. Computed tomographic signs can be useful indicators of a specific disease process. For instance, the air bronchogram sign indicates that an opacity is intrapulmonary in location, and signals the possibility of two types of neoplasm: lymphoma and bronchioloalveolar cell carcinoma. An air crescent sign indicates recovery of the immune system in an immunocompromised patient with invasive pulmonary aspergillosis. The fallen lung sign is diagnostic of a bronchial transection in the correct clinical setting. The gloved finger sign is very suggestive of allergic bronchopulmonary aspergillosis. The halo sign is highly suggestive of early angioinvasive pulmonary aspergillosis in patients with acute leukemia. When a split pleura sign is seen, the diagnosis is often empyema, although other causes of pleuritis can lead to a similar CT appearance.

4299.                  Cruciani M, Malena M, Bosco O, Gatti G, Serpelloni G. The impact of human immunodeficiency virus type 1 on infectiousness of tuberculosis: a meta-analysis. Clin Infect Dis  2001 Dec 1;33(11):1922-30


To assess if the relative infectiousness of patients with tuberculosis is enhanced by coinfection with human immunodeficiency virus type 1 (HIV-1), data from 6 studies of 1240 health care workers who had contact with tuberculosis patients were analyzed. Overall rates of tuberculin skin test conversion were similar regardless of HIV-1 positivity of tuberculosis patients (odds ratio [OR], 1.04; 95% confidence interval [CI], 0.23-1.84). However, when only 3 studies during nosocomial outbreaks of multidrug-resistant Mycobacterium tuberculosis were analyzed, rates of skin test conversion were higher among contacts of HIV-1-positive index cases (OR, 2.85; 95% CI, 1.85-3.85; P=.0002). A second meta-analysis included data from 11 studies of 10,714 household contacts of tuberculosis patients. Prevalence of both skin test positivity (OR, 0.45; 95% CI, 0.20-1.03) and active disease (OR, 1.17; 95% CI, 0.78-1.56) were similar regardless of HIV-1 positivity of index cases. These data suggest that tuberculosis patients with HIV-1 infection are not intrinsically more infectious to their contacts than are HIV-1-negative tuberculosis patients.

4300.                  Das S, Chattopadhyay U K: Role of silicon in modulating the internal morphology and growth of Mycobacterium tuberculosis. Indian J Tuberc 2000, 47(2), 87-91.(013142) July1, 2001.


Silicon is known to enhance the growth and pathogenicity of Mycobacterium tuberculosis. In this study the pattern of growth of different strains of M. tuberculosis was studied on a carbon free silicon culture medium and compared with that on conventional media. Thirty-two strains of M. tuberculosis from mostly clinical isolates were serially propagated on a carbon free silicate medium and on different conventional media using standard inocula. There was initial good growth on the silicon-based medium in comparison with the conventional media. However, the growth was considerably reduced after early serial transfers but improved again in late serial cultures. The initial good growth appears to be due to increased activity of silico induced fatty acid synthase and the late improvement due to slow adaptation of M. tuberculosis to the carbon free metabolism by the formation of silicon acid esterified cell wall and silicon induced genetic alteration . all these changes were probably responsible for the formation of fibrous, ropelike structures and dense granules seen under electron microscope. Since the silicon content of the lung tissue is comparatively higher than many other tissues of the human body, it could play a role in the pathogenicity of tuberculosis in the lungs. 26 ref.


4301.                  Davies P, Grange J. The genetics  of host resistance and susceptibility to tuberculosis. Ann N Y Acad Sci  2001 Dec;953:151-6


The study of human genomics has the potential to aid our understanding of the interindividual and interpopulation differences in susceptibility to tuberculosis. Resistance to infection is affected by the ability of macrophages to phagocytose and destroy the bacilli. Several genes are involved in this process, and two have been the focus of recent interest: the natural resistance-associated protein (NRAMP1) gene and the genes coding for the vitamin D receptor. Susceptibility genes have also been discovered--for example, one on the X chromosome that may explain the increased susceptibility of males to tuberculosis. Studies have also focused on the variations in virulence of the bacillus in both its drug-susceptible and drug-resistant forms. These mechanisms must be understood in order to prevent, or combat, the emergence of a virulent, multidrug-resistant form of the bacillus that would be uncontrollable by means of today's treatment strategies.

4302.                  de Maria A, Berardi M, Dignetti P, Ferrera L, Viassolo L, Canonica GW. Side effects of antituberculosis treatment. Thorax  2001 Dec;56(12):983  No abstract.

4303.                  de Maria A, Berardi M, Dignetti P, Ferrera L, Viassolo L, Canonica GW. Side effects of antituberculosis treatment. Thorax  2001 Dec;56(12):983 No abstract.

4304.                  de Pinho AM, Santoro-Lopes G, Harrison LH, Schechter M. Chemoprophylaxis for tuberculosis and survival of HIV-infected patients in Brazil.AIDS  2001 Nov 9;15(16):2129-35


OBJECTIVE: To study the impact of chemoprophylaxis for tuberculosis on the survival of HIV-infected patients with a positive tuberculin skin test. DESIGN: Prospective observational cohort study. SETTING: Outpatient clinic of a university hospital, in Rio de Janeiro, Brazil. PATIENTS: Two-hundred and ninety-seven patients with a positive tuberculin skin test (reaction > or = 5mm) who were admitted to the cohort between January 1991 and December 1994. Follow-up ended on September 30, 1998. INTERVENTION: The use of chemoprophylaxis for tuberculosis. MAIN OUTCOME MEASURES: Death was the primary outcome variable. The occurrence of tuberculosis was studied as a secondary outcome. Cox regression models were used in these analyses. RESULTS: The median follow-up time was 43.6 months. Chemoprophylaxis was used by 128 (43%) of the patients. The use of chemoprophylaxis was associated with a reduction in risk for tuberculosis (hazard ratio, 0.38; 95% confidence interval, 0.14-1.04; P = 0.05). In a regression model adjusted for baseline CD4 cell count, chemoprophylaxis was associated with longer survival (hazard ratio, 0.24; 95% confidence interval, 0.09-0.65; P = 0.002). CONCLUSIONS: Anti-tuberculosis chemoprophylaxis was associated with a substantially prolonged survival among purified protein derivative-positive HIV-infected patients in Brazil. These data have important implications for the clinical care of patients with HIV infection in areas of the world with a high prevalence of Mycobacterium tuberculosis infection.

4305.                  Deshmukh H, Prasad SR, Patankar T, Zankar M. Internal mammary artery pseudoaneurysms complicating chest wall infection in children: diagnosis and endovascular therapy. Clin Imaging  2001 Nov-Dec;25(6):396-9


Mycotic internal mammary artery (IMA) pseudoaneurysms are sparsely reported in medical literature. We report imaging findings of IMA pseudoaneurysms secondary to chest wall abscesses (staphylococcal and tuberculous) in two children. Both children were successfully treated by endovascular method thus obviating the need for surgery.

4306.                  Dhammi IK, Jain AK. Unusual tubercular abscesses in two elderly women. Trop Doct  2001 Oct;31(4):249 No abstract.

4307.                  Dhiman S R: some observations of ABO, Rh (D) blood groups in relation to pulmonary tuberculosis. Bionature, Bhopal 2001, 21(1), 49-53.(018321) Aug 16, 2001.No abstract.

4308.                  Dobbs KG, Lok KH, Bruce F, Mulcahy D, Benjamin WH, Dunlap NE. Value of Mycobacterium tuberculosis fingerprinting as a tool in a rural state surveillance program. Chest  2001 Dec;120(6):1877-82


OBJECTIVE: This study demonstrates the value of Mycobacterium tuberculosis fingerprinting used in conjunction with traditional epidemiologic methods to identify smoldering outbreaks of tuberculosis in endemic areas where background rates of tuberculosis are high. METHODS: IS6110 DNA fingerprinting was performed on isolates of M tuberculosis from verified cases of tuberculosis in Alabama from 1994 to 1998. A statewide database groups isolates into "clusters" and tracks them cumulatively over time. A large cluster was identified and was secondarily investigated using traditional epidemiologic methods. RESULTS: Twenty-five isolates were found to be identical by fingerprinting analysis. Patients were living within 10 counties across the state, and 12 cases were localized to a single county. This represented an ongoing, statewide tuberculosis outbreak previously unrecognized by local and state health officials. Secondary investigation of the cases revealed the primary sites of transmission to be a correctional facility and two homeless shelters. CONCLUSIONS: Population surveillance using M tuberculosis fingerprinting was successfully utilized to detect a significant and smoldering tuberculosis outbreak. Measures are currently in place to identify and prevent further transmission in the involved locations.

4309.                  Doyal L. Moral problems in the use of coercion in dealing with nonadherence in the diagnosis and treatment of tuberculosis. Ann N Y Acad Sci  2001 Dec;953:208-15


Coercion and detainment can be a morally acceptable strategy to fight the spread of tuberculosis, but these measures need to be placed into a much broader context than that of their short-term potential effectiveness. TB should be de-stigmatized by full acknowledgment that we all share the blame for its perpetuation. When coercion and detention are necessary, they should incorporate a strategy of optimum protection for minimum violation of autonomy. National and international health care programs should provide effective and nonthreatening treatments for TB and other related illnesses such as HIV and should develop policies to tackle the environmental causes of TB and provide support for vulnerable victims. Corporate pressures to continue world poverty must be undermined.

4310.                  Driver CR, Munsiff SS, Li J, Kundamal N, Osahan SS. Relapse in persons treated for drug-susceptible tuberculosis in a population with high coinfection with human immunodeficiency virus in New York City. Clin Infect Dis  2001 Nov 15;33(10):1762-9


The optimal duration of tuberculosis treatment for persons infected with human immunodeficiency virus (HIV) has been debated. A cohort of 4571 culture-positive drug-susceptible patients who received > or =24 weeks of standard 4-drug tuberculosis treatment were assessed to determine the incidence of tuberculosis relapse. Tuberculosis "recurrence" was defined as having a positive culture < 30 days after the last treatment date and "relapse" as having a positive culture > or =30 days after the last treatment. Patients infected with HIV were more likely than those who were uninfected to have recurrence or relapse (2.0 vs. 0.4 per 100 person-years, P< .001). Patients infected with HIV who received < or =36 weeks of treatment were more likely than those who received > 36 weeks to have a recurrence (7.9% vs. 1.4%, P< .001). Clinicians should be aware of the possibility of recurrence of tuberculosis 6-9 months after the start of treatment. Sputum evaluation to ensure cure or assessment 3 months after completion of treatment should be performed among persons infected with HIV who receive the shorter regimen.

4311.                  Farmer P, Bayona J, Becerra M. Multidrug-resistant tuberculosis and the need for biosocial  perspectives. Int J Tuberc Lung Dis  2001 Oct;5(10):885-6 No abstract.

4312.                  Franco J, Camarena JJ, Nogueira JM, Blanquer R, Ruiz MJ, Marin J. Serological response (Western blot) to fractions of Mycobacterium tuberculosis sonicate antigen in tuberculosis patients and contacts. Int J Tuberc Lung Dis  2001 Oct;5(10):958-62


OBJECTIVE: To assess the serological response to fractions of Mycobacterium tuberculosis sonicate antigen by Western blot analysis in patients with tuberculosis and contacts. METHODS: We studied 71 individuals including 43 patients with active tuberculosis, 16 contacts and 12 healthy blood donors. For Western blot analysis, M. tuberculosis (H37Rv strain) sonicate antigen extract was fractionated by electrophoresis on polyacrylamide gel (SDS-PAGE). RESULTS: We obtained antibody responses directed against four antigenic fractions with molecular weights of 71, 65, 26-38 and 19 kDa. Sixty per cent of pleural tuberculosis and 52.4% of smear-positive pulmonary tuberculosis had whole responses against all four fractions; there were no partial responses in these groups. For patients with smear-negative pulmonary tuberculosis whole responses were 17.6% and partial responses 41.2%. All contacts whose tuberculin tests converted from negative to positive (three cases) reacted exclusively against the 19 kDa fraction. CONCLUSIONS: Western blot-positive results in patients with pleural and smear-positive pulmonary tuberculosis were characterised by a whole pattern against all four antigenic fractions, whereas patients with smear-negative pulmonary tuberculosis showed heterogeneous results. The exclusive response against the 19 kDa fraction observed in contacts with tuberculin conversion could help to identify candidates for preventive therapy.

4313.                  Gillooly DJ, Simonsen A, Stenmark H. Phosphoinositides and  phagocytosis. J Cell Biol  2001 Oct 1;155(1):15-7


Phosphoinositide 3 kinases (PI3Ks)*Abbreviation used in this paper: PI3K, phosphoinositide 3 kinase. are known as regulators of phagocytosis. Recent results demonstrate that class I and III PI3Ks act consecutively in phagosome formation and maturation, and that their respective products, phosphatidylinositol 3,4,5-trisphosphate (PI[3,4,5]P(3)) and phosphatidylinositol 3-phosphate (PI[3]P), accumulate transiently at different stages. Phagosomes containing Mycobacterium tuberculosis do not acquire the PI(3)P-binding protein EEA1, which is required for phagosome maturation. This suggests a possible mechanism of how this microorganism evades degradation in phagolysosomes.


4314.                  Goh KS, Legrand E, Sola C, Rastogi N. Rapid differentiation of "Mycobacterium canettii" from other Mycobacterium tuberculosis complex organisms by PCR-restriction analysis of the hsp65 gene. J Clin Microbiol  2001 Oct;39(10):3705-8


A total of 102 isolates of the Mycobacterium tuberculosis complex, including available "M. canettii" isolates, were studied by PCR-restriction analysis of a 441-bp fragment of the hsp65 gene. PRA upon HhaI enzyme digestion (GCGC) allowed easy differentiation of "M. canettii" from other members of the M. tuberculosis complex (three bands of 260, 105, and 60 bp for "M. canetti," compared to four bands of 185, 105, 75, and 60 bp for other members of the M. tuberculosis complex). Sequencing of the 441-bp hsp65 fragment of "M. canettii" isolates showed the disappearance of an HhaI site at position 235 due to a C-to-T transition that corresponded to position 631 of the homologous hsp65 gene of M. tuberculosis H37Rv. Considering that "M. canettii" may also exist as a stable rough morphotype, we suggest that the true number of "M. canettii" isolates may be underestimated in clinical microbiology laboratories.

4315.                  Gupta SK. Pediatric sarcoidosis in India. Indian J Pediatr  2001 Oct;68(10):931-5


OBJECTIVE: Since 1957, when the first pediatric case of sarcoidosis was reported, 11 more cases have been traced in the Indian literature. METHODS: Nine of them were reported from general wards of hospitals (while the remaining 3 were from pediatric unit of AIIMS, New Delhi). Failure of initial treatment with anti-tuberculosis drugs for some months, necessitated search for an alternative diagnosis. Considerable delay (several months to years) occurred due to several parent- or physician-dependant factors. RESULTS: Affection more in girls (9 to 12), universal fever and constitutional symptoms, loss of weight, scanty lung features, hepatomegaly, often with massive splenomegaly, frequent lymphadenopathy etc. caused initial confusion. CONCLUSION: Treatment with oral steroid or with chloquine and NSAIDS with or without steroid MDI gave equally good results. Long follow-up was done in a few cases only, showing relapses in nearly 66%. One case had a superinfection with acid-fast bacilli.

4316.                  Haimi-Cohen Y, Zeharia A, Mimouni M, Soukhman M, Amir J.  Skin indurations in response to tuberculin testing in  patients with nontuberculous mycobacterial lymphadenitis. Clin Infect Dis  2001 Nov 15;33(10):1786-8


Mantoux results were examined for 29 children with culture-proven nontuberculous mycobacterial lymphadenitis, and 4 species were isolated: Mycobacterium avium-intracellulare complex (from 14 patients [48%]), Mycobacterium haemophilum (from 12 [41%]), Mycobacterium simiae (from 2 [7%]), and Mycobacterium scrofulaceum (from 1 [3%]); the median indurations for each species were 15.5 mm, 14.5 mm, 20 mm, and 23 mm, respectively, and in 17 cases (59%), they were > or =15 mm. In regions with a low incidence of tuberculosis, lymphadenitis thought to be due to nontuberculous mycobacteria should be managed as such, regardless of Mantoux results, thereby avoiding antituberculosis treatment.


4317.                  Jai Prakash, Kar C R, Srivastava P K: Tuberculosis in renal transplant recipients: a single centre experience from northern India. Indian J Nephrol 2000, 10(1), 9-12. (013178). July1, 2001.


Study included 79 (71 male and 8 female) renal allograft recipients bertween Jan. 1991 to June 1997. The age of patients ranged between 21-48 (mean 34.2) years. Seventy persons had received live related (88.6%) and remaining nine had been transplanted with live related donor kidneys. Conventional immunosuppression was used in 64 (81%) patients and 15 cases received  cyclosporine in addition. 13 patients (16.4%) were identified to have tubercular infection in post transplant period. All patients had normal chest radiograph prior to transplantation. They developed tuberculosis for the first time during 6.65 months of successful post transplant period. Pulmonary tuberculosis was found in 6 patients, 7 cases had extra pulmonary tuberculosis which included: abdominal 3, disseminated 2, spinal and meningeal tuberculosis 1 each. The mortality was 23%. is an important cause of morbidity in renal transplant patients and lesions of pulmonary and extra pulmonary tuberculosis are nearly equal in our transplant patients.


4318.                  JH, Mulcahy D, Benjamin WH, Bishai WR. Epidemiologic usefulness of spoligotyping for secondary typing of Mycobacterium tuberculosis isolates with low copy numbers of IS6110. J Clin Microbiol  2001 Oct;39(10):3709-11


Restriction fragment length polymorphism (RFLP) analysis of IS6110 is commonly used to DNA fingerprint Mycobacterium tuberculosis. However, low-copy (< or =5) IS6110 M. tuberculosis strains are poorly differentiated, requiring secondary typing. When spoligotyping was used as the secondary method, only 13% of Maryland culture-positive tuberculosis (TB) patients with low-copy IS6110-spoligotyped clustered strains had epidemiologic linkages to another patient, compared to 48% of those with high-copy strains clustered by IS6110 alone (P < 0.01). Spoligotyping did not improve a population-based molecular epidemiologic study of recent TB transmission.

4319.                  Katti MK. Assessment of RD 1-encoded mycobacterial antigens in the immunodiagnosis of pulmonary, extrapulmonary, and latent tuberculosis infections. J Infect Dis   2001 Dec 1;184(11):1497-8 No abstract.

4320.                  Khanna M, Myneedu V P, Sharma S K, Srivastava L M: Immunological abnormalities in pulmonary tuberculosis. Proc Indian Sci Congr Ass-Pt IV, Sect-II 1997, 24-5.(015331) Aug 1,  2001.


Twenty patients with pulmonary tuberculosis (PTB) and healthy volunteers were studied. Peripheral blood examination and Branchoalveolar Lavage (BAL) were performed. Serum immunoglobulins (n=20) IgG (P<0.01) and IgM (<) were significantly raised as compared to normal controls. Serum complement components (C3 and C4) level was also increased significantly as compared to normal controls. The CD3+ and CD4+ cells decreased in peripheral blood and increased in BAL fluid as compared to normal controls. the decrease in IL-2 and IL-2 receptor level was observed in culture supernatant of blood lymphocytes in patients with tuberculosis as compared to normal controls. It is concluded that patients with pulmonary tuberculosis have increased immunoglobulins due to hypergammaglobulemia and increased CD3* and CD4* cells in BAL fluid due to formation of granuloma inside the lungs. The decrease in IL-2 and IL-2 receptor due to improper priming of naïve T cell.


4321.                  Kingston M, Childs K, Carlin E. Adverse reaction to antimycobacterials administered as a combination tablet with no reaction to the same drugs in isolation. Sex Transm Infect  2001 Oct;77(5):392-3 No abstract.

4322.                  Kisembo HN, Kawooya MG, Zirembuzi G, Okwera A. Serial chest radiographs in the management of children with a clinical suspicion of pulmonary tuberculosis. J Trop Pediatr  2001 Oct;47(5):276-83


The aim of the study was to define the role of serial chest radiographs (SCR) in the management of children with a clinical suspicion of pulmonary tuberculosis (PTB) and to determine the interval at which they should be taken. Eighty children with a clinical suspicion of PTB were studied and followed-up for a duration of 18 months. SCR during the time of treatment were taken at monthly intervals for the first 3 months, then at 2-monthly intervals up to the end of therapy, and finally 2 months post-therapy. These were reviewed and the changes while on treatment noted and correlated with the clinical picture. Lung opacities were observed in 73 children (91 per cent) and were the most common radiological finding on the initial chest X-ray. These were followed by reduced chest wall muscle bulk present in 66 children (83 per cent). Mediastinal and/or hilar lymphadenopathy was noted in 47 children with a significant occurrence in the 0-4 age group (p = 0.004). Pleural effusions, cavities and calcification were rare. Human immunodeficiency virus (HIV) seropositive children with PTB accounted for 87 per cent and carried a poor prognosis (p = 0.0007). The common chest radiographic findings in children with PTB include lung opacities with hilar/mediastinal lymphadenopathy. Pleural effusions, cavitation, calcifications, miliary spread and normal chest X-rays were rare. SCR are useful in monitoring response to treatment, detection of onset of secondary infections and complications. HIV positive patients carry a poor prognosis. Based on the results of this study, pre-treatment, 2 months after onset of treatment, and end of therapy radiographs are recommended as routine in children with a clinical suspicion of PTB.


4323.                  Klein JL, Brown TJ, French GL. Rifampin resistance in Mycobacterium kansasii is associated with rpoB mutations. Antimicrob Agents Chemother  2001 Nov;45(11):3056-8


Rifampin is the most potent drug used in the treatment of disease due to Mycobacterium kansasii. A 69-bp fragment of rpoB, the gene that encodes the beta subunit of the bacterial RNA polymerase, was sequenced and found to be identical in five rifampin-susceptible clinical isolates of M. kansasii. This sequence showed 87% homology with the Mycobacterium tuberculosis gene, with an identical deduced amino acid sequence. In contrast, missense mutations were detected in the same fragment amplified from five rifampin-resistant isolates. A rifampin resistant strain generated in vitro also harbored an rpoB gene missense mutation that was not present in the parent isolate. All mutations detected (in codons 513, 526, and 531) have previously been described in rifampin-resistant M. tuberculosis isolates. Rifampin MICs determined by E-test were <1 mg/liter for all rifampin-susceptible isolates and >256 mg/liter for all rifampin-resistant ones. In addition, four of the five rifampin-resistant isolates were also resistant to rifabutin. We have thus shown a strong association between rpoB gene missense mutations and rifampin resistance in M. kansasii. Although our results are derived from a small number of isolates and confirmation with larger numbers would be useful, they strongly suggest that mutations within rpoB form the molecular basis of rifampin resistance in this species.

4324.                  Lalvani A. Direct ex vivo analysis of antigen-specific IFN-gamma-secreting CD4 T cells in Mycobacterium tuberculosis-infected individuals: associations with clinical disease state and effect of treatment. J Immunol  2001 Nov 1;167(9):5217-25


The wide spectrum of clinical outcomes following infection with Mycobacterium tuberculosis is largely determined by the host immune response; therefore, we studied several clinically defined groups of individuals (n = 120) that differ in their ability to contain the bacillus. To quantitate M. tuberculosis-specific T cells directly ex vivo, we enumerated IFN-gamma-secreting CD4 T cells specific for ESAT-6, a secreted Ag that is highly specific for M. tuberculosis, and a target of protective immune responses in animal models. We found that frequencies of circulating ESAT-6 peptide-specific IFN-gamma-secreting CD4 T cells were higher in latently infected healthy contacts and subjects with minimal disease and low bacterial burdens than in patients with culture-positive active pulmonary tuberculosis (p = 0.009 and p = 0.002, respectively). Importantly, the frequency of these Ag-specific CD4 T cells fell progressively in all groups with treatment (p = 0.005), suggesting that the lower responses in patients with more extensive disease were not due to tuberculosis-induced immune suppression. This population of M. tuberculosis Ag-specific Th1-type CD4 T cells appears to correlate with clinical phenotype and declines during successful therapy; these features are consistent with a role for these T cells in the containment of M. tuberculosis in vivo. Such findings may assist in the design and evaluation of novel tuberculosis vaccine candidates.

4325.                  Leiner S. Management of  tuberculosis. N Engl J Med  2001 Nov 15;345(20):1501; discussion 1502 No abstract.

4326.                  Locham K K, Garg R, Manjit Singh: Tuberculosis of lower cervical spine. Indian Pediat 2001, 38(5), 546-9.(015335) No abstract.

4327.                  M, Abe C, Toyoda T, Kishimoto T, Ogura T. Clinical evaluation of anti tuberculous glycolipid immunoglobulin G antibody assay for rapid serodiagnosis of pulmonary tuberculosis. J Clin Microbiol  2001 Oct;39(10):3603-8


Previously we reported the development of a highly sensitive enzyme-linked immunosorbent assay specific for anti-tuberculous glycolipid (anti-TBGL) for the rapid serodiagnosis of tuberculosis. In this study, the usefulness of an anti-TBGL antibody assay kit for rapid serodiagnosis was evaluated in a controlled multicenter study. Antibody titers in sera from 318 patients with active pulmonary tuberculosis (216 positive for Mycobacterium tuberculosis in smear and/or culture tests and 102 smear and culture negative and clinically diagnosed), 58 patients with old tuberculosis, 177 patients with other respiratory diseases, 156 patients with nonrespiratory diseases, and 454 healthy subjects were examined. Sera from 256 younger healthy subjects from among the 454 healthy subjects were examined as a control. When the cutoff point of anti-TBGL antibody titer was determined as 2.0 U/ml, the sensitivity for active tuberculosis patients was 81.1% and the specificity was 95.7%. Sensitivity in patients with smear-negative and culture-negative active pulmonary tuberculosis was 73.5%. Even in patients with noncavitary minimally advanced lesions, the positivity rate (60.0%) and the antibody titer (4.6 +/- 9.4 U/ml) were significantly higher than those in the healthy group. These results indicate that this assay using anti-TBGL antibody is useful for the rapid serodiagnosis of active pulmonary tuberculosis.

4328.                  Machado N, Grant CS, Scrimgeour E. Abdominal tuberculosis--experience of a University hospital  in Oman. Acta Trop  2001 Oct 22;80(2):187-90


OBJECTIVE: To determine the clinical presentation and assess the usefulness of various diagnostic modalities and outcome of treatment of abdominal tuberculosis (TB). Materials and methods: The files of patients admitted to Sultan Qaboos University Hospital (SQUH) with a diagnosis of abdominal TB from January 91 to December 99 were studied retrospectively and data abstracted. RESULTS: Eighteen patients were diagnosed during this period, of which ten were males. The median age was 27 years (range 5-65). The common symptoms were fever, weight loss, anorexia, and abdominal pain. Abdominal signs were less frequent and included hepatomegaly and ascites. Eight patients had co-existent immunocompromised disorders; two of these had active pulmonary TB. Diagnostic investigations included gastrointestinal contrast studies in two, ultrasound (US) guided fine needle aspiration cytology (FNAC) in nine, and laparoscopy and/or laparotomy in seven. All patients underwent antituberculous therapy for 9-12 months, in addition to the treatment of associated disorders. The response to antituberculous therapy was good except in one patient with HIV. Four patients died from associated primary disorders. CONCLUSIONS: The clinical presentation was non-specific and nearly half of the patients had associated immunocompromised disorders; thus a high index of clinical suspicion is required. US guided FNAC and selective laparoscopy were the most useful diagnostic modalities. Antituberculous therapy was effective.

4329.                  Marshall BG, Wangoo A, O'Gaora P, Cook HT, Shaw RJ, Young DB. Enhanced antimycobacterial response to recombinant Mycobacterium bovis BCG expressing latency-associated peptide. Infect Immun  2001 Nov;69(11):6676-82


With a view to exploring the role of transforming growth factor beta (TGF-beta) during mycobacterial infection, recombinant clones of bacillus Calmette-Guerin (BCG) were engineered to express the natural antagonist of TGF-beta, latency-activated peptide (LAP). Induction of TGF-beta activity was reduced when macrophages were infected with BCG expressing the LAP construct (LAP-BCG). There was a significant reduction in the growth of LAP-BCG in comparison to that of control BCG following intravenous infection in a mouse model. The enhanced control of mycobacterial replication was associated with an increase in the production of gamma interferon by splenocytes challenged during the acute stage of infection but with a diminished recall response assessed after 13 weeks. Organ weight and hydroxyproline content, representing tissue pathology, were also lower in mice infected with LAP-BCG. The results are consistent with the hypothesis that TGF-beta has a detrimental effect on mycobacterial immunity. While a reduction in TGF-beta activity augments the initial response to BCG vaccination, early bacterial clearance may adversely affect the induction of a long-term memory response by LAP-BCG.

4330.                  McMurray DN, Gennaro ML. Immunological characterization of antigens encoded by the RD1 region of the Mycobacterium tuberculosis genome. Scand J Immunol  2001 Nov;54(5):448-52


Development of immunoassays specific for the diagnosis of tuberculosis requires antigens unique to Mycobacterium tuberculosis. In a search for such antigens we tested six proteins encoded by RD1, a region present in M. tuberculosis and virulent M. bovis genomes but missing from the DNA of all substrains of M. bovis Bacillus Calmette-Guerin (BCG). The six proteins (Rv3871, Rv3872, Rv3873, MTSA-10, ESAT-6 and Rv3878) were purified to near-homogeneity from recombinant Escherichia coli. When tested for the ability to elicit antibody responses and delayed type hypersensitivity in tuberculous guinea pigs, only two of six antigens, ESAT-6 and MTSA-10, elicited strong skin reactions, while vigorous antibody responses were observed to all six proteins. When antibody responses to RD1 antigens were evaluated in sera from patients having pulmonary tuberculosis and from control subjects (patients having mycobacterioses other than tuberculosis, and healthy persons), a sizeable proportion (25%) of tuberculosis patients but none of the control subjects, had antibodies against MTSA-10 and/or ESAT-6. We conclude that MTSA-10 and ESAT-6 are promising candidates for immunodiagnostic assays specific for tuberculosis.



4331.                  MF, Rothel JS. Comparison of a whole-blood interferon gamma assay with tuberculin skin testing for detecting latent Mycobacterium tuberculosis infection. JAMA  2001 Oct 10;286(14):1740-7


CONTEXT: Identifying persons with latent tuberculosis infection (LTBI) is crucial to the goal of TB elimination. A whole-blood interferon gamma (IFN-gamma) assay, the QuantiFERON-TB test, is a promising in vitro diagnostic test for LTBI that has potential advantages over the tuberculin skin test (TST). OBJECTIVES: To compare the IFN-gamma assay with the TST and to identify factors associated with discordance between the tests. DESIGN AND SETTING: Prospective comparison study conducted at 5 university-affiliated sites in the United States between March 1, 2024 and June 30, 1999. PARTICIPANTS: A total of 1226 adults (mean age, 39 years) with varying risks of Mycobacterium tuberculosis infection or documented or suspected active TB, all of whom underwent both the IFN-gamma assay and the TST. MAIN OUTCOME MEASURE: Level of agreement between the IFN-gamma assay and the TST. RESULTS: Three hundred ninety participants (31.8%) had a positive TST result and 349 (28.5%) had a positive IFN-gamma assay result. Overall agreement between the IFN-gamma assay and the TST was 83.1% (kappa = 0.60). Multivariate analysis revealed that the odds of having a positive TST result but negative IFN-gamma assay result were 7 times higher for BCG-vaccinated persons compared with unvaccinated persons. The IFN-gamma assay provided evidence that among unvaccinated persons with a positive TST result but negative IFN-gamma assay result, 21.2% were responding to mycobacteria other than M tuberculosis. CONCLUSIONS: For all study participants, as well as for those being screened for LTBI, the IFN-gamma assay was comparable with the TST in its ability to detect LTBI, was less affected by BCG vaccination, discriminated responses due to nontuberculous mycobacteria, and avoided variability and subjectivity associated with placing and reading the TST.

4332.                  Morye V K, Thatte U M, Dahanukar S A: Drug use in tuberculosis. Indian J Pharmac 2001, 32(2), 138. (016406) Aug 16, 2001.

Reports the drug use pattern in tuberculosis, and examines patient’s knowledge of drug therapy and the reasons of any for defaulting treatment. This study identified that several problems exist in the implementation of DOTS. These are mainly in the area of patient’s education and intervention must be planned.

4333.                  Namavar Jahromi B, Parsanezhad ME, Ghane-Shirazi R. Female genital tuberculosis and  infertility. Int J Gynaecol Obstet  2001 Dec;75(3):269-72


OBJECTIVES: This study was performed to evaluate the rate of diagnosed female genital tuberculosis and its presentational symptoms and methods of diagnosis. METHODS: A total of 3088 cases of tuberculosis (TB) who had been registered and treated in the Health Center of Fars Province from 1989 to 1999 were retrospectively studied. From this group, 46 women were diagnosed as having genital TB. The diagnosis in 41 cases was based on the standard pathological criteria of tissue specimens. The other five cases were excluded from this study due to the lack of classical diagnostic criteria. Statistical analysis was performed using the Z-test. RESULTS: The mean age of the patients at the time of diagnosis was 30.4 years. Seven patients presented with abdominal or pelvic pain (17.07%). In this group three cases underwent laparatomy due to abdominal mass and four patients for tubo-ovarian abscess, which led to the diagnosis. Abnormal uterine bleeding was the cause of diagnostic dilatation and curettage in three other patients (7.31%). However, in 31 cases (75.6%) TB was diagnosed during studies performed to evaluate the cause of their infertility, and the most common diagnostic procedure was endometrial curettage (25 cases). Female genital TB accounted for 1.32% of all tuberculous patients in this study. Of these, 75.6% were infertile by definition (Z=12.13 P<0.0001). TB endometritis was detected in 72.03%, tubal involvement in 34.03%, ovarian TB in 12.9% and cervical TB in 2.4% of the patients. CONCLUSIONS: This study confirms the presence of a strong relationship between genital TB and infertility; therefore genital TB would be more frequently diagnosed if this possibility was considered in the evaluation of every infertile patient in areas where tuberculosis is endemic.

4334.                  Passmore JS, Glashoff RH, Lukey PT, Ress SR. Granule-dependent cytolysis of Mycobacterium tuberculosis-infected macrophages by human gammadelta+ T cells has no effect on intracellular mycobacterial viability. Clin Exp Immunol  2001 Oct;126(1):76-83


One of the most important effector functions of activated gammadelta+ T cells in tuberculosis is their strong cytolytic activity against a variety of target cells, including M. tuberculosis-infected macrophages. In the present study, we investigated the relationship between the mechanism of cytolysis utilized by gammadelta+ CTL and intracellular M. tuberculosis survival using a panel of cytolytic human M. tuberculosis-specific gammadelta+ CTL clones. Cytolysis mediated by the gammadelta+ T-cell clones was found to be Ca2+-dependent, sensitive to Cyclosporin A, and was completely abrogated following Sr2+-induced de-granulation of the gammadelta+ T cell effectors. These data demonstrate that gammadelta+ T-cell-mediated cytoxicity was mediated via the granule exocytosis/perforin pathway. Despite significant cytolytic activity against mycobacteria infected U937 cells, the gammadelta+ CTL clones had no impact on the survival of intracellular M. tuberculosis.

4335.                  Patel R K, Trivedi R, Bhagat R, Kadri N, Thaker P, Joshi A: Worsening of CNS-tuberculosis after initiation of anti-tuberculosis therapy. Gujarat med J 2000, 57(1), 85-6. (016431) Aug 16, 2001.

With advent of CT scan and MRI diagnosis of T.B. is possible early in the course of disease. Most patients respond to sensitive and complaint Anti Koch’s Disease treatment (AKT). Many cases of worsening of CNS tuberculosis and appearance of new ring enhancing lesions after initiation of AKT are reported. Most of these worsened cases respond to addition of steroids. Rest may need timely neurosurgical intervention. Appearance of new lesions after initiation of AKT in C.N.S tuberculosis do not suggest drug resistance, so addition of second generation AKT is not necessary. With therapy complete recovery generally ensues within 6-8 weeks.

4336.                  Peloquin CA. Pharmacological issues in the treatment of tuberculosis. Ann N Y Acad Sci  2001 Dec;953:157-64


A thorough review of the clinical trial data combined with new in vitro experimental information may make the optimization of dosages of TB drugs possible. Several factors can affect the selection and dosage of TB drugs including hepatic and renal impairment, pregnancy, duration of disease before treatment, and extent of debilitation. Drug interactions and pharmacodynamics must be considered, and their roles are discussed.

4337.                  Prasad K N: Tuberculosis-relevance of tuberculin skin test in diagnosis. Indian med Gaz 2001, 135(4), 108-13. (018373) Sept 1, 2001.No abstract.

4338.                  Prasad P L, Wilson C G, Harjai M M, Kailash Chand: Multidrug resistant tuberculosis(MDRTB) in children. Med  J Armed Forces India 2001,57(2), 151-3.(015358), Aug 1, 2001. No abstract.

4339.                  Raja A, Ranganathan UD, Bethunaickan R, Dharmalingam V. Serologic response to a secreted and a cytosolic antigen of Mycobacterium tuberculosis in childhood tuberculosis. Pediatr Infect Dis J  2001 Dec;20(12):1161-4

BACKGROUND AND AIM: Bacteriologic diagnosis of childhood tuberculosis is difficult, and alternate methods are needed. The utility of a serologic test for major secretory antigen (30 kDa) and a cytosolic antigen (16 kDa) of Mycobacterium tuberculosis was evaluated for the diagnosis of tuberculosis in children. METHODS: Enzyme-linked immunosorbent assay was used. Specific IgG, IgA and IgM antibodies were measured in the sera from 26 clinically and/or bacteriologically diagnosed cases of childhood tuberculosis and 61 normal children. RESULTS: Anti-IgG antibodies alone, against both 30- and 16-kDa antigens, were detected in 65.4% of patients. However, by combination of all three isotypes, increased sensitivities of 84.6 and 73%, with a specificity of 96.7% each, were obtained for 30- and 16-kDa antigens, respectively. CONCLUSIONS: We found good specificity and reasonably good sensitivity for detection of antibodies by enzyme-linked immunosorbent assay to 30-kDa antigen alone. The 16-kDa antigen did not perform as well.

4340.                  Rajagopalan S. Tuberculosis and aging: a global health problem. Clin Infect Dis  2001 Oct 1;33(7):1034-9


Despite the World Health Organization's declaration that the spread of tuberculosis is a global emergency and despite the implementation of strong tuberculosis-control initiatives, this highly infectious disease continues to affect all vulnerable populations, including the elderly population (age > or =65 years). Tuberculosis in aging adults remains a clinical and epidemiological challenge. Atypical clinical manifestations of tuberculosis in older persons can result in delay in diagnosis and initiation of treatment; thus, unfortunately, higher rates of morbidity and mortality from this treatable infection can occur. Underlying illnesses, age-related diminution in immune function, the increased frequency of adverse drug reactions, and institutionalization can complicate the overall clinical approach to tuberculosis in elderly patients; maintenance of a high index of suspicion for tuberculosis in this vulnerable population is, thus, undoubtedly justifiable.

4341.                  Rajiv J, Dam T, Kumar S, Bose M, Aggarwal KK, Babu CR. Inhibition of the in-vitro growth of Mycobacterium tuberculosis by a phytosiderophore. J Med Microbiol  2001 Oct;50(10):916-8


Non-compliance by patients and poor clinical management due to the use of incorrect regimens are the main reasons for the development of drug resistance by mycobacterial strains. New strategies for the control of multi-drug-resistant mycobacterial strains have become a necessity for proper management of tuberculosis, which, according to the WHO report (1997), is estimated to remain among the top 10 mortality-causing diseases of the twenty-first century. One of the strategies is the use of iron-sequestering agents like siderophores as active therapeutic agents in the treatment of tuberculosis. This report describes for the first time the inhibition of the growth of Mycobacterium tuberculosis H37Ra in vitro by a phytosiderophore isolated from the root washings of Tephrosia purpurea. This finding may help in the establishment of a new drug regimen which will be more effective in the treatment of tuberculosis.

4342.                  Rattan A: PCR for diagnosis of tuberculosis : where are we now. Indian J tuberc 2000, 47(2), 79-82. (013261) July 1,  2001.  No abstract.

4343.                  Raviglione MC, Gupta R, Dye CM, Espinal MA. The burden of drug-resistant tuberculosis and mechanisms for its control. Ann N Y Acad Sci  2001 Dec;953:88-97


Drug resistance in tuberculosis is largely a man-made phenomenon caused by erroneous prescribing practices on the part of physicians and noncompliance on the part of patients. The global epidemiology of drug-resistant TB, the impact of standardized short-course chemotherapy (SSC), and the potential future evolution of MDR TB are discussed in this chapter.

4344.                  Raviglione MC. Determinants of drug-resistant tuberculosis: analysis of 11 countries. Int J Tuberc Lung Dis  2001 Oct;5(10):887-93


SETTING: Eleven countries/territories. OBJECTIVES: Global information on the determinants of drug-resistant tuberculosis (TB) based on representative data is not available. We therefore studied the relationship between demographic characteristics, prior TB treatment, and human immunodeficiency virus (HIV) infection with anti-tuberculosis drug resistance. METHODS: Population-based representative data on new and previously treated patients with TB collected within an international drug resistance surveillance network. RESULTS: Of 9,615 patients, 8,222 (85.5%) were new cases of TB and 1,393 (14.5%) were previously treated cases. Compared with new cases, previously treated cases were significantly more likely to have resistance to one (OR = 2.5,95% CI 2.1-3.0; P < 0.001), two (OR = 4.6, 95%CI 3.7-5.6; P < 0.001), three (OR = 11.5, 95%CI 8.6-15.3; P < 0.001), and four (OR = 18.5, 95% CI 12.0-28.5; P < 0.001) drugs. An approximately linear increase in the likelihood of having multidrug-resistant tuberculosis (MDR-TB) was observed as the total time (measured in months) of prior anti-tuberculosis treatment increased (P < 0.001, chi2 for trend). In multivariate analysis, prior TB treatment for 6-11 months (OR = 7.6, 95% CI 2.6, 22.4; P < 0.001) and > or = 12 months (OR 13.7, 95% CI 4.5-41.6; P < 0.001), but not HIV positivity, was associated with MDR-TB. CONCLUSION: This study shows that prior but ineffective treatment is a strong predictor of drug resistance, and that HIV is not an independent risk factor for MDR-TB. The association between length of treatment and drug resistance may reflect longer treatment as a result of treatment failure in patients with drug resistance; it may also reflect irregular prior treatment for TB, leading to drug resistance.

4345.                  Scanga CA, Mohan VP, Tanaka K, Alland D, Flynn JL, Chan J. The inducible nitric oxide synthase locus confers protection against aerogenic challenge of both clinical and laboratory strains of Mycobacterium tuberculosis in mice. Infect Immun  2001 Dec;69(12):7711-7


Murine macrophages effect potent antimycobacterial function via the production of nitric oxide by the inducible isoform of the enzyme nitric oxide synthase (NOS2). The protective role of reactive nitrogen intermediates (RNI) against Mycobacterium tuberculosis infection has been well established in various murine experimental tuberculosis models using laboratory strains of the tubercle bacillus to establish infection by the intravenous route. However, important questions remain about the in vivo importance of RNI in host defense against M. tuberculosis. There is some evidence that RNI play a lesser role following aerogenic, rather than intravenous, M. tuberculosis infection of mice. Furthermore, in vitro studies have demonstrated that different strains of M. tuberculosis, including clinical isolates, vary widely in their susceptibility to the antimycobacterial effects of RNI. Thus, we sought to test rigorously the protective role of RNI against infection with recent clinical isolates of M. tuberculosis following both aerogenic and intravenous challenges. Three recently isolated and unique M. tuberculosis strains were used to infect both wild-type (wt) C57BL/6 and NOS2 gene-disrupted mice. Regardless of the route of infection, NOS2(-/-) mice were much more susceptible than wt mice to any of the clinical isolates or to either the Erdman or H37Rv laboratory strain of M. tuberculosis. Mycobacteria replicated to much higher levels in the organs of NOS2(-/-) mice than in those of wt mice. Although the clinical isolates all exhibited enhanced virulence in NOS2(-/-) mice, they displayed distinct growth rates in vivo. The present study has provided results indicating that RNI are required for the control of murine tuberculous infection caused by both laboratory and clinical strains of M. tuberculosis. This protective role of RNI is essential for the control of infection established by either intravenous or aerogenic challenge.

4346.                  Sonika Gupta. Niraj Shende. Swati Banrjee. Satish Kumar. M.V.R. Reddy. Bhaskar C. Harinath. Analysis of Seva Tb ES-31 antigen specific immunoglobulins IgM, IgA and IgG in sera of sputum and culture positive pulmonary tuberculosis. 2002 Jan;17:5-8.

Tuberculosis remains major health problem in India and developing countries. Immunodiagnosis has important role in screening, diagnosis and management of tuberculosis. SEVA TB ES-31 antigen has shown potential in detecting tuberculous IgG antibody in earlier studies from our laboratory. In the present study we have analysed SEVA Tb ES-31 antigen specific immunoglobulins IgM, IgA and IgG in clinically and bacteriologically confirmed pulmonary tuberculosis cases to determine the usefulness of specific immunoglobulin class in the diagnosis of  patients attending the hospital.

            Of the 30 cases of pulmonary tuberculosis 25 (83.3%) were positive for IgG, 19 (63.3%) for IgM and 16 (53.3%) for IgA. On combining IgG and IgM positivity, sensitivity was increased to 93.3%. While combining IgG and IgA positivity sensitivity increased to 90%. However specificity was decreased to 66.6% and 70% for both of these combinations respectively. It could be envisaged from this study that IgG antibody detection against ES-31 antigen showed acceptable sensitivity (83.3%) and specificity (86.6%) compared to IgM or IgA alone or in combination. When immuneresponses were analysed according to degree of sputum positivity, IgG response was observed to be predominant in all grades, compared to IgM or IgA antibody. The addition of IgM or IgA as an adjunct test increases the sensitivity but at the cost of specificity. Hence the detection of IgG alone is more useful compared to IgM or IgA assay, in detecting tuberculosis disease cases coming to the hospital.

4347.                  Sterling TR, Dorman SE, Chaisson RE, Ding L, Hackman J, Moore K, Holland SM. Human immunodeficiency virus-seronegative adults with extrapulmonary tuberculosis have abnormal innate immune responses. Clin Infect Dis  2001 Oct 1;33(7):976-82


Extrapulmonary tuberculosis is presumably a marker of underlying immunodeficiency, but cytokine response pathways in these patients have not been well studied. Cytokine responses of peripheral blood mononuclear cells from human immunodeficiency virus-seronegative adults with prior culture-confirmed extrapulmonary tuberculosis were compared with those of persons with latent Mycobacterium tuberculosis infection. Mitogen-stimulated interferon (IFN)-gamma production, interleukin (IL)-12 production, and IFN-gamma receptor- and IL-12 receptor-mediated cytokine production did not differ between case patients and control patients. However, median resting IL-8 production was significantly lower in case patients than control patients (8051 vs. 19,290 pg/mL; P=.009). In addition, the median tumor necrosis factor (TNF)-alpha response was lower in case patients than control patients after stimulation with lipopolysaccharide (833 vs. 1149 pg/mL; P=.06) and lipopolysaccharide plus IFN-gamma (3301 vs. 4411 pg/mL; P=.04). These abnormalities in resting IL-8 and lipopolysaccharide-induced TNF-alpha production were not associated with IFN-gamma or IL-12 abnormalities and were detected up to several years after cure of disease, suggesting an abnormality in innate immunity.

4348.                  T, Kasvosve I, Gomo ZA, Rouault T, Boelaert JR, Gordeuk VR. Association of pulmonary tuberculosis with increased dietary iron. J Infect Dis  2001 Oct 1;184(7):936-9


To determine whether increased dietary iron could be a risk factor for active tuberculosis, dietary iron history and human immunodeficiency virus (HIV) status were studied in 98 patients with pulmonary tuberculosis and in 98 control subjects from rural Zimbabwe. Exposure to high levels of dietary iron in the form of traditional beer is associated with increased iron stores in rural Africans. HIV seropositivity was associated with a 17.3-fold increase in the estimated odds of developing active tuberculosis (95% confidence interval [95% CI], 7.4-40.6; P<.001), and increased dietary iron was associated with a 3.5-fold increase (95% CI, 1.4-8.9; P=.009). Among patients treated for tuberculosis, HIV seropositivity was associated with a 3.8-fold increase in the estimated hazard ratio of death (95% CI, 1.0-13.8; P=.046), and increased dietary iron was associated with a 1.3-fold increase (95% CI, 0.4-6.4; P=.2). These findings are consistent with the hypothesis that elevated dietary iron may increase the risk of active pulmonary tuberculosis. To determine whether increased dietary iron could be a risk factor for active tuberculosis, dietary iron history and human immunodeficiency virus (HIV) status were studied in 98 patients with pulmonary tuberculosis and in 98 control subjects from rural Zimbabwe. Exposure to high levels of dietary iron in the form of traditional beer is associated with increased iron stores in rural Africans. HIV seropositivity was associated with a 17.3-fold increase in the estimated odds of developing active tuberculosis (95% confidence interval [95% CI], 7.4-40.6; P<.001), and increased dietary iron was associated with a 3.5-fold increase (95% CI, 1.4-8.9; P=.009). Among patients treated for tuberculosis, HIV seropositivity was associated with a 3.8-fold increase in the estimated hazard ratio of death (95% CI, 1.0-13.8; P=.046), and increased dietary iron was associated with a 1.3-fold increase (95% CI, 0.4-6.4; P=.2). These findings are consistent with the hypothesis that elevated dietary iron may increase the risk of active pulmonary tuberculosis.

4349.                  Trautner BW, Darouiche RO. Tuberculous pericarditis: optimal diagnosis and management. Clin Infect Dis  2001 Oct 1;33(7):954-61


Pericarditis is a rare manifestation of tuberculous disease. The appropriate diagnostic workup and optimal therapeutic management are not well defined. We present 10 new cases of tuberculous pericarditis and review the relevant literature. The specific topics addressed are (1) the importance of tissue for diagnosis, (2) the optimal surgical management, (3) the role of corticosteroids, and (4) the impact of human immunodeficiency virus (HIV) on the management of this disease. The cases and the literature suggest that the optimal management includes an open pericardial window with biopsy, both for diagnosis and to prevent reaccumulation of fluid. Corticosteroids probably offer some benefit in preventing fluid reaccumulation as well. The data are inconclusive regarding whether open drainage or corticosteroid use prevents progression to constrictive pericarditis. No studies have addressed these issues specifically in HIV-positive patients, but the 3 HIV-positive patients in our series had an excellent response to drainage and antituberculous therapy.

4350.                  Trollip A, Albert H, Maskell T. Bacteriophage-based technologies for the rapid diagnosis and drug susceptibility testing of tuberculosis. Am Clin Lab  2001 Oct-Nov;20(9):39-42 No abstract.

4351.                  Vijayan V K: Role of bal in the diagnosis and immunological evaluation of patients with pulmonary tuberculosis. Indian J Tuberc 2000, 47(2), 73-8. (013323) July 1 2001 No abstract.

4352.                  Wong DA, Yip PC, Cheung DT, Kam KM. Simple and rational approach to the identification of Mycobacterium tuberculosis, Mycobacterium avium complex species, and other commonly isolated mycobacteria. J Clin Microbiol  2001 Oct;39(10):3768-71 No abstract.

4353.                  Yilmaz A, Boga S, Sulu E, Durucu M, Yilmaz D, Baran A, Poluman A. Delays in the diagnosis and treatment of hospitalized patients with smear-positive pulmonary tuberculosis. Respir Med  2001 Oct;95(10):802-5


The aim of present study was to investigate whether there was any delay in the diagnosis and treatment of inpatients with smear-positive pulmonary tuberculosis followed-up in our centre. We reviewed clinical records in February 1999 and identified 134 hospitalized patients with smear-positive pulmonary tuberculosis. Clinical files of the patients were analysed and a questionnaire was completed. Several intervals and delays were calculated. Median application interval was 17.5 days [95% confidence interval (CI) 21.3-32.4 days], median referral interval was 3.5 days (95% CI 6.8-11.4 days), median diagnosis interval was 3 days (95% CI 3.3-4.5 days) and median initiation of treatment interval was 1 day (95% CI 1.1-1.6 days). Patients delay was present in 28.4% of cases. The referral interval was longer than 2 days in 82 patients (institutional delay). Ninety-three patients (69.4%) had delays in the diagnosis and 34 patients (25.4%) had delays in the treatment. There was a doctor's delay in 119 of 134 patients (88.8%) and clinic's delay in 98 patients (73.2%). Our results have suggested that hospitalized patients with smear-positive pulmonary tuberculosis experience several delays. These delays may result in increased risk for transmission of infection. Decrease in the risk of infection for community and medical personal may only be obtained by preventing these delays.

4354.                  Young D. Letting the genome out of the bottle: prospects for new drug development. Ann N Y Acad Sci  2001 Dec;953:146-50


Use of the information gained from sequencing the Mycobacterium tuberculosis genome will enable scientists to accelerate the development of reagents for improved tuberculosis control. Cloning and expressing genes encoding the enzymes involved in cell-wall biosynthesis will provide the tools for screening millions of novel compounds. Cell wall inhibitors will be mainly useful in treating resistant disease, but cost factors are likely to limit the application of novel compounds in the design of new treatment regimens. More effective might be an approach to target metabolic processes that are essential even in nondividing bacteria. A third target for drug action is elimination of latent disease through a drug that acts in synergy with the immune response.

4355.                  Zahrt TC, Deretic V. Mycobacterium tuberculosis signal transduction system required for persistent infections. Proc Natl Acad Sci U S A  2001 Oct 23;98(22):12706-11


It is estimated that nearly 2 billion people currently suffer from latent Mycobacterium tuberculosis infection. Although the key front-line antituberculosis drugs are effective in treating individuals with acute tuberculosis, these drugs are ineffective in eliminating M. tuberculosis during the persistent stages of latent infection. Consequently, therapeutics that directly target persistent bacilli are urgently needed. We have conducted a global analysis on a group of regulatory determinants that may play a role in M. tuberculosis virulence, and identified a two-component response regulator whose expression is required for entrance into and maintenance of persistent infection. Inactivation of this response regulator, Rv0981 (termed here mprA for mycobacterial persistence regulator), affected M. tuberculosis H37Rv growth in vivo in an organ- and infection stage-specific fashion. These results indicate that two-component systems are important for adaptation of the tubercle bacillus during stages of persistent infection.

4356.                  Zheng X, Pang M, Engler HD, Tanaka S, Reppun T. Rapid detection of Mycobacterium tuberculosis in contaminated BACTEC 12B broth cultures by testing with Amplified Mycobacterium Tuberculosis Direct Test. J Clin Microbiol  2001 Oct;39(10):3718-20


Contamination of broth cultures of acid-fast bacilli (AFB) by bacterial species other than Mycobacterium species frequently occurs. Many of these contaminated cultures require redecontamination and reincubation before the appropriate tests can be performed for identification, significantly affecting the turnaround time for reporting culture results. In this study, the Amplified Mycobacterium Tuberculosis Direct Test (MTD; Gen-Probe) was performed to detect the Mycobacterium tuberculosis complex (MTBC) in 125 BACTEC 12B broth cultures with positive growth indices. Among these, 41 grew non-AFB bacteria only, and all 41 were negative by the MTD. The remaining 84 bottles contained contaminated cultures that grew both AFB and other bacteria or yeasts. Repeat decontamination and reincubation of these specimens required a mean time of 13 days (range, 3 to 40 days). The MTD results were positive for 10 samples, 9 of which were MTBC culture positive and 1 of which grew Myobacterium celatum, a species known to cross-react in the MTD. All cultures growing other mycobacterial species were negative by the MTD. The results of this study demonstrate that the MTD is both sensitive and specific in detecting MTBC in contaminated broth cultures and that, when used selectively, the MTD can potentially rule in or out a diagnosis of MTBC as much as 12 days earlier than using nonamplified DNA probe testing alone can.


July 02


4878.                  Abrol R, Nagarkar NM, Mohan H, Srivastava M.  Primary bilateral tuberculous dacryocystitis with preauricular lymphadenopathy: a diagnostic difficulty of recent times. Otolaryngol Head Neck Surg. 2002 Feb;126(2):201-3.

No Abstract

4879.                  Agarwal N, Sharma SK. Concomitant endobronchial tuberculosis, myocarditis and congestive heart failure. Indian J Tuberc 2000, 47(3), 169-70.


 Rare case of endobronchial as well myocardial tuberculosis, which presented as acute congestive heart failure, is being reported. The patient gradually improved on anti-tuberculosis drug therapy, steroids, digoxin, enalapril and diuretics. The presence of myocardial tuberculosis without pericardial or endocardial involvement or miliary dissemination is considered extraordinary.


4880.                  Ajay Kumar R, Paul KL, Indulakshmi R, Manju YK, Vinod Kumar K, Ayyappan P, Joshi M, Mundayoor S. Analysis of drug susceptibility in Mycobacterium tuberculosis isolated from Thiruvananthrapuram using Alamar blue assay. Curr Sci  2001, 80(1), 70-3.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis and the control of the disease is hampered by widespread emergence of drug resistance in this pathogen. An early information on drug susceptibility would greatly facilitate an effective treatment of TB. Seventy eight isolates of M. tuberculosis were obtained from TB patients from Thiruvananthapuram over a period of about 18 months. Resistance and susceptibility of these isolates to four frontline drugs were assayed using Alamar Boue, and oxidation-reduction dye. Thirty-six per cent of the isolates were susceptible to all the four drugs used, 21.8% were resistant to isoniazid, 8.9% to ethambutol and 2.6% to rifampicin. none was found resistant to streptomycin alone. Multidrug resistance (resistance to at least rifampicin and isoniazid) was found in 7.7% of the isolates. The remaining ones were resistant to combinations of two or more of the drugs. Alamar Blue-based assay promises to be an economical and fast method to determine drug susceptibility and resistance of M. tuberculosis to aid effective drug therapy. 26 ref.


4881.                  Akhan O, Pringot J.  Imaging of abdominal tuberculosis. Eur Radiol. 2002 Feb;12(2):312-23.


The concept of "abdominal tuberculosis" in this review refers to peritoneum and its reflections, gastrointestinal tract, abdominal lymphatic system, and solid visceral organs, as they are subject to varying degrees of involvement alone or in combination. Some features, including free or loculated ascites with thin-mobile septa, smooth peritoneal thickening and enhancement, misty mesentery with large lymph nodes, smudged omental involvement, and advanced ileocecal changes demonstrated by US, CT, or gastrointestinal series are deemed suggestive radiological findings. The diagnosis still requires a high index of suspicion,

once the suggestive features have been demonstrated by imaging modalities.


4882.                  Al-Dossary FS, Ong LT, Correa AG, Starke JR.  Treatment of childhood tuberculosis with a six month directly observed regimen of only two weeks of daily therapy. Pediatr Infect Dis J. 2002 Feb;21(2):91-7.


BACKGROUND: Recommended treatment of childhood tuberculosis is 6 months in duration with at least 3 drugs. We studied a regimen requiring as few as 58 doses, given entirely by directly observed therapy (DOT), under program conditions. METHODS: An observational trial was conducted to determine the effectiveness of a completely DOT 6-month regimen for pulmonary, pleural and lymph node tuberculosis in children with the use of 2 weeks of daily isoniazid, rifampin and pyrazinamide therapy; then 6 weeks of twice weekly isoniazid, rifampin and pyrazinamide therapy; followed by 16 weeks of twice weekly isoniazid and rifampin. All therapy was given by workers from the health department, and patients were followed by the Children's Tuberculosis Clinic in Houston, TX. Patients were evaluated for changes in symptoms, weight, clinical or radiographic findings and adherence to therapy. RESULTS: Of the 175 evaluable children (159 pulmonary/thoracic node, 4 pleural, 12 cervical lymph node), 81% of children completed treatment in 6 months. Of the 33 patients who received extended treatment, 3 did so because of physician choice, 17 had an inadequate response to initial therapy, 2 had significant adverse reactions to drugs and 16 had poor adherence to the DOT. Only 37% of patients had complete resolution of disease at the end of treatment, but all continued to improve after therapy was stopped. There was only 1 patient who relapsed after 4 years. CONCLUSION: This regimen had results comparable with those of 6-month regimens with longer durations of daily therapy. Determining treatment response in pediatric tuberculosis is difficult because of the slow resolution of chest radiograph abnormalities. DOT is an important aspect of treatment but does not solve all problems with treatment adherence.

4883.                  Andronikou S, Smith B.  "Spina ventosa"--tuberculous dactylitis. Arch Dis Child. 2002 Mar;86(3):206.

No Abstract

4884.                  Aribas OK, Kanat F, Gormus N, Turk E.  Cold abscess of the chest wall as an unusual complication of BCG vaccination. Eur J Cardiothorac Surg. 2002 Feb;21(2):352-4.


Bacillus-Calmette-Guerin (BCG) vaccination often results in local adverse effects; however, serious or long-term complications are rare. The involvement of sternum among skeletal BCG osteomyelitis is a rarely seen complication of BCG vaccination. Such a complication may confuse with a chest wall tumor and a surgical intervention may be needed for the definite diagnosis. A 9-month-old infant who had a parasternal cold abscess in the anterior chest wall and sternal osteomyelitis of tuberculosis in the late period of BCG vaccination of whom the etiological diagnosis was histopathologically confirmed after surgery is presented and the preoperative diagnostic problems are discussed.

4885.                  Ashitani J, Mukae H, Hiratsuka T, Nakazato M, Kumamoto K, Matsukura S.  Elevated levels of alpha-defensins in plasma and BAL fluid of patients with active pulmonary tuberculosis. Chest. 2002 Feb;121(2):519-26.


STUDY OBJECTIVES: To investigate the role of neutrophil peptides named alpha-defensins in patients with pulmonary tuberculosis (TB). PATIENTS: Thirty-seven patients with TB and 25 healthy subjects. MEASUREMENTS AND RESULTS:

Concentrations of alpha-defensins (human neutrophil peptide [HNP]-1, HNP-2, and HNP-3) were measured by radioimmunoassay in plasma and BAL fluid (BALF). Concentrations of alpha-defensins were significantly higher in plasma and BALF of patients with TB than in healthy subjects. In BALF of patients with TB, the concentration of alpha-defensins correlated positively with the levels of interleukin 8, and higher concentrations of alpha-defensins in BALF were also detected in patients with cavitary lesions. There was an inverse relationship between plasma alpha-defensins and FEV(1)/FVC ratio before treatment, and between plasma concentrations of alpha-defensins before treatment and the improvement in percentage of vital capacity after treatment. Plasma alpha-defensin concentrations returned to the normal range after treatment. CONCLUSION: Our data suggest that alpha-defensins released from neutrophils may play an important role in the pathogenesis of TB, and that plasma alpha-defensin concentration may be a useful marker of disease severity and deterioration of pulmonary function.

4886.                  Atasoy C, Kaya A, Fitoz S, Yildirim Z.  Discrete pleural nodules associated with a parasternal mass: an unusual manifestation of tuberculosis. J Thorac Imaging. 2002 Jan;17(1):74-7.


SUMMARY: The case presented describes an unusual appearance of thoracic tuberculosis with multiple pleural nodules associated with a parasternal mass as depicted on computed tomography. The patient is a 22-year-old woman who

presented with pleuritic chest pain, a left parasternal mass, and weight loss. The pleura of the left hemithorax was studded with multiple low-attenuation, rim-enhancing nodules, and a left parasternal mass with similar imaging features

was seen anterior to an enlarged left internal mammary lymph node. There were no pulmonary parenchymal changes nor any mediastinal or hilar lymphadenopathy. Cytologic examination of the specimen obtained with fine needle aspiration of

the pleural and parasternal masses yielded granulomatous inflammation. The symptoms remitted with antituberculous chemotherapy and a follow-up CT obtained 6 months later showed complete resolution of the pleural nodules and parasternal

mass and considerable regression of the left internal mammary lymph node. Involvement of the pleura with discrete nodules in the absence of parenchymal changes or mediastinal lymphadenopathy is rare in tuberculosis. To the best of  the present authors' knowledge, the combination of a tuberculous parasternal mass and multiple pleural nodules as the sole manifestations of thoracic tuberculosis has not been reported previously.


4887.                  Atasoy C, Oztekin PS, Ozdemir N, Sak SD, Erden I, Akyar S.  CT and MRI in tuberculous sternal osteomyelitis: a case report. Clin Imaging. 2002 Mar-Apr;26(2):112-5.


We report a 58-year-old male patient presenting with a 1-year history of presternal swelling and pain. Plain radiography revealed increased soft tissue density anterior to the body of the sternum, which showed cortical sclerosis. Computed tomography (CT) demonstrated ring-enhancing hypodense soft tissue masses surrounding the sternum, whose anterior and posterior cortices were markedly thickened. On three-phase technetium bone scintigraphy, the left side of the sternum showed increased radiotracer uptake and the central part of the bone was photopenic. The bone marrow of the sternum and peristernal soft tissue lesions were hypo- and hyperintense on T1- and T2-weighted magnetic resonance (MR) images, respectively, and showed marked enhancement postgadolinium. Treatment included both surgical intervention and medical therapy.


4888.                  Aung H, Sherman J, Tary-Lehman M, Toossi Z.  Analysis of transforming growth factor-beta 1 (TGF-beta1) expression in human monocytes infected with Mycobacterium avium at a single cell level by ELISPOT assay. J Immunol Methods. 2002 Jan 1;259(1-2):25-32.


Transforming growth factor beta 1 (TGF-beta1) has been implicated in the pathogenesis of a number of diseases including infection with intracellular pathogens such as Mycobacterium avium complex (MAC). In this study, we developed an ELISPOT assay for measurement of active TGF-beta1 produced by peripheral blood mononuclear cells (PBMC) from healthy individuals in response to LPS or MAC. The frequency of TGF-beta1 producing cells was significantly (p<0.04) higher in response to LPS (10 microg/ml) as compared to unstimulated cells (n=4). Moreover, the frequency of TGF-beta1 producing cells was threefold higher  in monocyte (MN)-enriched cell population than those in PBMC indicating that the source of TGF-beta1 producing cells in PBMC was MN. In addition, the frequency of TGF-beta1 producing cells in response to MAC (10:1, cfu:MN) was significantly higher (p<0.03) than unstimulated cells. However, the frequency of TGF-beta1 producing cells in response to MAC (10:1) was eight to ninefold lower than that by LPS (10 microg/ml). Moreover, there was a correlation between the level of total TGF-beta1 in 24-h culture supernatants and the number of TGF-beta1 producing cells upon MAC stimulation. TGF-beta1 ELISPOT-assay may be a sensitive and a powerful tool for detection of TGF-beta1 producing cells, and may be helpful in elucidation of the nature of TGF-beta1 production at sites of diseases.


4889.                  Bailey HL, Gabriel SM, Hodgson AR, Shin JS.  Tuberculosis of the spine in children. 1972 [classical article] Clin Orthop. 2002 Jan;(394):4-18.


4890.                  Bailey WC, Gerald LB, Kimerling ME, Redden D, Brook N, Bruce F, Tang S, Duncan S, Brooks CM, Dunlap NE.  Predictive model to identify positive tuberculosis skin test results during contact investigations. JAMA. 2002 Feb 27;287(8):996-1002.


CONTEXT: Budgetary constraints in tuberculosis (TB) control programs require streamlining contact investigations without sacrificing disease control. OBJECTIVE: To develop more efficient methods of TB contact investigation by creating a model of TB transmission using variables that best predict a positive  tuberculin skin test among contacts of an active TB case. DESIGN, SETTING, AND SUBJECTS: After standardizing the interview and documentation process, data were collected on 292 consecutive TB cases and their 2941 contacts identified by the Alabama Department of Public Health between January and October 1998. Generalized estimating equations were used to create a model for predicting positive skin test results in contacts of active TB cases. The model was then validated using data from a prospective cohort of 366 new TB cases and their 3162 contacts identified between October 1998 and April 2000. MAIN OUTCOME MEASURE: Tuberculin skin test result. RESULTS: Using generalized estimating equations to build a predictive model, 7 variables were found to significantly predict a positive tuberculin skin test result among contacts of an active TB case. Further testing showed this model to have a sensitivity, specificity, and positive predictive value of approximately 89%, 36%, and 26%, respectively. The false-negative rate was less than 10%, and about 40% of the contact workload could be eliminated using this model. CONCLUSIONS: Certain characteristics can be used to predict contacts most likely to have a positive tuberculin skin test result. Use of such models can significantly reduce the number of contacts that public health officials need to investigate while still maintaining excellent disease control.


4891.                  Bakardjiev A, Glaser C, Schuster F, Visvesvara GS.  Three-year-old girl with fever and coma. Pediatr Infect Dis J. 2002 Jan;21(1):75, 85-6.

No Abstract

4892.                  Bansal D, Singhi PD, Ray M, Paramjeet.  Cervical intramedullary tuberculoma: acute presentation and rapid response to medical therapy. J Trop Pediatr. 2002 Feb;48(1):55-7.


A case of an 11-year-old boy with rapidly progressing quadriparesis with bowel and bladder incontinence is reported. MRI of the spine revealed an intramedullary tuberculoma at the level of C5-7. Investigations further revealed evidence of tuberculosis in the brain and lungs as well. The child made a rapid recovery with medical management alone.


4893.                  Behr MA.  BCG--different strains, different vaccines? Lancet Infect Dis. 2002 Feb;2(2):86-92. Review.


After nearly a century of use, BCG vaccines continue to generate controversy and confusion. Their ability to prevent tuberculosis in studies has been inconsistent. When they have been protective, no clear mechanism of action has been established. Furthermore, the existence of different BCG strains has been described since the 1940s. These strains vary according to several laboratory properties, which may or may not translate into a discernible effect on vaccination. With recent genomic comparisons, it is now clear that different BCG vaccine strains have evolved and differ from each other and from the original BCG first used in 1921. Some of these genetic alterations explain certain variations in laboratory properties of BCG. However, these mutations in BCG strains have yet to be shown to affect BCG-associated protection and/or adverse effects. Continuing research is attempting to assess the effect of these genetic alterations on properties of BCG strains, with the goals of suggesting the ideal BCG for vaccination and providing avenues for improvement on existing BCG vaccines.


4894.                  Bemer P, Palicova F, Rusch-Gerdes S, Drugeon HB, Pfyffer GE.  Multicenter evaluation of fully automated BACTEC Mycobacteria Growth Indicator Tube 960 system for susceptibility testing of Mycobacterium tuberculosis. J Clin Microbiol. 2002 Jan;40(1):150-4.


The reliability of the BACTEC Mycobacteria Growth Indicator Tube (MGIT) 960 system for testing of Mycobacterium tuberculosis susceptibility to the three front-line drugs (isoniazid [INH], rifampin [RIF], and ethambutol [EMB]) plus streptomycin (STR) was compared to that of the BACTEC 460 TB system. The proportion method was used to resolve discrepant results by an independent arbiter. One hundred and ten strains were tested with an overall agreement of 93.5%. Discrepant results were obtained for seven strains (6.4%) with INH (resistant by BACTEC MGIT 960; susceptible by BACTEC 460 TB), for one strain (0.9%) with RIF (resistant by BACTEC MGIT 960; susceptible by BACTEC 460 TB), for seven strains (6.4%) with EMB (six resistant by BACTEC MGIT 960 and susceptible by BACTEC 460 TB; one susceptible by BACTEC MGIT 960 and resistant by BACTEC 460 TB), and for 19 strains (17.3%) with STR (resistant by BACTEC MGIT 960 and susceptible by BACTEC 460 TB). After resolution of discrepant results, the sensitivity of the BACTEC MGIT 960 system was 100% for all four drugs and specificity ranged from 89.8% for STR to 100% for RIF. Turnaround times were 4.6 to 11.7 days (median, 6.5 days) for BACTEC MGIT 960 and 4.0 to 10.0 days (median, 7.0 days) for BACTEC 460 TB. These data demonstrate that the fully automated and nonradiometric BACTEC MGIT 960 system is an accurate method for rapid susceptibility testing of M. tuberculosis.

4895.                  Bermudez LE, Sangari FJ, Kolonoski P, Petrofsky M, Goodman J.  The efficiency of the translocation of Mycobacterium tuberculosis across a bilayer of epithelial and endothelial cells as a model of the alveolar wall is a consequence of transport within mononuclear phagocytes and invasion of alveolar epithelial cells. Infect Immun. 2002 Jan;70(1):140-6.


The mechanism(s) by which Mycobacterium tuberculosis crosses the alveolar wall to establish infection in the lung is not well known. In an attempt to better understand the mechanism of translocation and create a model to study the different stages of bacterial crossing through the alveolar wall, we established a two-layer transwell system. M. tuberculosis H37Rv was evaluated regarding the ability to cross and disrupt the membrane. M. tuberculosis invaded A549 type II alveolar cells with an efficiency of 2 to 3% of the initial inoculum, although it was not efficient in invading endothelial cells. However, bacteria that

invaded A549 cells were subsequently able to be taken up by endothelial cells with an efficiency of 5 to 6% of the inoculum. When incubated with a bicellular transwell monolayer (epithelial and endothelial cells), M. tuberculosis translocated into the lower chamber with efficiency (3 to 4%). M. tuberculosis was also able to efficiently translocate across the bicellular layer when inside monocytes. Infected monocytes crossed the barrier with greater efficiency when A549 alveolar cells were infected with M. tuberculosis than when A549 cells were not infected. We identified two potential mechanisms by which M. tuberculosis gains access to deeper tissues, by translocating across epithelial cells and by traveling into the blood vessels within monocytes.


4896.                  Bifani PJ, Mathema B, Kurepina NE, Kreiswirth BN.  Global dissemination of the Mycobacterium tuberculosis W-Beijing family strains. Trends Microbiol. 2002 Jan;10(1):45-52. Review.


A large, genetically related group of Mycobacterium tuberculosis strains, variously called W or Beijing, is distinguished by specific molecular markers and referred to as the W-Beijing family strains. Molecular epidemiological studies suggest that these strains are highly prevalent throughout Asia and the countries of the former Soviet Union and they have also been reported in several other geographical regions, including North America. Although the spread of W-Beijing family strains in diverse populations is well documented, the underlying host-pathogen factors accounting for their continued dissemination and burden of disease have yet to be determined.


4897.                  Bothamley GH, Rowan JP, Griffiths CJ, Beeks M, McDonald M, Beasley E, van den Bosch C, Feder G.  Screening for tuberculosis: the port of arrival scheme compared with screening in general practice and the homeless. Thorax. 2002 Jan;57(1):45-9.


BACKGROUND: Tuberculosis is increasing in London, especially in those recently entering the UK from an area of high incidence. Screening through the port of arrival scheme has a poor yield and has been considered discriminatory. METHODS: A study was undertaken to compare the yield and costs of screening new entrants in a hospital based new entrants' clinic (1262 referrals from the port of arrival), general practice (1311 new registrations), and centres for the homeless (267 individuals) using a symptom questionnaire and tuberculin testing if indicated. Clinical outcome measures were cases of tuberculosis, tuberculin reactors requiring chemoprophylaxis and BCG vaccinations. Cost outcomes were cost per individual screened and cost per individual per case of tuberculosis prevented. RESULTS: Verbal screening limited tuberculin testing to 16% of those in general practice; most were tested at the other two locations. Intervention (BCG vaccination, chemoprophylaxis or treatment) occurred in 27% of those who

 received tuberculin testing. Attendance for screening was 17% of the port of arrival notifications (63% had registered with a GP), 54% in primary care, and 67% in the homeless (42% registered with a GP). Costs for screening an individual in general practice, hostels for the homeless, and the new entrants'

clinic were 1.26 pounds sterling, 13.17 pounds sterling and 96.36 pounds sterling, respectively, while the cost per person screened per case of tuberculosis prevented was 6.32 pounds sterling, 23.00 pounds sterling, and 10.00 pounds sterling, respectively. The benefit of screening was highly sensitive to the number of cases of tuberculosis identified and case holding

during treatment. CONCLUSION: Screening for tuberculosis in primary care is feasible and could replace hospital screening of new arrivals for those registered with a GP.


4898.                  Carter EJ.  Tuberculosis--elimination in the third millennium? Med Health R I. 2002 Feb;85(2):48-51.

No Abstract

4899.                  Casado JL, Moreno S, Fortun J, Antela A, Quereda C, Navas E, Moreno A, Dronda F.  Risk factors for development of tuberculosis after isoniazid chemoprophylaxis in human immunodeficiency virus-infected patients. Clin Infect Dis. 2002 Feb 1;34(3):386-9.


The long-term benefit of isoniazid chemoprophylaxis in human immunodeficiency virus (HIV)-infected patients and risk factors for isoniazid failure were studied in 131 HIV-infected patients who received >9 months of isoniazid preventive therapy. During a median follow-up of 43 months, 8 patients developed tuberculosis (TB) (6%; 0.61 cases per 100 patient-years). Only the persistence of risk factors for exposure to TB was statistically associated with development of disease (relative hazard, 3.17; 95% confidence interval, 1.56-17; P<.001). Our data suggest reinfection as the main cause of TB after isoniazid prophylaxis.

4900.                  Chadha S L, Bhagi RP. Treatment outcome in tuberculosis patients placed under directly observed treatment short course (dots). Indian J Tuberc 2000, 47(3), 155-8.

: Study was carried out to evaluate treatment outcome in tuberculosis patients under DOTS. The 639 subjects in the cohort comprised 432 males and 207 females. The patients were diagnosed and administered/standard regimens of antituberculosis drugs as prescribed under DOTS guidelines along with lesions of the radiological assessment. The sputum conversion rate was 92.6% and 76.9% in category I and at the end of intensive phase. The cure rate was 91% and 73.3% in category II patients respectively. Defaulter rate was 7.7% treatment failure rate was 1.6%; three fourth patients were asymptomatics and 95% had gained weight, ranging from 1 kg to 5 kg. The radiological lesions showed significant improvement in 76.3% patients.


4901.                  Chadha VK, Jagannath PS, Suryanarayana HV.  Tuberculin sensitivity in BCG vaccinated children and its implication for ARI estimation. Indian J Tuberc 2000, 47(3), 139-46.


Tuberculin sensitivity patterns among BCG vaccinated and unvaccinated children and possibility of estimating annual risk of tuberculosis infection (ARI) from among BCG vaccinated children, a total of 11,132 children (5.107) aged 0-4 years and 6.025 aged 5-9 years) were tested using ITU of PPD RT23 with Tween 80. Children with BCG scar comprised 68.2% of the test-read population aged 0-4 years and 47.5% of those aged 5-9 years. Overall, 68.9% of the children with BCG scar had either no test reaction or reaction <10 mm in size. In the 0-4 year age group, a bimodal distribution of reaction sizes was observed among the unvaccinated children, but not so in the vaccinated children. In the 5-9 year age group, the distributions were bimodal in both the vaccinated as well as unvaccinated children. The mode on the right side of the  distribution was at 25 mm in the vaccinated as well as unvaccinated 5-9 years old children. Based on this mode, the prevalence of infection was estimated to be 8.08% and 8.6% among the unvaccinated and vaccinated children respectively. The respective ARI rates were 1.12% and 1.19%. Indicates that in the event of non-availability of a sufficient number of unvaccinated children for estimation of ARI.tuberculin surveys may be conducted among the 5-9 year aged, including vaccinated children. 13 ref.


4902.                  Chao SS, Loh KS, Tan KK, Chong SM.  Tuberculous and nontuberculous cervical lymphadenitis: a clinical review. Otolaryngol Head Neck Surg. 2002 Feb;126(2):176-9.


OBJECTIVES: The aim of the present study was to identify differences in clinical characteristics between patients with tuberculous cervical lymphadenitis and those with nontuberculous cervical lymphadenitis and to determine the diagnostic

accuracy of fine needle aspiration (FNA) cytology. STUDY DESIGN AND SETTING: Seventy-two patients with inflammatory cervical lymphadenitis were studied retrospectively. They were divided into 2 groups: group 1 consisted of those

with tuberculous lymphadenitis and group 2 consisted of those with non-tuberculous lymphadenitis. The demographic characteristics, clinical parameters, and hematological and cytological results of the 2 groups were compared. RESULTS: Other than there being a significantly higher proportion of foreign-born patients in group 1, there were no differences in clinical

characteristics between the 2 groups. The sensitivity and specificity of FNA cytology in the diagnosis of tuberculous lymphadenitis were 88% and 96%, respectively. CONCLUSION: It is difficult to clinically differentiate tuberculous from nontuberculous lymphadenitis. FNA cytology is useful in the diagnosis of tuberculous lymphadenitis. SIGNIFICANCE: In regions where tuberculosis is endemic, treatment can be instituted without the need for excisional biopsy if the FNA results show characteristic caseating granuloma.


4903.                  Choi SH, Kim YS, Bae IG, Chung JW, Lee MS, Kang JM, Ryu J, Woo JH.  The possible role of cerebrospinal fluid adenosine deaminase activity in the diagnosis of tuberculous meningitis in adults. Clin Neurol Neurosurg. 2002 Jan;104(1):10-5.

We studied an adenosine deaminase (ADA) activity in the cerebrospinal fluid (CSF) of 182 patients with meningitis. The patients were subdivided into four groups, (1) 36 cases of tuberculous meningitis; (2) 130 cases of viral or aseptic meningitis; (3) nine cases of bacterial meningitis; (4) seven cases of cryptococcal meningitis. Mean+/-S.D. ADA activity was 12.76+/-7.53 U/l in group 1; 2.58+/-2.37 U/l in group 2; 7.38+/-3.27 U/l in group 3; 7.42+/-4.38 U/l in group 4. Comparing the ADA activity in each group with the other groups, the difference is significant (P<0.001), except between groups 3 and 4. The

sensitivity of the test for group 1 compared with group 2 was 0.83 and the specificity was 0.95 when a cut-off value of 7 U/l was used. When group 1 was compared with groups 3 and 4, the sensitivity was 0.58 and the specificity was 0.89 and 0.71 with groups 3 and 4, respectively, when a cut-off value of 10 U/l was used. Values >15 U/l were not observed  in any of the non-tuberculou meningitis patients; therefore, ADA activity >15 U/l could be a strong indication of tuberculous meningitis. We conclude that a determination of CSF ADA can aid in the early differential diagnosis of tuberculous meningitis.

4904.                  Chua-Intra B, Wilkinson RJ, Ivanyi J.  Selective T-cell recognition of the N-terminal peptide of GroES in tuberculosis. Infect Immun. 2002 Mar;70(3):1645-7.

Peptides derived from the whole sequence of mycobacterial GroES heat shock proteins were tested for the ability to induce the proliferation of blood mononuclear cells from tuberculosis patients and sensitized healthy subjects. The response to the N-terminal peptide (residues 1 to 16) was found to be more frequent and stronger in tuberculosis patients. This finding is exceptional, considering that recognition of all other GroES peptides by patients was either diminished or not different from that of controls.


4905.                  Cobo J, Moreno S.  Predicting tuberculosis at hospital admission. Arch Intern Med. 2002 Mar 11;162(5):611-2.

 No Abstract


4906.                  Collins KR, Quinones-Mateu ME, Wu M, Luzze H, Johnson JL, Hirsch C, Toossi Z, Arts EJ.  Human immunodeficiency virus type 1 (HIV-1) quasispecies at the sites of Mycobacterium tuberculosis infection contribute to systemic HIV-1 heterogeneity. J Virol. 2002 Feb;76(4):1697-706.

We have recently reported an increased heterogeneity in the human immunodeficiency virus type 1 (HIV-1) envelope gene (env) in HIV-1-infected patients with pulmonary tuberculosis (TB) compared to patients with HIV-1 alone. This increase may be a result of dissemination of lung-derived HIV-1 isolates from sites of Mycobacterium tuberculosis infection and/or the systemic activation of the immune system in response to TB. To distinguish between these two mechanisms, blood and pleural fluid samples were obtained from HIV-1-infected patients with active pleural TB in Kampala, Uganda (CD4 cell

counts of 34 to 705 cells/microl, HIV-1 plasma loads of 2,400 to 280,000 RNA copies/ml, and HIV-1 pleural loads of 7,600 to 4,500,000 RNA copies/ml). The C2-C3 coding region of HIV-1 env was PCR amplified from lysed peripheral blood

mononuclear cells and pleural fluid mononuclear cells and reverse transcriptase-PCR amplified from plasma and pleural fluid HIV-1 virions of eight HIV-1 patients with pleural TB. Phylogenetic and phenetic analyses revealed a compartmentalization of HIV-1 quasispecies between blood and pleural space in four of eight patients, with migration events between the compartments. There was a trend for a greater genetic heterogeneity in the pleural space, which may be the result of an M. tuberculosis-mediated increase in HIV-1 replication and/or selection pressure at the site of infection. Collectively, these findings suggest that HIV-1 quasispecies in the M. tuberculosis-infected pleural space may leak into the systemic circulation and lead to increased systemic HIV-1 eterogeneity during TB.


4907.                  Daniel TM.  Origins of tuberculosis in North America. Clin Infect Dis. 2002 Jan 15;34(2):291.

No Abstract


4908.                  Das S, Mahajan RC, Ganguly NK, Sawhney IM, Dhawan V, Malla N.  Detection of antigen B of Cysticercus      cellulosae in cerebrospinal fluid for the diagnosis of human neurocysticercosis. Trop Med Int Health. 2002 Jan;7(1):53-8.


Neurocysticercosis (NCC) is a major cause of morbidity and mortality in developed and developing countries. The diagnosis of this disease remains a problem. We report the detection of specific antigenic fraction (antigen B) of Cysticercus cellulosae by enzyme-linked immunosorbent assay (ELISA) in various fractions of cerebrospinal fluid (CSF) obtained by high performance liquid chromatographic (HPLC) separation, for the diagnosis of human NCC. Forty patients attending or admitted to Nehru Hospital, Chandigarh were included in the study: 10 with suspected NCC, 20 with other neurological diseases and 10 undergoing surgery under spinal anaesthesia for non-neurological conditions, who served as controls. CSF samples collected from all patients and controls were subjected to chromatographic separation on an HPLC system. Antigen B (AgB) was detected in separated fractions by an ELISA test and compared with the detection of antibody response in CSF samples by indirect haemagglutination (IHA) technique. Antigen B was detected in 9 out of 10 patients with suspected NCC based on clinical symptoms and radioimaging reports, but in none of the control subjects. However, antigen B was also detected in 9 out of 20 patients with other neurological disorders, mostly tubercular meningitis. Antibody response by IHA was found positive in only 2 of 10 cases clinically suspected of NCC. In conclusion, antigen B detection in CSF samples may be a useful adjunct to clinical suspicion and radiological reports for the diagnosis of NCC as there is no gold standard criteria to confirm this disease. However, the test needs to be evaluated on more patients in countries where tuberculosis and cysticercosis are endemic due to the high cross reactivity with samples from tubercular meningitis patients.


4909.                  De Rosa FG, Bonora S, Di Perri G.  Tuberculosis and treatment with infliximab. N Engl J Med. 2002 Feb 21;346(8):623-6.

No Abstract

4910.                  Dean GL, Edwards SG, Ives NJ, Matthews G, Fox EF, Navaratne L, Fisher M, Taylor GP, Miller R, Taylor CB, de Ruiter A, Pozniak AL. Treatment of tuberculosis in HIV-infected persons in the era of highly active antiretroviral therapy. AIDS. 2002 Jan 4;16(1):75-83.


OBJECTIVE: To assess the risks and benefits of administering highly active antiretroviral therapy (HAART) during the treatment of tuberculosis (TB) in HIV-infected patients. DESIGN AND METHODS: HIV-1 patients presenting to 12 HIV

centres in Greater London and south-east England with culture-proven TB were identified from January 1996 to June 1999. Case-notes were reviewed retrospectively. RESULTS: Patients (n = 188) were severely immunocompromised with a median CD4 cell count at TB diagnosis of 90 x 106 cells/l (IQR: 30-180). At presentation, 85% (n = 159) were not taking antiretrovirals. A total of 45% commenced HAART during TB treatment, which was associated with significant reductions in viral load, AIDS-defining illness (ADI) [3.5 versus 24.5%; relative risk (RR) = 0.14] and mortality. Only nine of 91 (10%) patients with a CD4 count > 100 x 106 cells/l at TB diagnosis experienced a further ADI, whereas 18 of 92 (20%) patients with a CD4 count < 100 x 106 cells/l developed this complication. Adverse events (AE) occurred in 99 (54%) of 183 patients, one-third of whom changed or interrupted HIV and/or TB medication. The majority of AE occurred within the first 2 months, with peripheral neuropathy (21%), rash (17%) and gastrointestinal upset (10%) occurring most commonly. CONCLUSIONS: Many physicians delay HAART in patients presenting with TB because of pill burden, drug/drug interactions and toxicity. Although the use of HAART led to significant reductions in viral load, ADI and mortality, co-infected patients commonly experienced AE leading to interruptions in TB/HIV therapy. We therefore recommend starting HAART early for patients with advanced HIV disease (CD4 < 100 x 106 cells/l) and deferring HAART until the continuation phase of TB therapy (i.e. after 2 months) for patients who are clinically stable (CD4 > 100 x 106 cells/l).


4911.                  Eishi Y, Suga M, Ishige I, Kobayashi D, Yamada T, Takemura T, Takizawa T, Koike M, Kudoh S, Costabel U, Guzman J, Rizzato G, Gambacorta M, du Bois R, Nicholson AG, Sharma OP, Ando M.  Quantitative analysis of mycobacterial and propionibacterial DNA in lymph nodes of Japanese and European patients with sarcoidosis. J Clin Microbiol. 2002 Jan;40(1):198-204.


The cause(s) of sarcoidosis is unknown. Mycobacterium spp. are suspected in Europe and Propionibacterium spp. are suspected in Japan. The present international collaboration evaluated the possible etiological links between sarcoidosis and the suspected bacterial species. Formalin-fixed and paraffin-embedded sections of biopsy samples of lymph nodes, one from each of 108 patients with sarcoidosis and 65 patients with tuberculosis, together with 86 control samples, were collected from two institutes in Japan and three institutes in Italy, Germany, and England. Genomes of Propionibacterium acnes, Propionibacterium granulosum, Mycobacterium tuberculosis, Mycobacterium avium subsp. paratuberculosis, and Escherichia coli (as the control) were counted by quantitative real-time PCR. Either P. acnes or P. granulosum was found in all but two of the sarcoid samples. M. avium subsp. paratuberculosis was found in no sarcoid sample. M. tuberculosis was found in 0 to 9% of the sarcoid samples but in 65 to 100% of the tuberculosis samples. In sarcoid lymph nodes, the total numbers of genomes of P. acnes or P. granulosum were far more than those of M. tuberculosis. P. acnes or P. granulosum was found in 0 to 60% of the tuberculosis and control samples, but the total numbers of genomes of P. acnes or P. granulosum in such samples were less than those in sarcoid samples. Propionibacterium spp. are more likely than Mycobacteria spp. to be involved in the etiology of sarcoidosis, not only in Japanese but also in European patients with sarcoidosis.


4912.                  Engele M, Stossel E, Castiglione K, Schwerdtner N, Wagner M, Bolcskei P, Rollinghoff M, Stenger S. Induction of TNF in human alveolar macrophages as a potential evasion mechanism of virulent Mycobacterium tuberculosis. J Immunol. 2002 Feb 1;168(3):1328-37.

The ability of macrophages to release cytokines is crucial to the host response to intracellular infection. In particular, macrophage-derived TNF plays an important role in the host response to infection with the intracellular pathogen Mycobacterium tuberculosis. In mice, TNF is indispensable for the formation of tuberculous granulomas, which serve to demarcate the virulent bacterium. TNF is also implicated in many of the immunopathological features of tuberculosis. To investigate the role of TNF in the local immune response, we infected human alveolar macrophages with virulent and attenuated mycobacteria. Infection with virulent strains induced the secretion of significantly higher levels of bioactive TNF than attenuated strains correlating with their ability to multiply  intracellularly. Treatment of infected macrophages with neutralizing anti-TNF Abs reduced the growth rate of intracellular bacteria, whereas bacterial replication was augmented by addition of exogenous TNF. Infected and uninfected macrophages contributed to cytokine production as determined by double-staining of M. tuberculosis and intracellular TNF. The induction of TNF by human alveolar macrophages at the site of infection permits the multiplication of intracellular bacteria and may therefore present an evasion mechanism of human pathogens.


4913.                  Feng YH, Chou MT, Hsu JJ, Chuang SS.  Ascites and leg edema as the first manifestations of tuberculous effusive  constrictive pericarditis. Int J Cardiol. 2002 Jan;82(1):55-7.

No abstract

4914.                  Ferguson JS, Voelker DR, Ufnar JA, Dawson AJ, Schlesinger LS.  Surfactant protein D inhibition of human macrophage uptake of Mycobacterium tuberculosis is independent of bacterial agglutination. J Immunol. 2002 Feb 1;168(3):1309-14.


The innate immune system in the lung is essential for controlling infections due to inhaled pathogens. Mycobacterium tuberculosis (M.tb) encounters components of the innate immune system when inhaled into the lung, but the consequences of these interactions are poorly understood. Surfactant protein D (SP-D) binds to and agglutinates M.tb bacilli, and reduces the uptake of the bacteria by human macrophages. In the current studies, we utilized a recombinant SP-D variant (CDM) that lacks the collagen domain to further characterize the interaction of SP-D with M.tb, and determine the effects of agglutination on bacterial uptake by human monocyte-derived macrophages. These studies demonstrate that the binding of SP-D and CDM to M.tb is saturable and inhibited by carbohydrate competition and Ca(2+) chelation, implicating the carbohydrate recognition domain in the interaction. Fluorescence microscopy reveals that dodecameric SP-D leads to agglutination of the bacilli, whereas the trimeric CDM does not, demonstrating that the multivalent nature of SP-D is essential for agglutination of M.tb. However, preincubation of M.tb with increasing concentrations of SP-D or CDM leads to a concentration-dependent reduction in the uptake of the bacteria by macrophages, indicating that agglutination does not play a direct role in this observation. Finally, the reduced uptake of M.tb by SP-D is associated with reduced growth of M.tb in monocyte-derived macrophages. These studies provide direct evidence that the inhibition of phagocytosis of M.tb effected by SP-D occurs independently of the aggregation process.

4915.                  Francis J, Reed A, Yohannes F, Dodard M, Fournier AM.  Screening for tuberculosis among orphans in a developing country. Am J Prev Med. 2002 Feb;22(2):117-9.


BACKGROUND: There has been a recent resurgence of tuberculosis (TB) as a worldwide public health concern. It is a well-documented health problem in Haiti, where the reported prevalence is 123.9 per 100,000 population. While the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) policy papers for the eradication of TB recommend screening in shelters, prisons, and other congregate-living facilities, screening in institutional orphanages is not specifically mentioned. METHODS: A total of 445 orphans with no documentation of Bacillus Calmette-Guerin (BCG) vaccine at six orphanages representing urban, suburban, and rural Haiti were screened for TB using standardized purified protein derivative (PPD). An inoculum of 0.1 cc was introduced intradermally, with site checks for induration at 48-72 hours after inoculation. Induration >5 mm was recorded as positive. Active cases of TB were defined by symptoms such as fever, night sweats, cough greater than 1 month, or signs of extrapulmonary TB (like scrofula or Pott's disease). RESULTS: The number of positive PPD tests was 170 of the 445 children tested, or 38,202 per 100,000; there were 10 active cases. The overall prevalence of tuberculin positivity in the three orphanages with one or more active cases was 44%, compared to 13% in the three with no identified active cases. CONCLUSIONS: The data indicate that TB prevalence among the orphans screened was 1123 per 100,000. This is substantially greater than that reported for the general Haitian population. These data thus suggest children living in orphanages as a previously unidentified high-risk group for TB infection. Further investigation of TB is recommended for orphans in developing countries.


4916.                  Franco-Paredes C, Leonard M, Jurado R, Blumberg HM, Smith RM.  Tuberculosis of the pancreas: report of two cases and review of the literature. Am J Med Sci. 2002 Jan;323(1):54-8. Review.


Tuberculosis of the pancreas is a clinical entity rarely described in the literature. The pancreas is biologically protected from infection by Mycobacterium tuberculosis, probably because of the presence of pancreatic enzymes that interfere with the seeding of M. tuberculosis. However, when pathogens are able to overcome the resistance, they can have diverse presentations, such as pancreatic masses that can mimic carcinoma, obstructive jaundice, pancreatitis, and gastrointestinal bleeding. Herein we describe 2 cases of pancreatic tuberculosis that presented as multicystic masses, and we review the literature to describe the diverse clinical manifestations of this condition.


4917.                  Garcia MR, Rodriguez JC, Navarro JF, Sampert S, Martin C, Royo G.  Molecular epidemiology of tuberculosis in Elche, Spain: a 7-year study. J Med Microbiol. 2002 Mar;51(3):273-7.


The epidemiology of tuberculosis in Elche (Spain) was studied by restriction fragment-length polymorphism (RFLP) typing of clinical isolates of Mycobacterium tuberculosis over a 7-year period. A total of 165 isolates was typed and the clinico-epidemiological data of the patients were studied retrospectively. An overall cluster aggregation of 52.4% was found, rising to 71.43% in HIV-positive patients. There was greater aggregation in younger patients, but no statistically significant differences when other variables were analysed. The percentage of aggregation was higher than in other studies in Spain and this may be due to the longer time period of this study. The high percentage of aggregation in young patients and in thosewho were HIV-positive suggests increased recent transmission in both groups.


4918.                  Gioia C, Agrati C, Casetti R, Cairo C, Borsellino G, Battistini L, Mancino G, Goletti D, Colizzi V, Pucillo LP, Poccia F. Lack of CD27-CD45RA-V gamma 9V delta 2+ T cell effectors in immunocompromised hosts and during active pulmonary tuberculosis. J Immunol. 2002 Feb 1;168(3):1484-9.


In humans, the circulating pool of mycobacteria-reactive Vgamma9Vdelta2+ T cells is expanded with age and may contribute to Mycobacterium tuberculosis immunosurveillance. We observed that two subsets of Vgamma9Vdelta2+ T cells could be identified on the basis of CD27 expression in immunocompetent adults, showing that functionally differentiated gammadelta T cells have lost CD27 expression. In contrast, the CD27-CD45RA-Vgamma9Vdelta2+ T cell subset of effector cells was absent in cord blood cells from healthy newborns and lacking in the peripheral blood from HIV-infected patients. Moreover, circulating Vgamma9Vdelta2+ T cell effectors were significantly reduced in patients with acute pulmonary tuberculosis, resulting in a reduced frequency of IFN-gamma-producing cells after stimulation with nonpeptidic mycobacterial ligands. These observations indicate that monitoring and boosting gammadelta T cell effectors could be clinically relevant both in immunocompromised hosts and during active tuberculosis disease.


4919.                  Hatem CM, Kantis GA, Christoforou D, Gold JP, Plestis KA.  Tuberculous aneurysm of the\ descending thoracic aorta. J Thorac Cardiovasc Surg. 2002 Feb;123(2):373-4.

No Abstract

4920.                  Heffelfinger JD, Davis TE, Gebrian B, Bordeau R, Schwartz B, Dowell SF.  Evaluation of children with recurrent pneumonia diagnosed by World Health Organization criteria. Pediatr Infect Dis J. 2002 Feb;21(2):108-12.


BACKGROUND: A World Health Organization (WHO) case management approach has been used to identify and treat children with pneumonia worldwide since 1987. Many children are treated repeatedly: 23% of children with pneumonia in our rural Haitian district had met the WHO criteria on two or more occasions; but underlying disease in such children has not been systematically studied. METHODS: We enrolled 103 children who had been diagnosed with pneumonia on 3 or more occasions by community health workers using WHO criteria. We compared them with 138 children similarly evaluated but never diagnosed with pneumonia, matching by health worker and age. We administered questionnaires to parents and performed complete physical examinations, tuberculin skin tests and serologic testing for HIV on all subjects and chest radiographs on case children. RESULTS: Two percent of case children and 1.5% of controls had positive tuberculin skin test reactions. None of the children tested was HIV-seropositive. Ninety-four case children had normal baseline chest radiographs and three had focal infiltrates. A history of wheezing was reported for 79% of case children and 61% of controls (P = 0.002), and wheezing with exercise was reported for 36% and 22%, respectively (P = 0.02). DISCUSSION: Most children in Haiti with recurrent pneumonia diagnosed by WHO criteria do not have evidence of tuberculosis, HIV infection or pulmonary anomalies, but they may be more likely to have asthma, and this should be considered as an alternative diagnosis. This information should help direct evaluation of such children in other settings and prompt further study of asthma in developing countries.


4921.                  Hersh A, von Reyn CF.  Interferon assay compared to tuberculin skin testing for latent tuberculosis detection. JAMA. 2002 Jan 23-30;287(4):450-1; discussion 451-2.

No Abstract

4922.                  Herzmann C.  Interferon assay compared to tuberculin skin testing for latent tuberculosis detection. JAMA. 2002 Jan 23-30;287(4):451-2.

No Abstract

4923.                  Hoey J.  Can you get tuberculosis twice? CMAJ. 2002 Feb 19;166(4):478.

No Abstract

4924.                  Hoshino Y, Nakata K, Hoshino S, Honda Y, Tse DB, Shioda T, Rom WN, Weiden M.  Maximal HIV-1 replication in alveolar macrophages during tuberculosis requires both lymphocyte contact and cytokines. J Exp Med. 2002 Feb 18;195(4):495-505.


HIV-1 replication is markedly upregulated in alveolar macrophages (AM) during pulmonary tuberculosis (TB). This is associated with loss of an inhibitory CCAAT enhancer binding protein beta (C/EBPbeta) transcription factor and activation of

nuclear factor (NF)-kappaB. Since the cellular immune response in pulmonary TB requires lymphocyte--macrophage interaction, a model system was developed in which lymphocytes were added to AM. Contact between lymphocytes and AM reduced inhibitory C/EBPbeta, activated NF-kappaB, and enhanced HIV-1 replication. If contact between lymphocytes and macrophages was prevented, inhibitory C/EBPbeta expression was maintained and the HIV-1 long terminal repeat (LTR) was not maximally stimulated although NF-kappaB was activated. Antibodies that cross-linked macrophage expressed B-7, and vascular cell adhesion molecule and CD40 were used to mimic lymphocyte contact. All three cross-linking antibodies were required to abolish inhibitory C/EBPbeta expression. However, the HIV-1 LTR was not maximally stimulated and NF-kappaB was not activated. Maximal HIV-1—LTR stimulation required both lymphocyte-derived soluble factors, and cross-linking of macrophage expressed costimulatory molecules. High level HIV-1—LTR stimulation was also achieved when IL-1beta, IL-6, and TNF-beta were added to macrophages with cross-linked costimulatory molecules. Contact between activated lymphocytes and macrophages is necessary to down-regulate inhibitory C/EBPbeta, thereby derepressing the HIV-1 LTR. Lymphocyte-derived cytokines activate NF-kappaB, further enhancing the HIV-1 LTR.


4925.                  Hsu HC, Lee YM, Su WJ, Huang CY, Yang CF, Ho CK, Ho CH, Wang SY, Liu WT.  Bone marrow samples from patients with aplastic anemia are not infected with parvovirus B19 and Mycobacterium tuberculosis. Am J Clin Pathol. 2002 Jan;117(1):36-40.


The majority of patients with aplastic anemia (AA) have an idiopathic form of the disease. The aim of this study was to detect the presence of parvovirus B19 DNA and Mycobacterium tuberculosis (MTB) DNA by nested polymerase chain reaction (N-PCR) assays in the bone marrow biopsy samples from 30 patients with idiopathic AA. Serologic assays for parvovirus B19 were based on indirect antibody capture enzyme-linked immunosorbent assay. Our results indicate that neither parvovirus B19 DNA nor MTB DNA could be demonstrated in any of the bone marrow samples by N-PCR. Moreover, IgM antibody against parvovirus B19 also was undetectable in the serum samples of 17 patients. Thus, our results suggest that parvovirus B19 and MTB are not associated with AA and, consequently, do not have a role in the pathogenesis of this disease.


4926.                  Jain SK, Jain S, Jain M, Yaduvanshi A.  Esophageal tuberculosis: is it so rare? Report of 12 cases and review of the literature. Am J Gastroenterol. 2002 Feb;97(2):287-91. Review.


OBJECTIVE: Mycobacterial involvement of the esophagus is rare in both immunocompetent and immunocompromised hosts with advanced pulmonary tuberculosis, even in countries with high prevalence rates like India. Most of the reported cases of esophageal tuberculosis (ET) are secondary to tuberculosis elsewhere in the body, most commonly pulmonary tuberculosis. Very few cases of isolated or primary ET have been reported, and most of them have been from developing countries. The upsurge in reported cases of tuberculosis linked to the AIDS epidemic has increased the incidence of this infection in developed countries also. Our aim is to study tuberculosis as an etiological factor in the causation of dysphagia, the role of cytology and histopathology in establishing its diagnosis, and the outcome of antitubercular treatment in these patients. METHODS: A hospital-based, retrospective study was performed. We reviewed records of all of the patients who underwent upper GI endoscopic examination for complaints of persistent dysphagia (>6 wk) in a tertiary care hospital in India between 1995 and 1999. Patients with abnormal endoscopic findings were subjected to endoscopic fine needle aspiration/brush cytology and biopsies. Those with pathological findings suggestive of tuberculosis were treated with antitubercular therapy. RESULTS: Tubercular involvement of the esophagus, confirmed by pathological examination, was found in 12 patients. They constituted 0.5% of all patients with persistent dysphagia, and 1.3% of all patients having abnormal esophagoscopic findings. Cytological examination provided a very useful diagnostic parameter in detection of these cases. Patients diagnosed as having ET responded well to antitubercular therapy. CONCLUSIONS: Tuberculosis as a causative factor for dysphagia should be considered in developing countries with high incidences of tuberculosis and in immunocompromised hosts. Detection of these cases by careful examination of cytological smears and biopsies and treatment with standard antitubercular therapy appear effective.

4927.                  Jayashri K, Balakrishna Murthi P, Sumathi G. Immune response to tuberculous infection. Proc Indian Sci Congr Ass - Pt III, Sect-XI 1998-99, 46-7.


Abstract : Humoral response to mycobacterial antigens is demonstrated by increase in antibody titers in experimental animals immunised with homologous killed organisms with adjuvant. Evidence for a regulatory or modulatory role of circulating immune complexes acting through lymphocytes expressing crystallizable fragment (Fc) receptors. The loss of cell mediated immune function that accompained the development of chronic, moderate protein deficiency in tuberculosis correlated with significant increase in Fc gamma Receptor + IgG in the circulation. On BCG vaccination it produced an increase in pertative helper T Cells bearing Fc receptors for IgM. Thus humoral immune response may modulate cellular reactivity and by its influence, also modulate antituberculous resistance. T-cell mediated immunity to mycobacterial antigen are demonstrated by a number of in vivo (Delayed hypersensitivity) or in vitro (proliferation to define) mycobacterial antigens recognized by the T lymphocytes. Several purified or recombinant mycobacterial antigens elicited an immunologically specific dermal reaction. T lymphocyte reactivity to mycobacterily antigens by in vitro  lymphoproliferative assay in lymphnodes, blood and spleen. Control of M. tuberculosis is brought about by the cooperative actions of CD 4, CD 8 T cells and macrophages, mediated by cytokines such as interferon gamma.

4928.                  Jha D, Deka RC, Sharma MC.  Tuberculosis of the maxillary sinus manifesting as a facial abscess. Ear Nose Throat J. 2002 Feb;81(2):102-4.

Tuberculosis of the maxillary sinus is rare. Likewise, an acute onset that necessitates incision and drainage is also very uncommon. We report the case of a 15-year-old girl who came to us with an abscess on the left side of her face. She was found to have tuberculosis of the left maxillary antrum.


4929.                  Kam KM, Yip CW, Tse LW, Leung OC, Sin LP, Chan MY, Wong WS. Trends in multidrug-resistant Mycobacterium tuberculosis in relation to sputum smear positivity in Hong Kong, 1989-1999. Clin Infect Dis. 2002 Feb 1;34(3):324-9.


We studied retrospectively the territory-wide occurrence and trends of multidrug-resistant tuberculosis (MDR-TB) in Hong Kong over an 11-year period during which a short-course directly observed therapy ("DOTS-Plus") strategy has been in operation. The overall MDR rate was 2.1% (primary, 1.4% and acquired,  9.5%) and declined at 0.08% per year: smear-positive primary MDR cases declined at yearly rate of -0.065% (R2=.23), and smear-negative primary MDR cases increased at 0.035% yearly. With declining rates of smear positivity, sputum culture has become the mainstay of detection of MDR-TB. Although the overall notification rates showed the elderly (age >65 years) age group to be most affected, the occurrence of MDR-TB has been consistently highest in the 35-65 year age group (60.4% of MDR caseload). We demonstrated declining rates of sputum smear positivity of MDR-TB in a DOTS-plus environment and that a centralized laboratory database is essential in gathering epidemiological information for identifying particular risk groups and monitoring trends of  MDR-TB in a community.


4930.                  Kimmatkar NV, Thawani VR.  Management of tuberculosis of lumbosacral spine. Antiseptic, Madurai 2001, 98(4),  144-7.


Abstract : Tuberculosis of lumbosacral spine is rare. Reports 15% incidence among spinal tuberculosis patients, which was more common in 20-30 age group with female preponderance. Sacral spine behaves in different way to the rest of spine. There  was high incidence of backache after healing of disease. Neural deficit was present in 15% of patients, which always recovered. Instability and deformities in terms of kyphosis, scoliosis and lordosis were significant. Backache had direct relationship with kyphosis and hypolordosis (0-10 degree). Implants like pedicular screws and plates might help to reduce the incidence of this. At 3 years 100% patients showed radiological healed or healing disease and 87.5% patients showed favourable status. 18 ref.

4931.                  Klein MR, Hammond AS, Smith SM, Jaye A, Lukey PT, McAdam KP.  HLA-B*35-restricted CD8(+)-T-cell epitope in Mycobacterium tuberculosis Rv2903c. Infect Immun. 2002 Feb;70(2):981-4.

Few human CD8(+) T-cell epitopes in mycobacterial antigens have been described to date. Here we have identified a novel HLA-B*35-restricted CD8(+) T-cell epitope in Mycobacterium tuberculosis Rv2903c based on a reverse immunogenetics approach. Peptide-specific CD88 T cells were able to kill M tuberculosis-infected macrophages and produce gamma interferon and tumor necrosis factor alpha. 


4932.                  Kulkarni AG; Prabhu VV. Dept. of orthopaedics, Dr. R N Cooper Hospital, Vileparle, Mumbai Tuberculosis presenting as carpal tunnel syndrome: a case report with review of literature Bombay Hospital Journal 2002 Jan; 44(1): 102-3

ABSTRACT: We present a case of tuberculosis presenting as carpal tunnel syndrome. Though it is not unusual, the aim is to draw attention that tuberculosis should be considered in the differential diagnosis on finding nonspecific tenosynovitis during carpal tunnel release and should be excluded by performing a biopsy.


4933.                  Lalloo S, Krishna D, Maharajh J.  Case report: abdominal cocoon associated with tuberculous pelvic inflammatory   disease. Br J Radiol. 2002 Feb;75(890):174-6.


Abdominal cocoon is a rare acquired condition in which there is encapsulation of the small bowel by a fibrous membrane. The authors describe a case wherein an organism was identified for the first time. The clinical, pathological and radiological features of this unusual disease are reviewed. Peritoneal encapsulation, a related subject, is also discussed.


4934.                  Lillebaek T, Dirksen A, Baess I, Strunge B, Thomsen VO, Andersen AB.  Molecular evidence of endogenous reactivation of Mycobacterium tuberculosis after 33 years of latent infection. J Infect Dis. 2002 Feb 1;185(3):401-4.


Since Robert Koch described the cause of tuberculosis in 1882, the natural history of the disease after primary infection has been subject to debate. Only approximately 10% of infected individuals develop active disease, which may appear years to decades after infection. Late onset has been attributed to the endogenous reactivation of dormant bacteria. However, this has not been documented by molecular means for latencies of more than a few years. In Denmark, we have recently recultured 205 freeze-dried Mycobacterium tuberculosis strains obtained from 1961 through 1967. These "historical" strains are analyzed

by DNA restriction fragment-length polymorphism testing, and their DNA patterns are compared with those of 4008 recently obtained clinical specimens. This has, surprisingly, yielded molecular evidence of M. tuberculosis reactivation after 33 years of latent infection. A father and son who developed tuberculosis in 1961 and in 1994, respectively, were the only patients infected with strains that share an identical DNA pattern.


4935.                  Mahdavi A, Malviya VK, Herschman BR.  Peritoneal tuberculosis disguised as ovarian cancer: an emerging clinical challenge. Gynecol Oncol. 2002 Jan;84(1):167-70.


BACKGROUND: The incidence of peritoneal tuberculosis in the western world has increased over the past decade. The diagnosis is often made at laparotomy for suspected peritoneal carcinomatosis. CASE: A 56-year-old Filipino female underwent exploratory laparotomy forp suspected ovarian cancer. Frozen-section analysis of her ovaries revealed noncaseating granuloma and the initial acid-fast stains were negative, consistent with non-tuberculous granulomatous disease. Later, all specimen cultures grew Mycobacterium tuberculosis. CONCLUSION: The diagnosis of peritoneal tuberculosis can be difficult and elusive. It mimics ovarian cancer and non-tuberculous granulomatous diseases by its vague symptoms and nonspecific radiographic, pathologic, and laboratory findings. In patients at high risk for peritoneal tuberculosis, we emphasize the importance of clinical suspicion in addition to frozen-section analysis to avoid unnecessary extensive surgery and delay in anti-tuberculous treatment.


4936.                  Masungi C, Temmerman S, Van Vooren JP, Drowart A, Pethe K, Menozzi FD, Locht C, Mascart F.  Differential T and B cell responses against Mycobacterium tuberculosis heparin-binding hemagglutinin adhesin in infected healthy individuals and patients with tuberculosis. J Infect Dis. 2002 Feb 15;185(4):513-20.


Because only 10% of individuals infected with Mycobacterium tuberculosis will eventually develop disease, antigens that are recognized differently by the immune systems of infected healthy and diseased subjects may constitute potential vaccine candidates. Here, the heparin-binding hemagglutinin adhesin (HBHA) is identified as such an antigen. Lymphocytes from 60% of healthy infected individuals (n=25) produced interferon (IFN)-gamma after stimulation with HBHA, compared with only 4% of patients with active tuberculosis (n=24). In the responders, both CD4(+) and CD8(+) cells secreted HBHA-specific IFN-gamma, and the antigen was presented by both major histocompatibility complex class I and II molecules. In contrast to the reduced ability of patients with tuberculosis to produce HBHA-specific IFN-gamma, most of them (82%) produced anti-HBHA antibodies, compared with 36% of the infected healthy subjects. These observations indicate that HBHA is recognized differently by the immune systems of patients with tuberculosis and infected healthy individuals and might provide a marker for protection against tuberculosis.


4937.                  McConkey SJ, Williams M, Weiss D, Adams H, Cave MD, Yang Z, Lindner T, Bailey TC.  Prospective use of molecular typing of Mycobacterium tuberculosis by use of restriction fragment-length polymorphism in a public tuberculosis-control program. Clin Infect Dis. 2002 Mar 1;34(5):612-9.


We performed a prospective, community-based evaluation of molecular typing of Mycobacterium tuberculosis isolates as a method for tuberculosis (TB) control. We performed restriction fragment-length polymorphism (RFLP) analysis of the insertion sequences IS6110 and pTBN12 for isolates recovered from 61 of 62 patients with culture-positive TB in St. Louis during 12 months. Twenty-four (39%) of the 61 patients were infected with an isolate with an RFLP pattern that was shared with >/=1 other isolate, and 11 (46%) also had epidemiologic links with patients in their cluster of cases. One case each of laboratory cross-contamination and occupational transmission were discovered. The patients in clusters were more likely to be younger, black, United States-born, to have substance abuse problems, and to live in poorer areas. A predictive algorithm for molecular identification of clusters had a sensitivity and a specificity of 75%. This study allowed the TB-control program in St. Louis to be redirected toward the affected subpopulations.


4938.                  Mohle-Boetani JC, Flood J.  Contact investigations and the continued commitment to control tuberculosis. JAMA. 2002 Feb 27;287(8):1040-2.

No Abstract

4939.                  Mohle-Boetani JC, Miguelino V, Dewsnup DH, Desmond E, Horowitz E, Waterman SH, Bick J.  Tuberculosis outbreak in a housing unit for human immunodeficiency virus-infected patients in a correctional facility: transmission risk factors and effective outbreak control. Clin Infect Dis. 2002 Mar 1;34(5):668-76.

In 1995, an outbreak of tuberculosis (TB) occurred among residents of a correctional-facility housing unit for inmates infected with human immunodeficiency virus (HIV). We isolated and treated patients who were suspected to have TB. To determine risk factors for in-prison transmission of TB, we conducted a case-control study to compare inmate case patients infected with a distinct outbreak strain of TB with control subjects who resided in the HIV unit. We identified 15 case patients during a 4-month period. Among inmates with a CD4 count of <100 cells/mm(3), case patients were more likely than control subjects to spend >/=20 hours per week in a communal day room (odds ratio, 42; P=.002) and were less likely to have a television in their single-person room (odds ratio, 0.10; P=.003). The communal day room was a likely site of transmission. Successful collaboration between the correctional system and public health departments halted the outbreak.


4940.                  Morgan D, Mahe C, Mayanja B, Whitworth JA.  Progression to symptomatic disease in people infected with HIV-1 in rural Uganda: prospective cohort study. BMJ. 2002 Jan 26;324(7331):193-6.


OBJECTIVES: To estimate the rate of progression from seroconversion to symptomatic disease in adults infected with HIV-1, and to establish whether the background level of signs and symptoms commonly associated with HIV-1 in uninfected controls are likely to affect progression rates. DESIGN: Longitudinal, prospective cohort study of people infected with HIV-1 and randomly selected subjects negative for HIV-1 antibodies identified during population studies. SETTING: Study clinic with basic medical care in rural Uganda. SUBJECTS: 275 patients infected with HIV-1 (107 prevalent cases and 168 incident cases) and 246 controls negative for HIV-1 antibodies. MAIN OUTCOME MEASURES: Signs and symptoms of HIV disease, as determined by stages 2 and 3 of the World Health Organization clinical staging system. RESULTS: The median time from seroconversion to WHO stage 2 was 25.4 months and to stage 3 was 45.5 months. 43% of the participants infected with HIV-1 had signs or symptoms by two years after seroconversion. The most common clinical conditions used to define progression of disease were weight loss, mucocutaneous manifestations, bacterial infections, chronic fever, and chronic diarrhoea. Although the rates of these conditions (apart from minor weight loss) were significantly higher in the participants infected with HIV-1, they were also relatively frequent in the control group. Herpes zoster, oral candidiasis, and pulmonary tuberculosis were not common events in the control group and therefore were more indicative of infection with HIV-1. CONCLUSIONS: Disease progression associated with infection with HIV-1 seems to be rapid in rural Uganda. This is most likely due to the high prevalence of conditions in the general population that could be taken as symptoms and signs of infection with HIV-1.


4941.                  Morris BS, Varma R, Garg A, Awasthi M, Maheshwari M.  Multifocal musculoskeletal tuberculosis in children: appearances on computed tomography. Skeletal Radiol. 2002 Jan;31(1):1-8.


PURPOSE AND PATIENTS: The incidence of skeletal tuberculosis (TB), which once accounted for a majority of cases of extrapulmonary tuberculosis, has fallen significantly in recent years with the advent of effective drug therapy. Disseminated bone involvement in TB is very uncommon but it may still occur in countries where TB is endemic. We present the imaging findings of four children ranging in age from 2 to13 years, each of whom had multiple osseous stigmata of   tuberculous infection. They presented to us over a period of 9 months. RESULTS AND CONCLUSION: Three of four children had calvarial lesions, with involvement of the bony orbit in one, and large abscesses were present in the chest wall and the mediastinum of another. Lesions along the dorsal spine were demonstrated in three cases, two of which showed epidural extensions. Bone lesions in the thoracic cage accompanying those in the spine were also seen in two children, one of whom had a solitary destructive focus in a rib distant from the site of vertebral involvement. Bone lesions involving the first metacarpal in one case and the scapular wing in two others are also described. The diagnosis in each of the cases was confirmed by the identification of epitheloid giant cells and caseous necrosis or tubercle bacilli in fine needle aspirates or on tissue culture studies.


4942.                  Morrison LK, Harrison A, Krishnaswamy P, Kazanegra R, Clopton P, Maisel A.  Utility of a rapid B-natriuretic peptide assay in differentiating congestive heart failure from lung disease in patients presenting with dyspnea. J Am Coll Cardiol. 2002 Jan 16;39(2):202-9.


OBJECTIVES: Since B-type natriuretic peptide (BNP) is secreted by the left ventricle (LV) in response to volume elevated LV pressure, we sought to assess whether a rapid assay for BNP levels could differentiate cardiac from pulmonary causes of dyspnea. BACKGROUND: Differentiating congestive heart failure (CHF) from pulmonary causes of dyspnea is very important for patients presenting to the emergency department (ED) with acute dyspnea. METHODS: B-natriuretic peptide levels were obtained in 321 patients presenting to the ED with acute dyspnea. Physicians were blinded to BNP levels and asked to give their probability of the patient having CHF and their final diagnosis. Two independent cardiologists were blinded to BNP levels and asked to review the data and evaluate which patients presented with heart failure. Patients with right heart failure from cor pulmonale were classified as having CHF. RESULTS: Patients with CHF (n = 134) had BNP levels of 758.5 +/- 798 pg/ml, significantly higher than the group of patients with a final diagnosis of pulmonary disease (n = 85) whose BNP was 61 +/- 10 pg/ml. The area under the receiver operating curve, which plots sensitivity versus specificity for BNP levels in separating cardiac from pulmonary disease, was 0.96 (p < 0.001). A breakdown of patients with pulmonary disease revealed: chronic obstructive pulmonary disease (COPD): 54 +/- 71 pg/ml (n = 42); asthma: 27 +/- 40 pg/ml (n = 11); acute bronchitis: 44 +/- 112 pg/ml (n = 14); pneumonia: 55 +/- 76 pg/ml (n = 8); tuberculosis: 93 +/- 54 pg/ml (n = 2); lung cancer: 120 +/- 120 pg/ml (n = 4); and acute pulmonary embolism: 207 +/- 272 pg/ml (n = 3). In patients with a history of lung disease but whose current complaint of dyspnea was seen as due to CHF, BNP levels were 731 +/- 764 pg/ml (n = 54). The group with a history of CHF but with a current COPD diagnosis had a BNP of 47 +/- 23 pg/ml (n = 11). CONCLUSIONS: Rapid testing of BNP in the ED should help differentiate pulmonary from cardiac etiologies of dyspnea.

4943.                  Murray M.  Determinants of cluster distribution in the molecular epidemiology of tuberculosis. Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1538-43.


Recently developed molecular techniques have revolutionized the epidemiology of tuberculosis. Multiple studies have used these tools to examine the population structure of Mycobacterium tuberculosis isolates in different communities. The distributions of clusters of M. tuberculosis isolates in these settings may variously reflect social mixing patterns or the differential fitness of specific clones of the organism. We developed an individual-based microsimulation of tuberculosis transmission to explore social and demographic determinants of cluster distribution and to observe the effect of transmission dynamics on the

empiric data from molecular epidemiologic studies. Our results demonstrate that multiple host-related factors contribute to wide variation in cluster distributions even when all strains of the organism are assumed to be equally transmissible. These host characteristics include interventions such as chemotherapy, vaccination and chemoprophylaxis, HIV prevalence, the age structure of the population, and the prevalence of latent tuberculosis infection. We consider the implications of these results for the interpretation of cluster studies of M. tuberculosis as well as the more general application of microsimulation models to infectious disease epidemiology.


4944.                  Narayani RI, Brady C 3rd.  GI bleeding from ileocecal Mycobacterium tuberculosis. Gastrointest Endosc. 2002 Jan;55(1):83.

No Abstract


4945.                  Nau GJ, Richmond JF, Schlesinger A, Jennings EG, Lander ES, Young RA.  Human macrophage activation programs induced by bacterial pathogens. Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1503-8.

Understanding the response of innate immune cells to pathogens may provide insights to host defenses and the tactics used by pathogens to circumvent these defenses. We used DNA microarrays to explore the responses of human macrophages to a variety of bacteria. Macrophages responded to a broad range of bacteria with a robust, shared pattern of gene expression. The shared response includes genes encoding receptors, signal transduction molecules, and transcription factors. This shared activation program transforms the macrophage into a cell primed to interact with its environment and to mount an immune response. Further study revealed that the activation program is innduced by bacterial component that are Toll-like receptor agonists, including lipopolysaccharide, lipoteichoic acid, muramyl dipeptide, and heat shock proteins. Pathogen-specific responses were also apparent in the macrophage expression profiles. Analysis of Mycobacterium tuberculosis-specific responses revealed inhibition of interleukin-12 production, suggesting one means by which this organism survives host defenses. These results improve our understanding of macrophage defenses, provide insights into mechanisms of pathogenesis, and suggest targets for therapeutic intervention.


4946.                  Navas E, Martin-Davila P, Moreno L, Pintado V, Casado JL, Fortun J, Perez-Elias MJ, Gomez-Mampaso E, Moreno S.  Paradoxical reactions of tuberculosis in patients with the acquired immunodeficiency syndrome who are treated with highly active antiretroviral therapy. Arch Intern Med. 2002 Jan 14;162(1):97-9.

No Abstract

4947.                  Nguyen HL, Diwan VK, Winkvist A.  Difference in symptoms suggesting pulmonary tuberculosis among men and women. J Clin Epidemiol. 2002 Feb;55(2):115-20. No abstract.


4948.                  Oursler KK, Moore RD, Bishai WR, Harrington SM, Pope DS, Chaisson RE.  Survival of patients with pulmonary tuberculosis: clinical and molecular epidemiologic factors. Clin Infect Dis. 2002 Mar 15;34(6):752-9.


Using restriction fragment-length polymorphism data, we conducted a retrospective cohort study of 139 adult patients with pulmonary tuberculosis to investigate the clinical impact of Mycobacterium tuberculosis infection with a clustered isolate. The cumulative all-cause mortality rate during treatment was 21%. Patients with clustered DNA fingerprint patterns had a reduced risk of death, compared with patients with unique patterns (hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.2-1.1), but this finding was confounded by age (adjusted HR, 0.8; 95% CI, 0.4-1.8). After adjustment for age, the strongest predictors of death were such underlying illnesses as diabetes mellitus, renal failure, chronic obstructive pulmonary disease, and human immunodeficiency virus infection. We conclude that comorbidity and immunosuppression are important predictors of survival for patients with pulmonary tuberculosis in an inner-city cohort. Recently transmitted infection, as determined by use of DNA fingerprinting to classify patients' isolates as being either clustered or unique, was not independently associated with death.


4949.                  Ozuah PO, Ozuah M.  Screening children for tuberculosis based on residence in a high-prevalence inner-city community. J Natl Med Assoc. 2002 Feb;94(2):119-20.

In January 1994, the Committee on Infectious Diseases of the American Academy of Pediatrics (AAP) published detailed guidelines on tuberculin skin testing of children. These guidelines required mandatory screening of all children residing in high-prevalence communities. In February 1996, the AAP published updated and revised guidelines that allowed for targeted screening of such children based on epidemiologic risk of acquiring tuberculosis. We report on an assessment of the effectiveness of mandatory screening for tuberculosis in a high prevalence community.


4950.                  Pal DK, Kundu AK, Das S. Genito-urinary tuberculosis in sub-Himalayan West Bengal. Indian J Surg 2001, 63(1), 37-9.

Abstract : Total of forty-six patients with confirmed genito-urinary tuberculosis were reviewed from January 1993 to December 1996. High index of suspicion lead to diagnosis in most of the cases. Third decade of life is the most common age of genito-urinary tuberculosis. Among the symptoms increased frequency of micturition (86.95%) was the most common followed by burning sensation during micturition (84.52%). Kidney was the most commonly involved organ in the present series. Fourteen patients (30.49%) required surgical intervention in addition to anti-tubercular chemotherapy and the others were treated by chemotherapy for nine months.


4951.                  Panigada M, Sturniolo T, Besozzi G, Boccieri MG, Sinigaglia F, Grassi GG, Grassi F.  Identification of a promiscuous T-cell epitope in Mycobacterium tuberculosis Mce proteins. Infect Immun. 2002 Jan;70(1):79-85.


The characterization of Mycobacterium tuberculosis antigens inducing CD4(+) T-cell responses could critically contribute to the development of subunit vaccines for M. tuberculosis. Here we performed computational analysis by using T-cell epitope prediction software (known as TEPITOPE) to predict promiscuous HLA-DR ligands in the products of the mce genes of M. tuberculosis. The analysis of the proliferative responses of CD4(+) T cells from patients with pulmonary tuberculosis to selected peptides displaying promiscuous binding to HLA-DR in vitro led us to the identification of a peptide that induced proliferation of CD4(+) cells from 50% of the tested subjects. This study demonstrates that a systematic computational approach can be used to identify T-cell epitopes in proteins expressed by an intracellular pathogen.


4952.                  Pattanaik D, Singh KB, Guresh K, Anand K, Kant S, Kapoor SK.  Prevalence of tuberculosis infection in children below fourteen years in rural Haryana. Indian Pediatr. 2002 Jan;39(1):70-4.

No Abstract

4953.                  Payne K, Yang J.  Osteoarticular tuberculosis: a case report and discussion. CMAJ. 2002 Mar 5;166(5):628-30.

No Abstract

4954.                  Pramesh CS, Tamhankar AP, Rege SA, Shah SR.  Splenic tuberculosis and HIV-1 infection. Lancet. 2002 Jan 26;359(9303):353.

No Abstract

4955.                  Pungrassami P, Johnsen SP, Chongsuvivatwong V, Olsen J.  Has directly observed treatment improved outcomes for patients with tuberculosis in southern Thailand? Trop Med Int Health. 2002 Mar;7(3):271-9.


OBJECTIVE: To validate the practice of directly observed treatment (DOT) and evaluate its effect on treatment outcomes. METHODS: This follow-up study conducted in 24 districts in southern Thailand included 411 new, smear-positive, pulmonary tuberculosis (TB) patients who started treatment between February and September 1999. Patients and/or their observers were interviewed about their actual DOT practice during the first 2 months of treatment. Treatment outcomes were evaluated at the end of the second month and at the end of treatment. RESULTS: Of 411 patients, 379 were assigned to DOT but only 68 practised strict DOT for every dose during the first 2 months. Adjusted odds ratios (ORs) for 'no sputum conversion' and 'unsuccessful treatment' were 1.1 (95% CI 0.6-2.1) and 1.3 (95% CI 0.6-2.8), respectively, for those who practised strict DOT vs. the rest. CONCLUSIONS: Actual practice of DOT was quite different from what was intended at the assignment. Practice of strict DOT during the first 2 months was not associated with sputum conversion or treatment success in this study area.

4956.                  Ray M, Goraya JS, Basu S, Parmar V. Perinatal tuberculosis. Indian J Pediat 2001, 68(4), 343-5.


Abstract : Perinatal tuberculosis is insufficiently understood. Its early diagnosis is essential but often difficult as the initial manifestations may be delayed. Improved screening of women at risk and sensitivity of the medical community are necessary. A coherent system of cooperation between the hospital and community services and between pediatricians and adult physicians is indispensable to find the index adult case to break the chain of contagion as well as to offer prophylactic therapy to the children at risk. Reports a baby with perinatal tuberculosis who was not offered any prophylactic therapy inspite of the mother being diagnosed to have pulmonay tuberculosis.


4957.                  Ray M, Kataria S, Singhi P.  Unusual presentation of disseminated tuberculosis. Indian Pediatr. 2002 Jan;39(1):88-     91.

4958.                  Reichler MR, Reves R, Bur S, Thompson V, Mangura BT, Ford J, Valway SE, Onorato IM.  Evaluation of investigations conducted to detect and prevent transmission of tuberculosis. JAMA. 2002 Feb 27;287(8):991-5.


4959.                  Reid J, Marciniuk D, Peloquin CA, Hoeppner V.  Pharmacokinetics of antituberculosis medications delivered via percutaneous gastrojejunostomy tube. Chest. 2002 Jan;121(1):281-4.


We treated a 23-year-old aboriginal woman with drug-resistant pulmonary tuberculosis (TB). She experienced intolerance to her oral anti-TB medications, had subtherapeutic drug levels, and failed to respond to treatment. She then was effectively treated with percutaneous gastrojejunostomy tube (PGJT) administration of drugs. We present our data on the serum drug levels of rifampin, para-aminosalicylic acid, and levofloxacin after PGJT administration, and compare these values to published levels for oral administration of these drugs. In our patient, serum drug levels peaked and began to decline earlier than in the published data for oral administration of the same drugs.


4960.                  Sahasrabudhe N, Sathe A, Kavatkar A, Jadhav MV.  Sclerosing mediastinitis with oesophageal involvement in miliary tuberculosis. Indian J Tuberc 2000, 47(3), 167-8.

Abstract : Sclerosing mediastinitis with superior vena caval compression and oesophageal involvement in a patient of disseminated miliary tuberculosis is reported because of its clinical importance.


4961.                  Sanchez-Albisua I, Baquero-Artigao F, Del Castillo F, Borque C, Garcia-Miguel MJ, Vidal ML.  Twenty years of pulmonary tuberculosis in children: what has changed? Pediatr Infect Dis J. 2002 Jan; 21(1):49-53.


OBJECTIVES: To compare the frequency, clinical and radiologic manifestations and source of infection of pulmonary tuberculosis in children treated in our hospital during two decades (1978 through 1987 and 1988 through 1997) and to evaluate the influence of the emergence of HIV infection (since 1985) and the effect of the discontinuation of Calmette-Guerin bacillus (BCG) vaccination (since 1987) on childhood tuberculosis. METHODS: We reviewed 324 children diagnosed with pulmonary tuberculosis in our hospital during the 20 years (1978 through 1997). The data from 2 decades, 1978 through 1987 and 1988 through 1997, were compared. BCG vaccination in Spain was discontinued in 1987, and HIV infection emerged significantly as a public health problem. RESULTS: An increase in the number of children with single hilar adenopathy was observed (32.2% in 1978 through 1987 vs. 43.4%, in 1988 through 1997, P < 0.05) in comparison with those with parenchymal involvement or a mixed pattern (62.4% in 1978 through 1987 vs. 45.7% in 1988 to 1997). Frequency in extrapulmonary manifestations in both periods was similar, with a nonsignificant trend toward a lower rate of tuberculous meningitis in the latter decade (10.4 vs. 5.6%, P = 0.07). We were able to identify an adult source case for 67.1% of the children (100 of 149) in the first decade vs.58.3% (102 of 175) in the second (P = NS); 10.8% of adult contacts but only 2.3% of children (all of them in the second period) were HIV-positive.CONCLUSIONS: Discontinuation of BCG vaccination and emergence of HIV infection have had little influence on childhood tuberculosis in our area.


4962.                  Santoro-Lopes G, de Pinho AM, Harrison LH, Schechter M.  Reduced risk of tuberculosis among Brazilian patients with advanced human immunodeficiency virus infection treated with highly active antiretroviral therapy. Clin Infect Dis. 2002 Feb 15;34(4):543-6.

This observational study assessed the effect of combination antiretroviral therapy on the risk of tuberculosis among 255 patients with human immunodeficiency virus (HIV) infection and advanced immunodeficiency who were living in an area of Brazil with a high incidence of tuberculosis. The use of highly active antiretroviral therapy in regions with a high prevalence of coinfection with HIV and Mycobacterium tuberculosis may contribute a lower incidence of tuberculosis.


4963.                  Saurborn DP, Fishman JE, Boiselle PM.  The imaging spectrum of pulmonary tuberculosis in AIDS. J Thorac Imaging. 2002 Jan;17(1):28-33.


SUMMARY: Pulmonary tuberculosis (TB) is the major opportunistic infection of acquired immunodeficiency syndrome (AIDS) on a worldwide basis. The purpose of this pictorial essay is to illustrate and review the spectrum of imaging findings associated with pulmonary TB in patients with AIDS and to describe important factors that may complicate the radiographic follow-up of patients being treated for TB.


4964.                  Schmaldienst S, Jansen M, Hollenstein U, Graninger W, Regele H, Horl WH, Derfler K.  Treatment of systemic lupus erythematosus by immunoadsorption in a patient suffering from tuberculosis. Am J Kidney Dis. 2002 Feb;39(2):415-8.


We report on a 40-year-old man, admitted with fever and weight loss, in whom systemic lupus erythematosus (lupus nephritis World Health Organization type IV) and concomitant acute lung tuberculosis were diagnosed. Conventional treatment of diffuse proliferative nephritis with cytotoxic drugs was thought to be too dangerous in the presence of active tuberculosis. A combination of immunoadsorption and steroids was instituted for the treatment of systemic lupus erythematosus. Antibodies against double-stranded DNA decreased, and proteinuria decreased from 10 g/24 hours to less than 1 g/24 hours. Tuberculosis was treated initially with quadruple-drug therapy, then a triple-drug protocol. Primarily enlarged lymph nodes decreased to normal size after 3 months. The combined treatment modality of steroids and immunoadsorption was effective and safe, even in this patient with active tuberculosis. Copyright 2002 by the National Kidney Foundation, Inc.


4965.                  Selvaraj P.  Role of human leucocyte antigen (HLA) and non-HLA genes in susceptibility or resistance to pulmonary tuberculosis. Indian J Tuberc 2000, 47(3), 133-8.

No Abstract

4966.                  Serane VT, Nalini P, Mahadevan S.  Predictive value of tuberculin induration at 24 h in healthy schoolchildren. J Trop Pediatr. 2002 Feb;48(1):29-32.


Tuberculin (1 TU PPD RT23 Tween 80) was administered to 500 healthy schoolchildren, aged 5-9 years. The induration at 24 h was compared with that at 72 h. The mean (standard deviation) induration of the tuberculin reaction at the end of 24,48 and 72 h was 4.5 (6.75), 4.4 (7.11) and 4.0 (6.91) mm, respectively. When the tuberculin reaction was 0-9 mm, a significant difference was noted between the 24- and 72-h reading (p = 0.0001). There was no difference in the size of the tuberculin reaction between the 24- and 72-h readings when the reaction size was > or = 10 mm (p > 0.05). Considering a tuberculin

induration of < 10 mm as negative tuberculin reaction for our reference population in South India, the sensitivity, specificity, positive predictive value and the negative predictive value in our study for the 24-h reading were found to be high. The predictive value of 24-h induration was not affected by age. Reading and interpretation of tuberculin test after 24 h needs due consideration in clinical practice.


4967.                  Shen Y, Zhou D, Chalifoux L, Shen L, Simon M, Zeng X, Lai X, Li Y, Sehgal P, Letvin NL, Chen ZW.  Induction of an AIDS virus-related tuberculosis-like disease in macaques: a model of simian immunodeficiency virus- mycobacterium coinfection. Infect Immun. 2002 Feb;70(2):869-77.


The mechanism by which human immunodeficiency virus (HIV)-Mycobacterium tuberculosis coinfection facilitates development of HIV-related tuberculosis is poorly characterized. Macaque models of simian immunodeficiency virus (SIV(mac))-Mycobacterium bovis BCG coinfection were employed to explore the pathogenesis of AIDS virus-related tuberculosis. Following BCG coinfection, SIV (SIV)-infected macaques with high viral loads developed an SIV-related tuberculosis-like disease. This disease was characterized clinically by a syndrome of diarrhea, anorexia, weight loss, and altered levels of consciousness and pathologically by the presence of disseminated granulomas. In contrast, SIV(mac)-infected macaques with low viral loads either showed no evidence of BCG-induced disease or developed focal granulomatous lesions. Pathogenic SIV-BCG interactions appeared to play a critical role in triggering the development of this SIV-related tuberculosis-like disease. BCG coinfection enhanced the destruction of CD4(+) T cells in SIV(mac)-infected macaques whose viral loads were high. Reciprocally, exacerbations of SIV disease led to marked suppression of BCG-specific T-cell responses, persistence of the BCG infection, and development of an SIV-related tuberculosis-like disease. Furthermore, development of this SIV-related tuberculosis-like disease was also seen in naïve macaques simultaneously inoculated with SIV(mac) and BCG. These results provide in vivo evidence that coinfection of AIDS virus-infected individuals with an avirulent mycobacterium can lead to development of a tuberculosis-like disease.


4968.                  Shenoy R, Kapadi SN, Pai KP, Kini H, Mallya S, Khadilkar UN, Prabha A.  Fine needle aspiration diagnosis in HIV-related lymphadenopathy in Mangalore, India. Acta Cytol. 2002 Jan-Feb;46(1):35-9.


OBJECTIVE: To evaluate the usefulness of fine needle aspiration (FNA) study of lymph nodes in HIV-positive patients. STUDY DESIGN: The study was conducted at Kasturba Medical College, Mangalore, India. Samples from lymph nodes of 48 HIV-positive patients were taken and air dried, and wet smears were made. After staining with routine cytologic stains and special stains, detailed cytomorphologic study was conducted. RESULTS: Tuberculosis accounted for nearly half (48%) the cases,followed by HIV lymphadenitis (36%), lymphoma (10%), suppurative lymphadenitis (2%), Mycobacterium avium-intracellulare lymphadenitis (2%) and metastases (2%), in descending order of their frequency. A suppurative picture, which was found in 13% of cases of tuberculous lymphadenitis in AIDS patients, occasionally was misleading without the help of acid fast bacilli stain. CONCLUSION: FNA is a useful tool in the diagnosis of lymphadenopathy in HIV-positive patients provided that proper safety measures are taken to avoid contracting the infection.


4969.                  Shor-Posner G, Miguez MJ, Pineda LM, Rodriguez A, Ruiz P, Castillo G, Burbano X, Lecusay R, Baum M.  Impact of selenium status on the pathogenesis of mycobacterial disease in HIV-1-infected drug users during the era of highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2002 Feb 1;29(2):169-73.


The risk of mycobacterial disease is significantly increased in drug abusers as well as in immunocompromised HIV-1-infected individuals. The essential trace element selenium has an important function in maintaining immune processes and may, thus, have a critical role in clearance of mycobacteria. The impact of selenium status on the development of mycobacterial diseases in HIV-1-seropositive drug users was investigated over a 2-year period (1999-2001). Twelve cases of mycobacterial disease (tuberculosis, 9; infection due to atypical Mycobacterium species, 3) occurred; these 12 cases were compared with 32 controls with no history of respiratory infections who were matched on age, sex, and HIV status. Significant risk for development of mycobacterial disease was associated with a CD4 cell count of <200/mm 3, malnutrition, and selenium levels of <or=135 microg/L (patients with these levels were 13 times more likely to develop mycobacterial disease). Multivariate analyses controlling for antiretroviral treatment and CD4 cell count revealed that both body mass index and selenium level remained significant factors in the relative risk for developing mycobacterial disease (relative risk, 3; p =.015); these findings

suggest that selenium status may have a profound impact on the pathogenesis of mycobacterial disease.


4970.                  Soruri A, Schweyer S, Radzun HJ, Fayyazi A.  Mycobacterial antigens induce apoptosis in human purified protein derivative-specific alphabeta T lymphocytes in a concentration-dependent manner. Immunology. 2002 Feb;105(2):222-30.

The morbidity and lethality of tuberculosis is partially the result of an ineffective delayed-type hypersensitivity reaction which causes caseating granulomas in the lung and other organs. Recently we showed that during caseation besides macrophages numerous Fas+ FasL+ lymphocytes undergo apoptosis and postulated that this phenomenon may be due to activation-induced cell death (AICD) as a consequence of T-lymphocyte reactivation via bacillary antigens. As purified protein derivative of Mycobacterium tuberculosis (Mtb-PPD) provokes caseation in tuberculosis patients, the question arose as to whether  bacillary antigens are responsible for AICD within caseous areas. In the present study Mtb-PPD-specific T helper 1 (Th1)-differentiated T lymphocytes were generated in vitro. Reactivation of these cells with Mtb-PPD resulted in a concentration-dependent hyporesponsiveness, which was due to an increase in apoptosis of gammadelta+, alphabeta+ CD4+ as well as alphabeta+ CD8+ T lymphocytes as assessed by the demonstration of the apoptosis-associated mitochondrial membrane protein 7A6 and DNA fragmentation. Blocking experiments demonstrated that Mtb-PPD antigens exploited the Fas/FasL system to induce apoptosis in Mtb-PPD-specific T lymphocytes. These results may support the hypothesis that in tubercle granulomas with caseation T lymphocytes undergo AICD following reactivation by bacillary antigens, thus contributing to the

persistence of tuberculosis.


4971.                  Sridhar CB, Kini U, Subhash K.  Comparative cytological study of lymph node tuberculosis in HIV-infected individuals and in patients with diabetes in a developing country. Diagn Cytopathol. 2002 Feb;26(2):75-80.


Tuberculosis (TB) is a common infection affecting patients with human immunodeficiency virus (HIV) and diabetes mellitus (DM). With the increasing incidence of HIV infection and DM in a developing country like India, TB is definitely on the rise. In a given population, one expects to see these three diseases in varying combinations, such as HIV and TB, DM and TB, HIV and DM with TB. In such combinations TB may lack the characteristic clinical and histological picture due to the associated depressed cell-mediated immunity seen in both diseases and TB may have an unusual clinical presentation and cytology picture. In this retrospective study of 36 months, from January 1997 to December 1999, 109 cases diagnosed cytologically as tuberculous lymphadenitis and tested for HIV infection and investigated as well for DM were selected. Forty-six (42%) were nondiabetic HIV patients, 13 (12%) were non-HIV DM patients, and 50 (46%) had TB without HIV infection or DM. The coexistence of both HIV and DM was not noted. The cytomorphological characteristics supplemented by culture studies of

each of these three groups were compared in detail and based on these four cytological patterns, Pattern 1, Pattern 2, Pattern 3, and Pattern 4 emerged and were characterized. This study highlights the usefulness of cytomorphology of the lymph nodes to characterize the cytopathological profile of TB in both HIV and DM, which have many clinical and immunological similarities, and indirectly postulate the extent of immune suppression and evolve effective strategies in the management of coexisting diseases. Such a comparative study has not been carried out in the past.


4972.                  Sridhar MK.  Prescription charges for tuberculosis drugs. Lancet. 2002 Jan 26;359(9303):360.


4973.                  Stout JE, Ratard R, Southwick KL, Hamilton CD.  Epidemiology of human immunodeficiency virus testing among patients with tuberculosis in North Carolina. South Med J. 2002 Feb;95(2):231-8.

BACKGROUND: Human immunodeficiency virus (HIV) testing is recommended for all patients with tuberculosis (TB). METHODS: Surveillance data for all reported cases of TB in North Carolina from 1993 to 1999 were examined to assess HIV testing practices. RESULTS: Of 3,680 TB patients, 3,119 (85%) had HIV testing data reported. Of these, 604 (19%) were not offered HIV testing, 465 (18%) refused testing, 379 (15%) were HIV seropositive, 29 (0.8%) were tested but

results were not reported, and 1 (0.03%) had an indeterminate result. Older patients were significantly less likely to be offered HIV testing and more likely to refuse testing. Males and African Americans were more likely to be offered and to accept testing. CONCLUSIONS: At least 34% of TB patients in North Carolina from 1993 to 1999 did not receive HIV testing. Patients in higher-risk groups were more likely to be tested, but even within the highest-risk groups, testing was not universal. Health care providers should offer HIV testing to all individuals with TB.


4974.                  Thakur SK. Some thoughts of osteoarticular tuberculosis. Calcutta med J 2000, 97(1-2), 27-8.

No Abstract

4975.       Tobin MJ.  Tuberculosis, lung infections, interstitial lung disease, and socioeconomic issues in AJRCCM 2001. Am J     Respir Crit Care Med. 2002 Mar 1;165(5):631-41. Review.

No Abstract

4976.                  Tureyen K.  Tuberculoma of the conus medullaris: case report. Neurosurgery. 2002 Mar;50(3):651-2; discussion 652-3.

OBJECTIVE AND IMPORTANCE: Intramedullary spinal tuberculoma is a rare form of central nervous system tuberculosis. This article describes an affected patient who presented with left leg paresis. CLINICAL PRESENTATION: A 46-year-old man presented with a 7-day history of left leg weakness. The patient's medical history included infection with pulmonary tuberculosis 15 years previously, at which time he had been treated with antituberculosis therapy. The neurological examination performed at admission revealed left leg paresis with Grade 2/5 power in all muscle groups. The patient reported no urinary or bowel problems. INTERVENTION: Surgery was performed with the patient in the prone position. The procedure involved laminectomies at T11, T12, and L1, followed by a midline myelotomy. The mass was excised completely. Histopathological examination revealed a granulomatous lesion that contained Langhans' giant cells, inflammatory cells, and evidence of caseating necrosis. The patient was prescribed a 6-month course of antituberculosis therapy with pyrazinamide, isoniazid, and rifampin. CONCLUSION: The outcome was favorable. Recently, a number of authors have reported success with medical management of intraspinal tuberculoma. Intraspinal tuberculoma produces a mass effect that can jeopardize spinal cord function. The optimal treatment is a combination of microsurgical resection and antituberculosis chemotherapy.


4977.                  van Crevel R, Karyadi E, Netea MG, Verhoef H, Nelwan RH, West CE, van der Meer JW.  Decreased plasma leptin concentrations in tuberculosis patients are associated with wasting and inflammation. J Clin Endocrinol Metab. 2002 Feb;87(2):758-63.

Tuberculosis patients often suffer from severe weight loss, which is considered to be immunosuppressive and a major determinant of severity and outcome of disease. Because leptin is involved in weight regulation and cellular immunity, its possible role in tuberculosis-associated wasting was investigated. In an urban clinic in Indonesia, plasma leptin concentrations, indicators of adipocyte mass, appetite, C-reactive protein (CRP), tuberculin reactivity, and cytokine response were measured in tuberculosis patients and healthy controls. Plasma leptin concentrations were lower in patients than in controls (615 vs. 2,550 ng/liter; P < 0.001). Multivariate regression analysis showed that body fat mass and inflammation were two independent factors determining plasma leptin concentrations; there was a positive correlation between fat and leptin, whereas, unexpectedly, leptin was inversely associated with CRP and tumor necrosis factor-alpha production. Concentrations of both CRP and leptin were independently associated with loss of appetite. Our results do not support the concept that weight loss in tuberculosis is caused by enhanced production of  leptin. Rather, loss of body fat leads to low plasma leptin concentrations, and prolonged inflammation may further suppress leptin production. Because leptin is important for cell-mediated immunity, low leptin production during active tuberculosis may contribute to increased disease severity, especially in cachectic patients.


4978.                  Villena V, Perez V, Pozo F, Lopez-Encuentra A, Echave-Sustaeta J, Arenas J, Escribano PM.  Amylase levels in pleural effusions: a consecutive unselected series of 841 patients. Chest. 2002 Feb;121(2):470-4.


STUDY OBJECTIVES: To describe the causes and relative frequency of amylase-rich pleural effusion (ARPE), and to study the origin and histologic type of the tumors with ARPE, the strength of the association between ARPE and the result of pleural cytology, and whether pleural amylase (PA) is a prognostic factor in the survival of patients with a malignant pleural effusion. SETTING: Tertiary-care, university-affiliated hospital. PATIENTS: Eight hundred forty-one consecutive patients with pleural effusion prospectively assessed from 1991 to 1999. RESULTS: There were 66 ARPEs: 40 neoplastic, and 26 benign with tuberculosis, pancreatitis, and liver cirrhosis as the most frequent causes. Thirty-six percent of patients in our series and 61% of patients with ARPE had a neoplastic disease (odds ratio [OR], 3; p < 0.001); this association got much stronger for cases with PA levels > or = 600 IU/L (95th percentile); [OR, 10; p < 0.001]. The most frequent tumor origin was lung cancer (13 cases). Adenocarcinoma was the most frequent histologic type (18 cases). Two mesothelioma effusions were ARPEs. There was a positive association between ARPE and the finding of tumor cells in pleural fluid (OR, 2.79; p < 0.01). In the malignant group, PA levels > or = 600 IU/L identified a group of patients with quite a short median survival (p = 0.016). CONCLUSIONS: The most common cause of ARPE was neoplasm. There was a positive association between ARPE and malignancy, stronger with the highest levels (95th percentile). Lung cancer and adenocarcinoma were the most common tumor and histologic type associated with ARPE. Mesothelioma may also produce ARPE. There was an association between ARPE and the finding of tumor cells in the pleural fluid. The highest PA levels identified a group of patients with a median shorter survival.


4979.                  Wagner D, Sangari FJ, Kim S, Petrofsky M, Bermudez LE.  Mycobacterium avium infection of macrophages results in progressive suppression of interleukin-12 production in vitro and in vivo. J Leukoc Biol. 2002 Jan;71(1):80-8.


Interleukin-12 (IL-12) has been shown to have an important role in the host defense against Mycobacterium avium. We sought to determine if human monocyte-derived macrophages produce IL-12 upon M. avium infection. Although IL-12 can be measured in supernatants of M. avium-infected macrophages at 24, 48, and 72 h following infection, intracellular staining showed that 24 to 48 h after infection, IL-12 was synthesized chiefly by uninfected macrophages in the monolayer, suggesting that M. avium infection inhibits IL-12 production. In addition, the data also suggest that the longer macrophage monolayers were infected, the less IL-12 they were able to produce. Stimulation of macrophages with IFN-gamma prior to infection with M. avium resulted in greater production of IL-12 compared with unstimulated macrophages. Culture supernatant of M. avium-infected macrophage monolayers, but not control macrophages, partially inhibited IL-12 production by IFN-gamma-stimulated macrophages. This partial inhibition was not reversed by anti-interleukin-10 (anti-IL-10) and anti-transforming growth factor beta 1 (anti-TGF beta 1)-neutralizing antibodies. M. avium infection of macrophages in vitro also suppressed IL-12 synthesis induced by Listeria monocytogenes infection. Immunohistochemistry staining of spleen of infected mice showed that IL-12 production by splenic macrophages was more pronounced in the beginning of the infection but decreased later. Our data indicate that M. avium infection of macrophages suppresses IL-12 production by infected cells and that the suppression was not a result of the presence of IL-10 and TGF beta 1 in the culture supernatant.


4980.                  Wagner TE, Huseby ES, Huseby JS.  Exacerbation of Mycobacterium tuberculosis enteritis masquerading as Crohn's disease after treatment with a tumor necrosis factor-alpha inhibitor. Am J Med. 2002 Jan;112(1):67-9.

No Abstract

4981.                  Wendel KA, Sterling TR.  Tuberculosis and HIV. AIDS Clin Care. 2002 Feb;14(2):9-15.

No Abstract

4982.                  Wong ML, Szkup P, Hopley MJ.  Percutaneous embolotherapy for life-threatening hemoptysis. Chest. 2002 Jan;121(1):95-102.


STUDY OBJECTIVES: The management of life-threatening hemoptysis frequently poses a therapeutic dilemma because such patients are often poor surgical risks. Less often, patients refuse surgical intervention. The value of percutaneous embolotherapy, a useful alternative in these situations, was assessed. DESIGN, SETTING, PATIENTS, INTERVENTIONS: Sixteen consecutive patients who underwent percutaneous embolotherapy for life-threatening hemoptysis in a tertiary-care

hospital were evaluated retrospectively. The bronchial arteries, as well as other intrathoracic arteries, were evaluated and selectively embolized if they were considered to supply the pathologic area from which the hemoptysis arose. RESULTS: The most common cause for hemoptysis was posttuberculous bronchiectasis (n = 12) with or without mycetomas. Ten patients required blood transfusions before embolotherapy. Pleural disease was noted on the chest radiograph in 13 patients and was generally associated with the presence of nonbronchial systemic collateral vessels. In three patients, arteries other than the bronchial arteries were the only source of hemoptysis. Percutaneous embolotherapy was successful in controlling the hemoptysis in all patients. The only complication documented was a transient paraparesis in one patient. Six patients did not return for follow-up. Of the remaining 10 patients, 3 patients had minor episodes of hemoptysis that were treated conservatively with success. One patient had significant recurrent hemoptysis that was managed with radiotherapy. One patient subsequently underwent a lobectomy. CONCLUSION: Percutaneous embolotherapy is a useful therapeutic modality in the management of life-threatening hemoptysis. The contribution of nonbronchial systemic collateral vessels, particularly where there is evidence of coexistent pleural disease, should always be suspected. In experienced hands, this is a safe and potentially life-saving procedure.


4983.                  Zhang Y, Permar S, Sun Z.  Conditions that may affect the results of susceptibility testing of Mycobacterium tuberculosis to pyrazinamide. J Med Microbiol. 2002 Jan;51(1):42-9.

Pyrazinamide (PZA) is an important front-line anti-tuberculosis drug that is active only at acid pH. However, acid pH causes significant difficulty for PZA susceptibility testing. A common problem in PZA testing is false resistance caused by large bacterial inocula. This study investigated the relationship of false resistance to numbers of bacilli, pH and other factors that potentially affect susceptibility to PZA. Large inocula (10(7-8) bacilli/ml) of M. tuberculosis H37Ra caused significant increase in medium pH from 5.5 towards neutrality, and thus produced false resistance results. The increase in medium pH was determined to be a function of live bacilli; heat-killed bacilli had little or no effect. Susceptibility to PZA and its active derivative pyrazinoic acid (POA) was comparable on 7H11 agar medium, but POA was less active than PZA in liquid medium containing bovine serum albumin (BSA), suggesting that susceptibility to PZA or POA was reduced in the presence of BSA, because of its neutralising effect on medium pH and significant POA binding. A 3-month-old H37Ra culture was shown to be more susceptible to PZA exposure than a 4-day log-phase culture, suggesting that PZA is more active for non-growing bacilli. Finally, reserpine, an inhibitor of POA efflux pump, increased susceptibility to PZA even near neutral pH 6.8, with an MIC of 400 mg/L compared with 1,000 mg/L without reserpine. These findings should have implications for understanding the mode of action of PZA and for PZA susceptibility testing.



5663.      Ahrens N, Genth R, Salama A. Belated diagnosis in three patients with rifampicin-induced immune haemolytic anaemia. Br J Haematol. 2002 May;117(2):441-3.


We report three patients who developed haemolysis following rifampicin

treatment. Initially, autoimmune haemolytic anaemia (AIHA) of the warm type and/or an acute haemolytic transfusion reaction (AHTR) was suggested. The direct antiglobulin tests (DAT) were strongly positive for IgG and C3d, and tests for rifampicin-dependent antibodies were positive in all three cases, featuring C-specificity in one case. The outcome was fatal in two out of the three cases, presumably due to belated diagnosis. This shows that rifampicin may stimulate the production of autoantibodies (aab) and/or drug-dependent antibodies (ddab), and that the resulting haemolytic syndrome bears similarities with AIHA and AHTR.

5664.      Albrecht H. Resistance in intermittent TB therapy. AIDS Clin Care. 2002 May;14(5):46-7. No abstract.

5665.      Babhulkar S, Pande S. Tuberculosis of the hip. Clin Orthop. 2002 May;(398):93-9. Review.


Tuberculosis of the hip constitutes approximately 15% of all cases of osteoarticular tuberculosis. The common age of presentation is in the second and third decades. In Stages II and III of the disease, the radiologic features are very obvious and diagnostic, and almost always predict the final clinical outcome. A progressive pattern of destruction of the hip occurs in patients who are not treated. Treatment must be instituted early with an aim of salvaging the hip. Treatment comprised of drug therapy, traction, and supervised mobilization produces good results in patients with early stages of the disease. Patients who do not have a favorable clinical response to conservative treatment should have surgery before the hip is destroyed. In the eastern hemisphere, patients prefer a painless but mobile joint, for satisfying the customary needs of squatting, sitting cross-legged, and kneeling. Therefore, excision arthroplasty produces satisfactory results as compared with hip arthrodesis. Total hip arthroplasty should be considered only after a safe period of absolute disease quiescence.

5666.      Babhulkar SS, Pande SK. Unusual manifestations of osteoarticular tuberculosis. Clin Orthop. 2002 May;(398):114-20. Review.


Unusual manifestations of osteoarticular tuberculosis, especially tubercular osteomyelitis, are described. Diagnostic problems may arise and lead to delay in treatment if these conditions are not considered in the differential diagnosis. The importance of bacteriologic and histopathologic confirmation of the disease is stressed.

5667.      Bai SS, Devi RL. Clinical spectrum of tuberculosis in BCG vaccinated children. Indian Pediatr. 2002 May;39(5):458-62. No abstract.

5668.      Bakambal R. Profile of DOT providers in private sector. Indian J Tuberc. 2001; 48(2), 73-5. No abstract.

5669.      Banerjee S, Nair ER, Kumar S, Gangane N, Reddy MVR, Harinath BC. Sero-reactivity of two different antigenic protein fractions of M.tb H37Ra  excretiry – secretory antigen in pulmonary and extra-pulmonary tuberculosis. J. Commun. Dis. 2001; 33(2):63-71


Excretory-secretory  proteins of Mycobacterium tuberculosis H37Ra, have been of  diagnostic interest in pulmonary (PTB) and extrapulmonary tuberculosis (EPTB).  Two different  excretory-secretory antigenic  proteins of  M.tb H37Ra  viz.,  EST-DE1 (a 6% TCA soluble  and DEAE  anion exchange purified antigen) and  ESAS-7 (50%  ammoniun sulphate solubilized and SDS-PAGE fractionated antigen) were studied in stick-indirect penicillinase ELISA for detecting tuberculous IgG antibodies in sera samples of pulmonary as well as extrapulmonary tuberculosis (tuberculous lymphadenopathy ( TBLN), tuberculous meningitis (TBM), bone and joint tuberculosis (B&J TB), abdominal tuberculosis (Abd. TB)  patients. The ESAS-7 antigen has shown comparatively better seroreactivity (90%) than that of  EST-DE1 antigen in pulmonary  tuberculosis cases. The overall specificity of 93.2%  using ESAS-7 antigen was also found better compared to 86.4% obtained using EST-DE1 antigen. Further, in extra pulmonary tuberculosis group, using ESAS-7 antigen 84% (21/25) of histopathologically confirmed TBLN cases and 90% (9/10) clinically diagnosed  and ATT responded TBM cases showed positive reaction for tuberculous IgG antibody. The percent positivity using EST-DE1 antigen, was however comparatively low in TBLN and TBM cases, (76% and 80% respectively). In histopathologically proven bone and joint tuberculosis and abdominal tuberculosis cases EST-DE1 antigen showed better sensitivity of  75% and 83.3% respectively in IgG antibody  detection compared to that of ESAS-7 antigen (50% and 66% respectively). From the present study, it can be envisaged that ESAS-7 antigenic fraction has a good potential in the diagnosis of pulmonary and certain extra-pulmonary tuberculosis infections (TBLN & TBM) whereas EST-DE1 was found to be better in detecting specific antibodies in bone and joint and abdominal tuberculosis. 

5670.      Bhaskar S, Banavaliker JN, Bhardwaj K, Upadhyay P. A novel ultrasound-enhanced latex agglutination test for the detection of antibodies against Mycobacterium tuberculosis in serum. J Immunol Methods. 2002 Apr 1;262(1-2):181-6.


A novel ultrasound-enhanced latex agglutination test is described for the detection of serum antibodies against Mycobacterium tuberculosis. The use of ultrasound to detect the low level of antibodies in serum enhances the sensitivity of the test. The technique is based on the fact that suspended latex particles become concentrated in an ultrasonic standing wave field, thereby increasing the rate of particle-particle collisions compared to the standard agglutination test procedure. Reactions were performed on piezo-ceramic wafers, which were connected to an oscillator at a frequency of 100 kHz. This method improved sensitivity significantly so that even 20 times diluted serum samples exhibited agglutination, which was clearly visible to the naked eye.

5671.      Bhutey AK, Manjal KA. Trace elements in tissue and their relation to tissue pathology. Antiseptic, Madurai. 2001; 98(9), 36. No abstract.

5672.      Birring SS, Heartin E, Williams T, Brightling CE, Pavord IL. Peak expiratory flow sequence in acute exacerbations of asthma. Selection BMJ – South Asia Edn. 2001; 17(6), 513.
Investigates weather the effect of deep inspiration, as reflected by the change in peak expiratory flow from the first to last of a sequence of three blows, in exacerbations of asthma is a marker of more chronic bronchoconstriction and longer length of stay in hospital.


5673.      Black GF, Weir RE, Floyd S, Bliss L, Warndorff DK, Crampin AC, Ngwira B, Sichali L, Nazareth B, Blackwell JM, Branson K, Chaguluka SD, Donovan L, Jarman E, King E, Fine PE, Dockrell HM. BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies. Lancet. 2002 Apr 20;359(9315):1393-401.


BACKGROUND: The efficacy of BCG vaccines against pulmonary tuberculosis varies between populations, showing no protection in Malawi but 50-80% protection in the UK. To investigate the mechanism underlying these differences, randomised controlled studies were set up to measure vaccine-induced immune responsiveness to mycobacterial antigens in both populations. METHODS: 483 adolescents and young adults in Malawi and 180 adolescents in the UK were tested for interferon-gamma (IFN-gamma) response to M tuberculosis purified protein derivative (PPD) in a whole blood assay, and for delayed type hypersensitivity (DTH) skin test response to tuberculin PPD, before and 1 year after receiving BCG (Glaxo 1077) vaccination or placebo or no vaccine. FINDINGS: The percentages of the randomised individuals who showed IFN-gamma and DTH responses were higher in Malawi than in the UK pre-vaccination-ie, 61% (331/546) versus 22% (47/213) for IFN-gamma and 46% (236/517) versus 13% (27/211) for DTH. IFN-gamma responses increased more in the UK than in Malawi, with 83% (101/122) and 78% (251/321) respectively of the vaccinated groups responding, with similar distributions in the two populations 1 year post-vaccination. The DTH response increased following vaccination in both locations, but to a greater extent in the UK than Malawi. The IFN-gamma and DTH responses were strongly associated, except among vaccinees in Malawi. INTERPRETATION: The magnitude of the BCG-attributable increase in IFN-gamma responsiveness to M tuberculosis PPD, from before to 1 year post-vaccination, correlates better with the known levels of protection induced by immunisation with BCG than does the absolute value of the IFN-gamma or DTH response after vaccination. It is likely that differential sensitisation due to exposure to environmental mycobacteria is the most important determinant of the observed differences in protection by BCG between populations.

5674.      Blanc FX, Atassi K, Bignon J, Housset B. Diagnostic value of medical thoracoscopy in pleural disease: a 6-year retrospective study. Chest. 2002 May;121(5):1677-83.


STUDY OBJECTIVES: Unlike thoracocentesis and closed pleural biopsy (CPB), medical thoracoscopy permits biopsy with direct visualization. In a 6-year retrospective study of patients having undergone at least one medical thoracoscopy, we analyzed the diagnostic yield of thoracoscopy and its value in the management of pleural disease. SETTING/PATIENTS: From January 1, 1989, to December 31, 1994, 168 medical thoracoscopies were performed on 154 patients (123 men; mean age +/- SE, 61 +/- 1 years), of which 149 were diagnostic and 19 were indicated for therapeutic assessment in malignant mesothelioma (MM). Prior to thoracoscopy, at least one CPB had been performed in 120 of 149 cases, yielding a diagnosis in 96 cases. RESULTS: Thoracoscopy challenged the CPB-based diagnosis in 43 of 96 cases. In 66 cases of nonspecific inflammation diagnosed by CPB, thoracoscopy revealed MM in 16 cases, adenocarcinoma in 10 cases, undetermined carcinoma in 3 cases, and pleural tuberculosis in 3 cases. In 18 cases in which the CPB diagnosis was MM, thoracoscopy, performed for precise staging, challenged the diagnosis in 4 cases. In 12 cases of carcinoma diagnosed by CPB, thoracoscopy specified the histologic type in 7 cases. Thoracoscopic diagnoses were found to be erroneous in 10 of 149 cases, mainly owing to pleural adhesions that limited access to the pleural cavity. There was one thoracoscopy-related death, one case of sepsis, and six cases of empyema. CONCLUSIONS: Medical thoracoscopy appears to be efficient and relatively safe in the management of pleural disease. Pleural adhesions can lower its diagnostic value.

5675.      Braun J, Brandt J, Listing J, Zink A, Alten R, Golder W, Gromnica-Ihle E, Kellner H, Krause A, Schneider M, Sorensen H, Zeidler H, Thriene W, Sieper J. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet. 2002 Apr 6;359(9313):1187-93.


BACKGROUND Treatment options for patients with ankylosing spondylitis are few. We aimed to assess the effectiveness of infliximab, an antibody to tumour necrosis factor (TNF)-alpha, in treatment of such patients. METHODS: In this 12-week placebo-controlled multicentre study, we randomly assigned 35 patients with active ankylosing spondylitis to intravenous infliximab (5 mg/kg) and 35 to placebo at weeks 0, 2, and 6. One patient in the infliximab group was withdrawn from the study. Our primary outcome was regression of disease activity of at least 50%. To assess response, we used validated clinical criteria from the ankylosing spondylitis assessment working group, including disease activity (BASDAI), functional indices (BASFI), metrology (BASMI), and quality of life (short form 36). Analyses were done by intention to treat. FINDINGS: 18 (53%) of 34 patients on infliximab had a regression of disease activity at week 12 of at least 50% compared with three (9%) of 35 on placebo (difference 44% [95% CI 23-61], p<0.0001). Function and quality of life also improved significantly on infliximab but not on placebo (p<0.0001 and p<0.0001, respectively). Treatment with infliximab was generally well tolerated, but three patients had to stop treatment because of systemic tuberculosis, allergic granulomatosis of the lung, or mild leucopenia. INTERPRETATION: Our results show that treatment with infliximab is effective in patients with active ankylosing spondylitis. Since there are some potentially serious adverse effects, we recommend that this treatment mainly be used in co-operation with rheumatological centres.


5676.      Cainelli F, Vento S. BCG efficacy and tuberculin skin testing. Lancet. 2002 Apr 27;359(9316):1521-2.  No abstract.

5677.      Chadha VK, Jagannatha PS, Savanur SJ. Annual risk of tuberculosis infection in Banglore city. Indian J Tuberc. 2001; 48(2), 63-71.
Tuberculin survey was conducted to estimate the Annual Risk of Tuberculosis Infection (ARI) in Bangalore city among 6 and 7 year old children attending 161 schools. A single stage cluster sampling design was adopted for selection of schools by random sampling, from a consolidated list of Govt-run, Govt-aided and Private-Schools. Based on the frequency distribution of reaction sizes among 9,4340 test-read children, 11.1% were estimated to be infected with tubercle bacilli. The children studying in Govt-run and Govt-aided school were more likely to be infected than those attending private schools. The ARI in Bangalore city was estimated to be 1.67%,; it is higher than the recent estimates obtained from the surrounding peri-urban and rural areas, suggesting need for further improving the efficiency of case-finding and treatment activities. The results further indicate that BCG vaccinated children can be included for the purpose of estimating ARI. 30 ref.

5678.      Chakraborty S et. al. Comparison of  antibiogram, virulence genes, ribotypes and DNA fingerprints of Vibrio cholerae of matching serogroups isolated from hospitalised diarrhoea cases and from the environment during 1997-98 in Calcutta, India. J Med Microbiol. 2001; 50(10), 879-88.
Identifies 17 matching serogroups of Vibrio cholerae belonging to serogroups other than 01 and 0139 isolated from human cases and from the environment during a concurrent clinical and environment stydy conducted in Calcutta, Cholera endemic area, isolates within these matching serogroups wer compared by various phenotype and genotypic traits to determine if the environment was the source of the organisms associated with the sedease. Clinical strains of V cholera were resistant to a greater numver of drugs and exhibited multi-drug resistance compared with their environmental counterparts. Except for the presence of the genes for the El Tor haemolysin and the regulatory element ToxR in most of the strains of V cholerae examined, non-01, non-0139 v cholerae strains lacked most of the other known virulence traits associated with tocigenic V cholerae 01 or 0139. Restriction fragment-length polymorphism of virulence-associated genes, ribotypes and DNA fingerprints of strains of matched serogroups showed considerable diversity, although some gene polymorphisms ribotypes of a few strains of different serogroups were similar. It is concluded that despite sharing the same seroheterogenous and were of different lineages.37 ref.

5679.      Cinar U, Seven H, Vural C, Basak T, Alkan S, Turgut S. Tuberculosis tonsillitis. Otolaryngol Head Neck Surg. 2002 Apr;126(4):448-9. No abstract.

5680.      Davies P. Industry funding in medical education. Lancet. 2002 Jun 1;359(9321):1949-50. No abstract.

5681.      Delgado JC, Tsai EY, Thim S, Baena A, Boussiotis VA, Reynes JM, Sath S, Grosjean P, Yunis EJ, Goldfeld AE. Antigen-specific and persistent tuberculin anergy in a cohort of pulmonary tuberculosis patients from rural Cambodia. Proc Natl Acad Sci U S A. 2002 May 28;99(11):7576-81.


Purified protein derivative (PPD) skin testing is used to identify persons infected with Mycobacterium tuberculosis (Mtb) and to assess cell-mediated immune responses to Mtb. However, lack of skin induration to intradermal injection of PPD or PPD anergy is observed in a subset of patients with active tuberculosis (TB). To investigate the sensitivity and persistence of PPD reactivity and its in vitro correlates during active TB disease and after successful chemotherapy, we evaluated the distribution of skin size induration after intradermal injection of PPD among 364 pulmonary TB patients in Cambodia. A subset of 25 pulmonary TB patients who had a positive skin reaction to mumps and/or candida antigens showed persistent anergy to PPD after successful completion of TB therapy. Strikingly, in vitro stimulation of T cells from persistently anergic TB patients with mumps but not PPD resulted in T cell proliferation, and lower levels of IL-2 and IFN-gamma and higher levels of IL-10 were detected in PPD-stimulated cellular cultures from PPD-anergic as compared with PPD-reactive pulmonary TB patients. These results show that anergy to PPD is antigen-specific and persistent in a subset of immunocompetent pulmonary TB patients and is characterized by antigen-specific impaired T cell proliferative responses and a distinct pattern of cytokine production including reduced levels of IL-2.


5682.      Dhillon MS, Nagi ON. Tuberculosis of the foot and ankle. Clin Orthop. 2002 May;(398):107-13.


Tuberculosis of the foot and ankle is an uncommon presentation of skeletal tuberculosis. The uncommon site, lack of awareness, and ability to mimic other disorders clinically and on radiographs, leads to diagnostic and therapeutic delays. In the early stages and when the disease is limited to bone, medical treatment leads to excellent healing and limited residual disabilities. Joint involvement occurs because of spread from a periarticular bony focus, and in the midfoot, the disease may spread to involve all the interconnected joints, leading to a stiff foot and residual deformities. Of 74 cases reviewed, the calcaneus was involved most commonly, followed by infection of the midtarsal, Lisfranc joints, and ankle. The most common radiologic finding is that of osteoporosis, which may be intense: cancellous bone involvement may present as a cystic lesion with or without sequestrum. Computed tomography scans and magnetic resonance imaging are helpful examinations. Because the disease is paucibacillary, a positive acid fast bacilli culture is rare and the diagnosis usually is confirmed by obtaining granulomatous tissue on biopsy. The treatment basically is medical, with surgical intervention being reserved for patients with intractable disease or as a salvage procedure for patients with deformed hindfoot joints.

5683.      Dogru D, Ozcelik U, Gocmen A. Pediatric primary pulmonary tuberculosis. Chest. 2002 May;121(5):1722; discussion 1722.  No abstract.

5684.      Donald PR. Childhood tuberculosis: out of control? Curr Opin Pulm Med. 2002 May;8(3):178-82.


Because of the difficulty of confirming the diagnosis of childhood tuberculosis and because children do not make a significant contribution to the spread of tuberculosis, the burden of childhood tuberculosis in the world is uncertain. Several estimates make use of an arbitrary calculation assigning 10% of the tuberculosis burden to children. Available data linking the incidence of tuberculosis to the proportion of the tuberculosis caseload represented by children suggest an exponential rise in the proportion of the tuberculosis caseload caused by children as the tuberculosis incidence rises so that children may constitute nearly 40% of the caseload in certain high incidence communities. This review discusses the global burden of childhood tuberculosis and attempts to quantify this, the role of HIV/AIDS and tuberculosis in children, the problems this creates for diagnosis, and the occurrence of drug resistant tuberculosis in children. In the developing world, childhood tuberculosis is not under control, and, despite its importance as a child health problem, remains a neglected orphan disease.

5685.      Garg RK. Proposed diagnostic criteria for neurocysticercosis. Neurology. 2002 Apr 23;58(8):1315; discussion 1315-6.  No abstract.

5686.      Geetharamani S, Munity Andi M, Rajeshwari R, Balsubramanium R, Theresa X, Venkaresan P. Socioeconomic impact of parental tuberculosis on children. Indian J Tuberc. 2001; 48(2), 91-4.
The impact of parental pulmonary tuberculosis on children was studied from a larger study of socio-economic effect of  the disease. The effect of disease was studied in respect of social, economic and demographic characteristics of the parents (who were patients), the child care functions of mothers who were patients and effect on children’s education. In all, 276 children of 167 tuberculous parents were studied. The socio-economic and demographic characteristics were generally the same as are commonly seen. The child caring on the part of mothers fell from 64% to 35% for rural females and from 74% to 33% for urban females; 11% of children 8% rural, 13% urban dropped out of school, significantly higher in families with 5 or more members and children living with both parents compared to single parent 34% of study parents could not buy school books or adequate food because of loss of income and 20% of the children were obliged to take up jobs in order to supplement income.

5687.      Geluk A, van Meijgaarden KE, Franken KL, Subronto YW, Wieles B, Arend SM, Sampaio EP, de Boer T, Faber WR, Naafs B, Ottenhoff TH. Identification and characterization of the ESAT-6 homologue of Mycobacterium leprae and T-cell cross-reactivity with Mycobacterium tuberculosis. Infect Immun. 2002 May;70(5):2544-8.


In this paper we describe identification and characterization of Mycobacterium leprae ESAT-6 (L-ESAT-6), the homologue of M. tuberculosis ESAT-6 (T-ESAT-6). T-ESAT-6 is expressed by all pathogenic strains belonging to the M. tuberculosis complex but is absent from virtually all other mycobacterial species, and it is a promising antigen for immunodiagnosis of tuberculosis (TB). Therefore, we analyzed whether L-ESAT-6 is a similarly powerful tool for the study of leprosy by examining T-cell responses against L-ESAT-6 in leprosy patients, TB patients, and exposed or nonexposed healthy controls from areas where leprosy and TB are endemic and areas where they are not endemic. L-ESAT-6 was recognized by T cells from leprosy patients, TB patients, individuals who had contact with TB patients, and healthy individuals from an area where TB and leprosy are endemic but not by T cells from individuals who were not exposed to M. tuberculosis and M. leprae. Moreover, leprosy patients who were not responsive to M. leprae failed to respond to L-ESAT-6. A very similar pattern was obtained with T-ESAT-6. These results show that L-ESAT-6 is a potent M. leprae antigen that stimulates T-cell-dependent gamma interferon production in a large proportion of individuals exposed to M. leprae. Moreover, our results suggest that there is significant cross-reactivity between T-ESAT-6 and L-ESAT-6, which has implications for the use of ESAT-6 as tool for diagnosis of leprosy and TB in areas where both diseases are endemic.

5688.      Gold JA, Rom WN, Harkin TJ. Significance of abnormal chest radiograph findings in patients with HIV-1 infection without respiratory symptoms. Chest. 2002 May;121(5):1472-7.


STUDY OBJECTIVES: Patients with HIV-1 infection or AIDS may present with abnormal chest radiograph (CXR) findings in the absence of symptoms specific to the lung. The objective was to determine the spectrum of disease and the diagnostic modalities employed in these patients. METHODS: From 1996 to 1998, we identified patients with HIV-1 infection presenting to the Bellevue Hospital Chest Service with abnormal CXR findings, and absence of specific pulmonary symptoms. Charts were reviewed for presence of constitutional symptoms, CD4 lymphocyte count, use of Pneumocystis carinii pneumonia (PCP) prophylaxis, eventual diagnosis, and all diagnostic modalities employed. CXR findings were classified according to their predominant abnormalities: nodules, infiltrates, cavity, mass, adenopathy, or effusion. RESULTS: Forty-four patients were eligible for inclusion. Eight-six percent of patients had a CD4 lymphocyte count < 200 cells/microL, and 57% were receiving PCP prophylaxis. Nodular disease was the most common radiographic abnormality (57%), followed by adenopathy (17%). A definitive diagnosis was obtained in 86% of the patients. The most common diagnosis was tuberculosis (26%), followed by nontuberculous mycobacteria (NTM; 23%) and Kaposi sarcoma (12%). No patients had PCP or bacterial pneumonia. Sixty-two percent of patients required an invasive modality to establish a diagnosis. Only 18% of patients with tuberculosis (2 of 11 patients) received diagnoses by sputum analysis. CONCLUSIONS: Patients with HIV-1 infection, abnormal CXR findings, and lack of pulmonary symptoms have a high incidence of infectious disorders, especially pulmonary tuberculosis and infection due to NTM. The high prevalence of treatable and potentially communicable disorders warrants an aggressive diagnostic approach in these patients.

5689.      Govender S. The outcome of allografts and anterior instrumentation in spinal tuberculosis. Clin Orthop. 2002 May;(398):60-6.


Spinal tuberculosis is the most common form of osteoarticular tuberculosis. Fractures, slippage, and increasing deformity have been reported with the use of autologous rib grafts after anterior spinal decompression. Forty-one patients with neurologic deficits caused by spinal tuberculosis had radical anterior decompression, and the anterior column was reconstructed with fresh-frozen femoral allografts and stabilized with a single-rod screw construct. Antituberculous therapy was administered for 12 months and complete neurologic recovery occurred in 32 patients. The incorporation of allografts commenced between 12 and 18 months. Fusion and remodeling was observed in 33 patients and partial remodeling with fusion was observed in eight patients at a mean followup of 6.4 years. Forty-two percent correction of the kyphosis was achieved and there were no cases of fracture or late sepsis. Fresh-frozen allografts and anterior instrumentation are superior to rib grafts in supporting the anterior spinal column, and although fusion occurred late, the grafts remained stable.

5690.      Griffith JF, Kumta SM, Leung PC, Cheng JC, Chow LT, Metreweli C. Imaging of musculoskeletal tuberculosis: a new look at an old disease. Clin Orthop. 2002 May;(398):32-9. Review. 


There are certain imaging features that help to differentiate tuberculosis from other bone and joint disorders with a similar presentation. The current authors discuss these distinguishing imaging features particularly with respect to ultrasound, computed tomography, and magnetic resonance imaging. The judicious and appropriate use of these newer imaging modalities coupled with aspiration or biopsy can lead to earlier recognition of musculoskeletal tuberculosis before the onset of debilitating disease.

5691.      Gupta I, Parihar A, Dev G, Gillani Z. Duodenal tuberculosis. JK Sci. 2001; 3(3), 132-4. No abstract.

5692.      Hemvani N, Chitnis DS, Joshi SP. C-reactive proteins in cerebro-spinal fluid and its role in differentiation  of meningitis. Indian J med Microbiol. 2001; 19(1), 26-9.
Study was carried out to test 499 CSF samples received in Pathology Department of Choithram Hospital and Research Centre, Indore from cases of viral, pyogenic, tuberculosis and fungal meningitis and 580 normal CSF sample. CRP positivity by qualitative latex agglutination test (level above 6 mg/L) was seen in 73.3% of CSF samples from partially treated pyogene meningitis cases. All suspected cases of tuberculosis meningitis were negative for CRP in the CSF while only 1 out of 15 CSF samples from bacteriologically confirmed tuberculous meningitis had CRP balue greater than 6 mg/L. CRP was raised in 27.2% and 12.5% of CSF samples from candidial and crytococcal meningitis cases respectively while none of the 102 samples from suspected viral meningitis and 580 non-meningitis cases was positive for CRP determination can be of value of differentiate pyogenic versus other microbial meningitis aetiology. However, it cannot differentiate between tuberculosis, fungal and viral meningitis. 1 table, 20 ref.

5693.      Hoffman EB, Allin J, Campbell JA, Leisegang FM. Tuberculosis of the knee. Clin Orthop. 2002 May;(398):100-6.



Fifty-two children with tuberculosis of the knee treated from 1979 to 1999 were reviewed retrospectively. The radiologic appearance of the joint at presentation was predictive of the outcome. Ninety-two percent of the patients had Stage 1 or Stage 2 involvement (synovitis) with or without bony erosions, but had a normal joint space. Treatment with antituberculous chemotherapy without synovectomy had an excellent or good result in all patients with Stage 1 or Stage 2 disease, and there was no difference in outcome whether the knee was immobilized or

mobilized. Patients with Stage 3 and Stage 4 disease who had a narrow joint space (arthritic) at presentation had a fair or poor result. In patients with monoarthritis of the knee with nonspecific histologic features and a negative culture, the differential diagnosis between tuberculosis and pauciarticular juvenile rheumatoid arthritis is problematic. The histologic evaluations of biopsy specimens of the synovium of 25 knees from 25 patients were reviewed for synovial lining hyperplasia. The sensitivity for the 17 knees that subsequently were diagnosed as having juvenile rheumatoid arthritis was only 53%. Deoxyribonucleic acid from 13 consecutive joints was subjected to polymerase chain reaction for Mycobacterium tuberculosis infection with only 40% sensitivity for tuberculosis.


5694.      Jain AK. Treatment of tuberculosis of the spine with neurologic complications. Clin Orthop. 2002 May;(398):75-84. Review.


Neurologic complications are the most dreaded complication of spinal tuberculosis. The patients who have paraplegia develop in the active stage of tuberculosis of the spine require active treatment for spinal tuberculosis and have a better prognosis than the patients who have paraplegia develop many years after the initial disease has healed. Neurologic dysfunctions in association with active tuberculosis of the spine can be prevented by early diagnosis and prompt treatment. Prompt treatment can reverse paralysis and minimize the potential disability resulting from Pott's paraplegia. When needed, a combination of conservative therapy and surgical decompression yields successful results in most patients with tuberculosis of the spine who have neurologic complications. The vertebral body primarily is affected in tuberculosis; therefore, decompression has to be anterior. Laminectomy is advocated in patients with posterior complex disease and spinal tumor syndrome. Late onset paraplegia is best avoided by prevention of the development of severe kyphosis. Patients with tuberculosis of the spine who are likely to have severe kyphosis develop (< 60 degrees) on completion of treatment should have surgery in the active stage of disease to improve kyphus.

5695.      Jayaswal R. Management of pulmonary tuberculosis in the Armed Forces over the last five decades. Indian J Tuberc. 2001; 48(2), 57-61. No abstract.

5696.      Johnson PD, Irving LB, Turnidge JD. 3: Community-acquired pneumonia. Med J Aust. 2002 Apr 1;176(7):341-7. Review.


Community-acquired pneumonia is caused by a range of organisms, most commonly Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae and respiratory viruses. Chest x-ray is required for diagnosis. A risk score based on patient age, coexisting illness, physical signs and results of investigations can aid management decisions. Patients at low risk can usually be managed with oral antibiotics at home, while those at higher risk should be further assessed, and may need admission to hospital and intravenous therapy. For S. pneumoniae infection, amoxycillin is the recommended oral drug, while benzylpenicillin is recommended for intravenous use; all patients should also receive a tetracycline (eg, doxycycline) or macrolide (eg, roxithromycin) as part of initial therapy. Flucloxacillin or dicloxacillin should be added if staphylococcal pneumonia is suspected, and gentamicin or other specific therapy if gram-negative pneumonia is suspected; a third-generation cephalosporin plus intravenous erythromycin is recommended as initial therapy for severe cases. Infections that require special therapy should be considered (eg, tuberculosis, melioidosis, Legionella, Acinetobacter baumanii and Pneumocystis carinii infection).

5697.      Khaan SA, Mohd Zahid, Sharma B, Hasan AS. Tuberculosis of frontal bone. Indian J Tuberc. 2001; 48(2), 95-6.
Tuberculosis of frontal bone in a 13 year old girl is presented. The occurrence of tuberculosis lesion in the bones of skull and face is extremely rare, with only six cases reported in the world literature.

5698.      Kim HC, Goo JM, Kim HB, Lee JW, Seo JB, Im JG. Tuberculosis in patients with myelodysplastic syndromes. Clin Radiol. 2002 May;57(5):408-14.


AIM: The purpose of our study was to describe radiological manifestations of tuberculosis in patients with myelodysplastic syndromes. MATERIALS AND METHODS: Chest radiographs and CTs of 12 patients with tuberculosis among 195 consecutive patients with myelodysplastic syndrome, proved by bone marrow biopsy, were reviewed. Six of the 12 patients presented with tuberculosis and were subsequently found to have myelodysplastic syndrome. RESULTS: Chest radiographs and CTs revealed pulmonary tuberculosis in all 12 patients and extrapulmonary tuberculous involvement in six (50%). Initial chest radiographic findings of pulmonary tuberculosis included a primary pattern (n = 6), a post-primary pattern (n = 3), a miliary pattern (n = 1), atypical infiltrates (n = 1) and normal radiograph (n = 1). Tuberculosis involved extrathoracic lymph nodes (n = 5), liver (n = 2), spleen (n = 2), kidney (n = 2), bowel (n = 2), pericardium (n = 2) peritoneum (n = 1) and rib (n = 1). CONCLUSION: Tuberculosis is a relatively common cause of infection in patients with myelodysplastic syndromes. The radiological appearance of pulmonary tuberculosis in myelodysplastic syndromes is often a primary pattern, and there is frequently extrapulmonary involvement. Copyright 2002 The Royal College of Radiologists.


5699.      Kutty S, Bennett D, Devitt A, Dowling FE. Tuberculous osteomyelitis of the sternum in an infant: a case report and review of the literature. Pediatr Int. 2002 Apr;44(2):186-8. Review. No abstract.

5700.      Lazarus AA. Who should be screened for TB? Postgrad Med. 2002 Apr;111(4):131. No abstract.

5701.      Leonard MK, Larsen N, Drechsler H, Blumberg H, Lennox JL, Arrellano M, Filip J, Horsburgh Jr CR. Increased survival of persons with tuberculosis and human immunodeficiency virus infection, 1991--2000. Clin Infect Dis. 2002 Apr 1;34(7):1002-7.


To determine factors associated with the occurrence of human immunodeficiency virus (HIV) infection and tuberculosis (TB) disease (HIV-TB) and the associated survival rate, we analyzed patients with HIV-TB at Grady Memorial Hospital, Atlanta, Georgia, from 1991 through 2000. Overall, 644 patients with HIV-TB were seen. The number of HIV-TB cases per year was highest in 1992 (102 cases) and declined to 39 cases in 2000. Over time, patients were more likely to be enrolled in the HIV outpatient clinic (P<.01), but, in 1997, only 21 (51%) of 41 patients were enrolled in HIV-infection care programs and only 9 (22%) of 41 received HAART. The 1-year survival rate for patients with HIV-TB was 58% in 1991, 81% in 1994, and 83% in 1997 (P<.001). The increase in survival for patients with HIV-TB between 1991 and 1994 was likely due to improved TB and HIV therapy. More effective strategies for enrolling and maintaining HIV-TB patients in HIV-infection care programs could further increase survival.


5702.      Lifson AR. Prevention of travel-associated tuberculosis in the high-risk traveler. Clin Infect Dis. 2002 Apr 15;34(8):1163.  No abstract.

5703.      Mitra S, Ghosh D, Pathak A, Kumar L. Bilateral subdural effusion and subcutaneous swelling with normally function CSF shunt. Neural India. 2001; 49(2), 178-81.
Reports a child with hydrocephalus due to tuberculosis meningitis who developed a subcutaneous fluid collection around the ventriculoperitoneal shout tube entry point, after one month of shunting. On investigation, he had decompressed ventricles with bilateral fronto parietal subdural hygroma. Bifrontal burr hole drainage helped resolution of both subdural effusion and subcutaneous scalp swelling. This complication is unique and its pathogenesis has been postulated.

5704.      Monoharan E, John KR, Jocob KS. Psychiatric morbidity, patients’ perspectives of illness and factors associated with poor medication compliance among the tuberculous in Vellore, south India. Indian J Tuberc. 2001; 48(2), 77-80. Study attempts to examine the factors, including psychiatric morbidity and  patients beliefs associated with non-compliance with medication among patients with tuberculosis. Of the 52 subjects recruited for the study, 45 (86.5%) had pulmonary tuberculosis. In all, 9(17.3%) subjects satisfied the International Classification of Diseases 10 Primary Care Criteria for psychiatric disorders. Depression was the commonest disorder. The majority of subjects knew the name of their disease (87.7%). A total of 48 subjects were followed up for 6 months, till the course of anti-tuberculosis treatment was completed; 32(66.7%) subjects completed their treatment. Only smoking was found to be associated with poor compliance in univariate analysis. 17 ref.

5705.      Nadal D. Is the in vitro interferon-gamma release assay an adequate replacement for the tuberculin skin test? Clin Infect Dis. 2002 Jun 1;34(11):1457-9.  No abstract.

5706.      Narayanan S, Vishwanath V, Narayanan PR. Differential expression of a unique protein by intracellular Mycobacterium tuberculosis complex. Curr Sci. 2001; 81(6), 689-92. Investigates the changes in the protein synthesis pattern in guinea pig peritoneal macrophases following infection with virulent Mycobacterium tuberculosis H37Rv in vitro. By 35S methionine labelling of the newly synthesized proteins followed by ultracentrifugation, SDS-PAGE (sodium dodecyl sulphate polyacrylamide gel electrphoresis) and autoradiography, the protein synthesis pattern of the control uninfected macrophages and the infected macrophages in vitro were compared. By adding cycloheximide to the macrophage cultures, the protein synthesis of macrophases was inhibited and the protein synthesis pattern of M. tuberculosis has been analysed. A mycobacterial protein of molecular weight 17 kDa which was expressed exclusively in the cyctosolic fraction of M. tuberculosis-infected guinea pig macrophages in vitro has been identified.

5707.      Ninomiya H, Maeda M, Matsuzaki Y, Nakamura K, Sekiya R, Onitsuka T. Giant cell tumor of the rib. Jpn J Thorac Cardiovasc Surg. 2002 May;50(5):224-6. Review.


In a rare case of a giant cell tumor of rib origin, a 25-year-old woman to be evaluated for an abnormal mass shadow in chest radiography was strongly positive in a tuberculin skin test, but showed no evidence of active tuberculosis. Chest computed tomography showed a heterogeneous mass originating in the posterior end of the right fourth rib and containing multiple calcifications and cystic lesions. Magnetic resonance imaging showed a high signal intensity with low signal intensity areas. Bone scintigraphy showed an abnormal marked accumulation at the tumor site. A thoracoscopic examination was conducted prior to complete tumor resection, including the fourth rib and related muscles. The pathological diagnosis returned was a giant cell tumor of the bone. The patient did not undergo chemotherapy or radiotherapy, and remains well, and tumor-free at 6 months after surgery.

5708.      Orndorff GR. Tuberculosis skin test conversion rates evaluated at an overseas military hospital. Mil Med. 2002 Apr;167(4):317-20.


As a result of a perceived increase in purified protein derivative skin test converters, purified protein derivative skin testing of hospital staff and epidemiological evaluation were undertaken. A possible common source of tuberculosis exposure was identified and evaluated. This patient was skin test positive but never provided prophylactic treatment in Spain, and normal case management procedures failed. The Andalusia region, where the naval base is located, has a reported rate of about 15 new tuberculosis cases per 100,000 persons per year, whereas the rate for the entire country of Spain is 22 per 100,000 persons. More than half of the new cases of tuberculosis reported in Spain come from this region. As a result of this work, improved personal prevention programs were instituted and hospital and base orientation regarding the unique risk of tuberculosis in this region was improved.

5709.      Pande KC, Babhulkar SS. Atypical spinal tuberculosis. Clin Orthop. 2002 May;(398):67-74. Review.


Typical spinal tuberculosis is readily diagnosed and treated. Certain atypical clinical and radiologic presentations of spinal tuberculosis are described. Failure to recognize these presentations may lead to delay in diagnosis and initiation of treatment. In some atypical forms of the disease, this may have disastrous consequences. The current authors present a new classification for atypical spinal tuberculosis and describe the various presentations. The role of advanced imaging studies such as computed tomography scanning and magnetic resonance imaging and imaging-guided aspiration cytology is discussed.

5710.      Porcel JM, Vives M. Adenosine deaminase levels in nontuberculous lymphocytic pleural effusions. Chest. 2002 Apr;121(4):1379-80.  No abstract.

5711.      Rajiv Nayan. Clarithromycin injectable compared to cefuroxime and amoxycillin+clavulanic acid. Hosp Today. 2001; 6(7), 389-91. No abstract.

5712.      Reber VB. Poor, ill, and sometimes abandoned: tubercular children in Buenos Aires, 1880-1920.J Fam Hist. 2002 Apr;27(2):128-49.


Ill children with chronic diseases, such as tuberculosis, have faced difficult lives. Poverty proved a factor in their susceptibility to disease, their abandonment, and their treatment. When public health policies in Buenos Aires shifted from ignoring children to viewing them as victims who needed protection, government agencies, charitable organizations, public schools, and hospitals developed special programs that emphasized both prevention and cure of childhood tuberculosis. Argentine physicians and hygienists supported programs that were similar to those in Europe and the United States. Despite efforts, from 1880 to 1920, diagnosis of tuberculosis remained problematic, health professionals failed to prevent tuberculosis in children, and physicians were unable to cure the disease.

5713.      Reichler M, Taylor Z, Castro KG.  Factors in tuberculosis contact investigations. JAMA. 2002 Jun 12;287(22):2944; discussion 2944-5. No abstract.

5714.      Rose AM, Sinka K, Watson JM, Mortimer JY, Charlett A. An estimate of the contribution of HIV infection to the recent rise in tuberculosis in England and Wales. Thorax. 2002 May;57(5):442-5.


BACKGROUND: The number of patients with tuberculosis has been increasing slowly in England and Wales since the late 1980s. HIV infection has been a contributory factor to increases in tuberculosis in a number of comparable industrialised countries. This study investigated the extent of tuberculosis and HIV co-infection in England and Wales in 1993 and 1998, and estimated its contribution to the increase in tuberculosis observed during this period. METHODS: Patients aged 16-54 years old at diagnosis on the 1993 and 1998 National Tuberculosis Survey databases were matched with those on the HIV/AIDS patient database. A coded process maintained patient confidentiality. Primary outcome measures were the increase between 1993 and 1998 in the numbers with both infections reported and an estimate of the proportion of the increase in tuberculosis during this period attributable to HIV co-infection. RESULTS: In 1993 61 (2.2%) tuberculosis patients aged 16-54 years matched with patients reported to the HIV database, increasing to 112 (3.3%) in 1998 (p=0.08; OR 1.35; 95% CI 0.97 to 1.87). Patients co-infected with HIV contributed an estimated 8.5% of the increase in number of tuberculosis patients between 1993 and 1998 nationwide (11% in London). In both years prevalence of co-infection was greatest in London and in patients of white and black African ethnic groups. CONCLUSIONS: In 1998 the number of tuberculosis patients co-infected with HIV in England and Wales, though still small, had nearly doubled since 1993, with most of the increase occurring in London. As HIV infection may be undiagnosed in patients with tuberculosis, and tuberculosis may be unreported in patients with diagnosed HIV infection, the true extent of co-infection will have been underestimated by this study. In addition, constraints in coded matching make it inevitable that some reported co-infections are missed. Routine HIV testing of all patients with tuberculosis should now be considered, particularly in patients of white or black African ethnic origin under 55 years of age.


5715.      Sardana K, Koranne RV, Langan U, Sharma RC, Bhatnagar SK.  Ocular scrofuloderma with unilateral proptosis. J Dermatol. 2002 Apr;29(4):232-4.


Proptosis due to an extraconal orbital abscess of tubercular origin with lacrimal gland involvement, representing ocular scrofuloderma, is a rare entity. This association has not been reported earlier in the literature. We describe a 7-year-old boy who presented with nodulo-ulcerative lesions of tubercular etiology with discharging sinuses on right side of the face and a similar lesion on the right lower eyelid along with proptosis of 4 months duration. Computerized tomography (CT) scan of the head confirmed the extraconal, intraorbital, hyperdense, homogeneously enhancing mass separated from the lateral rectus muscle and further revealed involvement of lacrimal gland along with erosion of the temporal bone. The patient showed marked improvement of his dermatological and ophthalmological lesions with anti-tubercular treatment. Subsequent ultrasound examinations of the orbit revealed regression in the size of the abscess from 10.7 mm to 5.0 mm and then complete disappearance of the abscess obviating surgical intervention.


5716.      Schachar N, DiFrancesco L. Musculoskeletal images. Tuberculous osteomyelitis. Can J Surg. 2002 Jun;45(3):202-4.  No abstract.

5717.      Sepkowitz KA.  On the contagious nature of tuberculosis (continued). Am J Respir Crit Care Med. 2002 Apr 1;165(7):858-9.  No abstract.

5718.      Seth R, Sharma U. Diagnostic criteria for Tuberculous Meningitis. Indian J Pediatr. 2002 Apr;69(4):299-303.


OBJECTIVE: Tuberculous Meningitis is associated with a high morbidity and mortality if there is a delay in diagnosis. The diagnosis is based on clinical evaluation since the bacteriological diagnosis takes time and has a low yield. This study attempts to validate these criteria in children with TBM. METHODS: Forty-two children clinically suspected to have TBM were enrolled in the study. History, examination, CT scan and CSF findings were utilized to categorize patients into "definite", "highly probable", "probable" and "possible" TBM based on the criteria laid down by Ahuja et al. The validity of these criteria was tested against bacterial isolation and response to treatment. RESULTS: Thirty one children, with complete data, were included for analysis. Using "improvement on therapy as a criterion for definite TBM, we analyzed the sensitivity and specificity of the Ahuja criteria in diagnosing TBM. Using the criteria of "highly probable" TBM, the sensitivity was 65% with a specificity of 75%. When the criteria of "probable" TBM were used, the sensitivity increased to 96% while the specificity dropped to 38%. In an attempt to make these criteria more appropriate for children, we modified the criteria by including mantoux reaction, and family history of exposure in the criteria. The modified criteria gave a sensitivity of 83% and a specificity of 63%. DISCUSSION: A sensitivity of 65% (highly probable group) implies that 35% of TBM patients will be missed, while the probable criteria gave a 63% false positive rate suggesting that the trade-off for a higher sensitivity makes the criteria very unreliable. Our modification of the criteria gave us a reasonable sensitivity of 83% with a higher specificity of 63%. The false positive rate was also reduced to 38%. Thus the modified Ahuja criteria worked better for children with TBM. CONCLUSION: The modified Ahuja criteria are better applicable for use in pediatric patients with TBM . Since the number of patients was small in this study, the study needs to be validated with a larger sample size.

5719.      Sharma N, Kumar P. Miliary tuberculosis with bilateral pneumothorax: a rare complication. Indian J Chest Dis Allied Sci. 2002 Apr-Jun;44(2):125-7.Abstract: A 15-year-old girl presented with a history of cough, fever for five months and breathlessness of two days duration. Her chest roentgenogram showed bilateral miliary shadows with a left sided pneumothorax. Shortly afterwards, she developed a pneumothorax on the other side also. She was managed with intercostal tube drainage on both sides and antitubercular treatment. She made an uneventful recovery.

5720.      Sharma SK, Suesh V, Mohan A, Kaur P, Saha P, Kumar A, Pande JN. Prospective study and specificity of adenosine deaminase estimation in the diagnosis of tuberculosis pleural effusion. Indian J Chest Dis all Sci. 2001; 43(3), 149-55.
Evaluates the usefulness of adnosine deaminase [ADA] estimation in the diagnosis of tuberculosis [TB] pleural effusion. Seventy five subjects with pleural effusion were studied. Forty eight of them had TB pleural effusion [M:F::37:11; mean age 33 + 14.4 years range 17-761] and the remaining 27 had pleural effusion due to causes other than TB [non-TB group] [M:F::19:8; mean age 47.3 + 16.5 years; range 17-75]. Pleural fluied [PF] ADA levels were significantly higher in TB(n=48;mean 95.8 + 57.5 IU/L) compared with non-TB group (n=27; mean 30.7+ 27.2 IU/L) [p<0.001]. Serum ADA [S-ADA] levels were also significantly higher in TB (n=45; mean 39.6 + 18.3 IU/L) compared with non-TB group (n-26; mean18.0+ 13.7 IU/L) [p0.0001]. PF-ADA levels were higher compared with non-TB group (n=26; mean 18.0 + 13.7 IU/L) [p0.0001]. PF-ADA levels were higher compared to S-SDA in TB (p<0.001) and non diagnosis of TB groups [p<0.01]. using a cut off of 35 IU/L, the sensitivity and specificity of PF_ADA in the diagnosis of TB was computed to be 83.3% and 66.6% respectively. At a cut-off level of 100 IU/L, PF-ADA was found to have a sensitivity 40% and cut-off, it is possible to avoid pleural biopsy to ascertain the diagnosis of TB in as much as 40% of the patients.


5721.      Singh S, Madge S, Lipman M. Tuberculosis in primary care. Br J Gen Pract. 2002 May;52(478):357-8. No abstract.

5722.      Suri VS, Sakhuja P, Malhotra V, Gondal R, Singh S, Sidhu N. Co-existent tuberculosis and papillary carcinoma thyroid. Trop Doct. 2002 Apr;32(2):118. No abstract.

5723.      Suryanarayana L, Jagannatha PS. Scoring method for diagnosis of tuberculosis in children: an evaluation. Indian J Tuberc. 2001; 48(2), 101-3.No Abstract.

5724.      Tanaka A, Kato Y, Arai K, Oh-i T, Koga M. Unusual clinical features of cutaneous tuberculosis in an immune compromised patient.J Dermatol. 2002 Apr;29(4):226-31.

We report a case of an unusual form of cutaneous tuberculosis in an 82-year-old woman. She visited our hospital because of an intractable ulcer on the fifth finger of her right hand. While examining the ulcer surrounding half of her right fifth finger and covered with necrotic tissue, we also perceived a nodule with crust on the forearm, multiple subcutaneous nodules on the right forearm and upper arm, and a hen's-egg-sized agglomerative nodule on the axilla. All the lesions were located on her right arm. Skin biopsy specimens showed granulomatous tissue with necrosis in the lesions. Mycobacterium tuberculosis was identified by culture of a biopsied specimen, so the diagnosis was confirmed. Further examination revealed that she also had pulmonary tuberculosis. Cutaneous tuberculoses are classified morphologically with reference to host immune status, but no satisfactory classification exists. The present case can't be classified into any of the types which have been proposed so far. She is elderly and suffers from liver cirrhosis, hepatocellular carcinoma and myelodysplastic syndrome. The resulting acquired immunosuppression may have caused a unique form of cutaneous tuberculosis.

5725.      Tarumi K, Koga H, Iida M, Kobori Y, Matsumoto H, Fujita M, Takeda M, Hoshika K, Mikami Y.  Colonic aphthoid erosions as the only manifestation of tuberculosis: case report. Gastrointest Endosc. 2002 May;55(6):743-5.  No abstract.

5726.      Wedlock DN, Skinner MA, de Lisle GW, Buddle BM.  Control of Mycobacterium bovis infections and the risk to human populations. Microbes Infect. 2002 Apr;4(4):471-80. Review.


Conventional control methods based on test-and-slaughter policies have, in several countries, led to the successful eradication of bovine tuberculosis in cattle. However, new approaches for control of bovine tuberculosis are required in developing countries and those with a wildlife reservoir of infection. Recent developments include improved diagnostics and evaluation of new vaccination strategies.



5727.      Bannantine JP, Baechler E, Zhang Q, Li L, Kapur V. Genome scale comparison of Mycobacterium avium subsp. paratuberculosis with Mycobacterium avium subsp. avium reveals potential diagnostic sequences. J Clin Microbiol. 2002 Apr;40(4):1303-10.


The genetic similarity between Mycobacterium avium subsp. paratuberculosis and other mycobacterial species has confounded the development of M. avium subsp. paratuberculosis-specific diagnostic reagents. Random shotgun sequencing of the M. avium subsp. paratuberculosis genome in our laboratories has shown >98% sequence identity with Mycobacterium avium subsp. avium in some regions. However, an in silico comparison of the largest annotated M. avium subsp. paratuberculosis contigs, totaling 2,658,271 bp, with the unfinished M. avium subsp. avium genome has revealed 27 predicted M. avium subsp. Paratuberculosis coding sequences that do not align with M. avium subsp. avium sequences. BLASTP analysis of the 27 predicted coding sequences (genes) shows that 24 do not match sequences in public sequence databases, such as GenBank. These novel sequences were examined by PCR amplification with genomic DNA from eight mycobacterial species and ten independent isolates of M. avium subsp. paratuberculosis. From these analyses, 21 genes were found to be present in all M. avium subsp. paratuberculosis isolates and absent from all other mycobacterial species tested. One region of the M. avium subsp. paratuberculosis genome contains a cluster of eight genes, arranged in tandem, that is absent in other mycobacterial species. This region spans 4.4 kb and is separated from other predicted coding regions by 1,408 bp upstream and 1,092 bp downstream. The gene upstream of this eight-gene cluster has strong similarity to mycobacteriophage integrase sequences. The GC content of this 4.4-kb region is 66%, which is similar to the rest of the genome, indicating that this region was not horizontally acquired recently. Southern hybridization analysis confirmed that this gene cluster is present only in M. avium subsp. paratuberculosis. Collectively, these studies suggest that a genomics approach will help in identifying novel M. avium subsp. paratuberculosis genes as candidate diagnostic sequences.

5728.      Biswas J, Sharma T, Gopal L, Madhavan HN, Sulochana KN, Ramakrishnan S. Eales disease--an update. Surv Ophthalmol. 2002 May-Jun;47(3):197-214. Review.


Eales disease, first described by Henry Eales in 1880, remains an enigma. The disease, observed more commonly in the Indian subcontinent than in the rest of the world, occurs in young healthy adult males, initially presenting as retinal periphlebitis and later as retinal ischemia that may lead to vascular alterations and neovascularization. Recurrent vitreous hemorrhage with or without retinal detachment is the common sequelae. In recent years, immunological, molecular biological, and biochemical studies have indicated the role of human leukocyte antigen, retinal autoimmunity, mycobacterium tuberculosis genome, and free radical mediated damage in the etiopathogenesis of this disease. However, its etiology appears to be multifactorial. The management depends on the stage of the disease and consists of medical treatment with oral corticosteroids in the active inflammatory stage and laser photocoagulation in the advanced retinal ischemia and neovascularization stages. The results of vitreoretinal surgery have been found to be satisfactory in case of vitreous hemorrhage with or without retinal detachment.

5729.      Boras Z, Juretic A, Rudolf M, Uzarevic B, Trescec A. Cellular and humoral immunity to purified protein derivative (PPD) in PPD skin reactive and nonreactive patients with pulmonary tuberculosis: comparative analysis of antigen-specific lymphocyte proliferation and IgG antibodies. Croat Med J. 2002 Jun;43(3):301-5.


AIM: To evaluate in vitro reactivity against tuberculin purified protein derivative (PPD) in patients with active pulmonary tuberculosis scoring either positive or negative upon intradermal PPD application (PPD-DTH). METHOD: Two groups of patients with pulmonary tuberculosis, 22 PPD+ and 22 PPD-, were studied. Peripheral blood mononuclear cells (PBMC) were assayed for in vitro proliferation to PPD antigen, phytohaemagglutin, concanavalin A, and pokeweed mitogens. In the proliferation assay PBMC were incubated in a medium supplemented with serum (20% concentration) from healthy donors, autologous serum, or allogenic serum. Anti-PPD IgG concentration in patients sera were analyzed by ELISA. CD3+ lymphocytes from 10 patients in each group were tested for the expression of surface activation markers (HLA-DR and CD25/IL-2 receptors) by flow cytometry. RESULTS: PPD- patients showed clinically and radiologically more advanced forms of pulmonary tuberculosis as compared with PPD+ patients. PBMC from both groups of patients proliferated in response to PPD effectively, but significantly higher de novo DNA synthesis was observed in PPD+ patients (p<0.001). Proliferative activity was not affected by the type of the serum supplement (autologous or allogenic) in the culture medium. Mitogen stimulation elicited similar proliferative responses in both groups. Similar percentages of T-lymphocytes and T-lymphocytes expressing CD25 activation markers were observed in both groups of patients. There was a borderline difference in the percentage of CD3+HLA-DR+ lymphocytes between these two groups of patients (p=0.05). At 1:1000 serum dilution a significant difference (p=0.002) in anti-PPD IgG concentrations was found between PPD- and PPD+ patients. CONCLUSION: Patients with active pulmonary tuberculosis with a more favorable clinical course have a more potent specific cell-mediated immunity to PPD (positive skin reactivity in vivo and significantly greater lymphocyte proliferative response in vitro) than patients with a clinically more severe form of the disease. The concentration of PPD specific IgG in the serum appears to be higher in patients with relatively more severe forms of the disease.


5730.      Bouchonnet F, Boechat N, Bonay M, Hance AJ. Alpha/beta interferon impairs the ability of human macrophages to control growth of Mycobacterium bovis BCG. Infect Immun. 2002 Jun;70(6):3020-5.


Administration of alpha/beta interferon (IFN-alpha/beta) to mice infected with Mycobacterium tuberculosis has been shown to increase mycobacterial growth. Because IFN-alpha/beta has direct pleiotropic effects on the differentiation and functional activities of macrophages, we evaluated the effect of IFN-alpha/beta on mycobacterial growth in human monocytes/macrophages in vitro. Monocytes cultured at optimal cell density could control the growth of M. bovis BCG, as assessed both by measurement of luciferase activity expressed by a mycobacterial reporter strain and by counting of CFU. In contrast, unrestrained mycobacterial growth was observed when monocytes were treated with alpha interferon (IFN-alpha) 3 days prior to or concomitant with infection. This striking loss of mycobacteriostatic activity was observed with IFN-alpha and IFN-beta and was induced in both freshly isolated monocytes and culture-derived macrophages. Pretreatment of monocytes with IFN-alpha modified cellular morphology and reduced viability following culture, but neither was observed for culture-derived macrophages, indicating that the effects of IFN-alpha on mycobacteriostatic activity and cell differentiation and death could be dissociated. These results are compatible with the possibility that the secretion of IFN-alpha/beta could directly promote mycobacterial growth in patients harboring these organisms.

5731.      Brahmbhatt S, Hussain R, Zafar S, Dawood G, Ottenhoff TH, Drijfhout JW, Bothamley G, Smith S, Lopez FV, Dockrell HM.  Human T cell responses to peptides of the Mycobacterium leprae 45-kD serine-rich antigen. Clin Exp Immunol. 2002 Apr;128(1):140-8.


In order to identify T cell epitopes within the Mycobacterium leprae 45-kD serine-rich antigen, we analysed responses to overlapping 17-mer peptides encompassing the whole antigen in non-exposed UK controls, Pakistani leprosy patients and tuberculosis patients in both the United Kingdom and Pakistan. This antigen has been described as M. leprae-specific, although it has a hypothetical homologue in M. tuberculosis. Human peripheral blood mononuclear cells were stimulated with peptide for 5 days and IFN-gamma measured in supernatants by ELISA. Some peptides were recognized more frequently by T cells from tuberculoid leprosy patients than those from UK controls, suggesting that such T cell epitopes might have diagnostic potential, while other peptides induced greater responses among UK control subjects. Short-term cell lines confirmed that these assays detected specific T cell recognition of these peptides. However, many tuberculosis patients also recognized these potentially specific peptides suggesting that there could be a true homologue present in M. tuberculosis.

5732.      Brennan MJ, Delogu G. The PE multigene family: a 'molecular mantra' for mycobacteria. Trends Microbiol. 2002 May;10(5):246-9. Review.


The PE multigene family of Mycobacterium tuberculosis is remarkable in that it is composed of approximately 100 highly homologous genes that are found only in mycobacteria. Early evidence suggests that proteins encoded by certain members of this gene family could be present in the mycobacterial cell wall, impact antigen-presentation pathways and the ensuing host immune responses, and also provide a mechanism for generating antigenic diversity in mycobacteria.

5733.      Bruchfeld J, Aderaye G, Palme IB, Bjorvatn B, Ghebremichael S, Hoffner S, Lindquist L. Molecular epidemiology and drug resistance of Mycobacterium tuberculosis isolates from Ethiopian pulmonary tuberculosis patients with and without human immunodeficiency virus infection. J Clin Microbiol. 2002 May;40(5):1636-43.


We have analyzed the molecular epidemiology and drug resistance of 121 Mycobacterium tuberculosis isolates from consecutive patients with culture-positive pulmonary tuberculosis attending a university hospital outpatient department in Addis Ababa, Ethiopia. Restriction fragment length polymorphism analysis and spoligotyping were used to analyze the DNA fingerprinting patterns. Fifty-one (41.2%) of the isolates were found in 13 clusters with two or more identical DNA patterns. Two such clusters contained 49.0% of all clustered isolates. In a multivariate logistic regression model, human immunodeficiency virus (HIV)-positive serostatus was significantly associated with clustering of isolates for patients of both sexes (odds ratio [OR], 2.55; 95% confidence interval [CI], 1.17 to 5.80). There was a trend toward increased clustering of isolates from tuberculous women residing in Addis Ababa (OR, 2.10; 95% CI, 0.85 to 5.25). In total, 17 of 121 isolates (14.0%) were resistant to one or more of the antituberculosis drugs isoniazid (8.3%), streptomycin (7.4%), rifampin (2.5%), and ethambutol (1.7%). The high rate of drug-resistant isolates (29.6%) coincided with the peak prevalence of HIV infection (77.8%) in patients 35 to 44 years old. The majority (62.5%) of resistant isolates in this group were found within clusters. The simultaneous accumulation of certain bacterial clones in a patient population likely reflects recent transmission. Hence, we conclude that tuberculosis is commonly caused by recent infection with M. tuberculosis in HIV-positive Ethiopian patients. Furthermore, with the rapidly increasing prevalence of HIV infection in Ethiopia, the burden of tuberculosis, including drug-resistant tuberculosis, is likely to increase. Strengthening of classical tuberculosis control measures by promoting active case finding among HIV-positive adults with tuberculosis is warranted to reduce rates of transmission.

5734.      Collazos J, Quintas L, Mayo J. Tuberculous esophageal ulcer as the mode of presentation of Pott's disease (tuberculous spondylitis). Am J Med. 2002 Jun 15;112(9):737-9.  No abstract.

5735.      Cooksey RC, Morlock GP, Holloway BP, Limor J, Hepburn M. Temperature-mediated heteroduplex analysis performed by using denaturing high-performance liquid chromatography to identify sequence polymorphisms in Mycobacterium tuberculosis complex organisms. J Clin Microbiol. 2002 May;40(5):1610-6.


PCR products containing sequence polymorphisms were prepared from six mycobacterial genes, denatured, mixed with reference PCR products, and reannealed; the mixtures were then examined with a denaturing high-performance liquid chromatography system (WAVE) equipped with a temperature-controlled alkalated polystyrene divinyl benzene column. Mismatching of bases in heteroduplexes of the PCR products causes elution patterns of the DNA from the column to be altered. The six mycobacterial genes studied were oxyR, in which a specific polymorphism (G(1031)A) is found only in certain species of the Mycobacterium tuberculosis complex, and five genes in which mutations associated with antituberculosis drug resistance have been found. The resistance genes (with affected drug and PCR product sizes given parenthetically) were rpoB (rifampin; 258 bp), katG (isoniazid; 205 bp), pncA (pyrazinamide; 579 bp); rpsL (streptomycin; 196 bp), and embB (ethambutol; 185 bp). Elution patterns of heteroduplexes of all 20 polymorphisms studied shifted detectably at column temperatures ranging from 65.3 to 68 degrees C and elution times of 3.5 to 6 min. These results show that temperature-mediated heteroduplex analysis is a potentially useful genotypic screen for mutations associated with antituberculosis drug resistance and for the G(1031)A polymorphism in oxyR. The method may allow users to detect novel as well as heterogeneous mutations without using expensive kits or detection labels.

5736.      Cowan LS, Mosher L, Diem L, Massey JP, Crawford JT. Variable-number tandem repeat typing of Mycobacterium tuberculosis isolates with low copy numbers of IS6110 by using mycobacterial interspersed repetitive units. J Clin Microbiol. 2002 May;40(5):1592-602.


A study set of 180 Mycobacterium tuberculosis and Mycobacterium bovis isolates having low copy numbers of IS6110 were genotyped using the recently introduced method based on the variable-number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR). The results were compared with results of the more commonly used methods, IS6110 restriction fragment length polymorphism (RFLP) and spoligotyping. The isolates were collected in Michigan from 1996 to 1999 as part of a project to genotype all isolates from new cases of tuberculosis in the state. Twelve MIRU loci were amplified, and the amplicons were analyzed by agarose gel electrophoresis to determine the copy number at each MIRU locus. MIRU-VNTR produced more distinct patterns (80 patterns) than did IS6110 RFLP (58 patterns), as would be expected in this study set. Spoligotyping identified 59 patterns. No single method defined all unique isolates, and the combination of all three typing methods generated 112 distinct patterns identifying 90 unique isolates and 90 isolates in 22 clusters. The results confirm the potential utility of MIRU-VNTR typing and show that typing with multiple methods is required to attain maximum specificity.

5737.      Djuretic T, Herbert J, Drobniewski F, Yates M, Smith EG, Magee JG, Williams R, Flanagan P, Watt B, Rayner A, Crowe M, Chadwick MV, Middleton AM, Watson JM. Antibiotic resistant tuberculosis in the United Kingdom: 1993-1999. Thorax. 2002 Jun;57(6):477-82.


BACKGROUND: The re-emergence of tuberculosis as a global health problem over the past two decades, accompanied by an increase in tuberculosis drug resistance, prompted the development of a comprehensive national surveillance system for tuberculosis drug resistance in 1993. METHODS: The UK Mycobacterial Resistance Network (Mycobnet), which includes all mycobacterial reference and regional laboratories in the UK, collects a minimum dataset on all individuals from whom an initial isolate of Mycobacterium tuberculosis complex has been isolated and submitted by source hospital laboratories. Data sought include susceptibility to first line antibiotics, demographic, geographical, and risk factor information. RESULTS: There were 25 217 reports of initial isolates of M tuberculosis complex in the UK between 1993 and 1999. All were tested for sensitivity to isoniazid, rifampicin, and ethambutol and 12 692 of the isolates were also tested for sensitivity to pyrazinamide and streptomycin. A total of 1523 (6.1%) isolates were resistant to one or more drugs, 1397 isolates (5.6%) were resistant to isoniazid with or without resistance to other drugs, and 299 (1.2%) were multidrug resistant. Although the numbers of drug resistant isolates increased over the period, the proportions remained little changed. Certain groups of people were at a higher risk of acquiring drug resistant tuberculosis including younger men, residents of London, foreign born subjects, patients with a previous history of tuberculosis and those infected with HIV. CONCLUSION: Although the proportion of drug resistant tuberculosis cases appears to be stable in the UK at present, more than one in 20 patients has drug resistant disease at diagnosis and more than one in 100 has multidrug resistant disease. Tuberculosis control measures should be strengthened to minimise the emergence of drug resistance through rapid diagnosis, rapid identification of drug resistance, supervised treatment, and maintenance of comprehensive surveillance.


5738.      Dooley KE, Golub J, Goes FS, Merz WG, Sterling TR. Empiric treatment of community-acquired pneumonia with fluoroquinolones, and delays in the treatment of tuberculosis. Clin Infect Dis. 2002 Jun 15;34(12):1607-12.


Fluoroquinolones, which are widely used to treat community-acquired pneumonia, also have excellent in vitro activity against Mycobacterium tuberculosis. A retrospective cohort study was conducted among adults with culture-confirmed tuberculosis to assess the effect of empiric fluoroquinolone therapy on delays in the treatment of tuberculosis. Sixteen (48%) of 33 patients received fluoroquinolones for presumed bacterial pneumonia before tuberculosis was diagnosed and treated. There were no differences between the group who did and the group who did not receive fluoroquinolones, except that patients who received fluoroquinolones were more likely to present with shortness of breath. Among patients treated empirically with fluoroquinolones, the median time between presentation to the hospital and initiation of antituberculosis treatment was 21 days (interquartile range, 5-32 days); among those who were not, it was 5 days (interquartile range, 1-16 days; P=.04). Initial empiric therapy with a fluoroquinolone was associated with a delay in the initiation of appropriate antituberculosis treatment.

5739.      Fessler BJ. Infectious diseases in systemic lupus erythematosus: risk factors, management and prophylaxis. Best Pract Res Clin Rheumatol. 2002 Apr;16(2):281-91. Review.


Infections are one of the leading causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Therapeutic, disease-related and genetic factors all contribute to a lupus patient's increased susceptibility to infections. Although bacterial pathogens are the most common cause of infections, a wide variety of pathogens have been reported. In high-risk populations, identification and treatment of chronic infections such as tuberculosis, hepatitis B or human immunodeficiency virus, are important prior to the institution of immunosuppression to prevent reactivation or exacerbation of the infection. Judicious use of corticosteroids and cytotoxic drugs is critical in limiting infectious complications. Vaccines against influenza and pneumococcus appear to be safe and immunogenic in SLE patients and their routine administration should be encouraged. Copyright 2002 Elsevier Science Ltd.

5740.      Hamdan AL, Hadi U, Shabb N.  Tuberculous parotitis: a forgotten entity. Otolaryngol Head Neck Surg. 2002 May;126(5):581-2. No abstract.

5741.      Kumar R, Pandey CK, Bose N, Sahay S. Tuberculous brain abscess: clinical presentation, pathophysiology and treatment (in children). Childs Nerv Syst. 2002 Apr;18(3-4):118-23. Review.


BACKGROUND: Tubercular brain abscess (TBA) is a rare manifestation of CNS tuberculosis. It is characterised by an encapsulated collection of pus, containing viable tubercular bacilli without evidence of tubercular granuloma.PRESENTATION AND HISTORY: Patients may present with features of raised intracranial pressure and focal neurological deficit commensurate with the site of the abscess. A history of pulmonary tuberculosis may be present, as documented in one of our six cases; three of our six children developed TBA despite 3-weeks to 12-month courses of antitubercular chemotherapy prescribed for post-TBM hydrocephalus.DIAGNOSIS: Contrast CT head, MRI, MR spectroscopy is helpful in making the diagnosis and planning the treatment. TBA may be unilocular or multilocular on contrast CT scan. A relatively long clinical history and an enhancing capsule with thick wall are suggestive of TBA. Pyogenic abscess, however, has a thin rim on contrast CT. The capsule of TBA is formed of vascular granulation tissue containing acute and chronic inflammatory cells, particularly polymorphs. Proof of tubercular origin must be demonstrated either by presence of acid fast bacilli in culture or staining of pus or wall.TREATMENT: Treatment options include simple puncture, continuous drainage, fractional drainage, repeated aspiration through a burr hole, stereotactic aspiration and total excision of the abscess. Total excision usually becomes necessary in multilocular noncommunicating and thick-walled abscesses. Antitubercular therapy is the mainstay of management. The development of fulminant tubercular meningitis is sometimes problematic following surgical excision of TBA, as seen in one of our four operated cases. Mortality is reported to be high despite progress in treatment, while five of the six children treated by us responded well to the treatment.

5742.      Medinger A. Death associated with rifampin and pyrazinamide 2-month treatment of latent mycobacterium tuberculosis. Chest. 2002 May;121(5):1710-2.


We present the case of an elderly patient who died of fulminant hepatic failure in the course of receiving 2 months of treatment with pyrazinamide and rifampin for his latent tuberculosis. This 2-month course of treatment for latent tuberculosis is one of four options recently recommended by the Centers for Disease Control and Prevention. We discuss the safety of using this two-drug regimen to treat latent tuberculosis in stable elderly patients.

5743.      Melzer M, Brown TJ, French GL, Dickens A, McHugh TD, Bagg LR, Storring RA, Lacey S.  Molecular analysis of drug resistant TB. Thorax. 2002 Jun;57(6):562-3. No abstract.

5744.      Mhaskar R, Mhaskar AM. Methemoglobinemia following chromopertubation in treated pelvic tuberculosis. Int J Gynaecol Obstet. 2002 Apr;77(1):41-2.


Methylene blue administered through cervix is used to check tubal patency at laparoscopy. Although methylene blue is used to treat methemoglobinemia it can also produce methemoglobinemia in susceptible individuals. A case of methemoglobinemia induced by methylene blue in a patient with treated pelvic tuberculosis is presented.

5745.      Mokrousov I, Narvskaya O, Limeschenko E, Otten T, Vyshnevskiy B. Detection of ethambutol-resistant Mycobacterium tuberculosis strains by multiplex allele-specific PCR assay targeting embB306 mutations. J Clin Microbiol. 2002 May;40(5):1617-20.


We describe a multiplex allele-specific (MAS)-PCR assay to detect simultaneously mutations in the first and third bases of the embB gene codon 306ATG. These mutations are known to confer ethambutol (EMB) resistance in the majority of clinical Mycobacterium tuberculosis isolates worldwide. The mutated bases are revealed depending on the presence or absence of the respective indicative fragments amplified from the embB306 wild-type allele. Initially optimized on purified DNA samples, the assay was tested on crude cell lysates and auramine-stained sputum slide DNA preparations with the same reproducibility and interpretability of the generated profiles in agarose gel electrophoresis. Since EMB resistance is generally linked to multiple-drug resistance (MDR), the MAS-PCR assay for EMB resistance detection can be used in clinical laboratory practice in areas with a high prevalence and a high transmission rate of MDR-EMB-resistant tuberculosis.

5746.      Montalbano MM, Lemanske RF Jr. Infections and asthma in children. Curr Opin Pediatr. 2002 Jun;14(3):334-7. Review.


The temporal association of acute asthma exacerbations in children with viral infections such as rhinovirus, respiratory syncytial virus, and parainfluenza has been known for many years. Recently, the contributions of infections to the pathophysiology of asthma have been expanded beyond disease exacerbation to include disease inception, chronicity, and even prevention. Respiratory syncytial virus has been implicated in asthma inception, while Chlamydia pneumoniae, Mycoplasma pneumoniae, and latent adenovirus infections have been correlated with asthma chronicity. Measles, hepatitis A, and tuberculosis have been associated with a decreased incidence of asthma, implying a contribution to disease prevention. The following review will briefly highlight the relationships between various microbial infections and the pathophysiology of asthma.

5747.      Murray M. Sampling bias in the molecular epidemiology of tuberculosis. Emerg Infect Dis. 2002 Apr;8(4):363-9.


Among the goals of the molecular epidemiology of infectious disease are to quantify the extent of ongoing transmission of infectious agents and to identify host- and strain-specific risk factors for disease spread. I demonstrate the potential bias in estimates of recent transmission and the impact of risk factors for clustering by using computer simulations to reconstruct populations of tuberculosis patients and sample from them. The bias consistently results in underestimating recent transmission and the impact of risk factors for recent transmission.

5748.      Orndorff GR.  Tuberculosis skin test conversion rates evaluated at an overseas military hospital. Mil Med. 2002 Apr;167(4):317-20.


As a result of a perceived increase in purified protein derivative skin test converters, purified protein derivative skin testing of hospital staff and epidemiological evaluation were undertaken. A possible common source of tuberculosis exposure was identified and evaluated. This patient was skin test positive but never provided prophylactic treatment in Spain, and normal case management procedures failed. The Andalusia region, where the naval base is located, has a reported rate of about 15 new tuberculosis cases per 100,000 persons per year, whereas the rate for the entire country of Spain is 22 per 100,000 persons. More than half of the new cases of tuberculosis reported in Spain come from this region. As a result of this work, improved personal prevention programs were instituted and hospital and base orientation regarding the unique risk of tuberculosis in this region was improved.

5749.      Pai M, McCulloch M, Colford JM Jr. Meta-analysis of the impact of HIV on the infectiousness of tuberculosis: methodological concerns. Clin Infect Dis. 2002 May 1;34(9):1285-7. No abstract.

5750.      Pronczuk J, Akre J, Moy G, Vallenas C. Global perspectives in breast milk contamination: infectious and toxic hazards. Environ Health Perspect. 2002 Jun;110(6):A349-51.


Breast milk is the natural and optimal food for infants. In addition to meeting nutritional needs, breast milk provides numerous immunologic, developmental, psychologic, economic, and practical advantages. It is postulated that breast-feeding may also be related to the prevention of some adult health problems such as diabetes and coronary heart disease. Malnutrition among infants and young children, which remains one of the most severe global public health problems, is among the main reasons that the World Health Organization (WHO) so strongly supports breast-feeding. However, WHO recognizes the growing concern expressed by scientists, health professionals, environmentalists, and mothers about the potential risks posed by the presence of toxicants and infectious agents in breast milk. In this paper we review the main infectious hazards (tuberculosis, hepatitis B, and human immunodeficiency virus) and selected chemical hazards (tobacco, persistent contaminants) and the activities undertaken by WHO. We conclude that in cases where there is a high degree of pollution from chemical sources occurring simultaneously in a bacterially contaminated environment, the choice is not simply between polluted breast milk and risk-free substitutes. Rather, informed choice is based on assessing the known and unknown risks of artificial feeding versus the unknown, but potential, risks of chemical contamination of breast milk. Clearly, the possible toxicity of compounds requires further investigation. Of much greater importance, however, are effective measures to protect the environment for the entire population by controlling the use of these toxic products. Current scientific evidence does not support altering WHO's global public health recommendation of exclusive breast-feeding for 6 months followed by safe and appropriate complementary foods, with continued breast-feeding, up to 2 years of age or beyond.


5751.      Saukkonen JJ, Bazydlo B, Thomas M, Strieter RM, Keane J, Kornfeld H. Beta-chemokines are induced by Mycobacterium tuberculosis and inhibit its growth. Infect Immun. 2002 Apr;70(4):1684-93.


Chemokines (CK) are potent leukocyte activators and chemoattractants and aid in granuloma formation, functions critical for the immune response to Mycobacterium tuberculosis. We hypothesized that infection of alveolar macrophages (AM) with different strains of M. tuberculosis elicits distinct profiles of CK, which could be altered by human immunodeficiency virus (HIV) infection. RANTES, macrophage inflammatory protein-1 alpha (MIP-1 alpha), and MIP-1 beta were the major beta-CK produced in response to M. tuberculosis infection. Virulent M. tuberculosis (H37Rv) induced significantly less MIP-1 alpha than did the avirulent strain (H37Ra), while MIP-1 beta and RANTES production was comparable for both strains. MIP-1 alpha and MIP-1 beta were induced by the membrane, but not cytosolic, fraction of M. tuberculosis. M. tuberculosis-induced CK secretion was partly dependent on tumor necrosis factor alpha (TNF-alpha). AM from HIV-infected individuals produced less TNF-alpha and MIP-1 beta than did normal AM in response to either M. tuberculosis strain. We tested the functional significance of decreased beta-CK secretion by examining the ability of beta-CK to suppress intracellular growth of M. tuberculosis. MIP-1 beta and RANTES suppressed intracellular growth of M. tuberculosis two- to threefold, a novel finding. Thus, beta-CK contribute to the innate immune response to M. tuberculosis infection, and their diminution may promote the intracellular survival of M. tuberculosis.


5752.      Shah A, Panjabi C. Allergic bronchopulmonary aspergillosis: a review of a disease with a worldwide distribution. J Asthma. 2002 Jun;39(4):273-89. Review.


Allergic bronchopulmonary aspergillosis (ABPA), an immunologically mediated lung disease, occurs predominantly in patients with asthma. This chronic relapsing disorder ranges clinically from mild asthma to fatal destructive lung disease and is caused by hypersensitivity to colonized Aspergillus fumigatus (Af). The immunopathogenesis of the disease is yet to be understood clearly. Specific IgE-Af and IgG-Af, the serological markers, contribute to the diagnosis. Radiologically, ABPA is characterized by fleeting pulmonary infiltrates often confused with pulmonary tuberculosis. However, central bronchiectasis on computed tomography is considered to be the hallmark of the disease. Early diagnosis and therapy with prednisolone, the cornerstone of management, could alter the course of the disease and prevent the development of end-stage lung fibrosis.

5753.      van Crevel R, Ottenhoff TH, van der Meer JW.  Innate immunity to Mycobacterium tuberculosis. Clin Microbiol Rev. 2002 Apr;15(2):294-309. Review.


The different manifestations of infection with Mycobacterium tuberculosis reflect the balance between the bacillus and host defense mechanisms. Traditionally, protective immunity to tuberculosis has been ascribed to T-cell-mediated immunity, with CD4(+) T cells playing a crucial role. Recent immunological and genetic studies support the long-standing notion that innate immunity is also relevant in tuberculosis. In this review, emphasis is on these natural, innate host defense mechanisms, referring to experimental data (e.g., studies in gene knockout mice) and epidemiological, immunological, and genetic studies in human tuberculosis. The first step in the innate host defense is cellular uptake of M. tuberculosis, which involves different cellular receptors and humoral factors. Toll-like receptors seem to play a crucial role in immune recognition of M. tuberculosis, which is the next step. The subsequent inflammatory response is regulated by production of pro- and anti-inflammatory cytokines and chemokines. Different natural effector mechanisms for killing of M. tuberculosis have now been identified. Finally, the innate host response is necessary for induction of adaptive immunity to M. tuberculosis. These basic mechanisms augment our understanding of disease pathogenesis and clinical course and will be of help in designing adjunctive treatment strategies.

5754.      Van Rheenen P. The use of the paediatric tuberculosis score chart in an HIV-endemic area. Trop Med Int Health. 2002 May;7(5):435-41.


BACKGROUND: Diagnosing tuberculosis (TB) in a human immunodeficiency virus (HIV)-endemic area is extremely difficult, as the clinical symptoms of HIV-seropositive children can be easily confounded with TB. The paediatric tuberculosis score chart (TSC) was developed for resource-poor countries and its use continues to be promoted despite the fact that this scoring system has not been evaluated in countries with a high HIV prevalence. OBJECTIVE: To assess the utility of the TSC in an HIV-endemic area. METHOD: A prospective cohort study conducted between January and December 1999 at St Theresa's Mission Hospital, Copperbelt Province, Zambia. Results of the TSC (TB score) were compared with the results of a diagnostic algorithm, incorporating sputum smear microscopy, culture and polymerase chain reaction of Mycobacterium tuberculosis, tuberculin skin test, chest X-ray and histology eventually. RESULTS: A total of 147 children were enrolled in the study. On the basis of HIV-serology and clinical findings they were divided into four groups: children with TB (23 HIV-seropositive; 52 HIV-seronegative), 21 HIV-infected children without TB and 51 HIV-seronegative children without TB. The differences in TB scores between the groups were not significant. The sensitivity of the TSC to diagnose TB in this study was 88%; but the specificity was only 25%. CONCLUSION: The TSC should not be used as a diagnostic tool in countries with a high HIV prevalence. The low specificity of this scoring system leads to overdiagnosis of TB and unnecessary use of costly, antituberculous drugs. New tools for TB diagnosis in children in HIV-endemic areas are urgently needed.

5755.      Viallard JF, Parrens M, Boiron JM, Texier J, Mercie P, Pellegrin JL.  Reversible myelofibrosis induced by tuberculosis. Clin Infect Dis. 2002 Jun 15;34(12):1641-3.


Tuberculosis and myelofibrosis are reported in conjunction often enough to raise the possibility that a relationship exists between the 2 entities. However, whether tuberculosis stimulates a secondary fibrotic reaction or develops in patients who have preexisting myeloproliferative disorders is not clear. We describe the case of a 28-year-old man in whom myelofibrosis disappeared completely after administration of antituberculous treatment, which suggests that a causal relationship exists between the 2 disease entities.

5756.      Walker UA, Gutfleisch J, Peter HH. Case Number 23: Tuberculous tenosynovitis. Ann Rheum Dis. 2002 May;61(5):384. No abstract.

5757.      Warren RM, van der Spuy GD, Richardson M, Beyers N, Booysen C, Behr MA, van Helden PD. Evolution of the IS6110-based restriction fragment length polymorphism pattern during the transmission of Mycobacterium tuberculosis. J Clin Microobiol. 2002 Apr;40(4):1277-82


Interpretation of the molecular epidemiological data of Mycobacterium tuberculosis is dependent on the validity of the assumptions that have been made. It is assumed that the IS6110 banding pattern is sufficiently stable to define epidemiological events representing ongoing transmission. However, molecular epidemiological data also support the observation that the IS6110 banding pattern may change over time. Factors affecting this rate may include the nature and duration of disease in a host and the opportunity to experience different host environments during the transmission cycle. To estimate the rate of IS6110 change occurring during the process of transmission, M. tuberculosis isolates from epidemiologically linked patients were genotypically characterized by restriction fragment length polymorphism (RFLP) analysis. The identification of IS6110 banding pattern changes during ongoing transmission suggested that a rate could be estimated. IS6110 change was significantly associated with strains with >5 IS6110 elements (P = 0.013) and was not observed in low-copy-number isolates. The minimum rate of appearance of variant strains was calculated to be 0.14 variant cases per source-case per year. This data suggest that clustering of isolates based on identical RFLP patterns is expected to underestimate transmission in patients infected with high-copy-number isolates. A model based on the rate of appearance of both variant and invariant strains demonstrates that the genotypically defined population structure may change by 18.6% during the study period of approximately 6.5 years. The implications for the use of RFLP data for epidemiologic study are discussed.


5758.      Warren RM, van der Spuy GD, Richardson M, Beyers N, Borgdorff MW, Behr MA, van Helden PD.  Calculation of the stability of the IS6110 banding pattern in patients with persistent Mycobacterium tuberculosis disease. J Clin Microbiol. 2002 May;40(5):1705-8.


The interpretation of molecular epidemiologic data of Mycobacterium tuberculosis infection is dependent on the understanding of the stability and evolutionary characteristics of the DNA fingerprinting marker used to classify clinical isolates. This study investigated the stability of the IS6110 banding pattern in serial tuberculosis isolates collected from patients resident in an area with a high incidence of tuberculosis. Evolutionary changes were observed in 4% of the strains, and a half-life (t(1/2)) of 8.74 years was calculated, assuming a constant rate of change over time. This rate may be composed of a high rate of change seen during the early disease phase (t(1/2) = 0.57 years) and a low rate of change seen in the late disease phase (t(1/2) = 10.69 years). The early rate probably reflects change occurring during active growth prior to therapy, while the low late rate may reflect change occurring during or after treatment. We demonstrate that the calculation of these rates is strongly influenced by the time interval between onset of disease and sputum sampling. These calculations are further complicated by partial replacement of the original strain population, resulting in the sporadic appearance of clonal variants in sputum specimens. Therefore, the true extent of genetic diversity may be underestimated within each host, thereby influencing molecular epidemiological data used to establish transmission chains.

5759.      Warren RM, van Helden PD. HIV-1 and tuberculosis infection. Lancet. 2002 May 4;359(9317):1618-9; discussion 1619-20.  No abstract.

5760.      Zumla A, Grange J. Infection and disease caused by environmental mycobacteria. Curr Opin Pulm Med. 2002 May;8(3):166-72. Review.


Many species of mycobacteria that normally live as environmental saprophytes, the environmental mycobacteria (EM), are opportunist causes of disease in humans and animals. Many, but not all, cases are associated with some form of immune deficiency. An increasing number of species and clinical presentations are being described, and advances are being made in the understanding of the underlying predisposing factors. In recent years, four aspects of EM disease have become particularly relevant to human health: (1) the high prevalence of EM disease in patients with AIDS; (2) the emergence of Buruli ulcer, an ulcerative skin disease caused by Mycobacterium ulcerans, as the third most prevalent mycobacterial disease; (3) the effect of infection by EM on the immune responses to BCG vaccination and on the course and outcome of tuberculosis and leprosy; (4) the controversy over the involvement of mycobacteria, notably M. avium subspecies paratuberculosis, in human inflammatory bowel disease. These aspects change the status of EM from mere curiosities to important direct, indirect, and putative causes of serious and increasingly common human disease.



5761.      Elloumi-Zghal H, Barbouche MR, Chemli J, Bejaoui M, Harbi A, Snoussi N, Abdelhak S, Dellagi K.  Clinical and genetic heterogeneity of inherited autosomal recessive susceptibility to disseminated Mycobacterium bovis bacille calmette-guerin infection. J Infect Dis. 2002 May 15;185(10):1468-75.

Five patients from 4 unrelated Tunisian families who presented with disseminated neonatal infection by Mycobacterium bovis bacille Calmette-Guerin strain were investigated. Two unrelated patients had different homozygous interleukin-12 receptor beta1 subunit gene splice-site mutations (64+5G-->A and 550-2A-->G). Two siblings and 1 unrelated patient, all of whom were from the same town, carried the same mutation (297del8) within the interleukin-12p40 gene. This is the first description of familial cytokine deficiency reported so far. All patients had complete lack of expression of the affected polypeptide and a profound deficiency of in vitro interferon-gamma production. The clinical severity of the mycobacterial infection was heterogeneous, even among affected members of the same family, which suggests the intervention of modifying genes.


5762.      Maartens G. Advances in adult pulmonary tuberculosis. Curr Opin Pulm Med. 2002 May;8(3):173-7. Review.


The immune response is able to contain but not eliminate Mycobacterium tuberculosis. Antigens that are specific to M. tuberculosis can identify latent infection accurately even after BCG vaccination. Genes that are required for persistence of the organism have been identified and new drugs are being developed to disrupt their function. This offers the hope of shortened courses of therapy. New drugs are urgently needed for multidrug-resistant tuberculosis, particularly as some areas are reporting a high prevalence of fluoroquinolone resistance. The sputum smear is the standard rapid diagnostic test for pulmonary tuberculosis, but is frequently negative in HIV infection. The yield of smear can be increased by sputum induction and by concentration. Innovative methods of providing directly observed therapy have been devised. Preventive therapy is effective in HIV infection and probably improves survival. However, the duration of benefit of preventive therapy seems to be relatively short-lived. Effective long-term reduction of tuberculosis risk in HIV-infected patients can be achieved with highly active antiretroviral therapy.


5763.      Schaaf HS, Gie RP, Kennedy M, Beyers N, Hesseling PB, Donald PR. Evaluation of young children in contact with adult multidrug-resistant pulmonary tuberculosis: a 30-month follow-up. Pediatrics. 2002 May;109(5):765-71.


SETTING: The Western Cape Province of South Africa, an area with a high tuberculosis (TB) incidence, where initial multidrug resistance (MDR) among adult TB cases was 1.1% during 1992-1993. OBJECTIVE: To determine the long-term prevalence of TB infection and disease in children in household contact with adults with MDR pulmonary TB, and to establish the efficacy of chemoprophylaxis in preventing disease in these children. METHOD: Children <5 years old in contact with 73 MDR TB adults were evaluated. Disease was treated by prescribing at least 2 drugs to which the adult's strain was susceptible. The remaining children were classified as infected or noninfected and received chemoprophylaxis according to the index's strain susceptibility or were followed up and treated when indicated. All were followed up for 30 months. RESULTS: At the initial evaluation 125 children were seen, median age 27.5 months. Of these, 119 were followed up. Fourteen (12%) had disease, 61 (51%) were infected only, and 44 (37%) were noninfected. By 30-month follow-up, 29 (24%) had developed disease and 64 (54%) were infected only. Four adult-child pair Mycobacterium tuberculosis isolates were compared by DNA fingerprinting; 3 were identical. All children who developed TB disease were clinically cured. Two (5%) of 41 children who received appropriate chemoprophylaxis and 13 (20%) of 64 who did not, developed TB during follow-up (odds ratio: 4.97). CONCLUSION: The study confirms MDR TB transmission to childhood contacts. Seventy-eight percent of children were infected or developed disease. Appropriate chemoprophylaxis may prevent disease in these children.

5764.      Tuli SM. General principles of osteoarticular tuberculosis. Clin Orthop. 2002 May;(398):11-9. Review.


Since approximately 1985, with the pandemic of the human immunodeficiency virus and with the increase in the number of people who are immunocompromised, there is a resurgence of tuberculosis worldwide. The diagnosis in endemic areas generally can be made on clinical and radiologic examinations. However, whenever there is doubt because of an atypical clinical presentation or lack of clinical exposure, tissue diagnosis is mandatory. If osteoarticular tuberculosis is diagnosed and treated at an early stage, approximately 90% to 95% of patients would achieve healing with near normal function. The mainstay of treatment is multidrug antituberculous chemotherapy (for 12 to 18 months) and active - assisted non- eightbearing exercises of the involved joint throughout the period of healing. Operative intervention is required when the patient is not responding after 4 to 5 months of chemotherapy (synovectomy and debridement), the therapeutic outcome is not satisfactory (excisional arthroplasty for the hip or the elbow), or the healed status has resulted in a painful ankylosis (arthrodesis for the ankle, the wrist, or the knee). Joint replacement may be considered if the disease has remained inactive for 10 years or more. Multidrug resistance should be suspected if the activity of disease does not subside after 4 to 6 months of uninterrupted multidrug therapy. Such patients (5% to 10%) present a desperate therapeutic challenge. Second-line and potential antitubercular drugs, and possible immunomodulations may control such a disease.


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