(Diagnosis, Diagnostics, Immunodiagnosis, Immunodiagnostics, Pathogenesis,  Vaccines & Drugs)


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1441. Al-Marri MR.  Kirkpatrick MB. Erythrocyte sedimentation rate in childhood tuberculosis: is it still worthwhile?. International Journal of Tuberculosis & Lung Disease.  4(3):237-9, 2000  Mar.


OBJECTIVE: To evaluate the utility of the erythrocyte sedimentation rate  (ESR) in the diagnosis of childhood tuberculosis. DESIGN: Data were  collected retrospectively from the Qatar National Tuberculosis (TB)  Registry for children (birth to 14 years of age) from 1983 to 1996. The  diagnosis of active tuberculosis was based on positive sputum cultures (or  histology) or an abnormal chest radiograph that responded to  anti-tuberculosis chemotherapy. RESULTS: Of 144 childhood TB patients, 68  (47%) had an ESR documented at the time of diagnosis. Twenty-two children  (33%) had a normal ESR (<10 mm/hour) and 46 children (67%) had an elevated  ESR (> or =10 mm/hour) at the time of diagnosis. Culture positive and  symptomatic children had significantly higher ESR values than culture  negative and asymptomatic children, respectively, at the time of  diagnosis. There was no significant difference in ESR values for children  with extrapulmonary versus pulmonary disease, and likewise no significant  correlation between either age or size of tuberculin skin test reactivity  and ESR values. CONCLUSION: Although an elevated ESR may be expected in  children with tuberculosis, this study found that one-third of children  with TB had a normal ESR at the time of diagnosis, and consequently there  would seem to be little value in using ESR as a diagnostic test for childhood tuberculosis.


1442. Amaral L.  Kristiansen JE. Phenothiazines: an alternative to conventional therapy for the initial management of suspected multidrug resistant tuberculosis. A call for  studies. [Review] [26 refs] International Journal of Antimicrobial Agents.  14(3):173-6, 2000 Apr.


Increased frequency of multidrug resistant strains of Mycobacterium  tuberculosis results from inappropriate treatment and lack of patient  compliance. The Center for Disease Control/American Thoracic Society  (CDC/ATS) guidelines issued for the management of newly diagnosed cases of  tuberculosis (TB) will not be totally effective regardless of adherence to the guidelines and patient cooperation. The long interim period between the diagnosis of TB and confirmation of antibiotic susceptibility contributes to the infection rate. Consequently, the use of an adjuvant that is known to inhibit all encountered multidrug resistant strains of M. tuberculosis may be helpful until antibiotic susceptibility is known. Phenothiazines such as chlorpromazine, methdilazine and thioridazine are effective against strains of M. tuberculosis in vitro and in vivo. It is recommended that studies be designed and conducted for the purpose of managing new cases of TB that emanate from areas known to harbour  multidrug resistant strains of M. tuberculosis, with phenothiazines as  adjuvants to the regimen recommended by the CDC/ATS guidelines until  antibiotic susceptibility is defined. Because the normal maximum period  for obtaining conventional antibiotic susceptibility results is less than  7 or 8 weeks, the probability of serious side effects from the use of a  phenothiazine is remote. [References: 26]


1443. Arend SM.  Andersen P.  van Meijgaarden KE.  Skjot RL.  Subronto YW.  van  Dissel JT.  Ottenhoff TH. Detection of active tuberculosis infection by T cell responses to early-secreted antigenic target 6-kDa protein and culture filtrate protein 10. Journal of Infectious Diseases.  181(5):1850-4, 2000 May.


The purified protein derivative (PPD) skin test has no predictive value  for tuberculosis (TB) in Mycobacterium bovis bacillus Calmette-Guerin  (BCG)-vaccinated individuals because of cross-reactive responses to  nonspecific constituents of PPD. T cell responses to early-secreted  antigenic target 6-kDa protein (ESAT-6) and the newly identified culture  filtrate protein 10 (CFP-10), 2 proteins specifically expressed by M.  tuberculosis (MTB) but not by BCG strains, were evaluated. Most TB  patients responded to ESAT-6 (92%) or CFP-10 (89%). A minority of  BCG-vaccinated individuals responded to both ESAT-6 and CFP-10, their  history being consistent with latent infection with MTB in the presence of  protective immunity. No responses were found in PPD-negative controls. The  sensitivity and specificity of the assay were 84% and 100%, respectively,  at a cutoff of 300 pg of interferon-gamma/mL. These data indicate that  ESAT-6 and CFP-10 are promising antigens for highly specific  immunodiagnosis of TB, even in BCG-vaccinated individuals.



1444. Arend SM.  Geluk A.  van Meijgaarden KE.  van Dissel JT.  Theisen M.  Andersen P.  Ottenhoff TH. Antigenic equivalence of human T-cell responses to Mycobacterium  tuberculosis-specific RD1-encoded protein antigens ESAT-6 and culture  filtrate protein 10 and to mixtures of synthetic peptides. Infection & Immunity.  68(6):3314-21, 2000 Jun.


The early secreted antigenic target 6-kDa protein (ESAT-6) and culture  filtrate protein 10 (CFP-10) are promising antigens for reliable  immunodiagnosis of tuberculosis. Both antigens are encoded by RD1, a  genomic region present in all strains of Mycobacterium tuberculosis and M.  bovis but lacking in all M. bovis bacillus Calmette-Guerin vaccine  strains. Production and purification of recombinant antigens are laborious  and costly, precluding rapid and large-scale testing. Aiming to develop  alternative diagnostic reagents, we have investigated whether recombinant  ESAT-6 (rESAT-6) and recombinant CFP-10 (rCFP-10) can be replaced with  corresponding mixtures of overlapping peptides spanning the complete amino  acid sequence of each antigen. Proliferation of M. tuberculosis-specific  human T-cell lines in response to rESAT-6 and rCFP-10 and that in response  to the corresponding peptide mixtures were almost completely correlated (r  = 0.96, P < 0.0001 for ESAT-6; r = 0.98, P < 0.0001 for CFP-10). More  importantly, the same was found when gamma interferon production by  peripheral blood mononuclear cells in response to these stimuli was  analyzed (r = 0.89, P < 0.0001 for ESAT-6; r = 0.89, P < 0.0001 for  CFP-10). Whole protein antigens and the peptide mixtures resulted in  identical sensitivity and specificity for detection of infection with M.  tuberculosis. The peptides in each mixture contributing to the overall  response varied between individuals with different HLA-DR types.  Interestingly, responses to CFP-10 were significantly higher in the  presence of HLA-DR15, which is the major subtype of DR2. These results  show that mixtures of synthetic overlapping peptides have potency  equivalent to that of whole ESAT-6 and CFP-10 for sensitive and specific  detection of infection with M. tuberculosis, and peptides have the  advantage of faster production at lower cost.




1445. Arora SK.  Kumar B.  Sehgal S. Development of a polymerase chain reaction dot-blotting system for detecting cutaneous tuberculosis. British Journal of Dermatology.  142(1):72-6, 2000 Jan.


For a definitive diagnosis of cutaneous tuberculosis the demonstration of  mycobacteria is essential, but this is generally not possible in skin  lesions. Routinely available techniques have poor sensitivity and are time  consuming, therefore, delaying the institution of timely therapy. The high  sensitivity and speed of polymerase chain reaction (PCR) for the detection  of infectious agents has prompted investigators to use this technique for  the detection of Mycobacterium tuberculosis in body fluids such as  cerebrospinal fluid or pleural fluid. In the present study, PCR was used  to examine punch biopsy specimens from the affected skin of 10 patients  with clinical diagnoses of tuberculosis verrucosa cutis, lupus vulgaris,  scrofuloderma, papulonecrotic tuberculide and erythema induratum. A  control group of 20 patients included individuals having skin  manifestations with definite clinical diagnoses other than cutaneous  tuberculosis, such as leprosy, fungal mycetoma, chronic bullous disease of  childhood and pemphigus vulgaris. The PCR amplified products were dot  hybridized with a probe which was random prime labelled with 32P. The  results were compared with routine microbiological and histological  findings. Among the test group, six of 10 (60%) were positive for M. tuberculosis by PCR, although their histopathology showed non-specific  chronic inflammation with no definite diagnosis. Microbiological  investigations, including acid-fast bacillus smear and culture, were  positive in a single case of scrofuloderma. All patients in the control  group were negative by PCR for M. tuberculosis. The data indicate that the  combination of dot hybridization with PCR markedly increased the  sensitivity and specificity of PCR. This may be a useful tool in the  diagnosis of tuberculosis when conventional methods fail.


1446. Baron JH. Inflammatory bowel disease up to 1932. Mount Sinai Journal of Medicine.  67(3):174-89, 2000 May.


Inflammatory bowel diseases have been a major interest of generations of  Mount Sinai Hospital gastroenterologists. Although clinical descriptions  of diarrhea with or without blood go back thousands of years, clear  distinctions between enteritis and ulcerative colitis were possible only  in the 19th century. At that time, many case reports were published of, in  retrospect, classical regional enteritis. The term "ulcerative colitis"  dates from 1888; the introduction of the electric sigmoidoscope soon after  made it possible to make proper diagnosis of ulcerative colitis and  distinguish it from infective dysentery, membranous mucous or catarrhal  colitis, and nervous diarrhea. Doctors at The Mount Sinai Hospital adopted  this diagnostic approach in the 1870s and 1880s, and were particularly  interested in patients with tuberculosis-like ileocecal disease without  tubercle bacilli. Articles were written by Weiner in 1914, Moschcowitz and  Wilensky in 1923 and 1927, and Goldfarb and Suissman in 1931. Dr. A.A.  Berg, in 1925, encouraged his assistant Leon Ginzburg to conduct a study  of the inflammatory granulomatous diseases of the bowel, when Ginzburg and  Gordon Oppenheimer were working in Dr. Paul Klemperer's laboratory.  Initial reports came in 1927 and 1928, but Ginzburg and Oppenheimer "in  conjunction with Dr. Burrill B. Crohn" presented a definitive paper,  "Non-specific Granulomata of the Intestine," on May 2, 1932, to the  American Gastro-Enterological Association. On May 13, 1932, Dr. Crohn  presented a paper on "Terminal Ileitis" to the American Medical  Association; this was published later that year with the title "Regional  Ileitis: A Pathologic and Chronic Entity," under the authorship of Crohn,  Ginzburg and Oppenheimer.


1447. Bastian I.  Rigouts L.  Van Deun A.  Portaels F. Directly observed treatment, short-course strategy and multidrug-resistant tuberculosis: are any modifications required?. Bulletin of the World Health Organization.  78(2):238-51, 2000.


Multidrug-resistant tuberculosis (MDRTB) should be defined as tuberculosis with resistance to at least isoniazid and rifampicin because these drugs are the cornerstone of short-course chemotherapy, and combined isoniazid  and rifampicin resistance requires prolonged treatment with second-line agents. Short-course chemotherapy is a key ingredient in the tuberculosis control strategy known as directly observed treatment, short-course (DOTS). For populations in which multidrug-resistant tuberculosis is endemic, the outcome of the standard short-course chemotherapy regimen remains uncertain. Unacceptable failure rates have been reported and resistance to additional agents may be induced. As a consequence there have been calls for well-functioning DOTS programmes to provide additional services in areas with high rates of multidrug-resistant tuberculosis.  These "DOTS-plus for MDRTB programmes" may need to modify all five  elements of the DOTS strategy: the treatment may need to be individualized  rather than standardized; laboratory services may need to provide  facilities for on-site culture and antibiotic susceptibility testing;  reliable supplies of a wide range of expensive second-line agents would  have to be supplied; operational studies would be required to determine  the indications for and format of the expanded programmes; financial and  technical support from international organizations and Western governments  would be needed in addition to that obtained from local governments.


1448.  Becerra MC.  Bayona J.  Freeman J.  Farmer PE.  Kim JY. Redefining MDR-TB transmission 'hot spots'. International Journal of Tuberculosis & Lung Disease.  4(5):387-94, 2000  May.


  Halting further spread of multidrug-resistant tuberculosis (MDR-TB)

  requires both new resources and a renewed discussion of priority setting

  informed by estimates of the existing burden of this disease. The 1997

  report of the first phase of the global survey by the World Health

  Organization (WHO) and the International Union Against Tuberculosis and

  Lung Disease (IUATLD) uses the indicator of the proportion of TB cases

  that are MDR-TB to identify MDR-TB 'hot spots'. We sought to refine the

  definition of MDR-TB transmission 'hot spots'. For this purpose, we

  obtained estimates of two additional indicators for regions where data are

  available: MDR-TB incidence per 100,000 population per year, and expected

  numbers of new patients with MDR-TB per year. There is generally much

  agreement in the three indicators considered, and some differences also

  appear. We conclude that it is useful, when defining indicators of MDR-TB

  transmission 'hot spots', to include estimates of underlying TB incidence

  rates and of absolute numbers of MDR-TB cases. Estimating the force of

  morbidity of MDR-TB in a population is important for comparing this burden

  across settings with very different underlying TB incidence rates;

  estimating the absolute number of MDR-TB patients will be critical for

  planning the delivery of directly observed MDR-TB therapy and the rational

  procurement of second-line drugs. Through this exercise, we aim to

  initiate discussion about improved methods of quantifying and comparing

  current MDR-TB transmission 'hot spots' that require intervention.



1449. Benakappa A.  Benakappa N.  Benakappa DG. Management of tuberculosis.  Indian Journal of Pediatrics.  62(5):557-63, 1995 Sep-Oct.


  Tuberculosis is a common disease in children but it is highly mismanaged.

  It is bound to be triggered off by HIV infection in the near future. The

  importance of HIV and TB has become apparent from the high incidence of

  disease caused by mycobacteria in AIDS patients. The injudicious use of

  needles and syringes should be discouraged in high HIV prevalence

  countries. Multiple drug resistant tuberculosis is emerging as one of the

  most important problems in medical history. It is often created by health

  workers who administer anti-TB drugs improperly. The diagnostic aspects

  and treatment are discussed.


1450. Bleed D.  Dye C.  Raviglione MC. Dynamics and control of the global tuberculosis epidemic. [Review] [42 refs] Current Opinion in Pulmonary Medicine.  6(3):174-9, 2000 May.


  Studies of disease burden have reaffirmed that tuberculosis is among the

  top 10 causes of death in the world. The tuberculosis epidemic in most

  countries could eventually be brought under control by implementing the

  World Health Organization's (WHO) directly observed therapy, short course

  (DOTS) strategy, although tuberculosis linked to human immunodeficiency

  virus (HIV) in Africa and multidrug-resistant tuberculosis (MDR-TB) in the

  former Soviet Union urgently demand adaptations and extensions of DOTS.

  Most high-incidence countries have achieved treatment success rates

  approaching the WHO 85% target in pilot projects. In the long term, we may

  have better diagnostics, drugs, and vaccines to control the disease; for

  the next 5 years, the central problem in global tuberculosis control is to

  expand DOTS coverage in high-incidence countries. Improved case finding

  and diagnosis, coupled with best-practice short-course chemotherapy, could

  quickly and dramatically cut the number of years of healthy life lost due

  to tuberculosis, especially by preventing death. [References: 42]



1451. Bungay HK.  Adams RF.  Morris CM.  Haggett PJ.  Traill ZC.  Gleeson FV.  Cutting needle biopsy in the diagnosis of clinically suspected non-carcinomatous disease of the lung. British Journal of Radiology.  73(868):349-55, 2000 Apr.


  Most patients referred for lung biopsy have a focal lesion that is likely

  to be a carcinoma, and fine needle aspiration is usually sufficient to

  confirm the diagnosis. When non-carcinomatous disease is suspected, tissue

  architecture is important and potential diagnostic techniques include

  percutaneous cutting needle biopsy (CNB). We retrospectively reviewed 37

  CNBs performed for clinically suspected non-carcinomatous disease;

  recording the biopsy result, final diagnosis, radiological nature of the

  pulmonary abnormality, distance from the pleura of the lesion biopsied and

  biopsy complications. 9 patients had a single pulmonary nodule/mass; 13

  had multiple nodules/masses; 8 had a lobar consolidation/mass; and 7 had

  multifocal consolidation. The lesion abutted the pleura in 31 cases, lying

  within 1 cm in the other 6 cases. The minor complication rate was 14%,

  with no major complications. Specific malignant diagnoses were made in 9

  patients, and specific benign in 23, in all of whom clinicoradiological

  follow-up was concordant. CNB did not yield a specific diagnosis in five

  patients, including two lymphomas and one case of unsuspected tuberculosis

  in which the sample was not cultured. The overall accuracy of CNB was

  32/37 (86%). CNB is a safe and accurate means of achieving a tissue

  diagnosis for patients with peripheral pulmonary parenchymal disease

  thought not to represent carcinoma.


1452. Bustamante-Montes LP.  Escobar-Mesa A.  Borja-Aburto VH.  Gomez-Munoz A.  Becerra-Posada F. Predictors of death from pulmonary tuberculosis: the case of Veracruz, Mexico. International Journal of Tuberculosis & Lung Disease.  4(3):208-15, 2000  Mar.


  OBJECTIVES: To identify factors (particularly social, economic and

  cultural), associated with the risk of death from pulmonary tuberculosis

  in Mexico. METHODS: A case-control study of patients receiving medical

  attention from the official health services of Veracruz, Mexico. Cases

  were deaths from pulmonary tuberculosis in 1993. Controls were survivors

  randomly selected from the State Tuberculosis Case Registry. Next of kin

  provided information for both cases and controls. RESULTS: Multivariate

  analysis of 161 cases and 161 controls showed an increased risk of dying

  for those patients who withdrew from treatment (odds ratio [OR] = 3.52),

  who were refused medical attention during some period of time in any

  health center (OR = 4.45), and who had a concomitant disease at the time

  of diagnosis (OR = 2.62). A linear trend with age was observed (OR = 1.02

  per year), as well as a lower risk for those patients who were compliant

  with treatment and optimistic about surviving the disease (OR = 0.17). The

  risk of death was not associated with the presence of a health care unit

  in the town, time spent to get to the health center, or the residence of a

  patient in an urban area. CONCLUSIONS: These findings indicate that deaths

  due to tuberculosis in this area are not related to the geographical

  distribution of health services but to delays in treatment after the onset

  of disease and to the low adherence of patients to the treatment regimen.



1453. Chanteau S.  Rasolofo V.  Rasolonavalona T.  Ramarokoto H.  Horn C.   Auregan G.  Marchal G. 45/47 kilodalton (APA) antigen capture and antibody detection assays for the diagnosis of tuberculosis. International Journal of Tuberculosis & Lung Disease.  4(4):377-83, 2000  Apr.


  SETTING: APA complex (45/47 kDa) is an antigen specifically excreted by

  Mycobacterium tuberculosis and could therefore be a good candidate for

  diagnosis. OBJECTIVES: To develop three APA immunocapture ELISA assays

  using monoclonal antibodies (Mabs) and one IgG anti-APA ELISA test, and to

  determine their usefulness for the diagnosis of tuberculosis in

  Madagascar. DESIGN: For the Ag assays, 23 negative sputum and serum

  samples and 64 pairs of sputum and serum from active smear-positive

  patients (PTM+) were tested. For antibody assay, 116 negative controls,

  143 PTM+ and 54 extra-pulmonary tuberculosis patients were tested.

  RESULTS: The sensitivities of the APA antigen detection assays were low

  (less than 40%) for a specificity of 95.6%, using either monoclonal

  antibodies or clinical specimens. The anti-APA serology was more sensitive

  (76.9% for PTM+ patients) but less specific (73.2%). Due to their poor

  predictive values, these tests cannot be recommended for the routine

  diagnosis of tuberculosis in Madagascar.



1454. Char G.  Morgan OS. Tuberculous encephalopathy. A rare complication of pulmonary tuberculosis. West Indian Medical Journal.  49(1):70-2, 2000 Mar.


  A case of tuberculous encephalopathy, a rare form of neuro-tuberculosis,

  is reported in a 16-year-old girl who had pulmonary tuberculosis and

  extensive cerebral demyelination. The clinical, laboratory and

  pathological features of this entity are highlighted and the pathogenesis




1455. Churchyard GJ.  Corbett EL.  Kleinschmidt I.  Mulder D.  De Cock KM.

Drug-resistant tuberculosis in South African gold miners: incidence and  associated factors. International Journal of Tuberculosis & Lung Disease.  4(5):433-40, 2000  May.


SETTING: A gold mining company in the Free State Province of South Africa.

  OBJECTIVE: To document the incidence of and factors associated with

  drug-resistant tuberculosis (TB) in South African gold miners. DESIGN:

  Review of Mycobacterium tuberculosis drug susceptibility records for the

  period from 1 July 2023 to 30 June 1997. RESULTS: Over the study period,

  2241 miners had culture-positive M. tuberculosis pulmonary disease where

  isolates were tested for drug susceptibility to the four primary

  anti-tuberculosis drugs. The proportions of primary and acquired drug

  resistance were respectively 7.3% and 14.3% for isoniazid and 1.0% and

  2.8% for resistance to at least isoniazid and rifampicin (multidrug

  resistance). Resistance to streptomycin and ethambutol was uncommon, and

  rifampicin monoresistance was rare. No significant factors for primary

  drug resistance were identified. Patients with retreatment pulmonary TB

  who failed primary TB treatment (versus cure) were significantly more

  likely to have TB with resistance to any TB drug or MDR (odds ratios

  respectively 9.82, 95%CI 2.97-33.5, and 18.74, 95%CI 1.76-475). Human

  immunodeficiency virus (HIV) infection was not significantly associated

  with primary or acquired drug resistance, and there was no trend of

  increasing resistance over time. CONCLUSION: Anti-tuberculosis drug

  resistance has remained stable despite the HIV epidemic and increasing TB

  rates. Directly observed therapy may have contributed to containing the

  level of drug resistance. Adherence to and completion of treatment are

  essential to prevent drug resistance and treatment failure, including in

  situations with high HIV prevalence.



1456. Delogu G.  Howard A.  Collins FM.  Morris SL. DNA vaccination against tuberculosis: expression of a ubiquitin-conjugated tuberculosis protein enhances antimycobacterial immunity. Infection & Immunity.  68(6):3097-102, 2000 Jun.


  Genetic immunization is a promising new technology for developing vaccines

  against tuberculosis that are more effective. In the present study, we

  evaluated the effects of intracellular turnover of antigens expressed by

  DNA vaccines on the immune response induced by these vaccines in a mouse

  model of pulmonary tuberculosis. The mycobacterial culture filtrate

  protein MPT64 was expressed as a chimeric protein fused to one of three

  variants of the ubiquitin protein (UbG, UbA, and UbGR) known to

  differentially affect the intracellular processing of the coexpressed

  antigens. Immunoblot analysis of cell lysates of in vitro-transfected

  cells showed substantial differences in the degradation rate of

  ubiquinated MPT64 (i.e., UbG64 < UbA64 < UbGR64). The specific immune

  response generated in mice correlated with the stability of the

  ubiquitin-conjugated antigen. The UbA64 DNA vaccine induced a weak humoral

  response compared to UbG64, and a mixed population of interleukin-4

  (IL-4)- and gamma interferon (IFN-gamma)-secreting cells. Vaccination with

  the UbGR64 plasmid generated a strong Th1 cell response (high IFN-gamma,

  low IL-4) in the absence of a detectable humoral response. Aerogenic

  challenge of vaccinated mice with Mycobacterium tuberculosis indicated

  that immunization with both the UbA64- and UbGR64-expressing plasmids

  evoked an enhanced protective response compared to the vector control. The

  expression of mycobacterial antigens from DNA vaccines as fusion proteins

  with a destabilizing ubiquitin molecule (UbA or UbGR) shifted the host

  response toward a stronger Th1-type immunity which was characterized by

  low specific antibody levels, high numbers of IFN-gamma-secreting cells,

  and significant resistance to a tuberculous challenge.




1457. Divya Jyothi M.  Garg SK.  Singh NB. Mechanisms involved in protective immune response generated by secretory proteins of Mycobacterium habana against experimental tuberculosis. Scandinavian Journal of Immunology.  51(5):502-10, 2000 May.


  Live mycobacteria secrete a number of unique proteins early in their

  multiplication which are important for both the pathogenesis and the

  stimulation of specific host responses. We have investigated the

  mechanisms by which the host mounts immune response against tuberculosis

  after vaccination with secretory proteins (SP) of a vaccine candidate

  Mycobacterium habana TMC 5135. Mice vaccinated with SP of 10th day growth

  of M. habana, either alone or emulsified in Freund's incomplete adjuvant

  (FIA) possessed antituberculous resistance and cellular immune responses

  against M. tuberculosis H37Rv. These proteins induced a significant

  cutaneous delayed type hypersensitivity response in guinea pigs vaccinated

  with heat killed M. tuberculosis H37Rv, which was equivalent to that

  observed with a standard purified protein derivative (PPD). The

  splenocytes of these guinea pigs have shown higher proliferative response

  after stimulation with SP than with PPD. The SP + FIA immunization has

  been found to exert maximum prophylactic effect by potentiating both the

  oxygen dependent arms and enzymatic activities of macrophages. Macrophages

  from mice vaccinated with SP of M. habana produced enhanced levels of

  interleukin(IL)-2, interleukin-12 and interferon(IFN)-gamma. The

  protective as well as cell mediated immune responses were upregulated in

  SP immunized animals when compared to whole cell (M. habana) vaccinated

  animals. SDS-PAGE of SP from M. habana showed the prominent bands of 60,

  32, 31 and 30 kDa. Furthermore, the western analysis of SP with pulmonary

  tuberculosis patient's serum has revealed the presence of immunoreactive

  antigens of 36, 35, 33/32 kDa. Overall study demonstrated that the

  secretory antigens released by actively growing M. habana bacilli could

  activate different arms of effective immune response.



1458. Doherty TM.  Andersen P. Tuberculosis vaccines: developmental work and the future. [Review] [74  refs] Current Opinion in Pulmonary Medicine.  6(3):203-8, 2000 May.


  The last year in tuberculosis vaccine research has witnessed the initial

  flowering of the benefits promised by the tuberculosis genome sequencing

  product. Although the real benefits in terms of clinical treatments are

  yet to be realized, genomics is making its presence felt in the rapid

  identification and expression of proteins with vaccine potential from

  Mycobacterium tuberculosis, the definition of species-specific antigens

  for diagnostic use, and the construction of a variety of novel living

  vectors for vaccination. At the same time, the recent increase in work on

  animal models with more direct applicability to the situations likely to

  be encountered in human vaccine trials are providing the basic

  underpinnings needed for the assessment of these new vaccines.

  [References: 74]



1459. Donald PR. Childhood tuberculosis. [Review] [39 refs] Current Opinion in Pulmonary Medicine.  6(3):187-92, 2000 May.


  Childhood tuberculosis will reflect the incidence of cavitating pulmonary

  tuberculosis in adults and will consequently be encountered most

  frequently in those areas with a high incidence of tuberculosis. Problem

  areas include our continuing inability to confirm the diagnosis of

  tuberculosis in many children, the escalating interaction of the human

  immunodeficiency virus (HIV) pandemic and tuberculosis, which is now

  evident with greater frequency in childhood, and the scarcity of data

  relating to antituberculosis therapy in childhood, which necessitates

  reliance on adult studies in many cases. This review highlights several

  options for obtaining material for culture of Mycobacterium tuberculosis

  in children, aspects of tuberculin testing, which remains one of the

  cornerstones supporting a diagnosis of tuberculosis in childhood, the

  potential importance of therapeutic drug monitoring in problem cases, new

  data giving epidemiologic and clinical details of the interaction of HIV

  infection and tuberculosis in children, and studies describing the

  epidemiology of tuberculosis in the developed and developing world.

  [References: 39]


1460. Elis A.  Mulchanov I.  Radnay J.  Shapiro H.  Lishner M. The diagnostic significance of polyclonal lymphocytosis in pleural  effusions. New Zealand Medical Journal.  113(1104):56-8, 2000 Feb 25.


  AIM: To evaluate the diagnostic contribution and clinical relevance of

  analysing subpopulations of lymphocytes in pleural effusions. METHODS:

  Forty patients (age >60 years) with newly diagnosed, polyclonal,

  lymphocyte-rich pleural effusions were evaluated. The following data were

  collected: demographic characteristics, associated diseases, fluid type,

  fluid white blood cells count, differential morphology and

  immunephenotyping, and final diagnosis. RESULTS: Of the 33 patients for

  whom biochemical data were available, 18 had exudative effusion, while 15

  had transudate. Thirty-three fluids contained mostly T cells and only one

  was B-cell rich. (The lymphocytes of five patients with malignant

  epithelial cells in the effusion were not subtyped.) Thirty-two of the 33

  T-cell rich fluids contained mainly CD4+ lymphocytes. The most common

  causes of pleural effusion were congestive heart failure (17 patients) and

  epithelial malignant diseases (eight patients), while none of the patients

  had tuberculosis. Since most effusions were CD4+ rich, no correlation

  could be detected between lymphocyte subtyping and diagnosis or the

  biochemical type of the fluids. Congestive heart failure was significantly

  associated with transudates, while malignant diseases correlated with

  exudates. CONCLUSIONS: Most patients with pleural polyclonal

  lymphocytosis, especially those with transudates, have congestive heart

  failure. The presence of exudative, lymphocyte-rich effusion is an

  indication for further evaluation, since it is most commonly associated

  with malignancy. The clinical value of lymphocyte subtyping is low and

  this procedure should not be used routinely.



1461. Espinal MA.  Kim SJ.  Suarez PG.  Kam KM.  Khomenko AG.  Migliori GB. Baez J.  Kochi A.  Dye C.  Raviglione MC. Standard short-course chemotherapy for drug-resistant tuberculosis: treatment outcomes in 6 countries [see comments].  JAMA.  283(19):2537-45, 2000 May 17.


  CONTEXT: No large-scale study has investigated the impact of

  multidrug-resistant tuberculosis (TB) on the outcome of standard

  short-course chemotherapy under routine countrywide TB control program

  conditions in the World Health Organization's (WHO) directly observed

  treatment short-course strategy for TB control. OBJECTIVE: To assess the

  results of treatment with first-line drugs for patients enrolled in the

  WHO and the International Union Against Tuberculosis and Lung Disease's

  global project on drug-resistance surveillance. DESIGN AND SETTING:

  Retrospective cohort study of patients with TB in the Dominican Republic,

  Hong Kong Special Administrative Region (People's Republic of China),

  Italy, Ivanovo Oblast (Russian Federation), the Republic of Korea, and

  Peru. PATIENTS: New and retreatment TB cases who received short-course

  chemotherapy with isoniazid, rifampicin, pyrazinamide, and either

  ethambutol or streptomycin between 1994 and 1996. MAIN OUTCOME MEASURE:

  Treatment response according to WHO treatment outcome categories (cured;

  died; completed, defaulted, or failed treatment; or transferred). RESULTS:

  Of the 6402 culture-positive TB cases evaluated, 5526 (86%) were new cases

  and 876 (14%) were retreatment cases. A total of 1148 (20.8%) new cases

  and 390 (44.5%) retreatment cases were drug resistant, including 184 and

  169 cases of multidrug-resistant TB, respectively. Of the new cases 4585

  (83%) were treated successfully, 138 (2%) died, and 151 (3%) experienced

  short-course chemotherapy failure. Overall, treatment failure (relative

  risk [RR], 15.4; 95% confidence interval [CI], 10.6-22.4; P<.001) and

  mortality (RR, 3.73; 95% CI, 2.13-6.53; P<.001) were higher among new

  multidrug-resistant TB cases than among new susceptible cases. Even in

  settings using 100% direct observation, cases with multidrug resistance

  had a significantly higher failure rate than those who were susceptible

  (9/94 [10%] vs 8/1410 [0.7%]; RR, 16.9; 95% CI, 6.6-42.7; P<.001).

  Treatment failure was also higher among patients with any rifampicin

  resistance (n=115) other than multidrug resistance (RR, 5.48; 95% CI,

  3.04-9.87; P<.001), any isoniazid resistance (n=457) other than multidrug

  resistance (RR, 3. 06; 95% CI, 1.85-5.05; P<.001), and among patients with

  TB resistant to rifampicin only (n=76) (RR, 5.47; 95% CI, 2.68-11.2;

  P<.001). Of the retreatment cases, 497 (57%) were treated successfully, 51

  (6%) died, and 124 (14%) failed short-course chemotherapy treatment.

  Failure rates among retreatment cases were higher in those with

  multidrug-resistant TB, with any isoniazid resistance other than multidrug

  resistance, and in cases with TB resistant to isoniazid only. CONCLUSIONS:

  These data suggest that standard short-course chemotherapy, based on

  first-line drugs, is an inadequate treatment for some patients with

  drug-resistant TB. Although the directly observed treatment short-course

  strategy is the basis of good TB control, the strategy should be modified

  in some settings to identify drug-resistant cases sooner, and to make use

  of second-line drugs in appropriate treatment regimens. JAMA.



1462. Faerman M.  Jankauskas R. Paleopathological and molecular evidence of human bone tuberculosis in Iron Age Lithuania. Anthropologischer Anzeiger.  58(1):57-62, 2000 Mar.


  Skeletal remains of two individuals, showing lesions suggestive of bone

  tuberculosis, from the archaeological sites of Marvele and Sukioniai in

  Lithuania were analyzed at the DNA level. The diagnosis of bone

  tuberculosis was confirmed in the remains from Marvele by amplifiying a

  245-bp fragment of a repetitive insertion element-like sequence (IS 6110)

  of Mycobacterium tuberculosis DNA. This is direct evidence for the

  presence of tuberculosis in Lithuania at the beginning of the first

  millennium AD. The individual from Sukioniai was found to be

  tuberculosis-negative. No PCR product was obtained for the 245-bp target

  sequence or for a smaller 123-bp DNA fragment specific for Mycobacterium

  tuberculosis. However, amplifiable ancient DNA appeared to be present in

  the examined specimen as was shown by the results of the DNA-based sex

  identification, which indicated, consistent with the bone morphology, a

  male individual.



1463. Furin JJ.  Becerra MC.  Shin SS.  Kim JY.  Bayona J.  Farmer PE. Effect of administering short-course, standardized regimens in individuals infected with drug-resistant Mycobacterium tuberculosis strains. European Journal of Clinical Microbiology & Infectious Diseases. 19(2):132-6, 2000 Feb.


  Presented here are the cases of three siblings with multidrug-resistant

  tuberculosis who demonstrated increased antituberculous-drug resistance

  during the periods in which they received standard regimens of directly

  observed, short-course chemotherapy that were administered before the

  susceptibility patterns of their Mycobacterium tuberculosis isolates had

  been checked. More specifically, they acquired resistance to drugs they

  received as part of ineffective standard treatment and retreatment

  regimens. Development of antituberculous-drug resistance through

  inadvertent, inadequate therapy appears to be the most likely explanation

  for the increased resistance seen in these three patients.


1464. No Abstract

1465. Garay JE. Analysis of a simplified concentration sputum smear technique for pulmonary tuberculosis diagnosis in rural hospitals. Tropical Doctor. 30(2):70-2, 2000 Apr.


  Rural hospitals in Africa face the challenge of an increasing number of

  pulmonary tuberculosis (PTB) cases, much of it related with the AIDS

  pandemic. The main diagnostic tool in these hospitals is the direct sputum

  smears. Sensitivity of direct sputum smears is low, especially in cases of

  AIDS related PTB. Several concentration methods have been described but

  none is routinely used in Zimbabwe. Fluorescence microscopy of auramine

  stained samples increases sensitivity and saves laboratory time but it is

  not an appropriate technique for rural African hospitals. In a rural

  hospital of southwest Zimbabwe, we studied the sensitivity and

  appropriateness of a simplified concentration method. The sensitivity

  against culture was significantly higher with the concentration method

  (80%) than with the classical direct smear method (57%). However, when

  sputum is not adequate (with high number of squamous epithelial cells,

  meaning upper airway origin), the sensitivity of this method is low. A

  combination of both methods is proposed to increase the sensitivity of PTB

  diagnosis in rural hospitals.


1466. Glickman MS.  Cox JS.  Jacobs WR Jr. A novel mycolic acid cyclopropane synthetase is required for coding, persistence, and virulence of Mycobacterium tuberculosis. Molecular Cell.  5(4):717-27, 2000 Apr.


  Colonial morphology of pathogenic bacteria is often associated with

  virulence. For M. tuberculosis, the causative agent of tuberculosis (TB),

  virulence is correlated with the formation of serpentine cords, a

  morphology that was first noted by Koch. We identified a mycobacterial

  gene, pcaA, that we show is required for cording and mycolic acid

  cyclopropane ring synthesis in the cell wall of both BCG and M.

  tuberculosis. Furthermore, we show that mutants of pcaA fail to persist

  within and kill infected mice despite normal initial replication. These

  results indicate that a novel member of a family of cyclopropane

  synthetases is necessary for lethal chronic persistent M. tuberculosis

  infection and define a role for cyclopropanated lipids in bacterial




1467. Grange JM.  Zumla A. Advances in the management of tuberculosis: clinical trials and beyond. [Review] [23 refs] Current Opinion in Pulmonary Medicine.  6(3):193-7, 2000 May.


  Modern short-course treatment for tuberculosis is highly effective and

  cost-effective, yet the disease remains a leading cause of suffering and

  death. The problem has been exacerbated in recent years by the human

  immunodeficiency virus (HIV) pandemic and the increasing prevalence of

  multidrug-resistant tuberculosis. Improvements in diagnosis, vaccination,

  chemoprophylaxis, and therapy are thus urgently needed. Molecular

  techniques are facilitating the development of rapid and sensitive

  diagnostic tests and the rational approach to the production of new

  vaccines. New forms of treatment are being investigated and there is also

  considerable emphasis on optimizing the deployment of the available

  treatment regimens. This has resulted in the World Health Organization's

  five-point directly observed therapy, short course (DOTS) strategy and

  proposed modifications (DOTS-plus) for the management of

  multidrug-resistant (MDR) tuberculosis. Despite these advances, it is

  becoming abundantly clear that the failure to control tuberculosis is a

  direct consequence of the gross inequities in the distribution of wealth

  and health care provision worldwide, which do not allow for putting

  advances in the management of tuberculosis into practice. The control of

  tuberculosis will therefore require attention to justice and human rights

  as well as greatly increased technical and financial support from the

  developed nations. [References: 23]


1468. No Abstract

1469. Gurunathan S.  Klinman DM.  Seder RA. DNA vaccines: immunology, application, and optimization*. [Review] [244 refs] Annual Review of Immunology.  18:927-74, 2000.


  The development and widespread use of vaccines against infectious agents

  have been a great triumph of medical science. One reason for the success

  of currently available vaccines is that they are capable of inducing

  long-lived antibody responses, which are the principal agents of immune

  protection against most viruses and bacteria. Despite these successes,

  vaccination against intracellular organisms that require cell-mediated

  immunity, such as the agents of tuberculosis, malaria, leishmaniasis, and

  human immunodeficiency virus infection, are either not available or not

  uniformly effective. Owing to the substantial morbidity and mortality

  associated with these diseases worldwide, an understanding of the

  mechanisms involved in generating long-lived cellular immune responses has

  tremendous practical importance. For these reasons, a new form of

  vaccination, using DNA that contains the gene for the antigen of interest,

  is under intensive investigation, because it can engender both humoral and

  cellular immune responses. This review focuses on the mechanisms by which

  DNA vaccines elicit immune responses. In addition, a list of potential

  applications in a variety of preclinical models is provided. [References:




1470.  Hadley M.  Maher D. Community involvement in tuberculosis control: lessons from other health care programmes. [Review] [46 refs] International Journal of Tuberculosis & Lung Disease.  4(5):401-8, 2000  May.


  Decentralising tuberculosis control measures beyond health facilities by

  harnessing the contribution of the community could increase access to

  effective tuberculosis care. This review of community-based health care

  initiatives in developing countries gives examples of the lessons for

  community contribution to tuberculosis control learned from health care

  programmes. Sources of information were Medline and Popline databases and

  discussions with community health experts. Barriers to success in

  tuberculosis control stem from biomedical, social and political factors.

  Lessons are relevant to the issues of limited awareness of tuberculosis

  and the benefits of treatment, stigma, restricted access to drugs,

  case-finding and motivation to continue treatment. The experience of other

  programmes suggests potential for an expansion of both formal and informal

  community involvement in tuberculosis control. Informal community

  involvement includes delivery of messages to encourage tuberculosis

  suspects to come forward for treatment and established tuberculosis

  patients to continue treatment. A wide range of community members provide

  psychological and logistic support to patients to complete their

  treatment. Lessons from formal community involvement indicate that

  programmes should focus on ensuring that treatment is accessible. This

  activity could be combined with a variety of complementary activities:

  disseminating messages to increase awareness and promote adherence,

  tracing patients who interrupt treatment, recognising adverse effects, and

  case detection. Programmes should generally take heed of existing

  political and cultural structures in planning community-based tuberculosis

  control programmes. Political support, the support of health professionals

  and the community are vital, and planning must involve or stem from the

  patients themselves. [References: 46]



1471. Hendrickson RC.  Douglass JF.  Reynolds LD.  McNeill PD.  Carter D.  Reed  SG.  Houghton RL. Mass spectrometric identification of mtb81, a novel serological marker for tuberculosis. Journal of Clinical Microbiology.  38(6):2354-61, 2000 Jun.


  We have used serological proteome analysis in conjunction with tandem mass

  spectrometry to identify and sequence a novel protein, Mtb81, which may be

  useful for the diagnosis of tuberculosis (TB), especially for patients

  coinfected with human immunodeficiency virus (HIV). Recombinant Mtb81 was

  tested by an enzyme-linked immunosorbent assay to detect antibodies in 25

  of 27 TB patients (92%) seropositive for HIV as well as in 38 of 67

  individuals (57%) who were TB positive alone. No reactivity was observed

  in 11 of 11 individuals (100%) who were HIV seropositive alone. In

  addition, neither sera from purified protein derivative (PPD)-negative (0

  of 29) nor sera from healthy (0 of 45) blood donors tested positive with

  Mtb81. Only 2 of 57 of PPD-positive individuals tested positive with

  Mtb81. Sera from individuals with smear-positive TB and seropositive for

  HIV but who had tested negative for TB in the 38-kDa antigen

  immunodiagnostic assay were also tested for reactivity against Mtb81, as

  were sera from individuals with lung cancer and pneumonia. Mtb81 reacted

  with 26 of 37 HIV(+) TB(+) sera (70%) in this group, compared to 2 of 37

  (5%) that reacted with the 38-kDa antigen. Together, these results

  demonstrate that Mtb81 may be a promising complementary antigen for the

  serodiagnosis of TB.



1472. Heymann SJ.  Brewer TF.  Ettling M. Effectiveness and cost of rapid and conventional laboratory methods for Mycobacterium tuberculosis screening.Source  Public Health Reports.  112(6):513-23, 1997 Nov-Dec.


  OBJECTIVE: Because delay in the diagnosis of tuberculosis (TB) contributes

  to the spread of disease and the associated mortality risk, the authors

  examined the effectiveness and cost of recent advances in methods of

  diagnosing TB and testing for drug susceptibility, comparing these rapid

  methods to traditional approaches. METHODS: Decision analysis was used to

  compare newer rapid and older nonrapid methods for diagnosing TB and

  testing for drug susceptibility. The average time to diagnosis, average

  time to treatment, average mortality, and cost of caring for patients

  evaluated for TB were compared. RESULTS: Using a combination of solid

  medium and broth cultures, nucleic acid probes for identification, and

  radiometric broth drug susceptibility testing would lead to diagnosis on

  average 15 days faster and to appropriate therapy on average five days

  sooner than methods currently employed by many U.S. laboratories. The

  average mortality would drop by five patients per 1000 patients evaluated

  (31%) and the average cost per patient would drop by $272 (18%).

  CONCLUSIONS: In this era of cost containment, it is important to

  incorporate test sensitivity and specificity when evaluating technologies.

  Tests with higher unit costs may lead to lower medical expenditures when

  diagnostic accuracy and speed are improved. U.S. laboratories should

  employ available rapid techniques for the diagnosis of TB.



1473. Hudson CP.  Wood R.  Maartens G. Diagnosing HIV-associated tuberculosis: reducing costs and diagnostic  delay. International Journal of Tuberculosis & Lung Disease.  4(3):240-5, 2000 Mar.


  SETTING: University-affiliated hospital in South Africa. OBJECTIVE: To

  assess the time to diagnosis and the yield and laboratory cost of

  diagnostic procedures in human immunodeficiency virus (HIV) associated

  tuberculosis. DESIGN: Cohort study. PATIENTS: Adult HIV-infected patients

  with newly-diagnosed tuberculosis admitted over a 2-year period. RESULTS:

  A total of 141 admissions fulfilled the case definition. Sputum smear

  yield (43% overall) correlated strongly with chest radiograph appearance

  but not with CD4+ lymphocyte count. Sputum smear yield was approximately

  40% per sample sent, resulting in a high cumulative yield when > or =

  three samples were sent. Smear of sputum or wide needle lymph node

  aspirates were the most cost-effective diagnostic methods. Significant

  diagnostic delay occurred in sputum smear-negative patients. Most patients

  with sputum smear-negative tuberculosis had either pleural effusions or

  lymphadenopathy. Lymph node biopsy had a high diagnostic yield even in

  patients with symmetrical nodes, but was under-utilised in this group.

  There was unnecessary expenditure on cultures, with many patients having

  several positive cultures. CONCLUSION: Repeated sputum smear examination

  produces a high cumulative yield in HIV-associated tuberculosis.

  Considerable savings in laboratory utilisation and bed occupancy would

  have been made if a streamlined diagnostic approach with greater use of

  lymph node aspirate and early pleural or lymph node biopsy had been




1474. Jasmer RM.  Edinburgh KJ.  Thompson A.  Gotway MB.  Creasman JM.  Webb WR.

Huang L.Clinical and radiographic predictors of the etiology of pulmonary nodules in HIV-infected patients. Chest.  117(4):1023-30, 2000 Apr.


  STUDY OBJECTIVES: To determine the etiology and the clinical and

  radiographic predictors of the etiology of pulmonary nodules in a group of

  HIV-infected patients. DESIGN: Retrospective analysis. SETTING: A large

  urban hospital in San Francisco, CA. PATIENTS: HIV-infected patients

  evaluated at San Francisco General Hospital from June 1, 1993, through

  December 31, 1997, having one or more pulmonary nodules on chest CT. Main

  outcome measures: Three physicians reviewed medical records for clinical

  data and final diagnoses. Three chest radiologists blinded to clinical

  data reviewed chest CTs. Univariate and multivariate analyses were

  performed to determine clinical and radiographic predictors of having an

  opportunistic infection and the specific diagnoses of bacterial pneumonia

  and tuberculosis. RESULTS: Eighty seven of 242 patients (36%) had one or

  more pulmonary nodules on chest CT. Among these 87 patients, opportunistic

  infections were the underlying etiology in 57 patients; bacterial

  pneumonia (30 patients) and tuberculosis (14 patients) were the most

  common infections identified. Multivariate analysis identified fever,

  cough, and size of nodules < 1 cm on chest CT as independent predictors of

  having an opportunistic infection. Furthermore, a history of bacterial

  pneumonia, symptoms for 1 to 7 days, and size of nodules < 1 cm on CT

  independently predicted a diagnosis of bacterial pneumonia; a history of

  homelessness, weight loss, and lymphadenopathy on CT independently

  predicted a diagnosis of tuberculosis. CONCLUSIONS: In HIV-infected

  patients having one or more pulmonary nodules on chest CT scan,

  opportunistic infections are the most common cause. Specific clinical and

  radiographic features can suggest particular opportunistic infections.


1475. Jerant AF.  Bannon M.  Rittenhouse S. Identification and management of tuberculosis [see comments]. American Family Physician.  61(9):2667-78, 2681-2, 2000 May 1.


  Although the resurgence of tuberculosis in the early 1990s has largely

  been controlled, the risk of contracting this disease remains high in

  homeless persons, recent immigrants and persons infected with the human

  immunodeficiency virus (HIV). Purified protein derivative testing should

  be targeted at these groups and at persons with known or suspected

  exposure to active tuberculosis. Most patients with latent tuberculosis

  are treated with isoniazid administered daily for nine months. In patients

  with active tuberculosis, the initial regimen should include four drugs

  for at least two months, with subsequent therapy determined by

  mycobacterial sensitivities and clinical response. To avoid harmful drug

  interactions, regimens that do not contain rifampin may be employed in

  HIV-infected patients who are taking protease inhibitors or nonnucleoside

  reverse transcriptase inhibitors. To maximize compliance and minimize the

  emergence of mycobacterial drug resistance, family physicians should

  consider using directly observed therapy in all patients with



1476. Jindal SK.  Gupta D. Algorithm for diagnosing pulmonary fibrosis in tropical countries. [Review] [44 refs] Current Opinion in Pulmonary Medicine.  4(5):294-9, 1998 Sep.


  An algorithm for diagnosis of pulmonary fibrosis in the tropical countries

  has been developed on the basis of the common causes of fibrosis, and the

  availability and feasibility of different diagnostic techniques in those

  countries. First, it is important to exclude common diseases such as the

  atypical or occult forms of bronchiectasis, pulmonary tuberculosis, and

  chronic bronchitis, which often overshadow interstitial pulmonary

  fibrosis. A good history and physical examination supplemented with chest

  radiography and simple lung function tests are generally enough to narrow

  down the list of causes of diffuse lung disease to interstitial pulmonary

  fibrosis. The real difficulty lies in identifying the idiopathic or "lone"

  forms from the secondary forms of pulmonary fibrosis. High-resolution CT

  is helpful in a large number of patients. Transbronchial lung biopsy is

  performed in a select population of patients. Open surgical or

  thoracoscopy guided biopsy is the gold standard, but is rarely required.

  [References: 44]



1477. Joshi S.  Malik S.  Kandoth PW. Diagnostic and therapeutic evaluation of bronchoscopy. Indian Journal of Pediatrics.  62(1):83-7, 1995 Jan-Feb.


  The diagnostic and therapeutic efficacy of bronchoscopy was determined in

  85 children. The major indications were foreign body removal in younger

  patients and evaluation of tracheobronchial pathology in older children.

  Foreign body was commonly isolated in the toddlers and even in the elder

  age group (19%) as well as in those with suspected ingestion (44%).

  Groundnut was the predominant foreign body and right bronchus was the most

  frequent site. Tracheobronchitis (27%), bronchiectasis (13%) endobronchial

  tuberculosis (9.4%) and mucus plug (3%) were the other frequent findings.

  Bronchography was performed in 16 patients and it confirmed the diagnosis

  in 75% of the cases. Minor complications were encountered in 8% of

  patients. In the present study bronchoscopy yielded definite results in

  83% and in many, including those with normal findings it guided further



1478. Kakkar S.  Kapila K.  Singh MK.  Verma K. Tuberculosis of the breast. A cytomorphologic study. Acta Cytologica.  44(3):292-6, 2000 May-Jun.


  OBJECTIVE: Extrapulmonary tuberculosis occurring in the breast is rare

  despite the fact that 1-2 billion people worldwide suffer from

  tuberculosis. The aim of this study was to examine the cytomorphology of

  breast tuberculosis (breast TB) and to review the literature. STUDY

  DESIGN: Old records from the Cytopathology Laboratory, All India Institute

  of Medical Sciences, were reviewed from January 1980 to December 1998.

  Cases of breast TB where a cytologic diagnosis was rendered or a

  histologic diagnosis with prior fine needle aspiration cytology (FNAC) was

  available were selected. These slides were reviewed for determining the

  cytologic findings. RESULTS: One hundred sixty cases of breast TB were

  included in the study. Six males and 154 females with a clinical suspicion

  of carcinoma had undergone FNA that was reported as TB. The majority of

  the patients (111) were in the reproductive age group, 21-40 years. Of the

  160 cases, 118 (73.75%) had cytomorphology diagnostic of

  tuberculosis--epithelioid cell granulomas with caseous necrosis. Eleven of

  the remaining 42 cases were positive for acid-fast bacilli (AFB) on

  Ziehl-Neelsen (ZN) staining, while 31 cases were confirmed to be

  tubercular on histology. ZN staining was done in 44 cases, and AFB were

  demonstrated in only 38.6% of cases. CONCLUSION: Up to 73% of breast TB

  can be confidently diagnosed when both epithelioid cell granulomas and

  necrosis are present. Also, the possibility that a woman in the

  reproductive age group who presents with a palpable lump in the breast may

  have tuberculosis must be kept in mind, especially as the incidence of

  breast TB may increase in the future with the global spread of AIDS.


1479. Kamath AT.  Groat NL.  Bean AG.  Britton WJ. Protective effect of DNA immunization against mycobacterial infection is associated with the early emergence of interferon-gamma (IFN-gamma)-secreting lymphocytes. Clinical & Experimental Immunology.  120(3):476-82, 2000 Jun.


  The development of more effective anti-tuberculosis (TB) vaccines would

  contribute to the global control of TB. Understanding the activated/memory

  T cell response to mycobacterial infection and identifying immunological

  correlates of protective immunity will facilitate the design and

  assessment of new candidate vaccines. Therefore, we investigated the

  kinetics of the CD4+ T cell response and IFN-gamma production in an

  intravenous challenge model of Mycobacterium bovis bacille Calmette-Guerin

  (BCG) before and after DNA immunization. Activated/memory CD4+ T cells,

  defined as CD44hiCD45RBlo, expanded following infection, peaking at 3-4

  weeks, and decreased as the bacterial load fell. Activated/memory CD4+ T

  cells were the major source of IFN-gamma and the level of antigen-specific

  IFN-gamma-secreting lymphocytes, detected by ELISPOT, paralleled the

  changes in bacterial load. To examine the effects of a DNA vaccine, we

  immunized mice with a plasmid expressing the mycobacterial secreted

  antigen 85B (Ag85B). This led to a significant reduction in mycobacteria

  in the liver, spleen and lung. This protective effect was associated with

  the rapid emergence of antigen-specific IFN-gamma-secreting lymphocytes

  which were detected earlier, at day 4, and at higher levels than in

  infected animals immunized with a control vector. This early and increased

  response of IFN-gamma-secreting T cells may serve as a correlate of

  protective immunity for anti-TB vaccines.


1480. Khare MD.  Sharland M. Pulmonary manifestations of pediatric HIV infection. [Review] [26 refs] Indian Journal of Pediatrics.  66(6):895-904, 1999 Nov-Dec.


  Vertically acquired HIV infection is becoming increasingly common in

  India. The main clinical manifestations of HIV in childhood are growth

  failure, lymphadenopathy, chronic cough and fever, recurrent pulmonary

  infections, and persistent diarrhoea. Pulmonary disease is the major cause

  of morbidity and mortality in pediatric AIDS, manifesting itself in more

  than 80% of cases. The most common causes are Pneumocystis carinii

  pneumonia (PCP), lymphocytic interstitial pneumonitis (LIP), recurrent

  bacterial infections which include bacterial pneumonia and tuberculosis.

  The commonest AIDS diagnosis in infancy is PCP, presenting in infancy with

  tachypnea, hypoxia, and bilateral opacification on chest-X-ray (CXR).

  Treatment is with cotrimoxazole. LIP presents with bilateral

  reticulonodular shadows on CXR. It may be asymptomatic in the earlier

  stages, but children develop recurrent bacterial super infections, and can

  progress to bronchiectasis. LIP is a good prognostic sign in children with

  HIV infection in comparison to PCP. HIV should be considered in children

  with recurrent bacterial pneumonia, particularly with a prolonged or

  atypical course, or a recurrence after standard treatment. Pulmonary TB is

  common in children with HIV, but little data is available to guide

  treatment decisions. Much can be done to prevent PCP and bacterial

  infections with cotrimoxazole prophylaxis and appropriate immunisations,

  which may reduce hospital admissions and health care costs. [References:



1481. Khatri GR.  Frieden TR. The status and prospects of tuberculosis control in India [see comments]. International Journal of Tuberculosis & Lung Disease.  4(3):193-200, 2000  Mar.


  SETTING: India, where much of the global strategy for tuberculosis control

  was established, but where, every year, there are an estimated 2 million

  cases of tuberculosis. OBJECTIVE: To describe the policies, initial

  results, and lessons learned from implementation of a Revised National

  Tuberculosis Control Programme using the principles of DOTS (Directly

  Observed Treatment, Short-course). DESIGN: A Revised National Tuberculosis

  Control Programme (RNTCP) was designed and implemented starting in 1993.

  With funding from the Government of India, State Governments, the World

  Bank and bilateral donors, regular supply of drugs and logistics was

  ensured. Persons with chest symptoms who attend health facilities are

  referred to microscopy centres for diagnosis. Diagnosed cases are

  categorized as per World Health Organization guidelines, and treatment is

  given by direct observation. Systematic recording and cohort reporting is

  done. RESULTS: From October 1993 through mid-1999, 146,012 patients were

  put on treatment in the programme. The quality of diagnosis was improved,

  with the ratio of smear-positive to smear-negative patients being

  maintained at 1:1. Case detection rates varied greatly between project

  sites and correlated with the percentage of patients who were

  smear-positive among those examined for diagnosis, suggesting

  heterogeneous disease rates. Treatment success was achieved in 81% of new

  smear-positive patients, 82% of new smear-negative patients, 89% of

  patients with extra-pulmonary tuberculosis, and 70% of re-treatment

  patients. CONCLUSION: The RNTCP has successfully treated approximately 80%

  of patients in 20 districts of 15 states of India. Treatment success rates

  are more than double and death rates are less than a seventh those of the

  previous programme. Starting in late 1998, the programme began to scale up

  and now covers more than 130 million people. Maintaining the quality of

  implementation during the expansion phase is the next challenge.


1482. Krause KH. Professional phagocytes: predators and prey of microorganisms. [Review]  [13 refs] Schweizerische Medizinische Wochenschrift. Journal Suisse de Medecine.   130(4):97-100, 2000 Jan 29.


  Phagocytosis is an ancient cellular function. However, professional

  phagocytes have evolved only in higher organisms, where they play an

  important role in host defence. Professional phagocytes are capable of

  engulfing relatively large microorganisms and killing them with a

  combination of various microbicidal systems. Crucial killing mechanisms of

  phagocytes include superoxide generation by phagocyte NADPH oxidase and

  release of microbicidal proteins through exocytosis of performed granules.

  Phagocytes are also able to interfere with microbial growth through

  alteration of the phagosomal ionic environment (acidification, iron

  depletion). While the microbicidal mechanisms of phagocytes are extremely

  efficient and capable of killing most microorganisms, pathogenic

  microorganisms have developed mechanisms to resist phagocytes.

  Microorganisms capable of surviving within phagocytes are rare, but

  represent very successful pathogens, such as Mycobacterium tuberculosis.

  Other pathogens, such as S. aureus, have developed strategies to evade

  phagocytosis. How microorganisms are phagocytosed and killed, and why

  certain pathogens resist these mechanisms, are crucial questions for an

  understanding of the pathogenesis of infectious diseases and the

  development of innovative treatment approaches. [References: 13]




1483. Kuaban C.  Bercion R.  Jifon G.  Cunin P.  Blackett KN. Acquired anti-tuberculosis drug resistance in Yaounde, Cameroon. International Journal of Tuberculosis & Lung Disease.  4(5):427-32, 2000  May.


  SETTING: Tuberculosis centre of Hopital Jamot, Yaounde, Cameroon.

  OBJECTIVES: To determine the prevalence of acquired resistance (ADR) to

  the main anti-tuberculosis drugs, and to identify risk factors associated

  with its occurrence in Yaounde. DESIGN: A total of 111 previously treated

  adults admitted consecutively to the tuberculosis centre with sputum

  smear-positive pulmonary tuberculosis between June 1996 and July 1997 were

  included in the study. Information on potential risk factors for ADR was

  obtained from each patient, and human immunodeficiency virus (HIV)

  serostatus was determined. Drug susceptibility testing to the main

  anti-tuberculosis drugs was performed on cultures of Mycobacterium

  tuberculosis complex isolated from sputum samples of each patient by the

  indirect proportion method. All patients whose isolates tested resistant

  to at least one anti-tuberculosis drug were defined as having ADR.

  RESULTS: Growth of M. tuberculosis complex was obtained from sputum

  specimens of 98 (88.3%) of the 111 patients studied; 57 (58.2%) of these

  were resistant to at least one anti-tuberculosis drug. Resistance to

  isoniazid was the most common (54.1%), followed by resistance to

  rifampicin (27.6%), streptomycin (25.5%) and ethambutol (12.2%). Multidrug

  resistance was observed in 27 (27.6%) of the cases. In a multivariate

  logistic regression analysis, ADR was significantly associated only with

  monotherapy use in previous tuberculosis treatment(s) (P = 0.03).

  CONCLUSION: The rate of ADR of M. tuberculosis is quite high in Yaounde.

  Acquired resistance to rifampicin alone or in combination with isoniazid

  is also high. Monotherapy in previous anti-tuberculosis treatment(s) is a

  significant predictor of ADR in previously treated patients in Yaounde.

  These results underscore the urgent need for the re-establishment of a

  tuberculosis control programme, using the DOTS strategy, in Cameroon.


1484. Kwiatkowski D. Genetic dissection of the molecular pathogenesis of severe infection. [Review] [61 refs] Intensive Care Medicine.  26 Suppl 1:S89-97, 2000.


  A fundamental question for the intensivist is why some individuals but not

  others succumb to life-threatening infection. A growing body of evidence

  indicates that both the risk of acquiring infection and the risk of

  developing severe complications are determined by host genetic factors.

  These include a number of single gene defects with devastating

  consequences, e. g. interferon-gamma receptor mutations that lead to fatal

  infections with ubiquitous mycobacteria, but such examples are relatively

  rare. Of greater importance for routine clinical practice is the

  potentially vast number of genetic variants with subtle effects on the

  regulation or function of specific immunological, physiological and

  metabolic mediators. Such polygenic traits do not obey simple patterns of

  familial segregation seen for monogenic disorders, and their clinical

  investigation is further complicated by the environmental variability of

  infectious exposure. Recent advances in this field have therefore largely

  stemmed from hospital-based case-controlled studies that have uncovered

  disease associations with specific DNA polymorphisms in candidate gene

  regions. For example, tumour necrosis factor polymorphisms have been

  associated with susceptibility to malaria and other infections; chemokine

  receptor polymorphisms with susceptibility to HIV; natural

  resistance-associated macrophage protein 1 with tuberculosis; and mannose

  binding lectin polymorphisms with meningococcal disease. A much greater

  number of genetic associations will emerge as the full extent of human

  genomic diversity becomes known. The challenge for clinical investigators

  is to generate an epidemiological framework for population- and

  family-based association studies, which is sufficiently robust to exclude

  population artifacts and sufficiently powerful to be able to dissect true

  disease-causing polymorphisms from linked genetic markers. In the long

  term this approach promises to identify host mediators that are critical

  for pathogenesis and immunity and to yield molecular insights into the

  complex processes of human gene regulation. This information is likely to

  be of considerable value in designing more effective approaches to the

  treatment and prevention of life-threatening infectious disease.

  [References: 61]



1485. Lee NH.  Choi EH.  Lee WS.  Ahn SK. Tuberculous cellulitis. Clinical & Experimental Dermatology.  25(3):222-3, 2000 May.


  We report a case of cutaneous tuberculosis presenting as cellulitis. The

  patient was a 63-year-old Korean woman who also had diabetes mellitus and

  a 20-year-history of oral corticosteroid medication prescribed for

  arthralgia. In addition, she had had pulmonary tuberculosis 20-year

  previously for which she received systemic treatment for 1 year. Her

  clinical cellulitis failed to respond to antibiotic therapy. Subsequent

  investigations, using histopathology and polymerase chain reaction,

  established an alternative diagnosis of cutaneous tuberculosis. The skin

  eruption cleared after treatment with isoniazid, rifampicin, ethambutol

  and pyrazinamide. This case represents a most unusual presentation of

  tuberculosis in the skin. The atypical features may reflect the patient's

  general medical state.


1486. Lu W.  Cheng P.  Chen S. HSP60, HSP70 in the pathogenesis of Kawasaki disease: implication and  action. Journal of Tongji Medical University. 18(3):145-8, 1998.


  HSP60, HSP70 in plasma of 11 cases of Kawasaki diseases (KD) and 23

  healthy children were determined. The two groups were controlled for age.

  Determination of HSP60, HSP70 was conducted in lymphocytes of 14 cases of

  KD and 26 healthy children. The results were compared with those of 12

  patients with febrile diseases and 10 patients with tuberculosis. Our

  results showed that except a significant difference in plasma HSP70 found

  between acute phase and convalescent phase of KD (P < 0.01), no

  significant difference was found in HSP60, HSP70 among all groups (P >

  0.05). The differences in HSP60, HSP70 in lymphocytes were relatively

  obvious among all groups. The levels of HSP60, HSP70 in acute phase of KD

  were significantly higher than those in convalescent phase or in healthy

  controls (P < 0.01). The levels of HSP60 in KD were significantly higher

  than those of patients with febrile diseases. HSP60 of KD children was

  significantly lower than those of children with tuberculosis (P < 0.01).

  The findings showed that HSP60, HSP70 might contribute to the pathogenesis

  of KD. Determination of HSP60, HSP70 in lymphocytes is of help in the

  diagnosis of KD.


1487. MacIntyre CR.  Ansari MZ.  Carnie J.  Hart WG. No evidence for multiple-drug prophylaxis for tuberculosis compared with isoniazid alone in Southeast Asian refugees and migrants: completion and compliance are major determinants of effectiveness. Preventive Medicine.  30(5):425-32, 2000 May.


  BACKGROUND: The use of multiple-drug prophylaxis for tuberculosis (TB) has

  not been shown to be more effective than prophylaxis with isoniazid alone.

  The boundary between inactive pulmonary TB (class 4 TB) and

  culture-negative "active" pulmonary TB (class 3 TB) is often unclear, as

  is the intention to treat such patients as a preventive measure or as a

  curative measure. METHODS: We compared the effectiveness of single drug

  preventive therapy with isoniazid to the effectiveness of multiple drug

  preventive therapy for patients with asymptomatic, inactive TB, in a

  retrospective cohort study of 984 Southeast (SE) Asian migrants and

  refugees who received prophylaxis between 1978 and 1980. RESULTS: The rate

  of TB developing in this cohort was 122 per 100,000 person-years. There

  was no significant difference in development of TB between people who

  received isoniazid only and those who received multiple drugs. The only

  significant predictor of TB was noncompletion of prophylaxis [relative

  risk (RR) = 62, 95% confidence interval (CI) = 20-194]. Subgroup analysis

  on people who had completed therapy showed noncompliance as a significant

  predictor of TB (RR = 16, 95% CI = 1.4-179). The risk of noncompletion (RR

  = 4.7, 95% CI = 2.37-9.39, P < 0.0001) and noncompliance (RR = 2.2, 95% CI

  = 1.03-4.7, P = 0.03) was higher for patients who received multiple drugs

  compared with isoniazid alone. Multiple-drug therapy cost 30 times more

  than isoniazid alone. CONCLUSIONS: We did not find evidence in support of

  the empirical practice of giving multiple drugs for prevention of TB. This

  practice is also more costly and more likely to result in noncompliance

  and adverse drug reactions.


1489. Mahadevan S. Clinical utility of serodiagnosis of tuberculosis. [Review] [33 refs] Indian Journal of Pediatrics.  64(1):97-103, 1997 Jan-Feb.


  The use of TB-ELISA tests as a diagnostic tool offer a lot of scope in

  early diagnosis of serious forms of childhood tuberculosis. The

  characteristics of these tests have improved with the availability of

  purified and recombinant antigens and competition assays using monoclonal

  antibodies. Lower antibody titres to M. tuberculosis specific antigens in

  children and the presence of 'natural exposure' antibodies make the

  interpretation of these tests difficult at times. Caution must be

  exercised in interpreting their results due to problems inherent on

  currently available methods of TB-immunodiagnosis. The selection of best

  combination of antigens for serology, prospective clinical trials

  comparing success rate of serology with the standard different diagnostic

  procedures are required. [References: 33]



1490. Martin E.  Kamath AT.  Triccas JA.  Britton WJ. Protection against virulent Mycobacterium avium infection following DNA vaccination with the 35-kilodalton antigen is accompanied by induction of gamma interferon-secreting CD4(+) T cells. Infection & Immunity.  68(6):3090-6, 2000 Jun.


  Mycobacterium avium is an opportunistic pathogen that primarily infects

  immunocompromised individuals, although the frequency of M. avium

  infection is also increasing in the immunocompetent population. The

  antigen repertoire of M. avium varies from that of Mycobacterium

  tuberculosis, with the immunodominant 35-kDa protein being present in M.

  avium and Mycobacterium leprae but not in members of the M. tuberculosis

  complex. Here we show that a DNA vector encoding this M. avium 35-kDa

  antigen (DNA-35) induces protective immunity against virulent M. avium

  infection, and this protective effect persists over 14 weeks of infection.

  In C57BL/6 mice, DNA vaccines expressing the 35-kDa protein as a

  cytoplasmic or secreted protein, both induced strong T-cell gamma

  interferon (IFN-gamma) and humoral immune responses. Furthermore, the

  antibody response was to conformational determinants, confirming that the

  vector-encoded protein had adopted the native conformation. DNA-35

  immunization resulted in an increased activated/memory CD4(+) T-cell

  response, with an accumulation of CD4(+) CD44(hi) CD45RB(lo) T cells and

  an increase in antigen-specific IFN-gamma production. The protective

  effect of the DNA-35 vectors against M. avium infection was comparable to

  that of vaccination with Mycobacterium bovis BCG and significantly greater

  than that for previous treated infection with M. avium. These results

  illustrate the importance of the 35-kDa protein in the protective response

  to M. avium infection and indicate that DNA vaccination successfully

  promotes a sustained level of protection during chronic M. avium



1491. McLellan DG.  Philips KB.  Corbett CE.  Bronze MS. Sternal osteomyelitis caused by mycobacterium tuberculosis: case report and review of the literature. [Review] [31 refs] American Journal of the Medical Sciences.  319(4):250-4, 2000 Apr.


  Sternal osteomyelitis caused by Mycobacterium tuberculosis is rare; since

  the advent of modern antituberculous therapy, a limited number of detailed

  cases have been reported. Most patients were relatively young, free of

  underlying disease, and lived in a country in which tuberculosis is

  endemic. The disease presented indolently with sternal pain and swelling.

  Extrasternal disease is detectable in less than half. Diagnosis was based

  on histologic examination of infected tissues and mycobacterial cultures.

  Most patients recovered after surgical debridement and combination drug

  therapy. Tuberculous sternal osteomyelitis should be considered in

  patients with sternal pain and swelling. [References: 31]


1492. Miller RF.  Howling SJ.  Reid AJ.  Shaw PJ. Pleural effusions in patients with AIDS. Sexually Transmitted Infections.  76(2):122-5, 2000 Apr.


  OBJECTIVE: To describe the range of pathology causing pleural effusions in

  HIV infected patients with acute respiratory episodes and to attempt to

  identify whether any associated radiological abnormalities enabled

  aetiological discrimination. METHODS: Prospective study of chest

  radiographs of 58 consecutive HIV infected patients with pleural effusion

  and their microbiological, cytological, and histopathological diagnoses.

  RESULTS: A specific diagnosis was made in all cases. Diagnoses were

  Kaposi's sarcoma, 19 patients; para-pneumonic effusion, 16 patients;

  tuberculosis, eight patients; Pneumocystis carinii pneumonia, six

  patients; lymphoma, four patients; pulmonary embolus, two patients; and

  heart failure, aspergillus/leishmaniasis, and Cryptococcus neoformans, one

  case each. Most effusions (50/58) were small. Bilateral effusions were

  commoner in Kaposi's sarcoma (12/19) and lymphoma (3/4) than in

  para-pneumonic effusion (3/16). Concomitant interstitial parenchymal

  shadowing did not aid discrimination. A combination of bilateral

  effusions, focal air space consolidation, intrapulmonary nodules, and/or

  hilar lymphadenopathy suggests Kaposi's sarcoma. Unilateral effusion with

  focal air space consolidation suggests para-pneumonic effusion if

  intrapulmonary nodules are absent: if miliary nodules and/or mediastinal

  lymphadenopathy are detected, this suggests tuberculosis. CONCLUSIONS: A

  wide variety of infectious and malignant conditions cause pleural

  effusions in HIV infected patients, the most common cause in this group

  was Kaposi's sarcoma. The presence of additional radiological

  abnormalities such as focal air space consolidation, intrapulmonary

  nodules, and mediastinal lymphadenopathy aids aetiological discrimination.



1493. Morris S.  Kelley C.  Howard A.  Li Z.  Collins F. The immunogenicity of single and combination DNA vaccines against  tuberculosis. Vaccine.  18(20):2155-63, 2000 Apr 14.


  DNA immunization is a promising new approach for the development of novel

  tuberculosis vaccines. In this study, the immune responses following the

  administration of single and combination tuberculosis DNA vaccines were

  evaluated. Single DNA vaccines encoding the MPT-63 and MPT-83 tuberculosis

  antigens evoked partial protection against an aerogenic challenge with M.

  tuberculosis Erdman in the mouse model of pulmonary tuberculosis.

  Immunization with a multivalent combination DNA vaccine (containing the

  ESAT-6, MPT-64, MPT-63, and KatG constructs) generated immune responses

  that indicated an absence of antigenic competition since antigen-specific

  cell-mediated and humoral responses were detected to each component of the

  mixture. More importantly, the combination vaccine elicited a strong

  protective response relative to the protection evoked by live BCG vaccine.


1494. Morrison WI.  Bourne FJ.  Cox DR.  Donnelly CA.  Gettinby G.  McInerney  JP.  Woodroffe R. Pathogenesis and diagnosis of infections with Mycobacterium bovis in  cattle. Independent Scientific Group on Cattle TB. Veterinary Record.  146(9):236-42, 2000 Feb 26.


  In last week's Veterinary Record, members of the Independent Scientific

  Group on Cattle TB discussed the approach they are adopting in attempting

  to develop sustainable strategies for controlling bovine tuberculosis in

  cattle (VR, February 19, pp 207-210). In this second, complementary

  article, they consider the extent to which efforts to control the disease

  may be constrained by limitations in current testing procedures.


1496. Mustafa AS.  Shaban FA.  Abal AT.  Al-Attiyah R.  Wiker HG.  Lundin KE.  Oftung F.  Huygen K. Identification and HLA restriction of naturally derived Th1-cell epitopes from the secreted Mycobacterium tuberculosis antigen 85B recognized by antigen-specific human CD4(+) T-cell lines. Infection & Immunity.  68(7):3933-40, 2000 Jul.


  Antigen 85B (Ag85B/MPT59) is a major secreted protein from Mycobacterium

  tuberculosis which is a promising candidate antigen for inclusion in novel

  subunit vaccines against tuberculosis (TB). The present study was

  undertaken to map naturally derived T-cell epitopes from M. tuberculosis

  Ag85B in relation to major histocompatibility complex (MHC) class II

  restriction. Antigen-specific CD4(+) T-cell lines were established from

  HLA-typed TB patients and Mycobacterium bovis BCG vaccinees by stimulation

  of peripheral blood mononuclear cells with purified Ag85B in vitro. The

  established T-cell lines were then tested for proliferation and gamma

  interferon (IFN-gamma) secretion in response to 31 overlapping synthetic

  peptides (18-mers) covering the entire sequence of the mature protein. The

  results showed that the epitopes recognized by T-cell lines from TB

  patients were scattered throughout the Ag85B sequence whereas the epitopes

  recognized by T-cell lines from BCG vaccinees were located toward the

  N-terminal part of the antigen. The T-cell epitopes represented by

  peptides p2 (amino acids [aa] 10 to 27), p3 (aa 19 to 36), and p11 (aa 91

  to 108) were frequently recognized by antigen-specific T-cell lines from

  BCG vaccinees in both proliferation and IFN-gamma assays. MHC restriction

  analysis demonstrated that individual T-cell lines specifically recognized

  the complete Ag85B either in association with one of the self HLA-DRB1,

  DRB3, or DRB4 gene products or nonspecifically in a promiscuous manner. At

  the epitope level, panel studies showed that peptides p2, p3, and p11 were

  presented to T cells by HLA-DR-matched as well as mismatched allogeneic

  antigen-presenting cells, thus representing promiscuous epitopes. The

  identification of naturally derived peptide epitopes from the M.

  tuberculosis Ag85B presented to Th1 cells in the context of multiple

  HLA-DR molecules strongly supports the relevance of this antigen to

  subunit vaccine design.



1497. Mwandumba HC.  Squire SB. Fully intermittent dosing with drugs for tuberculosis. [Review] [1 refs] Cochrane Database of Systematic Reviews [computer file].  (2):CD000970,  2000.


  BACKGROUND: The number of people infected with tuberculosis continues to

  rise world-wide. Rifampicin-containing treatment regimens can achieve high

  cure rates. Intermittent drug treatment delivered in the community has the

  potential to improve adherence to treatment. OBJECTIVES: The objective of

  this review was to compare the effectiveness of rifampicin-containing

  short-course chemotherapy regimens, given two or three times a week, with

  similar regimens given daily in patients with pulmonary tuberculosis.

  SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials

  register, the Cochrane Controlled Trials Register, Medline, and reference

  lists of articles. We contacted experts in the field. SELECTION CRITERIA:

  Randomised and quasi-randomised trials of any multi-drug regimen

  containing rifampicin in patients with confirmed pulmonary tuberculosis.

  Treatment had to be given up to three times a week for up to nine months,

  with any initial daily dosing period not more than one month, and was

  compared to daily dosing throughout for the same period. DATA COLLECTION

  AND ANALYSIS: Two reviewers independently assessed trial eligibility and

  quality. MAIN RESULTS: One trial involving 399 patients was included. The

  trial compared treatment three times per week with daily treatment for six

  months. There was no difference in cure rate (198 out of 199 people in the

  intermittent group compared to all 200 in the daily group), but 5 patients

  relapsed in the group receiving intermittent therapy compared to one in

  the group receiving the daily regimen. REVIEWER'S CONCLUSIONS: There is

  not enough evidence to assess the equivalence of effect between fully

  intermittent, rifampicin-containing short-course chemotherapy and similar

  daily therapy in patients with pulmonary tuberculosis. Larger randomised

  studies are required to establish the effectiveness of fully intermittent,

  short-course chemotherapy. [References: 1]



1498. Osann KE.  Lowery JT.  Schell MJ. Small cell lung cancer in women: risk associated with smoking, prior respiratory disease, and occupation. Lung Cancer.  28(1):1-10, 2000 Apr.


  Small cell carcinoma of the lung (SCLC) occurs most frequently in heavy

  smokers, yet exhibits a lesser predominance among men than other

  smoking-associated lung cancers. Incidence rates have increased more

  rapidly in women than men and at a faster rate among women than other cell

  types. To investigate the importance of smoking and other risk factors, a

  case-control study of SCLC in women was conducted. A total of 98 women

  with primary SCLC and 204 healthy controls, identified by random-digit

  dialing and frequency matched for age, completed telephone interviews.

  Data collected include demographics, medical history, family cancer

  history, residence history, and lifetime smoking habits. Odds ratios (ORs)

  and 95% confidence intervals (95% CI) were calculated using logistic

  regression analysis. Risk for small cell carcinoma in women is strongly

  associated with current use of cigarettes. Ninety-seven of 98 cases had

  smoked cigarettes; 79% of cases were current smokers and 20% were former

  smokers at the time of diagnosis compared to 13% current and 34% former

  smokers among controls. The ORs associated with smoking are 108.7 (95% CI

  14.8-801) for ever-use of cigarettes, 278.9 (95% CI 37.0-2102) for current

  smoking, and 31.5 (95% CI 4. 1-241) for former smoking. Risk increases

  steeply with pack-years of smoking and decreases with duration of smoking

  cessation. After adjusting for age, education, and lifetime smoking

  history, medical history of physician-diagnosed respiratory disease

  including chronic bronchitis, emphysema, pneumonia, tuberculosis, asthma,

  and hay fever is not associated with a significant increase in lung cancer

  risk. Employment in blue collar, service, or other high risk occupations

  is associated with a two to three-fold non-significant increase in risk

  for small cell carcinoma after adjusting for smoking.


1499. Ozates M.  Ozkan U.  Kemaloglu S.  Hosoglu S.  Sari I. Spinal subdural tuberculous abscess. Spinal Cord.  38(1):56-8, 2000 Jan.


  OBJECTIVES: Spinal subdural abscess is rare and only 48 cases have been

  described to date. In this report, we present an additional spinal

  subdural tuberculous abscess. METHOD: Tuberculous meningitis was diagnosed

  with clinical and laboratory findings in a 45-year-old man. A spinal

  subdural abscess was demonstrated using MRI. Presence of the abscess was

  revealed by surgical intervention. The diagnosis was confirmed by

  pathological examination. RESULTS: The patient had been treated for

  tuberculous meningitis 2 years previously. The disease recurred when

  anti-tuberculous therapy was prematurely discontinued. During the second

  treatment, the patient also underwent a ventriculo-peritoneal shunt

  operation for hydrocephalus. Dizziness and weakness of both legs developed

  after the postoperative period. Spinal MRI showed a spinal subdural

  abscess as a iso-intense mass with spinal cord in the T1 and T2 weighted

  images, ring like enhancement and compression on the spinal cord at T3-T4

  level. The patient underwent surgery and the abscess was drained.

  CONCLUSION: Tuberculosis may cause a spinal subdural abscess and although

  it is a rare disorder, when encountered MRI is very useful in the



1500. Pereira Arias-Bouda LM.  Nguyen LN.  Ho LM.  Kuijper S.  Jansen HM.  Kolk  AH. Development of antigen detection assay for diagnosis of tuberculosis using  sputum samples. Journal of Clinical Microbiology.  38(6):2278-83, 2000 Jun.


  The rising incidence of tuberculosis worldwide means an increasing burden

  on diagnostic facilities, so tests simpler than Ziehl-Neelsen staining are

  needed. Such tests should be objective, reproducible, and have at least as

  good a detection limit as 10(4) bacteria/ml. A capture enzyme-linked

  immunosorbent assay (ELISA) was developed for detection of

  lipoarabinomannan (LAM) in human sputum samples. As a capture antibody, we

  used a murine monoclonal antibody against LAM, with rabbit antiserum

  against Mycobacterium tuberculosis as a source of detector antibodies. The

  sensitivity of the capture ELISA was evaluated by using purified LAM and

  M. tuberculosis whole cells. We were able to detect 1 ng of purified

  LAM/ml and 10(4) M. tuberculosis whole cells/ml. LAM could also be

  detected in culture filtrate of a 3-week-old culture of M. tuberculosis.

  The culture filtrate contained approximately 100 microgram of LAM/ml. The

  detection limit in sputum pretreated with N-acetyl-L-cysteine and

  proteinase K was 10(4) M. tuberculosis whole cells per ml. Thirty-one

  (91%) of 34 sputum samples from 18 Vietnamese patients with tuberculosis

  (32 smear positive and 2 smear negative) were positive in the LAM

  detection assay. In contrast, none of the 25 sputum samples from 21

  nontuberculous patients was positive. This specific and sensitive assay

  for the detection of LAM in sputum is potentially useful for the diagnosis

  of tuberculosis.


1501. Portillo-Gomez L.  Morris SL.  Panduro A. Rapid and efficient detection of extra-pulmonary Mycobacterium  tuberculosis by PCR analysis. International Journal of Tuberculosis & Lung Disease.  4(4):361-70, 2000  Apr.


  SETTING: The diagnosis of extra-pulmonary tuberculosis (EPTB) remains an

  important clinical problem, primarily because of the inadequate

  sensitivity of conventional bacteriologic methods for detecting

  Mycobacterium tuberculosis in extra-pulmonary specimens. OBJECTIVE: To

  evaluate whether a IS6110-based polymerase chain reaction (PCR) method can

  be utilized to detect M. tuberculosis in non-pulmonary specimens. DESIGN:

  Specimens from 286 Mexican patients with a presumptive clinical diagnosis

  of EPTB were prospectively examined by Ziehl-Neelsen staining,

  mycobacterial culture on Lowenstein-Jensen slants, and by PCR. The DNA for

  PCR was extracted by the buffer lysis method and phenol-guanidine

  thiocyanate-chloroform. Primers that amplify a 200 bp fragment from the

  insertion-like M. tuberculosis sequence element IS6110 were utilized.

  RESULTS: Our results demonstrate that this PCR method is highly specific

  (100%) for identifying M. tuberculosis from a variety of specimens

  including cerebrospinal fluid (CSF), pleural fluid, ascitic fluid,

  pericardial fluid, urine, and lymph node exudate. Moreover, the

  sensitivity of PCR for detecting M. tuberculosis in CSF (94%), pleural

  fluid (94%), ascitic fluid and other extrapulmonary specimens (93%)

  greatly exceeds the sensitivity of conventional smear and culture methods.

  CONCLUSION: These results demonstrate that PCR can be a highly specific

  and sensitive aid in the detection of M. tuberculosis from extra-pulmonary



1502. Pottumarthy S.  Wells VC.  Morris AJ.  A comparison of seven tests for serological diagnosis of tuberculosis. Journal of Clinical Microbiology.  38(6):2227-31, 2000 Jun.


  Seven serological tests, two immunochromatographic tests, ICT Tuberculosis

  and RAPID TEST TB, and five enzyme-linked immunosorbent assays,


  PATHOZYME-MYCO IgA, and PATHOZYME-MYCO IgM, were evaluated simultaneously

  with 298 serum samples from three groups of individuals: 44 patients with

  active tuberculosis, 204 controls who had undergone the Mantoux test (89

  Mantoux test-positive and 115 Mantoux test-negative controls), and 50

  anonymous controls. The sensitivities of the tests with sera from patients

  with active tuberculosis were poor to modest, ranging from 16 to 57%. All

  the tests performed equally with sera from subgroups of those with active

  tuberculosis, those with pulmonary (33 patients) versus extrapulmonary (11

  patients) disease, and those who were smear positive (24 patients) versus

  smear negative (12 patients) (P > 0.05). The specificities of the tests

  ranged from 80 to 97% with sera from the Mantoux test controls and 62 to

  100% with sera from the anonymous controls. The TUBERCULOSIS IgA EIA had

  the highest sensitivity (57%) with sera from patients with active

  tuberculosis, with a high specificity of 93% with sera from the Mantoux

  test controls, but a very poor specificity of 62% with sera from the

  anonymous controls. Overall, ICT Tuberculosis followed by PATHOZYME-MYCO

  IgG had the best performance characteristics, with sensitivities of 41 and

  55%, respectively, with sera from patients with active tuberculosis and

  specificities of 96 and 89%, respectively, with sera from the Mantoux test

  controls and 88 and 90%, respectively, with sera from the anonymous

  controls. By combining all the test results, a maximum sensitivity of 84%

  was obtained, with reciprocal drops in specificities to 55 and 42% for the

  Mantoux test controls and anonymous controls, respectively. The best

  combination was that of ICT Tuberculosis and PATHOZYME-MYCO IgG, with a

  sensitivity of 66% and a specificity of 86% for the Mantoux test controls

  and a sensitivity and specificity of 78% for the anonymous controls. While

  a negative result by any one of these tests would be useful in helping to

  exclude disease in a population with a low prevalence of tuberculosis, a

  positive result may aid in clinical decision making when applied to

  symptomatic patients being evaluated for active tuberculosis.


1503. Poveda F.  Camacho J.  Arnalich F.  Codoceo R.  del Arco A. Martinez-Hernandez P. Circulating cytokine concentrations in tuberculosis and other chronic  bacterial infections. Infection.  27(4-5):272-4, 1999.


  Cytokines are a group of hormone-like polypeptides that play a variety of

  regulatory roles in host defense against infection. Because of the

  possible different involvement of these mediators in bacterial infections

  and tuberculosis, enzyme immunoassay was used to measure comparatively the

  plasma levels of the proinflammatory cytokines interleukin-1 beta

  (IL-1beta), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6)

  and interferon gamma (IFN-gamma) in 25 immunocompetent patients divided

  into two groups: in 12 patients clinical and microbiological diagnosis

  showed a chronic bacterial infection and 13 patients had pleuropulmonar

  tuberculosis. After resolution of the infectious disorders (> or = 3

  months), these measurements were repeated for each patient. High levels of

  IL-1b, TNF-alpha and IL-6 were observed at study entry, but no significant

  difference was found between the groups. In contrast, plasma levels (mean

  +/- SEM) of IFN-gamma were significantly higher in patients with

  tuberculosis when compared with the bacterial group (0.753 +/- 0.201 vs

  0.325 +/- 0.105 IU/ml; P = 0.020). This different pattern of plasma

  proinflammatory cytokines could be ascribed to a prevaling role of the

  mediators of so-called Th-1 immune response (IFN-gamma) in host defense

  against infection with Mycobacterium tuberculosis.


1504. Rameshkumar K. Tuberculous lymphadenitis in children--role of fine needle aspiation  cytology. Journal of the Association of Physicians of India.  47(10):976-9, 1999  Oct.


  OBJECTIVES: Tuberculosis in children remains misdiagnosed, underdiagnosed

  or paradoxically overtreated as a result of diagnostic difficulties and

  non-specific manifestations such as lymphadenopathy. The aims of the study

  were, i) To assess the efficiency of fine needle aspiration cytology

  (FNAC) in comparison to histology to determine the prevalence of

  tuberculosis in lymph nodes, ii) To compare the cytological and

  histopathological features of lymphadenopathy in children to adults, iii)

  To analyse the clinical significance of the results in the context of

  diagnosis. MATERIAL AND METHODS: The biopsies of lymph nodes obtained

  during the seven year period from January 1989 to December 1995 and the

  lymph nodes on which fine needle aspiration cytology was done during the

  period, January 1990 to December 1995 were included for the study.

  Hemotoxylin and Eosin stain was used for basic evaluation of the

  histopathologic features. A grading system of 0 to 5+ was used to assess

  the smears to categorise them into diagnostic groups. RESULTS: Among 1396

  lymph node biopsies submitted for evaluation of non-neoplastic conditions

  54.12% (741) showed tuberculosis, in which children constituted 9.04%. A

  higher incidence of 68.61% was observed on FNAC. Both on cytology and

  histology, a necrotizing type of inflammation was observed more in

  children, which indicated hypersensitivity. CONCLUSION: FNAC was found to

  be a useful adjunct diagnostic technique especially in children, but the

  need to develop a sensitive and easily available method to diagnose in

  asymptomatic and high risk children still persists. Selection of patients

  with lymphadenopathy for more than three weeks is important, as otherwise

  nonspecific changes and acute inflammatory changes are likely to interfere

  with the diagnosis.


1505. Roring S.  Hughes MS.  Skuce RA.  Neill SD. Simultaneous detection and strain differentiation of Mycobacterium bovis directly from bovine tissue specimens by spoligotyping. Veterinary Microbiology.  74(3):227-36, 2000 Jun 1.


  Culture of Mycobacterium bovis is used routinely to support field

  diagnosis of bovine tuberculosis; however, this method is slow. Rapid

  detection and strain-typing of M. bovis directly from 37 lesioned bovine

  lymph node specimens was performed by the polymerase chain reaction (PCR)

  based method, spoligotyping. Mycobacterial DNA was extracted from the

  specimens using a nucleic acid sequence capture technique. Two sets of

  specimens were tested, the first set comprising 16 decontaminated tissue

  homogenates from lesioned lymph node specimens which had been processed

  for BACTEC culture and a second set of 21 non-decontaminated lesioned

  lymph node specimens. Both sets of specimens had been frozen before

  analysis. Sequence capture PCR enabled detection and strain-typing of M.

  bovis directly from 15 of the 16 decontaminated homogenates and all 21 of

  the non-decontaminated tissues. Four spoligotype (ST) patterns were

  obtained from each set; ST1, ST2, ST3 and ST16 were detected in the

  decontaminated specimens and ST1, ST2, ST11 and ST14 in the

  non-decontaminated specimens. For both sets of specimens, ST1 was the

  predominant strain type detected. ST patterns obtained from the BACTEC

  cultures of the decontaminated specimens were in agreement with those

  obtained directly from the tissue. The sensitivity of detection by

  sequence capture-PCR compared very favourably with that of BACTEC culture.

  ST patterns were obtained directly from tissues of 34 of the 35 culture

  positive specimens and the two culture negative specimens. DNA extraction

  from the 21 non-decontaminated specimens involved an initial stomaching

  treatment. An assessment of sequence capture on both liquid alone and

  liquid and tissue homogenate combined, following stomaching, indicated

  that PCR was less successful on the liquid component alone.


1506. Rossi MC.  Gori A.  Zehender G.  Marchetti G.  Ferrario G.  De Maddalena  C.  Catozzi L.  Bandera A.  Esposti AD.  Franzetti F. A PCR-colorimetric microwell plate hybridization assay for detection of  Mycobacterium tuberculosis and M. avium from culture samples and  Ziehl-Neelsen-positive smears. Journal of Clinical Microbiology.  38(5):1772-6, 2000 May.


  Differentiation between Mycobacterium tuberculosis and M. avium is

  essential for the treatment of mycobacterial infections. We have developed

  an easy and rapid detection assay for the diagnosis of mycobacterial

  diseases. This is a PCR-hybridization assay based on selective

  amplification of a 16S rRNA gene sequence using pan-Mycobacterium primers

  followed by hybridization of the amplification products to biotinylated M.

  tuberculosis and M. avium-specific probes. A total of 55 mycobacterial

  isolates were tested. For all isolates, results concordant with those of

  conventional identification methods were obtained. Moreover, we developed

  a method for extraction of DNA from Ziehl-Neelsen-positive smears which

  allows the recovery of intact target DNA in our PCR-hybridization assay.

  Our method was able to confirm all culture results for 59

  Ziehl-Neelsen-positive smears from clinical specimens (35 sputum, 11 lymph

  node biopsy, 6 stool, 4 pus, 2 urine, and 1 pericardial fluid specimens).

  These data suggest that our PCR-hybridization assay, which is simple to

  perform and less expensive than commercial probe methods, may be suitable

  for the identification of M. tuberculosis and M. avium. It could become a

  valuable alternative approach for the diagnosis of mycobacterial

  infections when applied directly to DNA extracted from

  Ziehl-Neelsen-positive smears as well.


1507. Salajka F.  Mezensky L.  Pokorny A. Commercial polymerase chain reaction test (Amplicor set) in the diagnosis of smear-negative pulmonary tuberculosis from sputum and bronchoalveolar  lavage. Monaldi Archives for Chest Disease.  55(1):9-12, 2000 Feb.


  The study presents experience with polymerase chain reaction (PCR) in the

  diagnosis of tuberculosis (TB) and compares the results obtained in sputum

  and bronchoalveolar lavage fluid (BALF). A total of 1,097 samples from 846

  smear-negative patients with suspected TB was examined using PCR and

  culture during a period of 40 months. TB was the final diagnosis in 160

  patients, based on the evidence of mycobacteria in 90 patients and on

  clinical criteria in the remaining 70. The PCR test had high specificity

  (98% and 99%, respectively) but poor sensitivity (37% and 34%,

  respectively) regardless of whether sputum or BALF was examined.

  Surprisingly, the sensitivity of culture (44% and 35% in sputum and BALF,

  respectively) was higher than that of PCR in this group. The contribution

  of BAL to establishing the diagnosis of tuberculosis was rather limited,

  yet substantial in some patients. The results obtained in this study were

  compared with the results published in the literature, and it was

  concluded that further clinical studies are necessary to establish an

  appropriate role for the polymerase chain reaction in the diagnosis of




1508. Scarparo C.  Piccoli P.  Rigon A.  Ruggiero G.  Scagnelli M.  Piersimoni  C. Comparison of enhanced Mycobacterium tuberculosis amplified direct test  with COBAS AMPLICOR Mycobacterium tuberculosis assay for direct detection of Mycobacterium tuberculosis complex in respiratory and extrapulmonary  specimens.  Journal of Clinical Microbiology.  38(4):1559-62, 2000 Apr.


  The new Roche COBAS AMPLICOR Mycobacterium tuberculosis Assay was compared

  to the Gen-Probe enhanced Mycobacterium tuberculosis Amplified Direct Test

  (AMTDII). A total of 486 specimens (296 respiratory and 190

  extrapulmonary) collected from 323 patients were tested in parallel with

  both assays. Results were compared with those of acid-fast staining and

  culture, setting the combination of culture and clinical diagnosis as the

  "gold standard." After resolution of discrepant results, the sensitivity,

  specificity, and positive and negative predictive values for AMTDII were

  85.7, 100, 100, and 90.4% for respiratory specimens and 82.9, 100, 100,

  and 95. 5% for extrapulmonary specimens, respectively. The corresponding

  values for AMPLICOR were 94.2, 100, 100, and 96.6% for respiratory

  specimens and 85, 100, 100, and 96.1% for extrapulmonary specimens,

  respectively. No significant differences were observed between the results

  of both assays or, within each one, between respiratory and extrapulmonary

  specimens. The difference between AMTDII and AMPLICOR sensitivities was

  related to the presence of inhibitory samples, which the former assay,

  lacking an internal amplification control (IAC), could not detect. The

  overall inhibition rate for the AMPLICOR assay was 3.9% (19 specimens). It

  is concluded that, although both amplification assays proved to be rapid

  and specific for the detection of M. tuberculosis complex in clinical

  samples, AMPLICOR, by a completely automated amplification and detection

  procedure, was shown to be particularly feasible for a routine laboratory

  setting. Finally, AMTDII is potentially an excellent diagnostic technique

  for both respiratory and extrapulmonary specimens, provided that an IAC is

  included with the assay.



1509. Sethi GR.  Batra V. Bronchiectasis: causes and management. Indian Journal of Pediatrics.  67(2):133-9, 2000 Feb.


  Bronchiectasis is a condition representing abnormal and permanent

  dilatation and distortion of medium sized bronchi, usually accompanied by

  destruction of the airway wall. Post inflammatory bronchiectasis remains

  very common in the developing countries as a sequel to pulmonary

  tuberculosis, whooping cough, and severe measles (among other causes).

  Cystic fibrosis is the most common cause of generalized bronchiectasis in

  developed countries. Symptoms primarily are chronic cough and

  expectoration of foul smelling sputum. Bronchography was, until recently,

  the investigation of choice for the diagnosis of bronchiectasis and the

  gold standard against which the current best imaging technique HRCT (high

  resolution computed tomography) has been compared. Treatment includes

  prompt attention to acute exacerbations, management of airway secretions

  and control of airway hyperreactivity. Treatment is aimed at the non

  progression of the disease and complete cure if possible. The role of

  surgical therapy has evolved from early curative resection for all

  patients to a more palliative approach. Patients with advanced generalized

  bronchiectasis should be considered for lung transplantation.




1510. Silva CL.  Lowrie DB. Identification and characterization of murine cytotoxic T cells that kill  Mycobacterium tuberculosis. Infection & Immunity.  68(6):3269-74, 2000 Jun.


  As we seek to develop and evaluate new vaccines against tuberculosis, it

  is desirable that we understand the mechanisms of protective immunity in

  our models. Adoptive transfer of protection with hsp65-specific T-cell

  clones from infected or vaccinated mice into naive mice had indicated that

  cytotoxic T cells can make a major contribution to protection. We

  characterized 28 CD4(+) CD8(-) and 28 CD4(-) CD8(+) hsp65-specific T-cell

  clones derived from infected or vaccinated mice. Half of the CD4(+) CD8(-)

  and 64% of the CD4(-) CD8(+) clones were cytotoxic. Cytotoxicity was

  associated with high expression of CD44 and gamma interferon production.

  Most (86%) of the cytotoxic CD4(+) CD8(-) clones lysed target cells via

  the Fas-FasL pathway, and most (83%) of the cytotoxic CD4(-) CD8(+) clones

  lysed target cells via cytotoxic granules. Only the clones using the

  granule-mediated pathway caused substantial loss of viability of virulent

  Mycobacterium tuberculosis during lysis of infected macrophages, and the

  degree of killing closely correlated with the availability of granule

  marker enzyme activity. Granule-mediated cytotoxicity thus may have a key

  role in protection against tuberculosis by delivering mycobactericidal

  granule contents.



1511. Silva CL.  The potential use of heat-shock proteins to vaccinate against  mycobacterial infections. [Review] [43 refs] Microbes & Infection.  1(6):429-35, 1999 May.


  Over the last few years, some of our experiments in which mycobacterial

  heat-shock protein (HSP) antigens were presented to the immune system as

  if they were viral antigens have had a significant impact on our

  understanding of protective immunity against tuberculosis. They have also

  markedly enhanced the prospects for new vaccines. We now know that the

  mycobacterial HSP65 antigen can confer protection equal to that from live

  BCG vaccine in mice. [References: 43]



1512. Singh KK.  Muralidhar M.  Kumar A.  Chattopadhyaya TK.  Kapila K.  Singh  MK.  Sharma SK.  Jain NK.  Tyagi JS. Comparison of in house polymerase chain reaction with conventional techniques for the detection of Mycobacterium tuberculosis DNA in granulomatous lymphadenopathy. Journal of Clinical Pathology.  53(5):355-61, 2000 May.


  AIMS: To evaluate the usefulness of the devR based polymerase chain

  reaction (PCR) in the detection of Mycobacterium tuberculosis in lymph

  node aspirates and tissues of lymphadenitis and to compare PCR with

  conventional diagnostic techniques. SUBJECTS AND METHODS: Coded specimens

  of fine needle aspirates and biopsies from 22 patients with tuberculous

  lymphadenitis, 14 patients with non-tubercular lymphadenitis, and nine

  patients with granulomatous lymphadenitis were processed and subjected to

  analysis by PCR, smear microscopy, M tuberculosis culture, histology, and

  cytology. RESULTS: Tuberculous lymphadenitis was correctly diagnosed by

  PCR in 18 patients, by culture in five patients, by histology in 13

  patients, and by cytology in seven patients. PCR gave two false positive

  results in 14 patients with non-tubercular lymphadenitis. The sensitivity

  of the conventional techniques was significantly higher with biopsies (17

  of 22 specimens; 77%) than with fine needle aspirates (nine of 22

  specimens; 41%). However, the sensitivity of PCR was not significantly

  higher with biopsies (68%) in comparison with fine needle aspirates (55%).

  The sensitivity of either biopsy PCR or fine needle aspirate PCR was not

  significantly different from that of either histology combined with

  culture or cytology combined with culture. The overall combined

  specificity of PCR was 86%. Mycobacterium tuberculosis DNA was detected in

  six of nine patients with granulomatous lymphadenitis. CONCLUSION: PCR is

  the most sensitive single technique available to date for the

  demonstration of M tuberculosis in specimens derived from patients with a

  clinical suspicion of tuberculous lymphadenitis. The value of PCR lies in

  its use as an adjunct test in the diagnosis of tuberculous lymphadenitis,

  particularly in those patients where conventional methods fail. Because

  fine needle aspiration is not an invasive procedure, it is the procedure

  of choice, and PCR should be performed initially on these samples.

  Excisional biopsy histology and PCR should be recommended only for

  patients in whom fine needle aspirate PCR is negative or when there is

  discrepancy with the clinical impression.


1513. Singh NP.  Parija SC. The value of fluorescence microscopy of auramine stained sputum smears for the diagnosis of pulmonary tuberculosis. Southeast Asian Journal of Tropical Medicine & Public Health.  29(4):860-3, 1998 Dec.


  Laboratory diagnosis of pulmonary tuberculosis rests on the

  bacteriological examination of sputum smears stained by the Ziehl-Neelsen

  (ZN) method for acid fast bacilli (AFB). In the present study, we have

  compared light microscopy of ZN stained smears with that of fluorescence

  microscopy of sputum smears stained by auramine-phenol flurochrome dye for

  detection of AFB in sputum specimens. Sputum specimens from a total of

  2,600 clinically suspected and diagnosed cases of pulmonary tuberculosis

  were examined by both the methods. Sputum specimens from a total of 1,104

  patients were found to be positive for AFB. These included sputa from 975

  (37.5%) patients positive for AFB by both ZN and auramine staining methods

  and sputa from an additional 129 (4.96%) patients positive for AFB by

  auramine staining only. Thus auramine staining of sputum smears in

  comparison to that of ZN staining is a better method of sputum microscopy

  for demonstration of AFB in sputum specimens. Fluorescence microscopy is

  relatively more sensitive and has the added advantage of allowing a large

  number of sputum specimens to be examined in a given time, in laboratories

  equipped with a fluorescent microscope.


1514. Singh S.  Cherian RS.  George B.  Nair S.  Srivastava A. Unusual extra-axial central nervous system involvement of non-Hodgkin's lymphoma: magnetic resonance imaging. Australasian Radiology.  44(1):112-4, 2000 Feb.


  The MR imaging findings in a patient with non-Hodgkin's lymphoma with

  unusual involvement of the sella, pituitary stalk and left parasellar

  region are reported here. On the basis of the MR imaging findings, the

  initial differential diagnosis included invasive pituitary adenoma, a

  granulomatous lesion and en plaque meningioma. Trans-sphenoidal biopsy of

  the sellar mass showed chronic inflammatory changes and the patient was

  initially treated for tuberculosis. Because follow-up imaging showed the

  lesion to be progressive, a biopsy was done of an enlarged right inguinal

  lymph node. This revealed non-Hodgkin's lymphoma.


1515. Stone DS. Health surveillance for health care workers. A vital role for the occupational and environmental health nurse. [Review] [33 refs] AAOHN Journal.  48(2):73-9, 2000 Feb.


  Health surveillance for the general health care worker includes

  surveillance for immunity to infectious diseases such as measles, mumps,

  rubella, varicella, and hepatitis B. Post exposure surveillance for

  bloodborne pathogens includes HIV, hepatitis B, and hepatitis C. Periodic

  surveillance of specialty practice areas as mandated by OSHA include

  workers exposed to lasers, radiation, formaldehyde, ethylene oxide,

  hazardous drugs, anesthetic gases, and tuberculosis. [References: 33]


1516. Strohmeier GR.  Fenton MJ. Roles of lipoarabinomannan in the pathogenesis of tuberculosis. [Review]  [63 refs] Microbes & Infection.  1(9):709-17, 1999 Jul.


  Tuberculosis is a worldwide public health threat caused by Mycobacterium

  tuberculosis. All mycobacteria express a unique cell envelope glycolipid,

  lipoarabinomannan, which can be released at sites of infection.

  Lipoarabinomannan is a potential virulence factor which can bind to

  leukocytes and modulate immune responses. Here, we provide an overview of

  the interactions of mycobacteria and lipoarabinomannan with immune cells.

  [References: 63]


1517. Swaminathan S.  Umadevi P.  Shantha S.  Radhakrishnan A.  Datta M.  Sero diagnosis of tuberculosis in children using two ELISA kits. Indian Journal of Pediatrics.  66(6):837-42, 1999 Nov-Dec.


  The diagnosis of childhood tuberculosis is based on circumstantial

  evidence in the absence of a gold standard in the majority of cases.

  Sero-diagnosis offers scope for an early diagnosis in a variety of

  clinical conditions and is simple to perform. A number of mycobacterial

  antigens have been used for antibody detection assays and several are

  available as kits in the market. This study was done to evaluate the value

  of antibody detection kits (ELISA) against the A60 antigen and 38 kDa

  antigen of Mycobacterium tuberculosis in the diagnosis of childhood

  tuberculosis at the outpatient department of the Institute of Social

  Paediatrics, Government Stanley Hospital in collaboration with

  Tuberculosis Research Centre, Chennai. Thirty five children with pulmonary

  tuberculosis, 7 with TB lymphadenitis and 22 healthy controls were

  studied. In addition to routine investigations including gastric lavage

  for AFB culture, serum antibodies against the A60 and 38 kDa antigens were

  assayed using commercially available ELISA kits. With A60, IgM serum

  levels were positive in 74% of pulmonary TB cases, 57% of TB lymphadenitis

  cases and 50% of controls. A60 IgG was positive in 17% of pulmonary TB,

  86% of TB lymphadenitis and 14% of controls. The 38 kDa IgG antibody was

  positive in 37% of pulmonary and 86% of TB lymphadenitis cases and 27% of

  controls. Among 10 culture confirmed cases, A60 IgM was positive in 8, A60

  IgG in 3 and 38 kDa IgG in 5 patients. The sensitivity of the tests ranged

  between 29% and 71% and specificity between 50% and 86%. Although the

  numbers are small, the results suggest that serodiagnosis using the

  currently available antigens of M. tuberculosis is unlikely to be a

  confirmatory test for tuberculosis in children.


1518. Swingler GH. Chest radiography in ambulatory children with acute lower respiratory  infections: effective tuberculosis case-finding?. Annals of Tropical Paediatrics.  20(1):11-5, 2000 Mar.


  A study was performed to determine the proportion of ambulatory children

  with acute lower respiratory infections in whom clinical management was

  changed by findings on routine chest radiography that suggested

  tuberculosis. The children studied were aged between 2 and 59 months and

  met the World Health Organization's case definition for pneumonia. They

  lived in an area with a very high prevalence of tuberculosis. Exclusion

  criteria included a cough of more than 14 days' duration and a history of

  a current household contact with active tuberculosis. Twelve (4.4%) of 273

  children had radiological findings suggesting tuberculosis, nine of which

  were suspected mediastinal lymphadenopathy. Eight children were further

  investigated for tuberculosis: seven of them did not require treatment for

  tuberculosis and one was lost to follow-up. It is concluded that chest

  radiography in ambulatory children with acute lower respiratory infections

  of less than 14 days' duration and not in contact with active tuberculosis

  does not result in a meaningful increase in the diagnosis of tuberculosis.


1519. van Pinxteren LA.  Ravn P.  Agger EM.  Pollock J.  Andersen P. Diagnosis of tuberculosis based on the two specific antigens ESAT-6 and CFP10. Clinical & Diagnostic Laboratory Immunology.  7(2):155-60, 2000 Mar.


  Tests based on tuberculin purified protein derivative (PPD) cannot

  distinguish between tuberculosis infection, Mycobacterium bovis BCG

  vaccination, or exposure to environmental mycobacteria. The present study

  investigated the diagnostic potential of two Mycobacterium

  tuberculosis-specific antigens (ESAT-6 and CFP10) in experimental animals

  as well as during natural infection in humans and cattle. Both antigens

  were frequently recognized in vivo and in vitro based on the induction of

  delayed-type hypersensitivity responses and the ability to induce gamma

  interferon production by lymphocytes, respectively. The combination of

  ESAT-6 and CFP10 was found to be highly sensitive and specific for both in

  vivo and in vitro diagnosis. In humans, the combination had a high

  sensitivity (73%) and a much higher specificity (93%) than PPD (7%).


1520. Walker D.  McNerney R.  Mwembo MK.  Foster S.  Tihon V.  Godfrey-Faussett  P. An incremental cost-effectiveness analysis of the first, second and third  sputum examination in the diagnosis of pulmonary tuberculosis. International Journal of Tuberculosis & Lung Disease.  4(3):246-51, 2000  Mar.


  SETTING: St. Francis Hospital in Katete District, Eastern Province,

  Zambia. OBJECTIVE: To compare the incremental cost-effectiveness of

  examining serial sputum smears for screening suspects for pulmonary

  tuberculosis at a rural district hospital in Zambia. DESIGN: An

  incremental cost-effectiveness analysis of serial sputum smear

  examinations for diagnosing pulmonary tuberculosis based on laboratory

  results collected during 1997 and 1998 in a rural district hospital in

  Zambia. The cost analysis took a health service provider perspective, and

  used the ingredients approach. The cost-effectiveness is expressed in

  terms of the incremental cost per tuberculosis case diagnosed. Relevant

  information was obtained from various sources, including administrative

  records, interviews and direct observation. RESULTS: Of a total of 166

  acid-fast bacilli positive suspects who had three sputum smears examined

  sequentially, 128 (77.1%) were found on the first smear, a further 25

  (15%) on the second smear and 13 (7.9%) additional cases were identified

  on the third smear. The economic analysis shows that the incremental cost

  of performing a third test, having already done two, increases rapidly

  with only a small gain in terms of additional cases of tuberculosis

  identified. CONCLUSION: A policy of examining two samples should be

  considered in resource-poor settings, if the remaining steps of the

  national diagnostic algorithm can be adhered to with respect to

  smear-negative suspects.


1521. Ward BJ. Vaccine adverse events in the new millennium: is there reason for concern? [see comments]. [Review] [62 refs] Bulletin of the World Health Organization.  78(2):205-15, 2000.


  As more and more infectious agents become targets for immunization

  programmes, the spectrum of adverse events linked to vaccines has been

  widening. Although some of these links are tenuous, relatively little is

  known about the immunopathogenesis of even the best characterized

  vaccine-associated adverse events (VAAEs). The range of possible use of

  active immunization is rapidly expanding to include vaccines against

  infectious diseases that require cellular responses to provide protection

  (e.g. tuberculosis, herpes viral infections), therapeutic vaccines for

  chronic infections (e.g. human immunodeficiency virus (HIV) infection,

  viral hepatitis B and C), and vaccines against non-infectious conditions

  (e.g. cancer, autoimmune diseases). Less virulent pathogens (e.g.

  varicella, rotavirus in the developed world) are also beginning to be

  targeted, and vaccine use is being justified in terms of societal and

  parental "costs" rather than in straightforward morbidity and mortality

  costs. In the developed world the paediatric immunization schedule is

  becoming crowded, with pressure to administer increasing numbers of

  antigens simultaneously in ever simpler forms (e.g. subcomponent, peptide,

  and DNA vaccines). This trend, while attractive in many ways, brings

  hypothetical risks (e.g. genetic restriction, narrowed shield of

  protection, and loss of randomness), which will need to be evaluated and

  monitored. The available epidemiological and laboratory tools to address

  the issues outlined above are somewhat limited. As immunological and

  genetic tools improve in the years ahead, it is likely that we shall be

  able to explain the immunopathogenesis of many VAAEs and perhaps even

  anticipate and avoid some of them. However, this will only happen if the

  human and financial resources needed for monitoring and studying vaccine

  safety stay in step with the accelerating pace of vaccine development.

  Failure to make such a commitment would put all immunization programmes at

  risk. [References: 62]


1522. Warren JR.  Bhattacharya M.  De Almeida KN.  Trakas K.  Peterson LR.  A minimum 5.0 ml of sputum improves the sensitivity of acid-fast smear for  Mycobacterium tuberculosis. American Journal of Respiratory & Critical Care Medicine.  161(5):1559-62,  2000 May.


  Detection of acid-fast bacilli (AFB) by sputum smear supports treatment

  decisions with pulmonary tuberculosis (TB), but smear sensitivity for

  Mycobacterium tuberculosis is only approximately 45 to 75%. In an effort

  to increase sensitivity, smears were prepared using a minimum sputum

  volume of 5.0 ml. Sensitivity of smears during a 39-mo period (n = 1,849)

  using >/= 5.0 ml of sputum was 92. 0%, significantly greater (p < 0.001)

  than a sensitivity of 72.5% in a previous 24-mo period (n = 3,486) when

  all specimens were processed regardless of volume. All new cases of TB (n

  = 18) were smear-positive with >/= 5.0 ml of sputum before treatment, and

  all were receiving antituberculosis drugs at hospital discharge. In

  contrast, significantly fewer new cases of TB (14 of 26, p = 0.002) were

  positive before treatment when smears were prepared using sputum of any

  volume, and significantly fewer of these new TB cases (18 of 26, p = 0.03)

  were receiving treatment at hospital discharge. The eight cases without

  treatment were smear-negative. These results indicate that acid-fast smear

  using >/= 5.0 ml of sputum increases sensitivity for M. tuberculosis and

  accelerates treatment of TB.



1523. Wilkinson D. Drugs for preventing tuberculosis in HIV infected persons. [Review] [6  refs] Cochrane Database of Systematic Reviews [computer file].  (2):CD000171,  2000.


  BACKGROUND: People with HIV have a increased risk of developing

  tuberculosis. Preventive therapy may help prevent progression of

  tuberculosis infection to disease. OBJECTIVES: The objective of this

  review was to assess the effects of preventive therapy with

  anti-tuberculosis drugs in people with HIV infection. SEARCH STRATEGY: The

  Cochrane Infectious Diseases Group trials register, the Cochrane

  Controlled Trials Register, Medline, Embase and reference lists of

  articles were searched. Researchers in the field were contacted. SELECTION

  CRITERIA: Randomised trials of anti-tuberculosis drugs in people with HIV

  infection but without evidence of active tuberculosis. DATA COLLECTION AND

  ANALYSIS: One reviewer assessed eligibility and trial quality. Study

  authors were contacted for additional information. MAIN RESULTS: Six

  trials were included. Compared to placebo, preventive therapy was

  associated with a lower incidence of active tuberculosis (relative risk

  0.54, 95% confidence interval 0.39 to 0.76). Risk of death (relative risk

  0.96, 95% confidence interval 0.82 to 1.13) was not significantly

  different in the two groups. Incidence of tuberculosis was reduced in

  people with a positive tuberculin skin test (relative risk 0.24, 95%

  confidence interval 0.14 to 0.40), but was not significantly lower in

  those with a negative skin test (relative risk 0.87, 95% confidence

  interval 0.56 to 1.36). Similarly death was less frequent in those with a

  positive skin test who received preventive therapy (relative risk 0.77,

  95% confidence interval 0.58 to 1.03), but this difference was not

  observed among those with a negative skin test (relative risk 1.07, 95%

  confidence interval 0.88 to 1.30). Each regimen (isoniazid alone,

  isoniazid plus rifampicin, isoniazid plus rifampicin plus pyrazinamide,

  rifampicin plus pyrazinamide) had similar protective effects against

  active tuberculosis for people with positive skin tests. REVIEWER'S

  CONCLUSIONS: Preventive therapy appears to be effective in reducing

  incidence of tuberculosis, and death from tuberculosis in HIV infected

  adults with a positive tuberculin skin test, at least in the short to

  medium term. [References: 6]


1524. Willcox PA. Drug-resistant tuberculosis. [Review] [49 refs] Current Opinion in Pulmonary Medicine.  6(3):198-202, 2000 May.


  There is increasing concern in many countries about the problem of

  drug-resistant tuberculosis, particularly so because no new classes of

  drugs have been developed for the treatment of tuberculosis since the

  1960s. Although drug resistance is thought to be fairly common in some

  countries and rare in others, the global extent of this condition is not

  precisely known. This problem is currently being investigated by a

  combined initiative of the World Health Organization and the International

  Union Against Tuberculosis and Lung Disease. Recently, there have been

  advances in the understanding of the genetic basis of drug-resistant

  tuberculosis. With the sequencing of the whole genome of Mycobacterium

  tuberculosis, the possibility of new targets for drug development has

  emerged. For the present, however, cure rates on average remain modest,

  and nonadherence with chemotherapy remains a major problem. Drug

  resistance is a man-made problem and efforts to prevent it through

  directly observed therapy, short course are essential. [References: 49]



1525. Yencha MW.  Linfesty R.  Blackmon A. Laryngeal tuberculosis. [Review] [15 refs] American Journal of Otolaryngology.  21(2):122-6, 2000 Mar-Apr.


  Since the introduction of antituberculous medications, the incidence of

  laryngeal tuberculosis (TB) has decreased and remains stable. However,

  with the incidence of TB increasing, mainly caused by the acquired

  immunodeficiency syndrome epidemic, the incidence of laryngeal involvement

  may be on the rise. The main presenting symptom of laryngeal TB is

  dysphonia. The diagnosis is confirmed with the identification of

  granulomatous inflammation, caseating granulomas, and acid-fast bacilli on

  histopathologic examination of biopsied laryngeal tissue. However, making

  the diagnosis difficult can be the presence of pseudoepitheliomatous

  hyperplasia, which mimics squamous cell carcinoma. Treatment is primarily

  with antituberculous medications with surgery reserved for those cases of

  airway compromise. Laryngeal complications can occur; thus, long-term

  follow-up is recommended. We report a case of laryngeal TB in a human

  immunodeficiency virus-negative patient and review the literature.

  [References: 15]


1526. Zedtwitz-Liebenstein K.  Podesser B.  Peck-Radosavljevic M.  Graninger W.  Intestinal tuberculosis presenting as fever of unknown origin in a heart  transplant patient. Infection.  27(4-5):289-90, 1999.


  Patients undergoing transplantation have an increased risk of developing

  infections such as tuberculosis, Pneumocystis carinii pneumonia, Candida

  infections or cytomegalovirus infections because of their

  immunosuppressive therapy with cyclosporin A, azathioprine and steroids.

  Mycobacterial infection is well recognized as a complication in the

  immunocompromised host but diagnosis and therapy are very difficult.



1884. Authors



  Update: Nucleic acid amplification tests for tuberculosis.


  MMWR - Morbidity & Mortality Weekly Report.  49(26):593-4, 2000 Jul 7.


  On September 30, 1999, the Food and Drug Administration approved a

  reformulated Amplified Mycobacterium Tuberculosis Direct Test (MTD)

  (Gen-Probe, San Diego, California) for detection of Mycobacterium

  tuberculosis in acid-fast bacilli (AFB) smear-positive and smear-negative

  respiratory specimens from patients suspected of having tuberculosis (TB).

  MTD and one other nucleic acid amplification (NAA) test, the Amplicor

  Mycobacterium Tuberculosis Test (Amplicor) (Roche Diagnostic Systems,

  Inc., Branchburg, New Jersey), previously had been approved for the direct

  detection of M. tuberculosis in respiratory specimens that have positive

  AFB smears. This notice updates the original summary published in 1996 (1)

  and provides suggestions for using and interpreting NAA test results for

  managing patients suspected of having TB. The appropriate number of

  specimens to test with NAA will vary depending on the clinical situation,

  the prevalence of TB, the prevalence of nontuberculous mycobacteria (NTM),

  and laboratory proficiency (2,3). Based on available information, the

  following algorithm is a reasonable approach to NAA testing of respiratory

  specimens from patients with signs or symptoms of active pulmonary TB for

  whom a presumed diagnosis has not been established.


1885. Authors

  Ardito F.  Sanguinetti M.  Sechi L.  Posteraro B.  Masucci L.  Fadda G.

  Zanetti S.


  Comparison of the mycobacteria growth indicator tube with radiometric and

  solid culture for isolation of mycobacteria from clinical specimens and

  susceptibility testing of Mycobacterium tuberculosis.


  New Microbiologica.  23(2):151-8, 2000 Apr.


  We compared the mycobacteria growth indicator tube (MGIT) system with the

  BACTEC 460 TB and Loewenstein-Jensen (LJ) systems for the recovery of

  mycobacteria (acid-fast bacilli [AFB]) from 600 clinical specimens. A

  total of 50 AFB (32 Mycobacterium tuberculosis complex, 10 M. avium

  complex, 3 M. gordonae, 3 M. xenopi, 1 M. terrae and 1 M. fortuitum) were

  detected. MGIT recovered 50 isolates of AFB (100% sensitivity), and BACTEC

  460 TB and LJ recovered 49 (98% sensitivity) and 19 (38% sensitivity) AFB

  isolates, respectively. The mean times to detect mycobacteria were 10, 10

  and 25 days for MGIT, BACTEC 460, and LJ slants. All isolates of M.

  tuberculosis complex were tested for susceptibility to streptomycin,

  isoniazid, rifampin, and ethambutol with the MGIT and BACTEC 460 TB. Both

  systems yielded identical susceptibility data with different mean times to

  report (5.38 days for MGIT versus 7.33 days for BACTEC 460 TB, P<0.05).

  The results suggest that MGIT is equivalent to BACTEC 460 TB in its

  ability to support the growth of mycobacteria, but significantly more

  efficient than LJ. MGIT may also be used for susceptibility testing of

  primary antituberculosis drugs.


1886. Authors

  Barnes PF.  Wizel B.


  Type 1 cytokines and the pathogenesis of tuberculosis [editorial;



  American Journal of Respiratory & Critical Care Medicine.  161(6):1773-4,

  2000 Jun.


1887. Authors

  Braibant M.  Gilot P.  Content J.


  The ATP binding cassette (ABC) transport systems of Mycobacterium

  tuberculosis. [Review] [114 refs]


  FEMS Microbiology Reviews.  24(4):449-67, 2000 Oct.


  We have undertaken the inventory and assembly of the typical subunits of

  the ABC transporters encoded by the complete genome of Mycobacterium

  tuberculosis. These subunits, i.e. the nucleotide binding domains (NBDs),

  the membrane-spanning domains (MSDs) and the substrate binding proteins

  (SBPs), were identified on the basis of their characteristic stretches of

  amino acids and/or conserved structure. A total of 45 NBDs present in 38

  proteins, of 47 MSDs present in 44 proteins and of 15 SBPs were found to

  be encoded by M. tuberculosis. Analysis of transcriptional clusters and

  searches of homology between the identified subunits of the transporters

  and proteins characterized in other organisms allowed the reconstitution

  of at least 26 complete (including at least one NBD and one MSD) and 11

  incomplete ABC transporters. Sixteen of them were unambiguously classified

  as importers whereas 21 were presumed to be exporters. By searches of

  homology with already known transporters from other organisms, potential

  substrates (peptides, macrolides, carbohydrates, multidrugs, antibiotics,

  iron, anions) could be attributed to 30 of the ABC transporters identified

  in M. tuberculosis. The ABC transporters have been further classified in

  nine different sub-families according to a tree obtained from the

  clustering of their NBDs. Contrary to Escherichia coli and similarly to

  Bacillus subtilis, there is an equal representation of extruders and

  importers. Many exporters were found to be potentially implicated in the

  transport of drugs, probably contributing to the resistance of M.

  tuberculosis to many antibiotics. Interestingly, a transporter (absent in

  E. coli and in B. subtilis) potentially implicated in the export of a

  factor required for the bacterial attachment to the eukaryotic host cells

  was also identified. In comparison to E. coli and B. subtilis, there is an

  under-representation of the importers (with the exception of the phosphate

  importers) in M. tuberculosis. This may reflect the capacity of this

  bacterium to synthesize many essential compounds and to grow in the

  presence of few external nutrients. The genes encoding the ABC

  transporters occupy about 2.5% of the genome of M. tuberculosis.

  [References: 114]


1888. Authors

  Brennan MJ.


  Moving new vaccines for tuberculosis through the regulatory process.


  Clinical Infectious Diseases.  30 Suppl 3:S247-9, 2000 Jun.


  The development of novel vaccines for the prevention of tuberculosis is an

  area of intense interest for scientific researchers, public health

  agencies, and pharmaceutical manufacturers. Development of effective new

  vaccines directed against tuberculosis for use in target populations will

  require close cooperation among several different international

  organizations, including regulatory agencies responsible for evaluating

  the safety and effectiveness of new biologics for human use.


1889. Authors

  Casal M.  Ruiz P.  Herreras A.


  Study of the in vitro susceptibility of M. tuberculosis to ofloxacin in

  Spain. Spanish Study Group of M. tuberculosis resistance.


  International Journal of Tuberculosis & Lung Disease.  4(6):588-91, 2000



  The aim of this study was to determine the proportion of antituberculosis

  ofloxacin resistance among Mycobacterium tuberculosis strain isolates in

  Spain. Over a period of one month, 213 M. tuberculosis strains collected

  from 14 different hospitals were studied, including strains both

  susceptible and resistant to primary antituberculosis drugs. In 28.1% of

  the strains, a minimum inhibitory concentration (MIC) for ofloxacin of

  0.25 microg/ml was obtained; in 43.6% the MIC was 0.5 microg/ml; in 22.06%

  it was 1 microg/ml; and in 6.1% it was > or =2 microg/ml. Ofloxacin

  currently seems to be an effective antimicrobial in vitro against

  susceptible or multiresistant strains of M. tuberculosis in human

  immunodeficiency virus (HIV)-negative or HIV-positive patients in Spain.


1890. Authors

  Castellano I.  Gomez-Martino JR.  Hernandez T.  Mateos L.  Arguello C.


  Hemophagocytic syndrome as an unusual form of presentation of tuberculosis

  in a hemodialysis patient: case report and review of the literature.

  [Review] [22 refs]


  American Journal of Nephrology.  20(3):214-6, 2000 May-Jun.


  We present an unusual manifestation of tuberculosis in a patient on

  hemodialysis. A 73-year-old woman was admitted to our hospital with a

  picture of fever, dyspnea and weight loss. She had chronic renal failure

  and had started periodic hemodialysis 5 years before. Fifteen days after

  admission, she began with pancytopenia, abnormal liver function and

  coagulopathy. A bone marrow aspiration was made 1 week later showing

  macrophage elements with phagocytic activity. Eight weeks later, bone

  marrow culture in Lowenstein media confirmed the presence of tuberculosis.

  After the beginning of antituberculosis therapy, the laboratory

  disturbances disappeared and the clinical situation improved. We think

  that fever of unknown origin and pancytopenia in patients on maintenance

  hemodialysis must lead to an early bone marrow biopsy or aspiration since

  after the diagnosis a specific therapy can cure the disease. Copyright

  2000 S. Karger AG, Basel [References: 22]


1891. Authors

  Chambers MA.  Vordermeier H.  Whelan A.  Commander N.  Tascon R.  Lowrie

  D.  Hewinson RG.


  Vaccination of mice and cattle with plasmid DNA encoding the Mycobacterium

  bovis antigen MPB83.


  Clinical Infectious Diseases.  30 Suppl 3:S283-7, 2000 Jun.


  A scientific review of bovine tuberculosis in Great Britain has concluded

  that the development of a cattle vaccine holds the best prospect for

  long-term disease control. Recent reports of successful DNA vaccination

  against Mycobacterium tuberculosis in small animal models have raised the

  possibility of using a similar strategy to produce vaccines against

  Mycobacterium bovis infection in cattle. To test this possibility, BALB/c

  mice were immunized with DNA encoding the M. bovis antigen MPB83. The mice

  responded to vaccination with a mixed IgG1/IgG2a response to the antigen

  and were protected from intravenous challenge with virulent M. bovis to a

  similar extent as those vaccinated with bacille Calmette-Guerin. The

  immunogenicity of the DNA vaccine in cattle was tested, after having

  established that DNA encoding MPB83 was immunogenic and elicited

  protective immunity in mice. In these studies, vaccinated animals had

  strong proliferative responses to MPB83.


1892. Authors

  Coetsier C.  Vannuffel P.  Blondeel N.  Denef JF.  Cocito C.  Gala JL.


  Duplex PCR for differential identification of Mycobacterium bovis, M.

  avium, and M. avium subsp. paratuberculosis in formalin- fixed

  paraffin-embedded tissues from cattle.


  Journal of Clinical Microbiology.  38(8):3048-54, 2000 Aug.


  We previously isolated and sequenced two genomic segments of Mycobacterium

  avium subsp. paratuberculosis, namely, f57, a species-specific sequence,

  and the p34 gene, coding for a 34-kDa antigenic protein. Comparison of

  sequences upstream of the p34 open reading frame (us-p34) from M. avium

  subsp. paratuberculosis and M. tuberculosis showed a 79-base deletion in

  M. tuberculosis. Sequence analysis of the p34 genes in another two

  species, M. bovis (strain BCG) and M. avium (strain D4), confirmed the

  differences observed between tuberculous and nontuberculous species. A

  duplex diagnostic PCR strategy based on coamplification of nonhomologous

  us-p34 and species-specific f57 sequences was therefore developed. Duplex

  PCR yielded three different patterns, specific either for tuberculous

  bacilli (M. tuberculosis, M. bovis, and M. africanum), for both

  nontuberculous mycobacteria M. avium and M. intracellulare, or for M.

  avium subsp. paratuberculosis. The specificity of this single-step

  DNA-based assay was assessed on DNA from cultured mycobacterial strains,

  as well as on a panel of formalin-fixed and paraffin-embedded tissues from

  cattle. Molecular assay results from tissular DNA were compared to

  conventional bacteriological and histological test results, including

  those obtained by Ziehl-Neelsen staining on tissue biopsy specimens.

  Molecular discrimination was successful and confirmed the value of duplex

  us-p34 and f57 sequence amplification for differential diagnosis of

  tuberculosis, paratuberculosis, or infections caused by other members of

  the M. avium complex.


1893. Authors

  Coler RN.  Skeiky YA.  Ovendale PJ.  Vedvick TS.  Gervassi L.  Guderian J.

  Jen S.  Reed SG.  Campos-Neto A.


  Cloning of a Mycobacterium tuberculosis gene encoding a purifed protein

  derivative protein that elicits strong tuberculosis-specific delayed-type



  Journal of Infectious Diseases.  182(1):224-33, 2000 Jul.


  The purified protein derivative (PPD) skin test has been used for the

  diagnosis of tuberculosis for more than 75 years. However, the test lacks

  specificity because all mycobacteria share antigens present in PPD.

  Therefore, sensitization with nontuberculous pathogenic or with

  environmental nonpathogenic mycobacteria can lead to positive skin tests.

  This communication describes a novel PPD protein present only in

  tuberculous complex mycobacteria. A recombinant protein was obtained and

  named DPPD on the basis of the first 4 amino acids of its N-terminus

  sequence. DPPD elicited delayed-type hypersensitivity (DTH) in 100% of

  Mycobacterium tuberculosis-infected guinea pigs but in no animals

  sensitized with several organisms representative of all members of the

  Mycobacterium genus. Preliminary results indicate that DPPD induces strong

  and specific DTH in humans. This work points to the definition of a single

  recombinant M. tuberculosis protein that may be an alternative to the PPD



1894. Authors

  Collins DM.


  New tuberculosis vaccines based on attenuated strains of the Mycobacterium

  tuberculosis complex.


  Immunology & Cell Biology.  78(4):342-8, 2000 Aug.


  The world urgently needs a better tuberculosis vaccine. Bacille

  Calmette-Guerin (BCG), an attenuated strain of Mycobacterium bovis, has

  been very widely used as a vaccine for many years but has had no major

  effect on reducing the incidence of tuberculosis. A number of alternative

  living and non-living vaccines are being investigated. Live vaccine

  candidates include genetically modified forms of BCG, genetically

  attenuated strains of the Mycobacterium tuberculosis complex and

  genetically engineered vaccinia virus and Salmonella strains. Non-living

  vaccine candidates include killed mycobacterial species, protein subunits

  and DNA vaccines. One requirement for acceptance of any new vaccine will

  be a favourable comparison of the protection it induces relative to BCG in

  a range of animal models, some of which may need further development.

  Molecular genetic techniques are now available that enable production of

  live attenuated strains of the M. tuberculosis complex with vaccine

  potential. In the first of two broadly different approaches that are being

  used, large numbers of mutants are produced by transposon mutagenesis or

  illegitimate recombination and are screened for properties that correlate

  with attenuation. In the second approach, putative genes that may be

  required for virulence are identified and subsequently inactivated by

  allelic exchange. In both approaches, mutants that are attenuated need to

  be identified and subsequently tested for their vaccine efficacy in animal

  models. Many mutants of the M. tuberculosis complex have now been produced

  and the vaccine properties of a substantial number will be assessed in the

  next 3 years.


1895. Authors

  Comstock GW.


  Simple, practical ways to assess the protective efficacy of a new

  tuberculosis vaccine. [Review] [18 refs]


  Clinical Infectious Diseases.  30 Suppl 3:S250-3, 2000 Jun.


  There is strong evidence that tuberculin sensitivity cannot be used to

  evaluate the efficacy of different strains of bacille Calmette-Guerin

  (BCG). For identifying efficacious strains of BCG and evaluating

  candidates for new vaccines, the best method is a randomized trial. Simple

  trials in which newborns would be vaccinated with new and old vaccines in

  alternate years could demonstrate which vaccine was the better.

  [References: 18]


1896. Authors

  de La Rosa JM.  Escobedo M.


  Tuberculosis and other infectious diseases in the adolescent immigrant.

  [Review] [23 refs]


  Adolescent Medicine.  11(2):453-66, 2000 Jun.


  Adolescent medicine physicians are frequently the initial contact for

  adolescents newly arriving in the U.S. and it is important that they

  recognize the needs of their patients. The adolescent immigrant may be

  encountered in a school-based health setting, private practice, community

  health center, or other health care settings. This article begins with a

  review of the categories of immigrants comprising the adolescent

  population. It gives an extensive review of tuberculosis among

  Mexican-American adolescents, detailing history, epidemiology, diagnosis,

  social factors, and treatment modalities. It further delineates the impact

  of Mexican tuberculosis control strategies on the practice of medicine in

  the U.S., and outlines preventive, diagnostic, and therapeutic strategies

  that should be followed in the adolescent immigrant. This article also

  reviews viral hepatitis in its multiple forms and its impact on the

  adolescent immigrant. It concludes by delineating prevention practices

  required for the adolescent immigrant and summarizes the interventions an

  initial contact physician should undertake upon encountering such

  adolescents. [References: 23]


1897. Authors

  DeBarber AE.  Mdluli K.  Bosman M.  Bekker LG.  Barry CE 3rd.


  Ethionamide activation and sensitivity in multidrug-resistant

  Mycobacterium tuberculosis.


  Proceedings of the National Academy of Sciences of the United States of

  America.  97(17):9677-82, 2000 Aug 15.


  Ethionamide (ETA) is an important component of second-line therapy for the

  treatment of multidrug-resistant tuberculosis. Synthesis of radiolabeled

  ETA and an examination of drug metabolites formed by whole cells of

  Mycobacterium tuberculosis (MTb) have allowed us to demonstrate that ETA

  is activated by S-oxidation before interacting with its cellular target.

  ETA is metabolized by MTb to a 4-pyridylmethanol product remarkably

  similar in structure to that formed by the activation of isoniazid by the

  catalase-peroxidase KatG. We have demonstrated that overproduction of

  Rv3855 (EtaR), a putative regulatory protein from MTb, confers ETA

  resistance whereas overproduction of an adjacent, clustered monooxygenase

  (Rv3854c, EtaA) confers ETA hypersensitivity. Production of EtaA appears

  to be negatively regulated by EtaR and correlates directly with [(14)C]ETA

  metabolism, suggesting that EtaA is the activating enzyme responsible for

  thioamide oxidation and subsequent toxicity. Coding sequence mutations in

  EtaA were found in 11 of 11 multidrug-resistant MTb patient isolates from

  Cape Town, South Africa. These isolates showed broad cross-resistance to

  thiocarbonyl containing drugs including ETA, thiacetazone, and



1898. Authors

  Dillinger TL.  Barriga P.  Escarcega S.  Jimenez M.  Salazar Lowe D.

  Grivetti LE.


  Food of the gods: cure for humanity? A cultural history of the medicinal

  and ritual use of chocolate.


  Journal of Nutrition.  130(8S Suppl):2057S-72S, 2000 Aug.


  The medicinal use of cacao, or chocolate, both as a primary remedy and as

  a vehicle to deliver other medicines, originated in the New World and

  diffused to Europe in the mid 1500s. These practices originated among the

  Olmec, Maya and Mexica (Aztec). The word cacao is derived from Olmec and

  the subsequent Mayan languages (kakaw); the chocolate-related term

  cacahuatl is Nahuatl (Aztec language), derived from Olmec/Mayan etymology.

  Early colonial era documents included instructions for the medicinal use

  of cacao. The Badianus Codex (1552) noted the use of cacao flowers to

  treat fatigue, whereas the Florentine Codex (1590) offered a prescription

  of cacao beans, maize and the herb tlacoxochitl (Calliandra anomala) to

  alleviate fever and panting of breath and to treat the faint of heart.

  Subsequent 16th to early 20th century manuscripts produced in Europe and

  New Spain revealed >100 medicinal uses for cacao/chocolate. Three

  consistent roles can be identified: 1) to treat emaciated patients to gain

  weight; 2) to stimulate nervous systems of apathetic, exhausted or feeble

  patients; and 3) to improve digestion and elimination where

  cacao/chocolate countered the effects of stagnant or weak stomachs,

  stimulated kidneys and improved bowel function. Additional medical

  complaints treated with chocolate/cacao have included anemia, poor

  appetite, mental fatigue, poor breast milk production,

  consumption/tuberculosis, fever, gout, kidney stones, reduced longevity

  and poor sexual appetite/low virility. Chocolate paste was a medium used

  to administer drugs and to counter the taste of bitter pharmacological

  additives. In addition to cacao beans, preparations of cacao bark, oil

  (cacao butter), leaves and flowers have been used to treat burns, bowel

  dysfunction, cuts and skin irritations.


1899. Authors

  Donald PR.


  Preventing tuberculosis in childhood. [Review] [20 refs]


  Indian Journal of Pediatrics.  67(5):383-5, 2000 May.


  Almost half of the cases of tuberculosis requiring treatment may arise in

  children. The strategies to control tuberculosis in developing countries

  remain firmly focussed upon adults who are smear positive. The prevention

  of tuberculosis in childhood has two aspects: prevention of infection and

  management of infection once it has occurred. The steps for prevention of

  infection include early diagnosis of adults with tuberculosis who are

  culture positive but not yet smear positive. Use of ultraviolet lighting

  or at least large windows and ventilation in the area where patients are

  kept may reduce the infection rate. An appropriate regimen and supervised

  chemoprophylaxis to ensure good compliance may be an important step

  towards control of tuberculosis infection. [References: 20]


1900. Authors

  Dye C.  Williams BG.


  Criteria for the control of drug-resistant tuberculosis.


  Proceedings of the National Academy of Sciences of the United States of

  America.  97(14):8180-5, 2000 Jul 5.


  Antibiotic resistance is a growing impediment to the control of infectious

  diseases worldwide, tuberculosis (TB) being among them. TB kills two

  million people each year and foci of multidrug-resistant TB (MDR-TB) have

  been identified in Eastern Europe, Africa, Asia, and Latin America. A

  critical question for health policy is whether standardized short-course

  chemotherapy for TB, based on cheap first-line drugs, can prevent and

  reverse the spread of drug resistance. Here we use mathematical modeling,

  in conjunction with treatment results from six countries, to show that

  best-practice short-course chemotherapy is highly likely to bring strains

  resistant to either of the two key drugs isoniazid and rifampicin under

  control and to prevent the emergence of MDR-TB. However, it is not certain

  to contain MDR-TB once it has emerged, partly because cure rates are too

  low. We estimate that approximately 70% of prevalent, infectious MDR-TB

  cases should be detected and treated each year, and at least 80% of these

  cases should be cured, in order to prevent outbreaks of MDR-TB. Poor

  control programs should aim to increase case detection and cure rates

  together for three reasons: (i) these variables act synergistically; (ii)

  when either is low, the other cannot succeed alone; and (iii) the

  second-line drugs needed to raise MDR-TB cure rates are few and extremely

  costly. We discuss the implications of these results for World Health

  Organization policy on the management of antibiotic resistance.


1901. Authors

  Edwards RJ.  David KM.  Crockard HA.


  Management of tuberculomas of the craniovertebral junction.


  British Journal of Neurosurgery.  14(1):19-22, 2000 Feb.


  Tuberculosis of the craniovertebral junction is extremely rare. However,

  recent evidence suggests that the incidence of this condition may be

  increasing in the United Kingdom. The diagnosis is often difficult despite

  advances in imaging using MRI. CT guided biopsy of lesions often yields

  inconclusive results. The transoral approach to the anterior

  craniovertebral junction provides excellent access to this region with a

  low operative morbidity and mortality, enabling biopsy of lesions and

  decompression of the neuraxis. Management of secondary atlantoaxial

  instability, regarding both timing and method of stabilization, is

  controversial. We report two cases of tuberculomas of the craniovertebral

  junction, that illustrate the role of transoral surgery in both diagnosis

  and treatment of this condition. Previous management strategies are

  reviewed and future recommendations are presented.


1902. Authors

  Gennaro ML.


  Immunologic diagnosis of tuberculosis. [Review] [30 refs]


  Clinical Infectious Diseases.  30 Suppl 3:S243-6, 2000 Jun.


  Evaluation of new vaccines against tuberculosis requires diagnostic tools

  for accurately identifying asymptomatic individuals infected with

  Mycobacterium tuberculosis and persons with active tuberculosis. This

  article discusses limitations of current methods for the immunologic

  diagnosis of latent infection and active disease and presents novel

  approaches to developing skin tests and serodiagnostic assays based on

  "cocktails" of multiple antigens of M. tuberculosis. [References: 30]


1903. Authors

  Ginsberg AM.


  A proposed national strategy for tuberculosis vaccine development.


  Clinical Infectious Diseases.  30 Suppl 3:S233-42, 2000 Jun.


  The global tuberculosis epidemic causes approximately 5% of deaths

  worldwide. Despite recent concerted and largely successful tuberculosis

  control efforts, the incidence of tuberculosis in the United States

  remains 74-fold higher than the stated elimination goal of <1 case per

  million population by the year 2010. Current bacille Calmette-Guerin

  vaccines, although efficacious in preventing extrapulmonary tuberculosis

  in young children, have shown widely variable efficacy in preventing adult

  pulmonary tuberculosis, confound skin test screening, and are not

  recommended for use in the United States. The Advisory Council for

  Elimination of Tuberculosis recently stated that tuberculosis would not be

  eliminated from the United States without a more effective vaccine. Recent

  scientific advances have created unprecedented opportunity for

  tuberculosis vaccine development. Therefore, members of the broad

  tuberculosis research and control communities have recently created and

  proposed a national strategy, or blueprint, for tuberculosis vaccine

  development, which is presented here.


1904. Authors

  Glassroth J.


  Clinical considerations in designing trials of vaccines for tuberculosis.


  Clinical Infectious Diseases.  30 Suppl 3:S229-32, 2000 Jun.


  Despite remarkable strides in the treatment of tuberculosis, the disease

  continues to be a major public health problem in many parts of the world,

  a situation that is projected to remain unchanged for years into the

  future. The development of a highly effective vaccine could substantially

  reduce the magnitude of the tuberculosis problem. A tuberculosis vaccine

  could theoretically prevent initial infection by Mycobacterium

  tuberculosis and enhance host response to prevent the progression from

  infection to disease or even to augment response to treatment in cases of

  established disease. Assessment of candidate vaccines will require

  clinical trials. This article suggests how traditional end points of

  morbidity and mortality, a number of newer measures of disease impact, and

  surrogate markers of tuberculous infection and disease might be used in

  such studies.


1905. Authors

  Gupta A.  Kumar V.  Xess A.  Sharma HP.  Shahi SK.


  Role of enzyme linked immunosorbent assay in the diagnosis of suspected

  cases of genito urinary tuberculosis.


  Indian Journal of Pathology & Microbiology.  42(3):307-9, 1999 Jul.


  The aim of study was evaluation of the utility of ELISA test using A60

  Antigen for rapid diagnosis of Genitourinary Tuberculosis in various age

  groups. ELISA test based on mycobacterial antigen A60 (Anda biological,

  France) was used to estimate specific IgG antibodies in the sera of fifty

  four suspected cases of Genito urinary tuberculosis. (GUT)Sera of 30

  montoux negative healthy adults (age/sex matched) were taken as control by

  detecting IgG anti bodies to A60 antigen. It was concluded from this study

  that IgM was positive in 87.0% of cases.


1906. Authors

  Hermon-Taylor J.  Bull TJ.  Sheridan JM.  Cheng J.  Stellakis ML.  Sumar



  Causation of Crohn's disease by Mycobacterium avium subspecies

  paratuberculosis [see comments] [comment]. [Review] [369 refs]


  Canadian Journal of Gastroenterology.  14(6):521-39, 2000 Jun.


  Mycobacterium avium subspecies paratuberculosis (MAP) is a member of the M

  avium complex (MAC). It differs genetically from other MAC in having 14 to

  18 copies of IS900 and a single cassette of DNA involved in the

  biosynthesis of surface carbohydrate. Unlike other MAC, MAP is a specific

  cause of chronic inflammation of the intestine in many animal species,

  including primates. The disease ranges from pluribacillary to

  paucimicrobial, with chronic granulomatous inflammation like leprosy in

  humans. MAP infection can persist for years without causing clinical

  disease. The herd prevalence of MAP infection in Western Europe and North

  America is reported in the range 21% to 54%. These subclinically infected

  animals shed MAP in their milk and onto pastures. MAP is more robust than

  tuberculosis, and the risk that is conveyed to human populations in retail

  milk and in domestic water supplies is high. MAP is harboured in the

  ileocolonic mucosa of a proportion of normal people and can be detected in

  a high proportion of full thickness samples of inflamed Crohn's disease

  gut by improved culture systems and IS900 polymerase chain reaction if the

  correct methods are used. MAP in Crohn's disease is present in a

  protease-resistant nonbacillary form, can evade immune recognition and

  probably causes an immune dysregulation. As with other MAC, MAP is

  resistant to most standard antituberculous drugs. Treatment of Crohn's

  disease with combinations of drugs more active against MAC such as

  rifabutin and clarithromycin can bring about a profound improvement and,

  in a few cases, apparent disease eradication. New drugs as well as

  effective MAP vaccines for animals and humans are needed. The problems

  caused by MAP constitute a public health issue of tragic proportions for

  which a range of remedial measures are urgently needed. [References: 369]


1907. Authors

  Horsburgh CR Jr.


  A large, simple trial of a tuberculosis vaccine.


  Clinical Infectious Diseases.  30 Suppl 3:S213-6, 2000 Jun.


  Although there are no new tuberculosis vaccines currently available, it is

  possible to estimate the infrastructure needed for efficacy trials of such

  a vaccine. A randomized, placebo-controlled vaccine strategy for

  community-wide vaccination of adults is proposed: a large, simple trial

  with recipients stratified at enrollment by human immunodeficiency virus

  serologic status and purified protein derivative-skin test status. The

  outcome, tuberculous disease, would be assessed by community-wide

  surveillance. Such a trial could be carried out in populations in

  developed countries where the annual incidence of tuberculous disease is

  >100 cases per 100,000 persons and in developing countries where the

  incidence is >400 per 100,000 persons. In developed countries, enrollment

  of 14,600-80,000 persons would be needed, depending on the initial

  assumptions; in developing countries, enrollment would be 4400-27,000

  persons. Readiness for tuberculosis vaccine efficacy trials will require

  epidemiological field studies to identify potential trial sites and

  investment in local diagnostic, surveillance, and data management



1908. Authors

  Jain AK.  Jena A.  Dhammi IK.


  Correlation of clinical course with magnetic resonance imaging in

  tuberculous myelopathy.


  Neurology India.  48(2):132-9, 2000 Jun.


  Sixty cases of spinal tuberculosis with neurological deficit treated with

  'middle path regimen' were analysed and therapeutic response was

  correlated with the magnetic resonance imaging (MRI) observations.

  Tuberculous lesions were found to be more extensive than seen on plain

  X-ray in 60% of the cases. MRI showed the involvement of one or both

  pedicles in nearly 90% of the cases, in addition to the vertebral body

  lesion as seen in the X-rays. The patients showing predominantly

  extradural collection of fluid with relatively preserved cord size, and

  MRI evidence of myelitis/oedema, improved neurologically with treatment.

  The myelomalacia of cord was found to be a poor prognostic sign for neural

  recovery. The magnitude of thinning of cord did not always correlate with

  severity of neural deficit, however, thinning of cord in association with

  myelomalacia carried a bad prognosis. The complete neural recovery is not

  expected in patients with syrinx formation proximal or distal to the

  diseased spine, either with antitubercular drugs or after mechanical

  decompression. MRI changes in dura-subarachnoid complex suggesting

  arachnoiditis generally correlated with poor neural recovery. MRI provided

  a reliable guide to the level and extent of surgical decompression, and

  prognostication of the outcome of therapeutic measures.


1909. Authors

  Jeyakumar D.


  A case of primary drug resistant tuberculosis.


  Medical Journal of Malaysia.  55(2):129-31, 2000 Jun.


  A young man presented with primary multi-drug resistant tuberculosis. The

  institution of second-line regimes with insufficient efficacy due to

  clinical inexperience, unreliable sensitivity reports and the

  inavailability of second-line drugs led to the development of an organism

  that was resistant to ten anti-tuberculous drugs. Accurate sensitivity

  testing done in an overseas laboratory enabled the institution of a

  six-drug regimen that has resulted in clinical cure.


1910. Authors

  Jones PB.  Parrish NM.  Houston TA.  Stapon A.  Bansal NP.  Dick JD.

  Townsend CA.


  A new class of antituberculosis agents.


  Journal of Medicinal Chemistry.  43(17):3304-14, 2000 Aug 24.


  Long-chain lipid envelopes are characteristic of mycobacteria such as

  those that cause tuberculosis and leprosy. Inhibition of fatty acid

  synthesis or elongation is a strategy demonstrated to be clinically

  effective against M. tuberculosis. A new class of compounds designed to

  inhibit the beta-ketoacyl synthase reaction of fatty acid synthesis has

  been developed. Of >30 compounds described, the most active were

  acetamides containing alkylsulfonyl substituents. Inhibitory activities

  were acutely sensitive to net charge, chain length, and degree of

  unsaturation. The most active compound 5 (alkyl = C(10)) contained a

  single methylene spacer between the sulfone and carboxamide and exhibited

  an MIC of 0.75-1.5 &mgr;g/mL, comparable to first-line antituberculosis

  drugs. These compounds are species-specific, exhibiting no significant

  activity against bacterial species other than M. tuberculosis and closely

  related strains. The synthesis, biological activity, and specificity of

  these compounds are described.


1911. Authors

  Kakkar N.  Sharma M.  Ray P.  Sethi S.  Kumar S.


  Evaluation of E test for susceptibility testing of Mycobacterium

  tuberculosis to primary anti tubercular drugs.


  Indian Journal of Medical Research.  111:168-71, 2000 May.


  BACKGROUND & OBJECTIVES: Antimicrobial susceptibility tests for

  tuberculosis take weeks and delayed therapy can lead to an increase in

  disease incidence. The E test is a new concept for minimum inhibitory

  concentrations (MIC) determinations for antimicrobial agents that is based

  on a predefined antibiotic gradient on a plastic strip calibrated with a

  continuous logarithmic MIC scale covering 15 two-fold dilutions. The

  present study was undertaken to evaluate E test strips for susceptibility

  testing of Mycobacterium tuberculosis. METHODS: Twenty five clinical

  isolates of M. tuberculosis were tested for the four first line

  antitubercular drugs by E test and were compared with standard proportion

  method. The inoculum turbidity was adjusted to McFarland 3.0 standard and

  agar plates (Middle brook 7H11 agar) were inoculated and preincubated (37

  degrees C in 7-10% CO2) for 24 h after which time, the E test strips were

  placed on the agar surface which were incubated under same conditions. The

  MIC was interpreted as the point at which the ellipse intersected the 'E

  test' strip as described in E test technical guide. RESULTS: Of the 25

  strains, susceptibility as determined by both methods for isoniazid (INH),

  rifampin, ethambutol and streptomycin was found in 22 (88%), 20 (80%), 24

  (96%) and 18 (72%) strains respectively. Agreement between E test and

  proportion method was 96 per cent for INH, 92 per cent for rifampin and

  100 per cent for ethambutol and streptomycin each. However, sensitivity

  could be predicted after 7-10 days by E test and exact MIC could also be

  determined. INTERPRETATION & CONCLUSIONS: E test method was found to be

  rapid, accurate, reliable and easy to perform. It can be employed for

  routine susceptibility testing for antitubercular drugs.


1912. Authors

  Karia K.  Mathur SK.


  Tuberculous cold abscess simulating pancreatic pseudocyst.


  Journal of Postgraduate Medicine.  46(1):33-4, 2000 Jan-Mar.


  A patient with a peripancreatic lymph node tuberculosis mimicking

  pancreatic pseudocyst is reported, which was diagnosed on exploration to

  be a tuberculous cold abscess. The patient responded to antituberculous

  drugs after drainage of the cold abscess.


1913. Authors

  Klein DL.


  From pertussis to tuberculosis: what can be learned?. [Review] [37 refs]


  Clinical Infectious Diseases.  30 Suppl 3:S302-8, 2000 Jun.


  Following the introduction of whole-cell pertussis vaccines into the

  general population, the number of cases of Bordetella pertussis disease

  declined dramatically. As disease incidence declined, the public's concern

  for pertussis as a national health problem gradually waned. However, a

  shift in paradigm occurred, and various groups and the media began to

  voice their concerns regarding adverse events associated with whole-cell

  vaccines. These events provided an impetus for the expedited development

  of safer and as efficacious subunit acellular vaccines. Effective public

  health leadership, public advocacy, scientific ingenuity, and

  collaborative interactions between government, academia, and industry

  culminated in the licensure of acellular pertussis vaccines. In this

  article, emphasis is placed on conceptualizing how a national public

  health agenda was implemented that allowed better insight into various

  public health concerns related to the development and use of acellular

  pertussis vaccines, concerns that were eventually translated into concrete

  actions. Knowledge of the environment in which this occurred may play a

  major role in relating the pertussis experience to tuberculosis vaccine

  development. [References: 37]


1914. Authors

  Kwon KS.  Oh CK.  Jang HS.  Lee CW.  Jun ES.


  Detection of mycobacterial DNA in cervical granulomatous lymphadenopathy

  from formalin-fixed, paraffin-embedded tissue by PCR.


  Journal of Dermatology.  27(6):355-60, 2000 Jun.


  Cervical tuberculous lymphadenitis is the most common form of inflammatory

  neck mass in Korea. The diagnosis of tuberculosis requires proof of the

  presence of Mycobacterium tuberculosis by acid-fast staining or bacterial

  growth in culture. However, these are often difficult in cervical

  tuberculous lymphadenitis. The aim of this study was to investigate the

  value of the polymerase chain reaction (PCR) technique for detection of

  mycobacteria in routinely processed tissue sections of cervical

  granulomatous lymphadenopathy. In this retrospective study, twenty

  formalin-fixed, paraffin-embedded biopsy specimens from clinically and/or

  histopathologically diagnosed cervical granulomatous lymphadenopathy were

  analyzed for mycobacterial DNA by PCR. Two different primers to amplify

  mycobacterial-common 383-base pair (bp) DNA and Mycobacterium

  tuberculosis-complex-specific 123-bp DNA were used. Positive PCR products

  were sequenced directly. Mycobacterial-common DNA (383-bp positive) was

  found in 10 of the 20 cases. Among them, 7 cases were PCR positive with

  both primer sets. These seven cases can be considered as tuberculosis. The

  other three cases indicated possible atypical mycobacteriosis. PCR is a

  useful technique for the demonstration of mycobacterial DNA fragments in

  patients with clinically suspected cervical tuberculous lymphadenitis who

  have acid fast-negative histology and/or unsuccessful mycobacterial



1915. Authors

  Lazarus A.  Sanders J.


  Management of tuberculosis. Choosing an effective regimen and ensuring

  compliance. [Review] [20 refs]


  Postgraduate Medicine.  108(2):71-4, 77-9, 83-4, 2000 Aug.


  Management of active TB requires a team approach. All patients newly

  diagnosed with TB should be tested for HIV infection. Currently available

  anti-TB drug regimens are well tolerated and highly effective. Directly

  observed therapy has shown improved survival and decline in the rate of

  new cases of active TB. In suspected or proven drug-resistant TB, the

  regimen should be individualized in consultation with a specialist

  experienced in MDR TB. Primary care physicians play a pivotal role in

  reducing morbidity and emergence of drug resistance through early

  diagnosis and prompt initiation of an effective regimen under directly

  observed therapy. [References: 20]


1916. Authors

  Li JY.  Lo ST.  Ng CS.


  Molecular detection of Mycobacterium tuberculosis in tissues showing

  granulomatous inflammation without demonstrable acid-fast bacilli.


  Diagnostic Molecular Pathology.  9(2):67-74, 2000 Jun.


  Early diagnosis of tuberculosis (TB) is important for early medical

  intervention and prevention of spread of the bacteria. It is not uncommon

  to observe granulomatous inflammation but without demonstrable acid-fast

  bacilli (AFB) on Ziehl-Neelsen (ZN) staining in tissues sent for

  histologic examination, and the definitive diagnosis of TB cannot be made

  because no concurrent tissue is sent for TB culture. In this study, the

  authors explored the feasibility of using polymerase chain reaction (PCR)

  for early detection of Mycobacterium tuberculosis (Mtb) in formalin-fixed,

  paraffin-embedded tissues where a definite diagnosis of TB cannot be made.

  One hundred fifteen patients (131 paraffin blocks of biopsy specimens)

  with granulomatous inflammation but ZN-negative for AFB were studied. DNA

  was extracted from paraffin sections and amplified by PCR with the IS6110

  primers (specific for the Mtb complex) and the specific 122-base pairs

  (bp) PCR product was detected by agarose gel electrophoresis. Sixty-eight

  of the 115 (59%) patients were TB-PCR positive, thus enabling definite

  diagnosis of TB in significant numbers of these patients in 3 days. The

  authors conclude that molecular diagnosis by PCR is useful for early

  detection of TB in histologic material where morphologic features are

  suggestive but not confirmatory because of negative staining for AFB.


1917. Authors

  Lietman T.  Blower SM.


  Potential impact of tuberculosis vaccines as epidemic control agents.

  [Review] [24 refs]


  Clinical Infectious Diseases.  30 Suppl 3:S316-22, 2000 Jun.


  We use 2 simple mathematical models (one a preexposure vaccine model and

  the other a postexposure vaccine model) to provide general insight into

  the effects of vaccination on tuberculosis epidemics. We discuss how these

  models can be used as health policy tools: to identify which vaccines are

  "equivalent," to design control strategies, and to predict the

  epidemiological impact of different vaccination strategies. Our results

  show that even moderately effective vaccines could have a significant

  effect on reducing tuberculosis epidemics if they can be coupled with

  moderate to high treatment rates. We suggest that both preexposure and

  postexposure tuberculosis vaccines can be used to help eliminate

  tuberculosis in developing countries. In developed countries, only a

  preexposure vaccine (used in combination with a high level of treatment)

  would be necessary to eliminate tuberculosis. [References: 24]


1918. Authors

  Long R.


  Drug-resistant tuberculosis. [Review] [31 refs]


  CMAJ.  163(4):425-8, 2000 Aug 22.


  Globally the proportion of tuberculosis cases caused by drug-resistant

  strains is increasing. Interruptions in the drug supply, improper drug

  prescription and nonadherence to treatment protocols promote drug

  resistance through mechanisms that are now well understood. The treatment

  of tuberculosis must take into account the possibility of drug resistance

  and include at least 2 drugs, preferably 3, to which the isolate is proven

  or anticipated to be susceptible. [References: 31]


1919. Authors

  Louie M.  Louie L.  Simor AE.


  The role of DNA amplification technology in the diagnosis of infectious

  diseases. [Review] [81 refs]


  CMAJ.  163(3):301-9, 2000 Aug 8.


  Nucleic acid amplification and detection methods developed in the past

  decade are useful for the diagnosis and management of a variety of

  infectious diseases. The most widely used of these methods is the

  polymerase chain reaction (PCR). PCR assays can detect rapidly and

  accurately the presence of fastidious and slow-growing microorganisms,

  such as Chlamydia, mycoplasmas, mycobacteria, herpesviruses and

  enteroviruses, directly from clinical specimens. Commercial PCR assays for

  the diagnosis of tuberculosis and genital C. trachomatis infection are now

  routinely used in many diagnostic laboratories. Assays have also been

  developed that can detect antimicrobial resistance and are used to

  identify the cause of infection by organisms that cannot be cultivated.

  The value of viral load measurement by nucleic acid amplification in the

  management of patients with HIV infection or hepatitis C has also been

  well established. However, evaluations of this technology for rapid

  microbial diagnosis have generally been limited by small samples, and the

  cost of these assays may be as high as Can$125 per test. As nucleic acid

  amplification methods continue to evolve, their role in the diagnosis and

  management of patients with infectious diseases and their impact on

  clinical outcomes will become better defined. [References: 81]


1920. Authors

  Martin G.  Lazarus A.


  Epidemiology and diagnosis of tuberculosis. Recognition of at-risk

  patients is key to prompt detection. [Review] [20 refs]


  Postgraduate Medicine.  108(2):42-4, 47-50, 53-4, 2000 Aug.


  The increasing incidence of TB and HIV infection and the emergence of drug

  resistance worldwide poses a major threat, particularly in developing

  nations. In an era with an increasing number of Americans living with HIV

  infection or with immunosuppression associated with chemotherapy or organ

  transplants, the possibility of primary M tuberculosis and of unusual

  clinical and radiographic presentations of reactivation disease is

  becoming more common. The primary care physician plays a crucial role in

  recognizing high-risk patients and initiating prompt isolation and

  evaluation. [References: 20]


1921. Authors

  Matsuyama W.  Hashiguchi T.  Matsumuro K.  Iwami F.  Hirotsu Y.  Kawabata

  M.  Arimura K.  Osame M.


  Increased serum level of vascular endothelial growth factor in pulmonary



  American Journal of Respiratory & Critical Care Medicine.  162(3 Pt

  1):1120-2, 2000 Sep.


  Pulmonary tuberculosis, one of the granulomatous diseases, has few

  serological markers for its activity. Recently, an increased serum level

  of vascular endothelial growth factor (VEGF) was detected in patients with

  Crohn's disease, also a granulomatous disease. We hypothesized that VEGF

  might be associated with the pathogenesis of pulmonary tuberculosis. We

  investigated the serum level of VEGF in 43 patients with active pulmonary

  tuberculosis, 29 patients with old tuberculosis, and 25 patients with

  acute bronchitis. We were able to examine the serum VEGF levels every 3 mo

  for a period of 6 mo in seven patients with active pulmonary tuberculosis.

  We examined the presence of VEGF in the resected lungs of three patients

  with active pulmonary tuberculosis by immunohistochemistry. The serum

  levels of VEGF were significantly higher in patients with active pulmonary

  tuberculosis than in patients with old tuberculosis and acute bronchitis.

  The decrease in titer of serum VEGF paralleled the clinical improvement of

  patients with pulmonary tuberculosis. Immunohistochemical staining of the

  resected lungs demonstrated the presence of VEGF in alveolar macrophages

  surrounding the lesion. Therefore, VEGF may be associated with the

  pathogenesis of pulmonary tuberculosis.


1922. Authors

  McMurray DN.


  A nonhuman primate model for preclinical testing of new tuberculosis

  vaccines. [Review] [10 refs]


  Clinical Infectious Diseases.  30 Suppl 3:S210-2, 2000 Jun.


  Nonhuman primates appear to have significant advantages over conventional

  laboratory animals in terms of modeling pulmonary tuberculosis for

  purposes of vaccine evaluation. Primates are quite susceptible to

  infection by the aerosol route, develop a humanlike disease, exhibit

  antigen-induced T lymphocyte reactivity both in vitro and in vivo, and can

  be protected quite effectively by bacille Calmette-Guerin vaccination.

  There are fewer than a dozen published studies of experimental

  tuberculosis in primates, and all of the available data on the response of

  primates to vaccination have been generated in rhesus monkeys (Macaca

  mulatta). There have been no modern immunologic studies of primate

  tuberculosis. Thus, responses to tuberculosis vaccines in primates are

  only minimally characterized, and much additional baseline work remains to

  be done before the responses to new vaccines can be placed in the proper

  biological context. [References: 10]


1923. Authors

  McNab BD.  Marciniuk DD.  Alvi RA.  Tan L.  Hoeppner VH.


  Twice weekly isoniazid and rifampin treatment of latent tuberculosis

  infection in Canadian plains Aborigines.


  American Journal of Respiratory & Critical Care Medicine.  162(3 Pt

  1):989-93, 2000 Sep.


  Six months of twice weekly directly observed isoniazid and rifam-picin

  treatment of latent tuberculosis (TB) infection was implemented to improve

  the outcome of treatment. A total of 591 infected aborigines without

  previous tuberculosis or treatment of latent TB infection received twice

  weekly isoniazid and rifampicin for 6 mo from 1992 to 1995. The outcome

  was compared with 403 infected aborigines without previous tuberculosis or

  treatment of latent TB infection who received self-administered isoniazid

  daily for 1 yr from 1986 to 1989. Of patients, 487 (82%) completed the

  twice weekly 6-mo regimen compared with 77 (19%) who completed the daily

  12-mo regimen. The main reason for incomplete treatment was default. Both

  groups were followed over a 6-yr period. The rate of tuberculosis in the

  twice-weekly isoniazid and rifampicin-treated patients was 0.9/1,000

  patient-years compared with 9/1,000 patient-years in the daily

  isoniazid-treated patients. The rate of side effects was higher for

  directly observed treatment patients, 136/1,000 patient-years of drugs,

  compared with 39/ 1,000 patient-years for self-administered treatment

  patients. Life-threatening side effects such as skin allergic reactions

  and hepatitis were the same in both groups. A regimen of 52 doses of

  directly observed twice weekly isoniazid and rifampicin is an effective

  and well-tolerated regimen to improve the outcome of the treatment of

  latent tuberculosis infection in a population with a high rate of default

  with daily self-administered isoniazid.


1924. Authors

  Means-Markwell M.  O'Neil KM.


  Prevention of tuberculosis. Vigilance and infection control strategies are

  mainstays of efforts. [Review] [15 refs]


  Postgraduate Medicine.  108(2):87-90, 93-6, 2000 Aug.


  Until a vaccine is available, efforts to control the spread of TB will

  continue to rely on the effective use of our currently available tools and

  the diligence of primary care physicians. Rapid diagnosis, directly

  observed therapy, public health and infection control measures, and

  appropriate preventive therapy remain the mainstays of TB control.

  Physicians in the primary care setting, particularly those serving

  long-term-care institutions or other high-risk populations, need to be

  keenly aware of the possibility of TB in their patient population and of

  the methods available in their community for preventing its spread.

  [References: 15]


1925. Authors

  Moussa OM.  Eraky I.  El-Far MA.  Osman HG.  Ghoneim MA.


  Rapid diagnosis of genitourinary tuberculosis by polymerase chain reaction

  and non-radioactive DNA hybridization.


  Journal of Urology.  164(2):584-8, 2000 Aug.


  OBJECTIVE: To establish a polymerase chain reaction (PCR) assay for the

  rapid detection and identification of mycobacteria in urine, and to assess

  the value of such assay in routine laboratory diagnosis of genitourinary

  tuberculosis. MATERIALS AND METHODS: Urine specimens from 1000 patients

  with clinical suspicion of urinary tuberculosis were examined. Two assays

  for the detection and identification of Mycobacterium tuberculosis (M.

  tuberculosis) complex and mycobacteria other than tuberculosis (MOTT) by

  non-radioactive DNA hybridization of PCR-product were applied. The first

  assay used PCR primers and probe derived from M. tuberculosis

  species-specific DNA insertion sequence, IS6110. The second utilized

  mycobacterium genus-specific sequence encoding ribosomal ribonucleic acid

  (16S rRNA). The results obtained by PCR were compared with those obtained

  by standard microbiological methods, acid-fast bacilli (AFB) stain and

  culture. RESULTS: Compared with cultures, the sensitivity of AFB staining

  was 52.07% and the specificity was 96.7%. In comparison to the results of

  culture, the overall sensitivity and specificity of the IS6110-PCR assay

  was 95.59% and 98.12% respectively. While the corresponding results for

  the 16S rRNA gene-PCR were 87.05% and 98. 9%. CONCLUSION: The high

  sensitivity and specificity in addition to the potential for rapid

  detection of mycobacteria, makes this test a useful tool in the clinical

  management of mycobacterial infection in urine. Urine specimens may

  contain M. tuberculosis and/or other mycobacteria; therefore, there are

  advantages in using genus-specific primers in parallel with

  species-specific primers in PCR assay.


1926. Authors

  Mulholland K.


  Evaluation of vaccines to prevent childhood pneumonia: lessons relevant to

  planning tuberculosis vaccine trials. [Review] [11 refs]


  Clinical Infectious Diseases.  30 Suppl 3:S206-9, 2000 Jun.


  Bacterial pneumonia in children is usually caused by one of the two

  leading pathogens, Streptococcus pneumoniae (pneumococcus) and Haemophilus

  influenzae, either type b (Hib) or nonencapsulated types. Hib conjugate

  vaccines suitable for use in infants have been available for about a

  decade, and experience with a trial of one of these vaccines in Africa

  showed that the vaccines can prevent Hib pneumonia, as well as other

  manifestations of Hib disease. It also showed that vaccine trials can

  provide useful estimates of the role of Hib in childhood pneumonia. Trials

  of pneumococcal conjugate vaccines that are currently under way have been

  designed to estimate disease burden and efficacy. A major risk of vaccine

  trials that use bacteriologic end points is that the vaccine may affect

  the diagnostic test itself, creating a misleading impression of efficacy.

  Trials of future tuberculosis vaccines are discussed in light of these

  experiences. It is important that the trials are designed to measure the

  effect on all clinical disease, as well as strict microbiological end

  points. The existence of bacille Calmette-Guerin (BCG) complicates future

  trials, and such trials should take into account possible nonspecific

  effects of BCG in addition to its effect on tuberculosis. [References: 11]


1927. Authors

  Murray J.  Sonnenberg P.  Shearer S.  Godfrey-Faussett P.


  Drug-resistant pulmonary tuberculosis in a cohort of southern African

  goldminers with a high prevalence of HIV infection.


  South African Medical Journal.  90(4):381-6, 2000 Apr.


  OBJECTIVES: To determine rates of drug resistance to Mycobacterium

  tuberculosis and associated risk factors, including HIV infection. DESIGN:

  Prospective cohort study of patients with pulmonary tuberculosis. SETTING:

  The study population comprised 28,522 men working on four goldmines in

  Westonaria, Gauteng. Health care is provided at a 240-bed mine hospital,

  Gold Fields West Hospital, and its primary health care facilities.

  SUBJECTS: All 425 patients with culture-positive pulmonary tuberculosis

  identified in 1995. OUTCOME MEASURES: Tuberculosis drug resistance on

  enrollment and after 6 months' treatment. RESULTS: There were 292 cases of

  new tuberculosis, 77 of recurrent disease and 56 prevalent cases in

  treatment failure. Two hundred and seven patients (48.7%) were HIV

  infected. Primary resistance to one or more drugs (9%) was similar to the

  11% found in a previous study done on goldminers in 1989. Primary

  multidrug resistance (0.3%) was also similar (0.8%). Acquired multidrug

  resistance was 18.1%: 6.5% for recurrent disease and 33.9% in treatment

  failure cases. Neither HIV infection nor the degree of immunosuppression

  as assessed by CD4+ lymphocyte counts was associated with drug resistance

  at the start or end of treatment. New patterns of drug resistance were

  present in 9 of 52 patients in treatment failure at 6 months, 1 of whom

  was HIV-infected. CONCLUSION: Primary and acquired drug resistance rates

  are stable in this population and are not affected by the high prevalence

  of HIV infection.


1928. Authors

  Olsen AW.  Hansen PR.  Holm A.  Andersen P.


  Efficient protection against Mycobacterium tuberculosis by vaccination

  with a single subdominant epitope from the ESAT-6 antigen.


  European Journal of Immunology.  30(6):1724-32, 2000 Jun.


  We have investigated the vaccine potential of two peptides derived from

  the 6-kDa early secretory antigenic target (ESAT)-6 antigen in the mouse

  model of tuberculosis. The peptides were both strongly immunogenic in

  B6CBAF1 (H-2b,k) mice and primed recall responses of the same intensity

  after immunization. However, both tuberculosis infection and immunization

  with ESAT-6 resulted in responses focused towards ESAT-61-20. Multiple

  antigen peptide constructs as well as free peptides were emulsified with

  dimethyl dioctadecylammonium bromide/monophosphoryl lipid A/IL-2 and

  tested as experimental vaccines in an i.v. and aerosol model of

  tuberculosis in mice. The peptide were highly immunogenic and induced

  cellular responses of the same magnitude. However, only vaccines based on

  the subdominant ESAT-651-70 epitope promoted significant levels of

  protective immunity and the level of protection was equivalent to that

  achieved with ESAT-6 and BCG. These findings demonstrate the potential of

  peptide-based vaccines against tuberculosis and indicate that there is not

  direct correlation between the hierarchy of response to naturally

  processed peptides and their ability to induce protective immunity against

  Mycobacterium tuberculosis.


1929. Authors

  Paradisi F.  Corti G.


  Skeletal tuberculosis and other granulomatous infections. [Review] [57



  Best Practice & Research in Clinical Rheumatology.  13(1):163-77, 1999



  After several decades of steadily decreasing incidence, tuberculosis has

  had a resurgence in the past 15 years, not only in the lungs, but also in

  extrapulmonary sites. This is primarily a result of the AIDS pandemic,

  considering that HIV specifically affects cellular immunity, which is the

  first-line defence against tuberculosis. The generally non-specific

  clinical and radiological patterns of skeletal tuberculosis make it

  similar to other bacterial, fungal, inflammatory and neoplastic diseases

  of the bones and joints. Physicians must not omit tuberculosis in the

  differential diagnosis of any osteo-articular inflammatory process so that

  specific treatment may be initiated as soon as possible. Anti-tuberculous

  therapy is beset by important factors that limit its efficacy, such as the

  emergence of drug toxicity and of resistant or multiresistant

  mycobacterial strains. Surgical treatment may be indicated in selected

  cases where medical therapy alone is not sufficient to eradicate the

  problem. Copyright 1999 Harcourt Publishers Ltd. [References: 57]


1930. Authors

  Pavlou AK.  Turner AP.


  Sniffing out the truth: clinical diagnosis using the electronic nose.

  [Review] [118 refs]


  Clinical Chemistry & Laboratory Medicine.  38(2):99-112, 2000 Feb.


  Recently the use of smell in clinical diagnosis has been rediscovered due

  to major advances in odour sensing technology and artificial intelligence

  (AI). It was well known in the past that a number of infectious or

  metabolic diseases could liberate specific odours characteristic of the

  disease stage. Later chromatographic techniques identified an enormous

  number of volatiles in human clinical specimens that might serve as

  potential disease markers. "Artificial nose" technology has been employed

  in several areas of medical diagnosis, including rapid detection of

  tuberculosis (TB), Helicobacter pylori (HP) and urinary tract infections

  (UTI). Preliminary results have demonstrated the possibility of

  identifying and characterising microbial pathogens in clinical specimens.

  A hybrid intelligent model of four interdependent "tools", odour

  generation "kits", rapid volatile delivery and recovery systems,

  consistent low drift sensor performance and a hybrid intelligent system of

  parallel neural networks (NN) and expert systems, have been applied in

  gastric, pulmonary and urine diagnosis. Initial clinical tests have shown

  that it may be possible in the near future to use electronic nose

  technology not only for the rapid detection of diseases such as peptic

  ulceration, UTI, and TB but also for the continuous dynamic monitoring of

  disease stages. Major advances in information and gas sensor technology

  could enhance the diagnostic power of future bio-electronic noses and

  facilitate global surveillance models of disease control and management.

  [References: 118]


1931. Authors

  Prasad S.  Patankar T.


  Computed tomography demonstration of a fat-fluid level in tuberculous

  chylous ascites.


  Australasian Radiology.  43(4):542-3, 1999 Nov.


  The occurrence of fat-fluid levels in ascites, although rare, is

  pathognomic of chylous ascites. The ultrasound and CT scan findings of a

  fat-fluid level in the ascitic fluid of a patient with abdominal

  tuberculosis are described here. Recognition of this important sign, in

  conjunction with other ancillary findings of abdominal tuberculosis,

  assist in establishing the correct diagnosis. Anti-tuberculous

  chemotherapy suffices in treating the condition, thus obviating the need

  for surgical intervention.


1932. Authors

  Purkayastha S.  Madan T.  Shah A.  Krishnamurthy HG.  Sarma PU.


  Multifunctional antigens of A. fumigatus and specific antibodies.


  Applied Biochemistry & Biotechnology.  83(1-3):271-83; discussion 283-6,

  297-313, 2000 Jan-Mar.


  The majority of Aspergillus-induced infections in man are caused by the

  pathogenic fungus A. fumigatus, which secretes biologically and

  immunologically active glycosylated and nonglycosylated proteins. The

  complexity in the antigenic structure of A. fumigatus and the varying host

  immune responses lead to a wide spectrum of clinical conditions such as

  allergic bronchopulmonary aspergillosis (ABPA), aspergilloma, and invasive

  aspergillosis. It is reported that 15-20% of allergic asthmatics suffer

  from Aspergillus-induced allergies. The incidence of opportunistic

  infections, including Aspergillus infections, has risen because of the

  increase in the incidence of HIV and tuberculosis. Allergic

  bronchopulmonary aspergillosis is an immunologically significant clinical

  form where type I and type III hypersensitivity reactions are involved in

  pathogenesis. High levels of specific IgE and IgG antibodies in these

  patients are of diagnostic value. Molecular characterization of certain

  immunodominant allergens and antigens of A. fumigatus revealed the

  presence of complex carbohydrate moieties, heat-shock proteins, enzyme

  activities such as elastase, protease, catalase, dismutase, and cytotoxic

  ribonuclease. A Con A binding allergen/antigen (45 kDa) and Con A

  nonbinding allergen/antigen (18 kDa, Asp fI) have a multifunctional

  nature. The multifunctional nature of these antigens may play an important

  role in the pathogenesis of the disease. Significant amounts of a major

  allergen/antigen of molecular weight 18 kDa is excreted in large amounts

  through the urine of patients with invasive aspergillosis. Studies on the

  structure-function relationship of the 18-kDa allergen/antigen revealed

  the involvement of tryptophan residues in binding with monoclonal

  antibodies (MAbs). Also, the histidine residues and cysteine disulfide

  bonds of the 18-kDa allergen are involved in its catalytic activity. The

  high load of multifunctional antigens in the serum of patients for

  prolonged periods, the presence of high levels of specific antibodies, and

  the absence of protective antibodies in ABPA patients have necessitated

  studies on the functional properties of the antibodies. The present study

  shows significant immunoreactivity of antibodies in patients of ABPA to

  fibronectin and collagen. Analysis of IgG antibodies from the patients of

  ABPA showed the presence of DNA-cleaving activity. These observations

  offer a new line of thinking in understanding the mechanism of

  pathogenesis of Aspergillus-induced clinical manifestations, and may lead

  to novel approaches to intervention in the inflammation and infection

  caused by fungal pathogens.


1933. Authors

  Quiros E.  Bettinardi A.  Quiros A.  Piedrola G.  Maroto MC.


  Detection of mycobacterial DNA in papulonecrotic tuberculid lesions by

  polymerase chain reaction.


  Journal of Clinical Laboratory Analysis.  14(4):133-5, 2000.


  Tuberculids are a heterogeneous group of cutaneous lesions. Recent

  discoveries of M. Tuberculosis DNA in these lesions by PCR suggest that M.

  tuberculosis could play a role in their pathogenesis. The aim of this

  study was to demonstrate the presence of M. tuberculosis DNA by polymerase

  chain reaction in papulonecrotic tuberculid lesions. Skin biopsy specimens

  from ten patients with papulonecrotic tuberculid lesions (histopathologic

  features) were studied. All of them tested solidly positive in a

  tuberculin intradermal test. A gene-amplification PCR, using primers

  capable of amplifying DNA in the M. tuberculosis complex, was performed to

  detect M. tuberculosis DNA in the lesions. A 285-bp sequence specific of

  M. tuberculosis complex was amplified and confirmed by Southern-blot

  hybridation with a 32 p 5'-labelled internal probe. No inhibitors were

  detected in the negative PCR samples. The PCR technique makes the

  detection of mycobacterial DNA in tuberculids a possibility, and therefore

  provides a rational basis for antituberculous therapy and for the clinical

  management of these disorders. Copyright 2000 Wiley-Liss, Inc.


1934. Authors

  Ramanathan M.  Abdullah AD.  Sivadas T.


  Hypercalcaemic crisis as the presenting manifestation of abdominal

  tuberculosis: a case report.


  Medical Journal of Malaysia.  53(4):432-4, 1998 Dec.


  This report deals with a young man having prolonged fever presenting with

  hypercalcaemic crisis. Subsequent investigations confirmed tuberculosis

  (TB) peritonitis in the absence of pulmonary involvement as the cause of

  his symptoms. His hypercalcaemia and fever resolved with anti-TB therapy.

  Abdominal TB needs to be included in the differential diagnosis of

  otherwise unexplained hypercalcaemia especially in our region where TB is

  an endemic problem and is treatable.


1935. Authors

  Ruiz-Serrano MJ.  Alcala L.  Martinez L.  Diaz M.  Marin M.  Gonzalez-Abad

  MJ.  Bouza E.


  In vitro activities of six fluoroquinolones against 250 clinical isolates

  of Mycobacterium tuberculosis susceptible or resistant to first-line

  antituberculosis drugs.


  Antimicrobial Agents & Chemotherapy.  44(9):2567-8, 2000 Sep.


  Two hundred fifty isolates of Mycobacterium tuberculosis were evaluated

  for susceptibility to ciprofloxacin, ofloxacin, levofloxacin,

  grepafloxacin, trovafloxacin, and gemifloxacin (SB-265805). Levofloxacin,

  ciprofloxacin, and grepafloxacin showed the greatest activity (MIC for 90%

  of strains tested [MIC(90)] 1 microg/ml), although ofloxacin also showed

  good activity, with an MIC(90) of 2 microg/ml. Trovafloxacin and

  gemifloxacin showed lower in vitro activity, with MIC(90)s of 64 and 8

  microg/ml, respectively.


1936. Authors

  Schwander SK.  Torres M.  Carranza C C.  Escobedo D.  Tary-Lehmann M.

  Anderson P.  Toossi Z.  Ellner JJ.  Rich EA.  Sada E.


  Pulmonary mononuclear cell responses to antigens of Mycobacterium

  tuberculosis in healthy household contacts of patients with active

  tuberculosis and healthy controls from the community.


  Journal of Immunology.  165(3):1479-85, 2000 Aug 1.


  Protective immunity against Mycobacterium tuberculosis requires CD4+

  lymphocyte-mediated immune responses and IFN-gamma activity. As the

  primary portal of entry of M. tuberculosis is the lung, pulmonary immune

  responses against multiple M. tuberculosis Ags were compared between both

  M. tuberculosis-exposed tuberculin skin test-positive healthy household

  contacts (HHC) of patients with active sputum smear and culture-positive

  tuberculosis and tuberculin skin test-positive healthy control individuals

  from the community (CC). Frequencies of M. tuberculosis Ag-specific

  IFN-gamma-producing cells, IFN-gamma concentrations in culture

  supernatants, and DNA synthesis in bronchoalveolar cells (BAC) and PBMC

  were studied in HHC (n = 10) and CC (n = 15). Using enzyme-linked

  immunospot assay we found higher frequencies of IFN-gamma-producing cells

  with specificity to M. tuberculosis-secreted Ag 85 (Ag 85) in BAC from HHC

  than in BAC from CC (p < 0.022) and relative to autologous PBMC,

  indicating compartmentalization of Ag 85-specific cells to the lungs.

  Further, IFN-gamma-producing cells with specificity to components A and B

  of Ag 85 were specifically compartmentalized to the lungs in HHC (p < 0.

  05). IFN-gamma concentrations in culture supernatants of BAC and

  Ag-specific DNA synthesis were low and comparable in the two subject

  groups. Increased immune responses to Ag 85 at the site of repeated

  exposure to M. tuberculosis (the lung) may represent an important

  component of protective immunity against M. tuberculosis. Correlates of

  protective immunity against M. tuberculosis are required for assessment of

  the efficiency of anti-tuberculous vaccines.


1937. Authors

  Sheikh M.  Moosa I.  Hussein FM.  Qurttom MA.  Behbehani AI.


  Ultrasonographic diagnosis in abdominal tuberculosis.


  Australasian Radiology.  43(2):175-9, 1999 May.


  Sonographic findings were retrospectively analysed in 39 patients with

  proven abdominal tuberculosis (TB). The patients were treated over 15

  years at a major teaching hospital, Mubarak Al-Kabber Hospital, in Kuwait.

  The findings included clear or complex ascites with fine strands,

  loculations and debris. The other findings were lymphadenopathy, bowel

  wall thickening, omental mass, focal lesions in the liver and spleen and

  psoas abscess. The sonographic findings in abdominal TB are not specific

  but may give valuable information to prevent unnecessary laparotomy.


1938. Authors

  Shinnick TM.


  Diagnostic test needs for evaluating antituberculosis vaccines. [Review]

  [23 refs]


  Clinical Infectious Diseases.  30 Suppl 3:S276-8, 2000 Jun.


  To aid in the evaluation of preexposure and postinfection vaccines to

  prevent tuberculosis, diagnostic tests are needed that can clearly

  distinguish immunologic protection from vaccine failure in a timely

  manner. The currently available tests to detect infected persons

  (tuberculin skin-test) and confirm active disease (conventional culture

  methods) have limitations in specificity, sensitivity, or timeliness.

  Research to identify (1) surrogate markers of infection, disease, or

  protection and (2) stage-specific antigens or immune responses holds some

  promise for the development of new tests that can distinguish the various

  outcomes of an infection or a vaccination. [References: 23]


1939. Authors

  Sirgel FA.  Donald PR.  Odhiambo J.  Githui W.  Umapathy KC.  Paramasivan

  CN.  Tam CM.  Kam KM.  Lam CW.  Sole KM.  Mitchison DA.


  A multicentre study of the early bactericidal activity of

  anti-tuberculosis drugs.


  Journal of Antimicrobial Chemotherapy.  45(6):859-70, 2000 Jun.


  The early bactericidal activities (EBAs) of 300 mg isoniazid, 18.5 mg

  isoniazid, 600 mg rifampicin and 800 mg ofloxacin given daily to 262

  patients with newly diagnosed pulmonary tuberculosis in Cape Town,

  Nairobi, Madras and Hong Kong were measured by counting cfu and total

  acid-fast bacilli in sputum collections taken pre-treatment (S1), at 2

  days (S3) and at 5 days (S6). In Cape Town, Nairobi and Madras, the cfu

  findings suggested that isoniazid produced a massive kill, perhaps of

  actively growing organisms, during the first 2 days (mean S1-S3 EBAs of

  0.636-1.006) but was almost inactive thereafter (mean S3-S6 EBAs of

  0.000-0.081), whereas rifampicin maintained moderate activity against

  slowly growing organisms throughout the 5 days (mean S3-S6 EBAs of

  0.242-0.305). This finding suggests that EBAs measured during the 2-5 day

  interval might be able to assess the sterilizing activity of drugs.

  Ofloxacin had moderately high mean S1-S3 EBAs of 0.130-0.391. However, in

  Hong Kong rifampicin appeared to be the most bactericidal drug from the

  start, possibly because patients had more chronic disease. A method of

  adjusting the cfu EBAs using total counts was devised which decreased the

  variability between patients within a treatment group without altering the

  mean cfu EBA. This resulted in a large gain in precision in Hong Kong,

  suggesting that their estimates were greatly affected by type II

  variation, due to dilution of pus by saliva and bronchial secretions,

  whereas small or no gains were obtained in the other three centres,

  suggesting that the main cause of variability was type I, due to other



1940. Authors

  Snider DE Jr.


  Ethical issues in tuberculosis vaccine trials. [Review] [31 refs]


  Clinical Infectious Diseases.  30 Suppl 3:S271-5, 2000 Jun.


  Bacille Calmette-Guerin (BCG) vaccines are widely used, even though

  estimates of efficacy have ranged from zero to 80%. BCG is a relatively

  safe vaccine, but it can cause disseminated infection, especially in

  immunocompromised hosts. Thus, the development of a more reliably

  efficacious and safer vaccine is important to the control of tuberculosis.

  The testing of any new vaccine in human populations presents a number of

  ethical challenges that must be addressed. These include (1) the

  appropriateness of conducting such trials in developing countries; (2) the

  use of a BCG-vaccinated population as the control group; (3) the provision

  of tuberculin skin-test screening and preventive therapy to study

  participants; (4) the involvement of various "communities" in the

  trial(s); (5) the structure and process of ethical review; (6)

  establishing an effective method of obtaining informed consent; and (7)

  the roles and responsibilities of researchers and others in ensuring that

  trial results are available to the study population after the trial ends.

  [References: 31]


1941. Authors

  Stobie L.  Gurunathan S.  Prussin C.  Sacks DL.  Glaichenhaus N.  Wu CY.

  Seder RA.


  The role of antigen and IL-12 in sustaining Th1 memory cells in vivo:

  IL-12 is required to maintain memory/effector Th1 cells sufficient to

  mediate protection to an infectious parasite challenge.


  Proceedings of the National Academy of Sciences of the United States of

  America.  97(15):8427-32, 2000 Jul 18.


  IL-12 plays a central role in both the induction and magnitude of a

  primary Th1 response. A critical question in designing vaccines for

  diseases requiring Th1 immunity such as Mycobacterium tuberculosis and

  Leishmania major is the requirements to sustain memory/effector Th1 cells

  in vivo. This report examines the role of IL-12 and antigen in sustaining

  Th1 responses sufficient for protective immunity to L. major after

  vaccination with LACK protein (LP) plus rIL-12 and LACK DNA. It shows

  that, after initial vaccination with LP plus rIL-12, supplemental boosting

  with either LP or rIL-12 is necessary but not sufficient to fully sustain

  long-term Th1 immunity. Moreover, endogenous IL-12 is also shown to be

  required for the induction, maintenance, and effector phase of the Th1

  response after LACK DNA vaccination. Finally, IL-12 is required to sustain

  Th1 cells and control parasite growth in susceptible and resistant strains

  of mice during primary and secondary infection. Taken together, these data

  show that IL-12 is essential to sustain a sufficient number of

  memory/effector Th1 cells generated in vivo to mediate long-term

  protection to an intracellular pathogen.


1942. Authors

  Stover CK.  Warrener P.  VanDevanter DR.  Sherman DR.  Arain TM.

  Langhorne MH.  Anderson SW.  Towell JA.  Yuan Y.  McMurray DN.  Kreiswirth

  BN.  Barry CE.  Baker WR.


  A small-molecule nitroimidazopyran drug candidate for the treatment of



  Nature.  405(6789):962-6, 2000 Jun 22.


  Mycobacterium tuberculosis, which causes tuberculosis, is the greatest

  single infectious cause of mortality worldwide, killing roughly two

  million people annually. Estimates indicate that one-third of the world

  population is infected with latent M. tuberculosis. The synergy between

  tuberculosis and the AIDS epidemic, and the surge of multidrug-resistant

  clinical isolates of M. tuberculosis have reaffirmed tuberculosis as a

  primary public health threat. However, new antitubercular drugs with new

  mechanisms of action have not been developed in over thirty years. Here we

  report a series of compounds containing a nitroimidazopyran nucleus that

  possess antitubercular activity. After activation by a mechanism dependent

  on M. tuberculosis F420 cofactor, nitroimidazopyrans inhibited the

  synthesis of protein and cell wall lipid. In contrast to current

  antitubercular drugs, nitroimidazopyrans exhibited bactericidal activity

  against both replicating and static M. tuberculosis. Lead compound PA-824

  showed potent bactericidal activity against multidrugresistant M.

  tuberculosis and promising oral activity in animal infection models. We

  conclude that nitroimidazopyrans offer the practical qualities of a small

  molecule with the potential for the treatment of tuberculosis.


1943. Authors

  Su WJ.  Tsou AP.  Yang MH.  Huang CY.  Perng RP.


  Clinical experience in using polymerase chain reaction for rapid diagnosis

  of pulmonary tuberculosis.


  Chung Hua i Hsueh Tsa Chih - Chinese Medical Journal.  63(7):521-6, 2000



  BACKGROUND: Polymerase chain reaction (PCR) techniques have revolutionized

  the diagnosis of tuberculosis (TB). PCR has significantly improved the

  sensitivity and specificity of existing diagnostic methods. In this study,

  we report our experience using a modified IS6110-based nested PCR assay

  for rapid diagnosis of pulmonary TB. METHODS: A total of 327 respiratory

  specimens from 275 patients suspected of having pulmonary TB at Taipei

  Veterans General Hospital were tested using the nested PCR assay,

  acid-fast smear and culture for the presence of Mycobacterium tuberculosis

  complex (MTB). Nested PCR was performed with IS6110-based primers specific

  for MTB. We reviewed the medical records of patients and analyzed the

  clinical features. The PCR results were compared with the final clinical

  diagnosis. RESULTS: We identified MTB in 167 of 327 samples by the nested

  PCR assay. No non-tuberculous Mycobacterium (NTM) was identified among the

  clinical samples. Diagnosis by PCR took about 6 hours in this study. The

  sensitivity and specificity compared with culture were 94.7% and 100%,

  respectively for the smear-positive, culture-positive samples, and 76.7%

  and 98.6% for the smear-negative, culture-positive samples. The overall

  sensitivity, specificity, positive and negative predictive values,

  compared with culture results, were 91.7%, 98.6%, 98.8% and 90.6%,

  respectively. Two specimens positive by PCR and negative by culture were

  taken from patients on anti-TB drug therapy. These specimens were

  culture-positive before anti-TB drug therapy. After resolution of the

  discrepancies by studying the patients' clinical data, both specificity

  and positive predictive value reached 100%. CONCLUSIONS: The results

  indicated that this in-house nested PCR assay is a rapid and sensitive

  method for diagnosing pulmonary TB. It is also good for excluding

  infections caused by NTM.


1944. Authors

  Tak S.  Ahluwalia G.  Sharma SK.  Mukhopadhya S.  Guleria R.  Pande JN.


  Haemoptysis in patients with a normal chest radiograph: bronchoscopy-CT



  Australasian Radiology.  43(4):451-5, 1999 Nov.


  The exact role of fibre-optic bronchoscopy (FOB) and CT of the chest in

  the diagnosis of patients presenting with haemoptysis and a normal or

  non-localizing chest radiograph has not been clearly defined. A study was

  designed to evaluate 50 patients presenting with haemoptysis and a normal

  or non-localizing chest radiograph using FOB and high-resolution computed

  tomography (HRCT). A definitive diagnosis was established in 17 (34%)

  patients. The aetiologies included bronchiectasis (24%), bronchial adenoma

  (6%), tuberculosis (2%) and bronchitis (2%). The diagnosis was made by

  HRCT in 15 (30%) patients, while FOB was diagnostic in five (10%)

  patients. The diagnosis was made by HRCT and FOB in all patients with

  focal airway abnormalities. Therefore, HRCT effectively delineated

  abnormalities of both the central and peripheral airways. It is concluded

  that CT should be obtained prior to FOB in all patients presenting with

  haemoptysis and a normal or non-localizing chest radiograph.


1945. Authors

  Triccas JA.  Gicquel B.


  Life on the inside: probing mycobacterium tuberculosis gene expression

  during infection. [Review] [60 refs]


  Immunology & Cell Biology.  78(4):311-7, 2000 Aug.


  The identification of Mycobacterium tuberculosis genes specifically

  expressed during infection is a key step in understanding mycobacterial

  pathogenesis. Such genes most likely encode products required for survival

  within the host and for progressive infection. Recent advances in

  mycobacterial genetics have permitted the development of new techniques

  and the adaptation of existing methods to analyse mycobacterial in vivo

  gene expression and virulence. This has revealed a subset of M.

  tuberculosis genes that are differentially expressed during infection and

  has demonstrated that a number of components contribute to the virulence

  of the organism. This information is expected to provide new strategies to

  prevent tuberculosis infection, new targets for antimicrobial therapy and

  new insights into the infectious process. [References: 60]


1946. Authors

  Van Rie A.  Warren R.  Richardson M.  Gie RP.  Enarson DA.  Beyers N.  Van

  Helden PD.


  Classification of drug-resistant tuberculosis in an epidemic area.


  Lancet.  356(9223):22-5, 2000 Jul 1.


  BACKGROUND: Traditionally, patients with drug-resistant tuberculosis are

  classified as having acquired drug-resistant or primary drug-resistant

  disease on the basis of a history of previous tuberculosis treatment. Only

  cases of primary drug resistance are assumed to be due to transmission of

  drug-resistant strains. METHODS: This descriptive study of 63 patients

  with drug-resistant tuberculosis assessed the relative contribution of

  transmission of drug-resistant strains in a high-incidence community of

  Cape Town, South Africa, by restriction-fragment length polymorphism

  (RFLP). The RFLP results were compared with the results obtained by

  traditional classification methods. FINDINGS: According to RFLP

  definitions, 52% (33 cases) of drug-resistant tuberculosis was caused by

  transmission of a drug-resistant strain. The proportion of cases due to

  transmission was higher for multidrug-resistant (64%; 29 cases) than for

  single-drug-resistant (no cases) tuberculosis. By the clinical

  classification, only 18 (29%) patients were classified as having primary

  drug-resistant tuberculosis (implying transmission). The clinical

  classification was thus misleading in 25 patients. INTERPRETATION: The

  term acquired drug resistance includes patients infected with strains that

  truly acquired drug resistance during treatment and patients who were

  initially infected with or reinfected with a drug-resistant strain. This

  definition could lead to misinterpretation of surveillance studies,

  incorrect evaluation of tuberculosis programmes, and delayed diagnosis and

  treatment of patients with multidrug-resistant disease. The clinical term

  acquired drug resistance should be replaced with the term "drug resistance

  in previously treated cases", which includes cases with drug resistance

  due to true acquisition as well as that due to transmitted drug-resistant



1947. Authors

  Viinanen AH.  Soini H.  Marjamaki M.  Liippo K.  Viljanen MK.


  Ligase chain reaction assay is clinically useful in the discrimination of

  smear-positive pulmonary tuberculosis from atypical mycobacterioses.


  Annals of Medicine.  32(4):279-83, 2000 May.


  We evaluated the usefulness of the ligase chain reaction (LCR) (Abbott LCx

  Mycobacterium tuberculosis assay) during the initial diagnosis of

  tuberculosis. LCx was carried out in parallel with conventional methods

  for the analysis of clinical samples. Out of 86 patients who were examined

  clinically, 53 were suspected of having pulmonary tuberculosis, eight had

  residual X-ray scars from previous tuberculosis and 25 served as

  asymptomatic controls. Ten bronchoscopy samples and 237 sputum samples

  were analysed by direct microscopy, culture and LCx. All 11 smear-positive

  and two of three smear-negative tuberculosis patients had at least one

  LCx-positive specimen. All samples that were both LCx- and smear-positive

  were culture-positive for M. tuberculosis. The smear-positive samples from

  the five patients with atypical mycobacteriosis were LCx-negative. There

  were three false-positive results: one in a smear-negative sample from a

  patient with M. malmoense infection and two from two pneumonia patients.

  All samples from controls and patients with previous tuberculosis were

  LCx-negative. The sensitivity, specificity and the positive and negative

  predictive values of LCx in patient analysis were 92.9%, 95.8%, 81.3% and

  98.6%, respectively. LCx assay of M. tuberculosis is useful in rapid

  confirmation of tuberculosis or atypical mycobacteriosis from a

  smear-positive sample and may aid in diagnosing smear-negative



1948. Authors

  Vogel FR.


  Improving vaccine performance with adjuvants. [Review] [66 refs]


  Clinical Infectious Diseases.  30 Suppl 3:S266-70, 2000 Jun.


  New vaccines are presently under development and in testing for the

  control of infectious diseases, including human immunodeficiency virus

  (HIV) and tuberculosis. Several of these vaccines are composed of

  synthetic, recombinant, or highly purified subunit antigens. Subunit

  vaccines are designed to include only the antigens required for protective

  immunization and to be safer than whole-inactivated or live-attenuated

  vaccines. However, the purity of the subunit antigens and the absence of

  the self-adjuvanting immunomodulatory components associated with

  attenuated or killed vaccines often result in weaker immunogenicity.

  Immunologic adjuvants are agents that enhance specific immune responses to

  vaccines. Formulation of vaccines with potent adjuvants is an attractive

  approach for improving the performance of vaccines composed of subunit

  antigens. Adjuvants have diverse mechanisms of action and should be

  selected for use on the basis of the route of administration and the type

  of immune response (antibody, cell-mediated, or mucosal immunity) that is

  desired for a particular vaccine. [References: 66]


1949. Authors

  Wiersma HE.  Van Aalderen WM.  Hoekstra MO.


  Sputum induction for the diagnosis of pulmonary tuberculosis [letter;



  Archives of Disease in Childhood.  83(3):276, 2000 Sep.


1950. Authors

  Wilson ME.


  Applying experiences from trials of bacille Calmette-Guerin vaccine.

  [Review] [39 refs]


  Clinical Infectious Diseases.  30 Suppl 3:S262-5, 2000 Jun.


  Bacille Calmette-Guerin (BCG) vaccine, a live vaccine developed to prevent

  tuberculosis (TB), has been given to billions of persons over more than 7

  decades. Studies of the efficacy of BCG vaccine have had widely divergent

  results, underscoring the complexity of the biology and immunology of TB.

  The long duration of TB infection, the heterogeneity of its clinical

  expression, and lack of inexpensive, reliable markers of infection and

  disease have made it difficult to study the impact of a vaccine,

  especially in resource-poor areas. A meta-analysis of data from trials of

  BCG vaccine found that studies conducted at sites that are a greater

  distance from the equator are associated with better vaccine efficacy, a

  finding that needs fuller study. BCG vaccine trials with higher validity

  scores showed higher rates of protection. Ongoing changes, including human

  immunodeficiency virus infection and demographic shifts, should be

  considered when developing trials of future vaccines. Analyses of past

  studies of BCG vaccine can identify sources of variation that may guide

  the design of studies of new vaccines. Rigorous study design and new tools

  are needed if studies are to provide clear, useful answers about new

  vaccines. [References: 39]


1951. Authors

  Worku S.  Hoft DF.


  In vitro measurement of protective mycobacterial immunity:

  antigen-specific expansion of T cells capable of inhibiting intracellular

  growth of bacille Calmette-Guerin.


  Clinical Infectious Diseases.  30 Suppl 3:S257-61, 2000 Jun.


  We investigated the ability of T cells expanded with mycobacterial

  antigens from healthy purified protein derivative-reactive donors and

  bacille Calmette-Guerin (BCG)-vaccinated volunteers to inhibit

  intracellular growth of BCG. Peripheral blood mononuclear cells were

  incubated for 7 days with mycobacterial whole lysate, live BCG, tetanus

  toxoid as control antigen, or medium alone. Autologous monocytes were

  separated by plastic adherence, allowed to mature for 6 days, and infected

  with BCG before serving as target cells. Expanded effector cells were

  cocultured with target cells for 72 h. Cocultures were then treated with

  0.2% saponin to lyse infected monocytes and release intracellular BCG.

  Quantities of viable BCG present in these lysates were studied by

  colony-forming unit counting and radiometric labeling. We reproducibly

  found that lymphocytes expanded with mycobacterial whole lysate or live

  BCG significantly inhibited the intracellular growth of BCG, compared with

  lymphocytes expanded with tetanus toxoid or rested in medium. In addition,

  BCG vaccination enhanced the ability of T cells to inhibit intracellular

  mycobacterial growth in 3 of 5 volunteers. This assay may be useful for

  estimates of protective immunity induced by tuberculosis vaccines in human



1952. Authors

  Young DB.


  Current tuberculosis vaccine development. [Review] [26 refs]


  Clinical Infectious Diseases.  30 Suppl 3:S254-6, 2000 Jun.


  Information derived from the complete genome sequence of Mycobacterium

  tuberculosis makes it possible to develop a range of new vaccine

  candidates. Strategies currently under investigation include construction

  of whole cell live attenuated mycobacterial vaccines, as well as the use

  of individual antigens delivered by a variety of subunit vaccination

  procedures. Fundamental questions associated with the rational design,

  preclinical testing, and future application of new tuberculosis vaccines

  are reviewed. [References: 26]


1953. Authors

  Zahrt TC.  Deretic V.


  An essential two-component signal transduction system in Mycobacterium



  Journal of Bacteriology.  182(13):3832-8, 2000 Jul.


  The bacterial two-component signal transduction systems regulate

  adaptation processes and are likely to play a role in Mycobacterium

  tuberculosis physiology and pathogenesis. The previous initial

  characterization of an M. tuberculosis response regulator from one of

  these systems, mtrA-mtrB, suggested its transcriptional activation during

  infection of phagocytic cells. In this work, we further characterized the

  mtrA response regulator from M. tuberculosis H37Rv. Inactivation of mtrA

  on the chromosome of M. tuberculosis H37Rv was possible only in the

  presence of plasmid-borne functional mtrA, suggesting that this response

  regulator is essential for M. tuberculosis viability. In keeping with

  these findings, expression of mtrA in M. tuberculosis H37Rv was detectable

  during in vitro growth, as determined by S1 nuclease protection and primer

  extension analyses of mRNA levels and mapping of transcript 5' ends. The

  mtrA gene was expressed differently in virulent M. tuberculosis and the

  vaccine strain M. tuberculosis var. bovis BCG during infection of

  macrophages, as determined by monitoring of mtrA-gfp fusion activity. In

  M. bovis BCG, mtrA was induced upon entry into macrophages. In M.

  tuberculosis H37Rv, its expression was constitutive and unchanged upon

  infection of murine or human monocyte-derived macrophages. In conclusion,

  these results identify mtrA as an essential response regulator gene in M.

  tuberculosis which is differentially expressed in virulent and avirulent

  strains during growth in macrophages.


1954. Authors

  Zimhony O.  Cox JS.  Welch JT.  Vilcheze C.  Jacobs WR Jr.


  Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI)

  of Mycobacterium tuberculosis [see comments].


  Nature Medicine.  6(9):1043-7, 2000 Sep.


  Tuberculosis treatment is shortened to six months by the indispensable

  addition of pyrazinamide (PZA) to the drug regimen that includes isoniazid

  and rifampin. PZA is a pro-drug of pyrazinoic acid (POA) (ref. 3), whose

  target of action has never been identified. Although PZA is active only

  against Mycobacterium tuberculosis, the PZA analog 5-chloro-pyrazinamide

  (5-Cl-PZA) displays a broader range of anti-mycobacterial activity. We

  have found that the eukaryotic-like fas1 gene (encoding fatty acid

  synthetase I, FASI) from M. avium, M. bovis BCG or M. tuberculosis confers

  resistance to 5-Cl-PZA when present on multi-copy vectors in M. smegmatis.

  5-Cl-PZA and PZA markedly inhibited the activity of M. tuberculosis FASI,

  the biosynthesis of C16 to C24/C26 fatty acids from acetyl-CoA (ref. 6).

  Importantly, PZA inhibited FASI in M. tuberculosis in correlation with PZA

  susceptibility. These results indicate that FASI is a primary target of

  action for PZA in M. tuberculosis. Further characterization of FASI as a

  drug target for PZA may allow the development of new drugs to shorten the

  therapy against M. tuberculosis and may provide more options for treatment

  against M. bovis, M. avium and drug resistant M. tuberculosis.



2437. Al-Matar MJ.  Cabral DA.  Petty RE. Isolated tuberculous monoarthritis mimicking oligoarticular juvenile rheumatoid arthritis. Journal of Rheumatology.  28(1):204-6, 2001 Jan.


  Isolatd monoarthritis caused by Mycobacterium tuberculosis in the absence of clinical pulmonary disease is extremely rare in North America. After decades of consistent declines in incidence, a remarkable resurgence of tuberculosis (TB) is occurring in North America. It must always be considered in the differential diagnosis of chronic monoarthritis if devastating sequelae are to be avoided. We describe 2 cases of tuberculous arthritis in young children presenting with monoarthritis of the knee. The presumptive diagnosis in each case was oligoarticular onset juvenile rheumatoid arthritis (JRA). Each had an atypical course for JRA, with lack of response to intraarticular corticosteroid. The diagnosis of TB arthritis was made only with synovial biopsy.


2439. Blomberg B.  Spinaci S.  Fourie B.  Laing R. The rationale for recommending fixed-dose combination tablets for treatment of tuberculosis.  Bulletin of the World Health Organization.  79(1):61-8, 2001.


  There is considerable exigency to take all necessary steps to cure tuberculosis cases and prevent further emergence of drug-resistant tuberculosis. The most important of these steps is to ensure that the treatment, particularly of sputum smear-positive cases, is adequate and that patients adhere to their treatment by supervised, direct observation of drug-taking according to the standardized regimens. Use of fixed-dose combinations (FDCs) of tablets against tuberculosis is now being recommended by WHO and the International Union Against Tuberculosis and Lung Disease (IUATLD) as an additional step to ensuring proper treatment. FDCs simplify the prescription of drugs and the management of drug supply, and may also limit the risk of drug-resistant tuberculosis arising as a  result of inappropriate drug selection and monotherapy. Only FDCs of  proven quality and proven rifampicin bioavailability should be purchased  and used. In most situations, blood levels of the drugs are inadequate  because of poor drug quality rather than poor absorption. This is true  irrespective of the human immunodeficiency virus (HIV) infection status of  the tuberculosis patients (other than those with overt acquired  immunodeficiency syndrome, with CD4 counts < 200 cells/mm3). Currently,  WHO, IUATLD and their partners are developing strategies for ensuring that  only quality FDCs are used in tuberculosis programmes. A simplified and effective protocol for assessment of rifampicin bioavailability has been developed, and laboratories are being recruited to form a supranational network for quality assurance of FDCs. Standardization of FDC drug formulations has been proposed, which limits rifampicin-containing preparations to nine (including a four-drug FDC and three paediatric FDCs).



2445. Gomez-Pastrana D.  Torronteras R.  Caro P.  Anguita ML.  Lopez-Barrio AM. Andres A.  Navarro J. Comparison of amplicor, in-house polymerase chain reaction, and conventional culture for the diagnosis of tuberculosis in children. Clinical Infectious Diseases.  32(1):17-22, 2001 Jan.


  A total of 251 clinical specimens (235 gastric aspirates and 16 bronchoalveolar lavages) from 88 children were prospectively tested in a  blinded manner for the presence of Mycobacterium tuberculosis complex, by  use of the Amplicor M. tuberculosis test and by means of in-house  polymerase chain reaction (PCR). The results were compared with those  obtained by conventional culture and by direct microscopy. All of the  children underwent extended follow-up to verify or exclude the clinical  diagnosis of tuberculosis. The results of the different tests, when  compared to the final clinical diagnosis, were a sensitivity of 60% and a  specificity of 96.8% for in-house PCR, 44% and 93.7% respectively for the  Amplicor test, 44% and 100% for mycobacterial culture and 12% and 100% for  microscopy. Amplicor tests presented false-positive findings in children  without tuberculous infection. We conclude that both in-house PCR and the  Amplicor test are rapid methods that can be helpful for difficult or  urgent diagnosis of tuberculosis in children. However, efforts should be aimed toward improvement of the sensitivity and specificity of an easy-to-use PCR kit.


2446. Gupta D.  Saiprakash BV.  Aggarwal AN.  Muralidhar S.  Kumar B.  Jindal  SK. Value of different cut-off points of tuberculin skin test to diagnose tuberculosis among patients with respiratory symptoms in a chest clinic.  Journal of the Association of Physicians of India.  49:332-5, 2001 Mar.


  OBJECTIVE: To assess the utility of various cut-off points of tuberculin  skin test in making a diagnosis of tuberculosis in patients with respiratory symptoms. METHODS: Tuberculin skin test was conducted on consecutive new patients attending chest clinic for various respiratory  symptoms. All subjects were then investigated to establish diagnosis, and  categorized into tuberculous and nontuberculous groups. Receiver operating  characteristic (ROC) curve was plotted to evaluate discrimination by  tuberculin skin test. Sensitivity, specificity and predictive value were  also calculated at various cut-off points. RESULTS: Of 250 patients, 59  (23.6%) had tuberculosis on clinical and microbiological criteria (other  than the tuberculin test). Sensitivity and specificity of tuberculin test  at readings greater than 5, 10 and 15 mm were 0.8136 and 0.7068, 0.6271  and 0.8901, and 0.2034 and 0.9738 respectively. Area under ROC curve for  this test was 0.80. CONCLUSION: A cut-off point of 10 mm is likely to be  useful in supporting a diagnosis of tuberculosis in patients with strong  clinical suspicion of tuberculosis, in other patients, 15 mm cut-off may be more suitable.


2449. Jha BC.  Dass A.  Nagarkar NM.  Gupta R.  Singhal S. Cervical tuberculous lymphadenopathy: changing clinical pattern and concepts in management. Postgraduate Medical Journal.  77(905):185-7, 2001 Mar.


  Tuberculosis is one of the biggest health challenges the world is facing.  In this study the clinical pattern of patients with cervical  lymphadenitis, who presented to the ear, nose, and throat outpatient  department of the Government Medical College Hospital, Chandigarh, India  between June 1997 and May 1998 is recorded. Tuberculosis accounted for 60  out of 94 cases of cervical lymph node enlargement. The commonest age  group affected was 11-20 years. Constitutional symptoms were not present  in most of the patients. Multiple matted nodes were seen in 23 patients  but a single discrete node was seen in 18 patients. Upper deep jugular  nodes were the most commonly affected lymph nodes. Discharging sinus and  abscess formation were uncommon. Fine needle aspiration cytology yielded a  positive diagnosis in 52 out of 56 patients. Chest lesions on radiography  were evident in 16% of the patients. Mantoux test was positive and was  more than 15 mm in most of the patients. This study shows that the  classical picture of "scrofula" is no longer seen nowadays and can  probably be explained by the earlier presentation of the disease.All the  patients were treated with short course daily chemotherapy for six months.  Surgery was not required in the majority of patients except in four cases  where excision biopsy was performed. Patients with abscess formation were  managed with wide bore needle aspiration only. With a minimum six month  period of follow up, no patient was found to have a recurrence of local or  systemic disease.This study emphasises the role of fine needle aspiration cytology in diagnosis and confirms the efficacy of six months short course chemotherapy.


2454. Kuyucu N.  Kuyucu S.  Bakirtas A.  Karacan C. BCG revaccination and tuberculin reactivity. Indian Journal of Pediatrics.  68(1):21-5, 2001 Jan.


  Interpretation of tuberculin reactions in revaccinated children is somewhat controversial among paediatricians. In this study, the effect of  the number of BCG vaccines on tuberculin reactivity is evaluated. In 2810  healthy children aged 7 to 14 years with purified protein derivative (PPD)  testing. Children were grouped according to the concordance of the number  of the reported/documented vaccinations to the number of scars. Group 1  and 2 comprised of children 7 to 10 years of age and 11 to 14 years of age  respectively, who had non-concordant scar numbers, and Group 3 and 4  included 7 to 10 and 11 to 14 years old children with concordant scar  numbers. Mean tuberculin induration sizes were 8.0 +/- 5.7 mm for Group 1,  10.6 +/- 4.9 mm for Group 2, 9.8 +/- 4.9 mm for Group 3 and 10.9 +/- 4 mm  for Group 4. As the time interval after the last dose of vaccination  increased, mean induration sizes decreased in Group 1 and Group 3. In  contrast, the mean reaction sizes of Group 2 and Group 4 showed a positive  correlation with the period after the last dose of vaccine. It seems  advisable that an induration size > or = 15 mm should not be attributed to  BCG vaccination in countries with a high tuberculosis infection prevalence  and routine BCG revaccination policies. A detailed investigation for tuberculosis infection and disease should be performed in those cases.

2455. Lenk S.  Schroeder J. Genitourinary tuberculosis. [Review] [17 refs] Current Opinion in Urology.  11(1):93-8, 2001 Jan.


  The worldwide prevalence of tuberculosis is still high and has remained

  almost unchanged over the past century as a result of increasing incidence

  in countries of the Third World. Twenty per cent of patients with

  tuberculosis will develop an extrapulmonary manifestation over time, the

  most common site being the genitourinary tract. The patient's history can

  lead to the sometimes difficult diagnosis. Radiological imaging helps in

  depicting genitourinary tuberculosis. However, the diagnosis of

  genitourinary tuberculosis is made on the basis of culture studies and is

  supported by polymerase chain reaction. The latter has impressive

  sensitivity and specificity, but lacks the ability to determine biological

  activity. The combination of three or four anti-tuberculosis drugs over a

  course of 6 to 9 months remains the treatment of choice. Drug resistance

  is increasing and necessitates tight therapy control. Tuberculosis of the

  male seminal duct may be an important cause of male infertility as a

  result of multiple epididymidal scarring. In these cases testicular sperm

  extraction is the method of choice for sperm retrieval. The outcome of

  sperm retrieval followed by intracytoplasmatic sperm injection is not

  affected. [References: 17]


2458. Moore SL.  Rafii M. Imaging of musculoskeletal and spinal tuberculosis. [Review] [49 refs] Radiologic Clinics of North America.  39(2):329-42, 2001 Mar.


  The diagnosis of tuberculosis of the musculoskeletal system is difficult

  for many reasons. As Walker states, to diagnose tuberculosis one must

  consider the possibility. The uncommonness of osteoarticular MTb results

  in clinician inexperience, which leads to overlooking the diagnosis.

  Subtle early manifestations may elude detection. Negative skin tests and

  normal chest films do not exclude the consideration of tuberculosis. The

  most conclusive means of reaching the diagnosis (biopsy and culture)

  necessitate invasive procedures that are not always definitive, and may

  require repeated attempts. Management and surgical decisions, however,

  rely on prompt diagnosis; diagnostic delay has prognostic implications and

  results in significant morbidity. Musculoskeletal tuberculosis produces no

  pathognomonic imaging signs, and in advanced stages mimics other disease

  processes. Despite these difficulties, the diagnostician's goal is to

  catch the disease as early as possible, because antibiotic treatment can

  lead to resolution and obviate more radical management. The radiologist

  must be aware of the groups at greatest risk, and typical and atypical

  presentations at imaging. The eventual eradication of MTb is conceivable,

  although not presently within our grasp. Maintaining reasonable suspicion

  and developing cognizance of the patterns of presentation allow the

  radiologist to diagnose efficiently the patient who presents with

  osteoarticular tuberculosis. [References: 49]


2459. Munk ME.  Arend SM.  Brock I.  Ottenhoff TH.  Andersen P. Use of ESAT-6 and CFP-10 antigens for diagnosis of extrapulmonary tuberculosis. Journal of Infectious Diseases.  183(1):175-6, 2001 Jan 1.


2461. Qureshi RN.  Samad S.  Hamid R.  Lakha SF. Female genital tuberculosis revisted. JPMA - Journal of the Pakistan Medical Association.  51(1):16-8, 2001 Jan.


  OBJECTIVE: To assess the clinical presentation of genital tuberculosis and

  to study various modes of diagnosis and treatment. SETTING: The Aga Khan

  University Hospital (AKUH), Karachi. METHOD: A retrospective case review

  of all index female cases of genital tuberculosis, admitted to AKUH over

  twelve years of period. RESULT: A total of 40 cases of genital

  tuberculosis were reported during this time period. Majority of cases were

  between 25-45 years. The commonest presenting symptoms were infertility

  (42.5%) and abdominal pain (42%). Others included fever, ascites,

  irregular vaginal bleeding, oligomenorrhea, chest pain and pain in the

  flanks. Main mode of treatment was antituberculous drug therapy for

  duration of nine months. Only 3 patients had successful pregnancies.

  CONCLUSION: Genital tuberculosis should be excluded when managing

  infertility in females.


2462. Raut VS.  Mahashur AA.  Sheth SS. The Mantoux test in the diagnosis of genital tuberculosis in women. International Journal of Gynaecology & Obstetrics.  72(2):165-9, 2001 Feb.


  OBJECTIVE: To analyze the usefulness of the Mantoux test in the diagnosis

  of genital tuberculosis in women of childbearing age. METHOD: In this

  report, the investigators studied the ability of a tuberculosis (TB)

  Mantoux test to diagnose pelvic tuberculosis. A positive TB Mantoux test

  was clearly defined. The positive control group was of 100 women treated

  for TB (study group C). The negative control group was of 100 postpartum

  women (study group B). The study group was 100 infertile women undergoing

  laparoscopy, in some of whom the diagnosis of TB was made (study group A).

  RESULT: The Mantoux test had a sensitivity of only 55% and a specificity

  of 80% in women with laparoscopically diagnosed tuberculosis. Pelvic focal

  reaction was absent in all groups including infertile women with a

  positive Mantoux test. CONCLUSION: Mantoux test has limited utility in

  diagnosing active genital tuberculosis during the childbearing age.

  However, in infertile women with positive a Mantoux test, laparoscopy may

  be advocated early.


2463. Research Committee of the British Thoracic Society. First randomised trial of treatments for pulmonary disease caused by M avium intracellulare, M malmoense, and M xenopi in HIV negative patients: rifampicin, ethambutol and isoniazid versus rifampicin and ethambutol. [see comments]. Thorax.  56(3):167-72, 2001 Mar.


  BACKGROUND: The treatment of pulmonary disease caused by opportunist

  mycobacteria is controversial. It is uncertain whether in vitro

  sensitivity testing predicts clinical response in the way it does for

  Mycobacterium tuberculosis. The literature suggests that the combination

  of rifampicin (R) and ethambutol (E) is important whereas isoniazid (H)

  may not be, but to date there have been no published reports of randomised

  controlled trials in the treatment of these conditions. The British

  Thoracic Society has conducted the first such trial, a randomised study of

  two regimens in HIV negative patients with pulmonary disease caused by M

  avium intracellulare (MAC), M malmoense, and M xenopi. METHODS: When two

  positive cultures were confirmed by the Mycobacterium Reference

  Laboratories for England, Wales and Scotland, the coordinating physician

  invited the patient's physician to enrol the patient. Patients were also

  recruited from Scandinavia. Randomisation to 2 years of treatment with RE

  or REH was performed from lists held in the coordinator's office.

  Clinical, bacteriological, and radiological progress was monitored at set

  intervals up to 5 years. RESULTS: From October 1987 to December 1992, 141

  physicians entered 223 patients (106 with M malmoense, 75 with MAC, 42

  with M xenopi). At entry the RE and REH groups were comparable over a

  range of demographic and clinical features. For each species there was no

  significant difference between RE and REH in the number of deaths, but

  when the three species were combined there were fewer deaths from the

  mycobacterial disease with RE (1% v 8%, p=0.018, odds ratio 0.10, exact

  95% CI 0.00 to 0.76). For M malmoense the failure of treatment/relapse

  rates did not differ appreciably between the regimens, but for MAC there

  were fewer failures of treatment/relapses with REH (16% v 41%, p=0.033)

  With M xenopi there was a non-significant trend in the same direction (5%

  v 18%, p=0.41) and when all three species were combined there was a

  significant difference in favour of REH (11% v 22%, p=0.033). There was no

  correlation between failure of treatment/relapse and in vitro resistance.

  M xenopi was associated with the greatest mortality (57% at 5 years), MAC

  was the most difficult to eradicate, and M malmoense had the most

  favourable outlook (42% known to be alive and cured at 5 years).

  CONCLUSIONS: The results of susceptibility tests performed by the modal

  resistance method do not correlate with the patient's response to

  chemotherapy. RE and REH are tolerated better than previous regimens

  containing second or third line anti-mycobacterial drugs. Treatment of M

  malmoense with RE for 2 years is preferable to REH. The addition of H

  reduces the failure of treatment/relapse rates for MAC and has a tendency

  to do so also for M xenopi, but there is a suggestion that REH is

  associated with higher death rates overall. Better regimens are required.


2464. Richter B.  Fradis M.  Kohler G.  Ridder GJ. Epiglottic tuberculosis: differential diagnosis and treatment. Case report and review of the literature. [Review] [32 refs] Annals of Otology, Rhinology & Laryngology.  110(2):197-201, 2001 Feb.


  A case of a 40-year-old man with tuberculous involvement of the epiglottis

  suffering from unsuspected pulmonary tuberculosis is described. The

  laryngeal lesions were primarily considered to be highly suspicious for a

  neoplastic process rather than an infectious one. After diagnosis, the

  patient was treated according a standard protocol and followed up for a

  period of 2 years. He is still free of disease. The clinical presentation,

  diagnosis, pathological findings, and therapy of the condition are

  described. The differential diagnosis and management of epiglottic

  tuberculosis are reviewed and discussed. Even though these cases are rare,

  otorhinolaryngologists should keep in mind the possibility of tuberculosis

  in the differential diagnosis of laryngeal tumors, as the incidence of

  tuberculosis in developed countries is steadily increasing. [References:



2465. Sakai  J.  Matsuzawa S.  Usui M.  Yano I. New diagnostic approach for ocular tuberculosis by ELISA using the cord factor as antigen. [see comments]. British Journal of Ophthalmology.  85(2):130-3, 2001 Feb.


  BACKGROUND/AIMS: Diagnosis of ocular tuberculosis is difficult,

  particularly the retinal vasculitis type, because most cases occur without

  concurrent active pulmonary tuberculosis. Recently, it has been reported

  that detection of antibodies against purified cord factor

  (trehalose-6,6'-dimycolate, TDM), the best studied, most antigenic, and

  most abundant cell wall component of tubercule bacilli, is very useful for

  rapid serodiagnosis of pulmonary tuberculosis. In this study, an attempt

  was made to evaluate whether the detection of anticord factor antibody is

  also useful for diagnosis of ocular tuberculosis and the necessity of

  antituberculous therapy for tuberculous retinochoroiditis was discussed.

  METHODS: Cases consisted of 15 patients with uveitis and retinal

  vasculitis, nine patients with presumed ocular tuberculosis, three

  patients with sarcoidosis, and three patients with Behcet's disease. IgG

  antibodies against purified cord factor prepared from Mycobacterium

  tuberculosis H37Rv were detected by enzyme linked immunosorbent assay.

  RESULTS: All cases of clinically presumed ocular tuberculosis were

  positive, whereas all of the cases of sarcoidosis or Behcet's disease were

  negative for anticord factor antibodies. When the anticord factor antibody

  titres were compared on the basis of the presence or absence of previous

  antituberculosis chemotherapy, the mean anticord factor antibody titre of

  the untreated group showed a tendency to be higher than in the treated

  group, but not significantly (p=0.07). CONCLUSIONS: The detection of

  anticord factor antibody may be useful to support the diagnosis of ocular

  tuberculosis. Additionally, a positive result for anticord factor antibody

  may indicate that tubercule bacilli are present in some organ(s) of the

  patient even in the absence of active systemic disease.


2466. Soler R.  Rodriguez E.  Remuinan C.  Santos M. MRI of musculoskeletal extraspinal tuberculosis. Journal of Computer Assisted Tomography.  25(2):177-83, 2001 Mar-Apr.


  PURPOSE: The aim of this study was to describe the MR findings in

  extraspinal musculoskeletal tuberculosis (EMT). METHOD: A retrospective

  review was conducted of the MR findings of 18 patients with

  microbiologically and/or pathologically proven EMT. All MR studies were

  performed using T1-and T2-weighted spin echo sequences. T1-weighted spin

  echo sequences after Gd-DTPA injection were obtained for 12 patients. The

  MR images were evaluated for abnormalities in joints, bones, and soft

  tissues, and the results were grouped by anatomic localization, frequency

  distribution of structures affected, and morphologic patterns of

  involvement. RESULTS: Isolated soft tissue tuberculosis was found in 10

  (55.5%) patients and involvement of more than one structure in 8 (44.4%).

  Pyomyositis (n = 6) and arthritis with involvement of adjacent soft

  tissues (n = 7) were the most common forms of presentation. One patient

  presented with isolated fascial superficial tissue involvement in one leg.

  Isolated pyomyositis involving one (n = 3) or two (n = 3) muscles was

  homogeneous in six cases and showed intermediate (n = 6), low (n = 2), or

  high (n = 1) signal intensity on T1-weighted images and a high and very

  hyperintense signal on T2-weighted images. The tenosynovitis synovial

  fluid was homogeneous (n = 1) or heterogeneous with multiple tiny

  hypointense nodules (n = 1) on T2-weighted images. The subdeltoid bursitis

  fluid was characterized by homogeneous low signal intensity with a

  hyperintense rim (n = 2) on T1-weighted images and homogeneous (n = 1) or

  heterogeneous hyperintense signals with areas of low signal intensity (n =

  1) on T2-weighted images. In tuberculous arthritis, the synovial joint

  fluid (n = 7) showed heterogeneous (n = 4) or homogeneous (n = 3) low

  signal intensity on T1-weighted images and high or very high signal

  intensity on T2-weighted images. Where involved, the adjacent muscle(s) (n

  = 8) were usually hypointense on T1-weighted images and very hyperintense

  on T2-weighted images. Associated cellulitis was found in arthritis with

  involvement of neighboring soft tissues (n = 5), pyomyositis (n = 2), and

  tenosynovitis (n = 1). The images obtained after Gd-DTPA showed peripheral

  (n = 10) or heterogeneous (n = 1) enhancement or no enhancement (n = 1).

  CONCLUSION: The MR findings for EMT are variable. Although diagnosis is

  dependent largely on prior presumption and clinical context, MRI provides

  valuable guidelines in defining the extent of the lesions to select the

  appropriate treatment and for follow-up of abnormalities.


2467. Souilamas R.  Riquet M.  Barthes FP.  Chehab A.  Capuani A.  Faure E. Surgical treatment of active and sequelar forms of pulmonary tuberculosis. Annals of Thoracic Surgery.  71(2):443-7, 2001 Feb.


  BACKGROUND: The incidence of tuberculosis has risen since 1990, and in

  some countries, the resistant forms are becoming more and more frequent.

  Surgical treatment is once again needed to manage these problems. The

  purpose of this study was to analyze the indications and results of

  resection, which we performed for pulmonary tuberculosis. METHODS: From

  1980 to 1997, 477 patients were operated on for thoracic or intrathoracic

  tuberculosis in Laennec Hospital, Paris (259 suffered lung diseases).

  There were 165 women and 94 men, aged 25 to 86 years (mean 46 years), from

  Europe (n = 148), North Africa (n = 65), Subsaharian Africa (n = 34), Asia

  (n = 7), and the West Indies (n = 5). This population was reviewed

  concerning the lung tuberculosis (sequelae or active lesions), the

  indications of lung resection, the type of resections performed, and the

  results at 1, 6, and 12 months. RESULTS: Active lesions were present in 97

  cases and sequelae in 162. Surgery was performed for a therapeutic purpose

  in 104 patients with sequelae, and in 10 patients with active tuberculosis

  (pneumonectomy, n = 19; pleuropneumonectomy, n = 19; lobectomy, n = 54;

  and segmentectomy, n = 22). Surgery was performed for a diagnostic purpose

  in 54 patients with sequelae, and in 87 patients with active lesions

  (lobectomy, n = 32; segmentectomy, n = 19; wedge resection, n = 94, of

  which 11 performed by video-assisted thoracoscopy since 1991). One patient

  died after pleuropneumonectomy. We observed 25 complications: empyema, n =

  7; hemothorax, n = 2; prolonged air leaks, n = 14; and pneumopathy, n = 2.

  All patients with active lesions subsequently were given antitubercular

  drugs. Follow-up was 100% at 1 month, 57% (n = 92) and 77% (n = 75) at 6

  months for patients with sequelae and for patients with active lesions,

  respectively. All were asymptomatic with a normal chest roentgenogram. The

  number of operations for active lesions is increasing over the years,

  while it is decreasing for sequelar lesions. CONCLUSIONS: In our

  department, surgery is being performed more frequently to make a diagnosis

  in cases of active tuberculosis, and to treat complicated lesions in case

  of sequelae. Lung resection for active tuberculosis evolving under

  treatment or for drug resistance was rare. However, our study confirms the

  good results commonly obtained by surgery and supports the idea that

  surgery may help eradicate tuberculosis when social and economic

  circumstances render its medical management difficult or hazardous.


2468. Toossi Z.  Mayanja-Kizza H.  Hirsch CS.  Edmonds KL.  Spahlinger T.  Hom DL.  Aung H.  Mugyenyi P.  Ellner JJ.  Whalen CW. Impact of tuberculosis (TB) on HIV-1 activity in dually infected patients. Clinical & Experimental Immunology.  123(2):233-8, 2001 Feb.


  Active TB in HIV-1-infected subjects is associated with increased

  HIV-1-related immunodeficiency and mortality. We assessed plasma viral

  load in HIV-1-infected patients with pulmonary TB (HIV/TB) and non-TB

  symptomatic HIV-1-infected patients (HIV). HIV-1 load was higher in HIV/TB

  compared with HIV at higher CD4 counts (> 500/microl) (P < 0.01), but not

  at lower CD4 counts (< 500/microl). We also evaluated the status of HIV-1

  gene expression in peripheral blood mononuclear cells (PBMC) and serum

  from HIV/TB and CD4-matched healthy HIV-infected patients (HIV/C) by

  reverse transcriptase-polymerase chain reaction over a range of CD4 (>

  900/microl to < 200/microl). HIV-1 RNA in serum and PBMC correlated to one

  another, and both were markedly higher in HIV/TB compared with HIV/C with

  higher CD4 counts. Also, during a longitudinal study of anti-tuberculous

  chemoprophylaxis in HIV-1-infected patients, 10 subjects who developed TB

  had serologies before, at the time, and after the diagnosis of TB. These

  HIV/TB patients had an increase in viral load (average 2.5-fold) at the

  time of diagnosis of TB (P < 0.05). Overall, these data indicate that the

  transcriptional activity of HIV-1 is enhanced in HIV-1-infected patients

  with active TB, especially during early HIV-1 disease. As TB often is an

  early HIV-1 opportunistic infection, it may particularly favour early

  viral replication and dissemination, and therefore contribute to

  progression of HIV-1 disease.


 2469. Toyoshima M.  Chida K.  Suda T.  Imokawa S.  Nakamura H. Wegener's granulomatosis responding to antituberculous drugs. Chest.  119(2):643-5, 2001 Feb.


  We present a case of Wegener's granulomatosis (WG) that responded to

  antituberculous drugs. A 44-year-old woman with multiple nodules on chest

  radiograph received a diagnosis of pulmonary tuberculosis because

  open-lung biopsy specimens showed caseous granulomas. Her chest shadows

  underwent repeated resolution after the start of antituberculous

  treatment, and relapse after the cessation of the drugs. Antineutrophil

  cytoplasmic antibody was positive (14 enzyme-linked immunosorbent assay

  units), and the second lung biopsy specimens showed necrotizing granulomas

  and vasculitis without pathogenic organisms. Thus, the patient received a

  diagnosis of WG and was successfully treated with

  trimethoprim/sulfamethoxazole 10 years after her initial evaluation.

  Antituberculous drugs were effective in this case of WG.


2471. van den Berge M.  Tinga CJ.  Bieger R. A 73-year-old man with chronic lymphocytic leukaemia and a haemorrhagic pleural effusion. Annals of Hematology.  80(3):183-6, 2001 Mar.


A 73-year-old man presented with haemorrhagic pleural effusion, having been diagnosed with chronic lymphocytic leukaemia (CLL). The differential diagnosis of haemorrhagic pleural effusion is considered. Tuberculosis and pleural infiltration of CLL are considered most likely. Pleural biopsy confirms the diagnosis of pleural involvement of CLL in this case. Although pleural involvement of CLL has been reported several times the presentation of pleural effusion as the first symptom of CLL has not previously been described.


2472. Van Soolingen D. Molecular epidemiology of tuberculosis and other mycobacterial infections: main methodologies and achievements. [Review] [314 refs] Journal of Internal Medicine.  249(1):1-26, 2001 Jan.


  In the last decade, DNA fingerprint techniques have become available to

  study the interperson transmission of tuberculosis and other mycobacterial

  infections. These methods have facilitated epidemiological studies at a

  population level. In addition, the species identification of rarely

  encountered mycobacteria has improved significantly. This article

  describes the state of the art of the main molecular typing methods for

  Mycobacterium tuberculosis complex and non-M. tuberculosis complex

  (atypical) mycobacteria. Important new insights that have been gained

  through molecular techniques into epidemiological aspects and diagnosis of

  mycobacterial diseases are highlighted. [References: 314]


2473. Walley JD.  Khan MA.  Newell JN.  Khan MH. Effectiveness of the direct observation component of DOTS for tuberculosis: a randomised controlled trial in Pakistan. Lancet.  357(9257):664-9, 2001 Mar 3.


  BACKGROUND: DOTS is the control strategy for tuberculosis promoted by WHO.

  Pakistan is currently developing its National Tuberculosis Programme, and

  requires guidance on types of direct observation of treatment appropriate

  for the local conditions. We did a randomised trial to assess the

  effectiveness of different packages for tuberculosis treatment under

  operational conditions in Pakistan. METHODS: We enrolled 497 adults with

  new sputum-positive tuberculosis. 170 were assigned DOTS with direct

  observation of treatment by health workers; 165 were assigned DOTS with

  direct observation of treatment by family members; and 162 were assigned

  self-administered treatment. The trial was done at three sites that

  provide tuberculosis services strengthened according to WHO guidelines for

  the purposes of the research, with a standard daily short-course drugs

  regimen (2 months of isoniazid, rifampicin, pyrazinamide, and ethambutol,

  followed by 6 months of isoniazid and ethambutol). The main outcome

  measures were cure, and cure or treatment completion. Analysis was by

  intention to treat. FINDINGS: Within the strengthened tuberculosis

  services, the health-worker DOTS, family-member DOTS, and

  self-administered treatment strategies gave very similar outcomes, with

  cure rates of 64%, 55%, and 62%, respectively, and cure or

  treatment-completed rates of 67%, 62%, and 65%, respectively.

  INTERPRETATION: None of the three strategies tested was shown to be

  superior to the others, and direct observation of treatment did not give

  any additional improvement in cure rates. The effectiveness of direct

  observation of treatment remains unclear, and further operational research

  is needed.


2474. Woods GL.  Bergmann JS.  Williams-Bouyer N. Clinical Evaluation of the Gen-Probe amplified mycobacterium tuberculosis direct test for rapid detection of Mycobacterium tuberculosis in select nonrespiratory specimens. Journal of Clinical Microbiology.  39(2):747-9, 2001 Feb.


  The performance of the Amplified Mycobacterium Tuberculosis Direct Test

  (MTD; Gen-Probe, Inc., San Diego, Calif.) for rapid diagnosis of

  extrapulmonary tuberculosis was evaluated by testing 178 nonrespiratory

  specimens from 158 patients. Criteria for specimen inclusion were (i) a

  positive smear for acid-fast bacilli (n = 54) and (ii) the source if the

  smear was negative (tissue biopsies and aspirates and abscess material

  were tested; n = 124). Results were compared to those of mycobacterial

  culture; clinical history was reviewed when MTD and culture results

  disagreed. Forty-eight specimens (27.0%) were positive for mycobacteria,

  including 23 Mycobacterium tuberculosis complex specimens; of which 21

  were smear positive. Twenty-five specimens were MTD positive; 20 of these

  grew M. tuberculosis complex. All of the five MTD-positive, M.

  tuberculosis complex culture-negative specimens were considered truly

  positive, based on review of the medical record. Of the three

  MTD-negative, M. tuberculosis complex culture-positive specimens, two

  contained inhibitory substances; one of the two was smear positive.

  Excluding the latter specimen from analysis, after chart review, the

  sensitivity, specificity, and positive and negative predictive values of

  the MTD were 92.6, 100, 100, and 98.7%, respectively, by specimen and

  89.5, 100, 100, and 98.6% by patient. Given the few smear-negative samples

  from patients with extrapulmonary tuberculosis in our study, additional

  similar studies that include more smear-negative, M. tuberculosis complex

  culture-positive specimens to confirm our data are desirable.



2475. Woods GL. Molecular techniques in mycobacterial detection. [Review] [35 refs] Archives of Pathology & Laboratory Medicine.  125(1):122-6, 2001 Jan.


  OBJECTIVE: To assess the clinical utility of the commercial nucleic acid

  amplification (NAA) tests (ie, Amplified Mycobacterium Tuberculosis Direct

  Test, Gen-Probe, Inc and AMPLICOR Mycobacterium tuberculosis Test, Roche

  Molecular Systems, Inc) for direct detection of Mycobacterium tuberculosis

  complex. DATA SOURCES: Review of the English-language literature.

  CONCLUSIONS: The performance of both NAA tests is excellent (sensitivity,

  > or = 95%; specificity, 100%) when testing respiratory specimens that are

  smear-positive for acid-fast bacilli (AFB). Only the Gen-Probe assay is

  approved for testing respiratory specimens regardless of the AFB smear

  result. Data from 3 studies showed that the sensitivity of the

  Mycobacterium Tuberculosis Direct Test in smear-negative patients ranged

  from 83% to 85%, and that the specificity was 99%. Both NAA tests have

  been used to test nonrespiratory specimens; in some studies, the

  performance was comparable to the performance obtained for respiratory

  specimens, whereas in others, it was lower. The NAA tests also appear to

  be reliable tools for rapid detection of M tuberculosis complex in

  positive broth cultures of all specimen types (except blood). The impact

  of the NAA tests on patient outcome varies based on the result of the AFB

  smear. In smear-positive patients, public health and hospital

  infection-control resources are predominantly affected. The potential for

  influencing patient outcome is much greater when the AFB smear is

  negative. In smear-negative patients, the NAA test could provide more

  rapid diagnosis of tuberculosis and subsequent initiation of therapy;

  eliminate the need for invasive diagnostic procedures, which are both

  costly and pose an added risk to the patient; and allow earlier discharge

  of hospitalized patients. Prospective studies concerning the

  cost-effectiveness of the NAA tests are needed. [References: 35]






2924.  Ameixa C.  Friedland JS.  Down-regulation of interleukin-8 secretion from Mycobacterium tuberculosis-infected monocytes by interleukin-4 and -10 but not by interleukin-13.  Infection & Immunity.  69(4):2470-6, 2001 Apr.


  Interleukin-8 (IL-8), a CXC chemokine, has a central role in leukocyte recruitment to areas of granuloma formation in tuberculosis. In the present studies, we investigated the effect of the T(H)2-derived cytokines IL-4, IL-10, and IL-13 on Mycobacterium tuberculosis-induced IL-8 secretion from purified human monocytes. Our results demonstrate that IL-4 and IL-10 have a down-regulatory effect on IL-8 secretion and that this effect is dose dependent. IL-10 has a greater effect than IL-4 on secretion, and autologous IL-10 secreted from M. tuberculosis-infected monocytes also down-regulates IL-8 secretion. The down-regulatory effect is partly a result of reduced IL-8 mRNA accumulation analyzed by reverse transcription-PCR. When combined, 1 microM IL-4 and IL-10 had an additive effect in decreasing IL-8 secretion and transcription; there was no synergy of action. IL-13 did not have any significant effect on IL-8 gene expression or secretion. The inhibitory effect of IL-10 but not of IL-4 is associated with decreased nuclear binding of the key activating transcription factor NF-kappaB. We show for the first time that M. tuberculosis causes up-regulation of nuclear binding of Oct-1 detected by electromobility gel shift assay. However, neither AP-1 nor Oct-1 nuclear binding was altered by IL-4 or IL-10. In summary, this study demonstrates that type 2 responses have an important role in the regulation of M. tuberculosis-induced IL-8 expression but that the mechanisms by which the different cytokines act are distinct.


2925.  Andersen P.  TB vaccines: progress and problems. [Review] [77 refs]  Trends in Immunology.  22(3):160-8, 2001 Mar.


  Tuberculosis (TB) is the biggest killer worldwide of any infectious disease, a situation worsened by the advent of the HIV epidemic and the emergence of multi-drug resistant strains of Mycobacterium tuberculosis. The existing vaccine, Mycobacterium bovis bacille Calmette-Guerin (BCG), has proven inefficient in several recent field trials. There is currently intense research using cutting-edge vaccine technology to combat this ancient disease. However, it is necessary to understand why BCG has failed before we can rationally develop the next generation of vaccines. Several hypotheses that might explain the failure of BCG and the strategies designed to address these shortcomings are discussed. [References: 77]


2926.  Arend SM.  van Soolingen D.  Ottenhoff TH.  van Dissel JT.  Repeatedly negative tuberculin skin tests followed by active tuberculosis in an immunocompetent  individual.  Netherlands Journal of Medicine.  58(2):76-81, 2001 Feb.


  We describe a woman who was repeatedly tuberculin (PPD) skin test negative after exposure to smear-positive tuberculosis (TB), but developed active TB with a positive skin test 7 years later. Molecular epidemiologic evidence is presented that the infection was contracted 7 years previously from the original source case. PPD skin testing is subject to many technical and biological variables and this report underscores that this tool can fail to detect latent TB infection in some cases. The causes of false-negative and false-positive PPD skin test results are reviewed.


2927.  Barnes PF.  Diagnosing latent tuberculosis infection: the 100-year upgrade. [letter; comment].  American Journal of Respiratory & Critical Care Medicine.  163(4):807-8, 2001 Mar.


2928.  Burton BJ.  Assi A.  Pavesio C.  Vogt-Koyanagi-Harada syndrome presenting as a severe systemic illness.   Eye.  15(Pt 2):228-9, 2001 Apr.


2929.      Caksen H.  Uzum K.  Tutus A. Pott's disease. Clinical Nuclear Medicine.  26(1):57, 2001 Jan.


  A 15-year-old boy was hospitalized with a 1-month history lumbago and fever. His family history was noncontributory for tuberculosis, and the findings of the physical examination were normal. The sedimentation rate and C-reactive protein level were 55 mm/hour and 48 mg/l, respectively. The result of a purified protein derivative test was 11 x 10 mm. Results of other tests, including rheumatologic studies, serum agglutination for brucellosis, chest radiography, abdominal ultrasonography, and myelography, were normal. The bone biopsy revealed chronic active inflammation. Mycobacterium tuberculosis was not cultured from clinical specimens. However, the patient's symptoms improved after antituberculosis drugs were begun.


2930.  Chen JS.  Chang YL.  Cheng HL.  Chang YC.  Lee YC. Video-assisted thoracoscopic surgery for the diagnosis of patients with hilar and mediastinal lymphadenopathy.  Journal of the Formosan Medical Association.  100(3):213-6, 2001 Mar.


  In areas where tuberculosis (TB) is rare, cases of hilar and mediastinal lymphadenopathy are often attributed to the diagnosis of sarcoidosis or a malignant process. However, these manifestations have been only sparsely reported in countries with high rates of TB. The role of simultaneous lung biopsy in the differential diagnosis of these patients using a thoracoscopic approach is also undetermined. In this prospective study, 15 adult patients with hilar and mediastinal lymphadenopathy were evaluated using video-assisted thoracoscopy during the period from May 1995 through September 1999. Biopsy of the hilar and mediastinal lymph nodes was undertaken in all 15 patients, and a wedge biopsy of the lungs was performed whenever frozen section of the nodes disclosed granulomatous inflammation. The final diagnoses included sarcoidosis (10 patients), TB (2), metastatic small cell carcinoma (2), and reactive lymphoid hyperplasia (1). No morbidity or mortality was associated with the operation. In patients with sarcoidosis and TB, most of the lymph node biopsy specimens disclosed extensive hyaline fibrosis. Lung biopsy specimens presented small non-necrotizing granulomas with multinucleated giant cells even in the absence of demonstrable parenchymal lesions. In the two patients with TB, identification of acid-fast bacilli and growth of Mycobacterium tuberculosis occurred only in lung specimens and not in specimens from lymph nodes. Video-assisted thoracoscopic surgery is a safe, simple, and effective procedure for the diagnosis of patients with hilar and mediastinal lymphadenopathy. Our results suggest that for a better differentiation between TB and sarcoidosis, an additional lung biopsy could be undertaken to provide specimens for microscopic examination and culture.


2931.    Chitale S.  Ehrt S.  Kawamura I.  Fujimura T.  Shimono N.  Anand N.  Lu S.  Cohen-Gould L.  Riley LW. Recombinant Mycobacterium tuberculosis protein associated with mammalian cell entry.  Cellular Microbiology.  3(4):247-54, 2001 Apr.


  The ability to gain entry and resist the antimicrobial intracellular environment of mammalian cells is an essential virulence property of Mycobacterium tuberculosis. A purified recombinant protein expressed by a 1362 bp locus (mce1) in the M. tuberculosis genome promoted uptake into HeLa cells of polystyrene latex microspheres coated with the protein. N-terminus deletion constructs of Mce1 identified a domain located between amino acid positions 106 and 163 that was needed for this cell uptake activity. Mce1 contained hydrophobic stretches at the N-terminus predictive of a signal sequence, and colloidal gold immunoelectron microscopy indicated that the corresponding native protein is expressed on the surface of the M. tuberculosis organism. The complete M. tuberculosis genome sequence revealed that it contained four homologues of mce (mce1, mce2, mce3, mce4) and that they were all located within operons composed of genes arranged similarly at different locations in the chromosome. Recombinant Mce2, which had the highest level of identity (67%) to Mce1, was unable to promote the association of microspheres with HeLa cells. Although the exact function of Mce1 is still unknown, it appears to serve as an effector molecule expressed on the surface of M. tuberculosis that is capable of eliciting plasma membrane perturbations in non-phagocytic mammalian cells.


2932.  D'Agata EM.  Wise S.  Stewart A.  Lefkowitz LB Jr. Nosocomial transmission of Mycobacterium tuberculosis from an extrapulmonary site. Infection Control & Hospital Epidemiology.  22(1):10-2, 2001 Jan.


  OBJECTIVE: To assess the extent of nosocomial transmission and risk factors associated with tuberculin skin test (TST) conversions among healthcare workers (HCWs) exposed to a patient with genitourinary Mycobacterium tuberculosis. DESIGN: Retrospective cohort study of exposed HCWs. SETTING: A 275-bed community hospital in Middle Tennessee. PARTICIPANTS: A total of 128 exposed HCWs and the index patient, who required drainage of a prostatic abscess and bilateral orchiectomy and expired after a 27-day hospitalization. Disseminated tuberculosis was diagnosed at autopsy. METHODS: Contact tracing was performed on exposed HCWs. Logistic regression was used to identify independent risk factors associated with TST conversion. RESULTS: A total of 128 HCWs were exposed to the index patient. There was no evidence of active pulmonary tuberculosis throughout the patient's hospitalization; TST conversions occurred only among HCWs who were exposed to the patient during or after his surgical procedures. A total of 12 (13%) of 95 exposed HCWs who were previously nonreactive had newly positive TST: 6 of 28 nurses, 3 of 3 autopsy personnel, 2 of 17 respiratory therapists, and 1 of 12 surgical staff. By logistic regression, irrigation or packing of the surgical site was the only independent risk factor associated with TST conversion among nurses (odds ratio, 9; 95% confidence interval, 1.2-67; P=.03). CONCLUSION: Manipulation of infected tissues of the genitourinary tract can result in nosocomial transmission of tuberculosis.


2933.  Das K.  Madan K.  Sukija P.  Gondyal R.  Pradhan G.  Kumar S.  Kar P.  Tubercular abscess of the liver.  Journal of the Association of Physicians of India.  49:588, 2001 May.


2934.  Dick T. Dormant tubercle bacilli: the key to more effective TB chemotherapy?. Journal of Antimicrobial Chemotherapy.  47(1):117-8, 2001 Jan.


2935.  Ellner JJ.  The human immune response to Mycobacterium Tuberculosis infection and disease. [Review] [18 refs]  Kekkaku.  76(2):83-91, 2001 Feb.

2936.  Equi A.  Redington A.  Rosenthal M.  Taylor GM.  Jaswon M.  Bush A. Pulmonary artery occlusion from tuberculous lymphadenopathy in a child. Pediatric Pulmonology.  31(4):311-3, 2001 Apr.


  Occlusion of the pulmonary artery is a rare complication of mediastinal tuberculosis. We report on a 10-year-old girl who presented with a tuberculous pericardial effusion in whom subsequent imaging showed a totally occluded right pulmonary artery from tuberculous lymphadenopathy. Diagnosis was confirmed by polymerase chain reaction from a lymph node biopsy. Failure of medical therapy necessitated surgical reconstruction of her right pulmonary artery. Postoperatively she has normal perfusion of the right lung and normal lung function. Copyright 2001 Wiley-Liss, Inc.


2937.  Frenz MB. A transient pleural effusion. Postgraduate Medical Journal.  77(906):273; discussion 283-4, 2001 Apr.


2938.  Ghobrial MW.  Albornoz MA. Immune thrombocytopenia: a rare presenting manifestation of tuberculosis. [Review] [16 refs] American Journal of Hematology.  67(2):139-43, 2001 Jun.


  We report the case of a 49 year-old male who presented with immune thrombocytopenia (ITP)-induced epistaxis and generalized purpura. During the same hospitalization the patient was also found to have clinical, microbiological, histological, and roentgenographic evidence of disseminated mycobacterial tuberculosis (TB). The hematological and infectious abnormalities, which did not respond to high-dose intravenous corticosteroids and immune globulin (IVIg), resolved after anti-tuberculous treatment. Herein we review the characteristics of this rarely documented association. Copyright 2001 Wiley-Liss, Inc. [References: 16]


2939.  Gillespie SH.  Antibiotic resistance in the absence of selective pressure. [Review] [50 refs]  International Journal of Antimicrobial Agents.  17(3):171-6, 2001 Mar.


  Antibiotic resistance poses a serious threat to modern medical practice making treatment more difficult and is associated with increased mortality among patients infected with resistant organisms. There is clear evidence that acquisition of resistance is associated with a decrease in the fitness of the organisms at least in the short term. Evidence from in vitro experiments indicates that bacteria have the ability to adapt to this deficit and recover fitness on serial passage. More recent results show that identical organisms isolated from patients in outbreaks have an initial deficit but that adaptation occurs in vivo. Strategies directed towards controlling resistance must move beyond wishful thinking that supposes that these organisms will disappear merely with control of prescribing. In some cases, resistance will not disappear because there is no evolutionary disadvantage in being resistant once adaptation has taken place. It is important, therefore, that we direct our efforts towards preventing primary resistance emerging and in limiting the spread of resistant strains. Ultimately, we must look again to new drug discovery to improve our therapeutic armoury. [References: 50]


2940.  Grosser M.  Dittert DD.  Luther T.  Re: Molecular detection of M. tuberculosis DNA in tuberculosis and sarcoidosis.  Diagnostic Molecular Pathology.  10(1):66-8, 2001 Mar.


2941.  Hanscheid T.  Salgado MJ.  Lito LM.  Valadas E. Löwenstein-Jensen media no longer necessary: too strong a statement?. American Journal of Clinical Pathology.  115(4):615-7, 2001 Apr.


2942.  Harboe M. 25th Kellersberger memorial lecture, 2000. The contribution of immunology to tuberculosis control. Ethiopian Medical Journal.  39(1):75-82, 2001 Jan.


2943.  Harries AD.  Kwanjana JH.  Hargreaves NJ.  Van Gorkom J.  Salaniponi FM. Resources for controlling tuberculosis in Malawi. Bulletin of the World Health Organization.  79(4):329-36, 2001.


  OBJECTIVE: To document resources for controlling tuberculosis (TB) in Malawi. METHODS: We performed a countrywide study of all 43 hospitals (3 central, 22 district and 18 mission) which register and treat patients with TB. To collect data for 1998 on the TB-related workload, diagnostic facilities, programme staff and treatment facilities, we used laboratory, radiographic and TB registers, conducted interviews and visited hospital facilities. FINDINGS: The data show that in 1998, 88,257 TB suspects/patients contributed approximately 230,000 sputum specimens for smear microscopy, 55,667 chest X-rays were performed and 23,285 patients were registered for TB treatment. There were 86 trained laboratory personnel, 44 radiographers and 83 TB programme staff. Of these, about 40% had periods of illness during 1998. Approximately 20% of the microscopes and X-ray machines were broken. Some 16% of the hospital beds were designated for TB patients in special wards, but even so, the occupancy of beds in TB wards exceeded 100%. Although stocks of anti-TB drugs were good, there was a shortage of full-time TB ward nurses and 50% of district hospitals conducted no TB ward rounds. In general, there was a shortage of facilities for managing associated HIV-related disease; central hospitals, in particular, were underresourced. CONCLUSION: Malawi needs better planning to utilize its manpower and should consider cross-training hospital personnel. The equipment needs regular maintenance, and more attention should be paid to HIV-related illness. The policies of decentralizing resources to the periphery and increasing diagnostic and case-holding resources for central hospitals should be continued.


2944.  Hawkes ND.  Thomas GA. Unexplained weight loss and a palpable abdominal mass in a middle aged woman. Abdominal tuberculosis. Postgraduate Medical Journal.  77(907):341, 348-9, 2001 May.



2945.  Herr H.  Kim JU.  Kang GH.  Moon KC.  Koh JK. Kaposi's sarcoma occurring during short-term dialysis: report of two cases.  Journal of Korean Medical Science.  16(1):130-4, 2001 Feb.


  Kaposi's sarcoma (KS) appears to develop in association with kidney transplantation, but unlikely with dialysis. We report two cases of classic KS that occurred in patients receiving short-term (less than 3 yr) dialysis. They have been suffering from chronic renal failure due to tuberculosis and diabetes mellitus, respectively. Several to multiple, reddened-violaceous patches, plaques and nodules were found on the hand and the lower extremities. Laboratory studies showed no evidence suggesting immunosuppressed state and there was no history of taking immunosuppressive agents. The biopsies of the two cases revealed proliferation of spindle-shaped cells focally arranged in bundles and multiple dilated vascular spaces outlined by an attenuated endothelium with intravascular and extravasated erythrocytes. The specimens expressed positivity with CD34 antigen. Human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) was detected in one case by polymerase chain reaction method.


2946.  Hertz C.  Kiertscher S.  Godowski P.  Bouis D.  Norgard M.  Roth M.  Modlin R. Microbial lipopeptides stimulate dendritic cell maturation via Toll-like receptor 2. Journal of Immunology.  166(4):2444-50, 2001 Feb 15.


  The ability of dendritic cells (DC) to initiate immune responses in naive T cells is dependent upon a maturation process that allows the cells to develop their potent Ag-presenting capacity. Although immature DC can be derived in vitro by treatment of peripheral blood monocytes with GM-CSF and IL-4, additional signals such as those provided by TNF-alpha, CD40 ligand, or LPS are required for complete maturation and maximum APC function. Because we recently found that microbial lipoproteins can activate monocytes and DC through Toll-like receptor (TLR) 2, we also investigated whether lipoproteins can drive DC maturation. Immature DC were cultured with or without lipoproteins and were monitored for expression of cell surface markers indicative of maturation. Stimulation with lipopeptides increased expression of CD83, MHC class II, CD80, CD86, CD54, and CD58, and decreased CD32 expression and endocytic activity; these lipopeptide-matured DC also displayed enhanced T cell stimulatory capacity in MLR, as measured by T cell proliferation and IFN-gamma secretion. The lipid moiety of the lipopeptide was found to be essential for induction of maturation. Preincubation of maturing DC with an anti-TLR2 blocking Ab before addition of lipopeptide blocked the phenotypic and functional changes associated with DC maturation. These results demonstrate that lipopeptides can stimulate DC maturation via TLR2, providing a mechanism by which products of bacteria can participate in the initiation of an immune response.


2947.  Hoal-van Helden EG.  Hon D.  Lewis LA.  Beyers N.  van Helden PD. Mycobacterial growth in human macrophages: variation according to donor, inoculum and bacterial strain. Cell Biology International.  25(1):71-81, 2001.


  The microbicidal capacity of the macrophage is frequently evaded by mycobacteria, leading to tuberculosis (TB). We investigated a number of parameters affecting the rate of growth of mycobacteria in human monocyte-derived macrophages (MDM). The results show a great deal of variation in the growth of both Mycobacterium bovis BCG and M. tuberculosis H37Rv, using a large number of human macrophage donors, (132 and 40, respectively), but no correlation was seen with the TB status of the MDM donor. Clumping of the mycobacteria resulted in more vigorous growth in MDM, suggesting that inoculum size could affect disease progression. The growth rates of 17 clinical isolates of M. tuberculosis were measured in macrophages derived from three donors and no consistent or marked differences between isolates were observed over the 5-day period of growth measurement. However, all 17 clinical strains grew consistently faster than H37Rv in the same experiments. Copyright 2001 Academic Press.


2948.  Hsu KF.  Hung CF.  Cheng WF.  He L.  Slater LA.  Ling M.  Wu TC. Enhancement of suicidal DNA vaccine potency by linking Mycobacterium tuberculosis heat shock protein 70 to an antigen. Gene Therapy.  8(5):376-83, 2001 Mar.


  Naked DNA vaccines represent an attractive approach for generating antigen-specific immunity because of their stability and simplicity of delivery. There are particular concerns with DNA vaccines however, such as potential integration into the host genome, cell transformation, and limited potency. The usage of DNA-based alphaviral RNA replicons (suicidal DNA vectors) may alleviate the concerns of integration or transformation since suicidal DNA vectors eventually cause lysis of transfected cells. To improve further the potency of suicidal DNA vaccines, we evaluated the effect of linking Mycobacterium tuberculosis heat shock protein 70 (Hsp70) to human papillomavirus type 16 (HPV-16) E7 as a model antigen on antigen-specific immunity generated by a DNA-based Semliki Forest virus (SFV) RNA vector, pSCA1. Our results indicated that this suicidal DNA vaccine containing E7/Hsp70 fusion genes generated significantly higher E7-specific T cell-mediated immune responses than vaccines containing the wild-type E7 gene in vaccinated mice. More importantly, this fusion converted a less effective vaccine into one with significant potency against established E7-expressing metastatic tumors. The antitumor effect was predominantly CD8-dependent. These results indicate that linkage of Hsp70 to the antigen may greatly enhance the potency of suicidal DNA vaccines.


2949.  Jaramillo E.  The impact of media-based health education on tuberculosis diagnosis in Cali, Colombia.  Health Policy & Planning.  16(1):68-73, 2001 Mar.


  Tuberculosis (TB) is one of the most worrying infectious diseases facing less developed countries. Diagnosis and treatment of those who are transmitting Mycobacterium tuberculosis is considered a very effective control strategy. Within this strategy the priority is to achieve high cure rates before attempting to increase case finding. However, there is a dearth of research on how to increase case finding and diagnostic coverage in those settings where high cure rates are being achieved. This paper presents an evaluation of the impact on case finding of a mass media health education campaign for TB control in Cali, Colombia. The campaign aimed at increasing case finding and reducing levels of prejudice against people with TB. The impact assessment shows that the campaign produced an increase of 64% in the number of direct smears processed by the laboratories and an increase of 52% in the number of new cases of positive pulmonary TB, with respect to the previous period. Unfortunately, the effects of the campaign were short-lived. These findings have at least two important implications. First, passive case finding is likely to be an insufficient strategy to reach the operational targets of diagnostic coverage. Secondly, providing basic information about the earliest symptoms of TB and the procedures for diagnosis can increase diagnostic coverage, and thus strengthen the effect on infection risk of control programmes with high cure rates. Further research is required to identify other strategies that could, first, increase diagnostic coverage and, secondly, make the intervention effects sustainable.


2950.  Julian E.  Cama M.  Martinez P.  Luquin M. An ELISA for five glycolipids from the cell wall of Mycobacterium tuberculosis: Tween 20 interference in the assay.  Journal of Immunological Methods.  251(1-2):21-30, 2001 May 1.


  Mycobacterium tuberculosis cell wall contains antigenic glycolipids: phenol-glycolipid (PGL), diacyltrehalose (DAT), triacyltrehalose (TAT), cord-factor (CF), and sulpholipid-I (SL-I). In the last decade, the usefulness of these antigens for the serodiagnosis of tuberculosis has been evaluated mainly using enzyme-linked immunosorbent assays (ELISA). Currently, there are no conclusive results about the utility of these glycolipidic antigens, because the results obtained by different groups are discrepant. In order to explain these discrepancies, we have investigated the methodological variations in the ELISAs used previously. Specifically, we have studied the following: the coating solvent, the optimum amount of glycolipid coated per well, the blocking agent, and the use of detergent (Tween 20) in the washing buffer. The most significant finding was that Tween 20 detaches PGL, DAT, TAT and SL-I from microtitre wells. However, Tween 20 does not remove CF from the wells. In addition, we have found that the best solvent for coating is n-hexane, that the optimum antigen coating concentration is 1000 ng/well, and that BSA and gelatin are equally effective blocking agents. We can therefore conclude that the use of Tween 20 as a detergent, and the lower antigen coating concentrations (100-200 ng/well), may well explain some of the discrepancies in previous studies.


2951.  Kato-Maeda M.  Bifani PJ.  Kreiswirth BN.  Small PM. The nature and consequence of genetic variability within Mycobacterium tuberculosis. [Review] [37 refs]  Journal of Clinical Investigation.  107(5):533-7, 2001 Mar.


2952.    Kato-Maeda M.  Rhee JT.  Gingeras TR.  Salamon H.  Drenkow J.  Smittipat N.  Small PM. Comparing genomes within the species Mycobacterium tuberculosis. Genome Research.  11(4):547-54, 2001 Apr.


  The study of genetic variability within natural populations of pathogens may provide insight into their evolution and pathogenesis. We used a Mycobacterium tuberculosis high-density oligonucleotide microarray to detect small-scale genomic deletions among 19 clinically and epidemiologically well-characterized isolates of M. tuberculosis. The pattern of deletions detected was identical within mycobacterial clones but differed between different clones, suggesting that this is a suitable genotyping system for epidemiologic studies. An analysis of genomic deletions among an extant population of pathogenic bacteria provided a novel perspective on genomic organization and evolution. Deletions are likely to contain ancestral genes whose functions are no longer essential for the organism's survival, whereas genes that are never deleted constitute the minimal mycobacterial genome. As the amount of genomic deletion increased, the likelihood that the bacteria will cause pulmonary cavitation decreased, suggesting that the accumulation of mutations tends to diminish their pathogenicity. Array-based comparative genomics is a promising approach to exploring molecular epidemiology, microbial evolution, and pathogenesis.


2953.  Khattab T.  Fryer C.  Felimban S.  Yousef A.  Noufal M.  Unusual complication of sickle cell crisis.  Journal of Pediatric Hematology/Oncology.  23(1):71-2, 2001 Jan.


2954.  Koss LG. Benign and malignant mesothelial proliferations.  American Journal of Surgical Pathology.  25(4):548-9, 2001 Apr.


2955.  Krishnan A.  Patkar D.  Patankar T.  Shah J.  Prasad S.  Bunting T.  Castillo M.  Mukherji SK.  Craniovertebral junction tuberculosis: a review of 29 cases.  Journal of Computer Assisted Tomography.  25(2):171-6, 2001 Mar-Apr.


  PURPOSE: The purpose of this work was to describe the various imaging findings in craniovertebral tuberculosis and the importance of imaging in treatment in these patients. METHOD: A retrospective review of MR and CT scans in 29 patients with craniovertebral tuberculosis was performed. The images were reviewed, paying special attention to both bony (skull base, atlas, and axis) and soft tissue involvement in addition to atlantoaxial dislocation, lateral subluxation of the dens, and compression of the spinal cord. RESULTS: Suboccipital pain with neck stiffness was the most common presenting symptom in our patients. The skull was involved in 19 of the 29 cases, clivus involvement was seen in 11 patients, and occipital condyle involvement was present in 14 patients. Detailed analysis of atlas involvement due to tuberculosis showed the lateral masses to be predominantly affected. The dens was involved in 18 cases (62%). Soft tissue masses in the prevertebral area were seen in 22 patients, paravertebral in 27 patients, and epidural involvement in 25 patients was identified. Atlantoaxial displacement was present in seven cases, lateral mass-dens subluxation in five, and superior subluxation of the dens through the foramen magnum compressing the medulla was seen in two cases. Spinal cord compression with intrinsic cord changes was noted in 12 cases. All patients received multidrug antituberculous therapy for 1 year. The presence of neurologic deficit and instability of the atlantoaxial complex was pivotal in further management in these patients. CONCLUSION: A high degree of clinical suspicion is necessary when confronted with patients with neck stiffness and tenderness over the upper cervical vertebrae. MRI in these patients provides a sensitive method for the diagnosis of craniovertebral tuberculosis.


2956.  Lam KY.  Lo CY. A critical examination of adrenal tuberculosis and a 28-year autopsy experience of active tuberculosis. Clinical Endocrinology.  54(5):633-9, 2001 May.


  OBJECTIVE: Tuberculosis is potentially fatal and adrenal gland involvement is uncommonly reported. The aims of the current study were to define the characteristics of tuberculosis in hospitalized patients and to analyse the features of adrenal tuberculosis. DESIGN: Retrospective analysis of autopsies and adrenalectomies. PATIENTS: 13,762 patients (13492 at autopsies and 270 at adrenalectomy). MEASUREMENTS: The presence of active tuberculosis, the predisposing factors, the pathological features and organs of involvement were examined. RESULTS: Active tuberculosis was present in 871 patients (6.5% of all 13492 autopsies). It was first diagnosed in 70% of these patients during autopsy. Cancers and a history of recent major operations were the 2 main concomitant factors in the patients with tuberculosis. Extra-pulmonary tuberculosis was seen in 261 patients (30%). The five most common extra-pulmonary sites of tuberculosis were the liver, spleen, kidney, bone and adrenal gland. Adrenal tuberculosis was seen in 52 of the 871 patients (6%) with active tuberculosis at autopsy and in 3 patients at adrenalectomy. The adrenal gland was the only organ involved by active tuberculosis in 14 of these 55 patients (25%; 35 men, 20 women). Tuberculosis was evident on macroscopic examination of the adrenal glands in 46% of the patients. On histological examination, caseous necrosis and granulomatous inflammation with Langhan's giant cells were seen in 71% and 40% of patients, respectively. Seven patients presented with signs and symptoms of Addison's disease due to bilateral adrenal involvement. Langhan's giant cells were frequently seen in histological sections and bilateral enlargement of the adrenal glands was often noted. Fine needle aspiration cytology was not useful for diagnosing adrenal tuberculosis. CONCLUSION: Unexpected and extra-pulmonary tuberculosis such as adrenal tuberculosis has been a common problem. A high index of suspicion, correct diagnosis and proper treatment are essential for the management of tuberculosis.


2957.  Lan SH.  Chang WN.  Lu CH.  Lui CC.  Chang HW. Cerebral infarction in chronic meningitis: a comparison of tuberculous meningitis and cryptococcal meningitis. QJM.  94(5):247-53, 2001 May.


  Twenty-eight patients with cerebral infarction secondary to chronic meningitis were retrospectively identified at our institution over a period of 5 years. They accounted for 47% (17/36) of tuberculous meningitis (TBM) and 32% (11/34) of cryptococcal meningitis cases. Single infarctions were found in 15 patients and multiple infarctions in 13. The distribution of single infarctions was: basal ganglia 7; internal capsule 3; thalamus 1; cerebellum 1; and cortical infarct 3. Therapeutic outcomes at 3 months were determined using a modified Barthel INDEX: At follow-up of 3 months or more, 10 had good outcomes while the other 18 had poor outcomes. The 18 with poor outcomes included six who died, and 12 who had severe neurological sequelae. TBM and cryptococcal meningitis shared similar clinical features, both being frequently associated with other neurological complications, including hydrocephalus, cranial nerve palsy, and seizures in our patients. However, extracranial involvement, such as spinal and pulmonary involvement, was more commonly found in TBM patients. Cerebral infarction can occur in both the acute stage and later stages of treatment. Mortality and morbidity are high, and early diagnosis and appropriate antimicrobial treatment are essential. If hydrocephalus is demonstrated, early ventricular decompression is needed to prevent further cerebral ischaemia.


2958.  Lauzardo M.  Lee P.  Duncan H.  Hale Y. Transmission of Mycobacterium tuberculosis to a funeral director during routine embalming. Chest.  119(2):640-2, 2001 Feb.


  Several studies have shown that funeral directors have an increased risk of tuberculosis (TB). Although there is indirect evidence of transmission of TB from cadavers to mortuary workers, there is only one recently documented case in the literature. We report here another case of occupationally acquired TB in a funeral director, which was confirmed by conventional epidemiology and genotyping. This case illustrates the risk of TB transmission to mortuary workers from routine embalming of deceased TB patients with active disease.


2959.  Lee Y.  Huang W.  Huang J.  Wang J.  Yu C.  Jiaan B.  Huang J. Efficacy of chemotherapy for prostatic tuberculosis-a clinical and histologic follow-up study. Urology.  57(5):872-7, 2001 May.


  OBJECTIVES: To characterize the clinical features of prostatic tuberculosis and to evaluate the short and long-term results of antituberculous chemotherapy. METHODS: Eighteen patients (mean age 66.7 +/- 10.2 years) with prostatic tuberculosis were included in this study. The median pretreatment prostate-specific antigen (PSA) level was 2.7 ng/mL (range 0.3 to 31). The PSA level was greater than 4.0 ng/mL in 6 patients (33.3%). Eight patients (44.4%) received a triple-drug regimen of rifampin, ethambutol, and isoniazid for more than 6 months. The mean duration of chemotherapy was 7.6 months (range 6 to 12). Of the 8 patients, 3 underwent chemotherapy longer because of concurrent tuberculosis of other organs. Follow-up studies included digital rectal examination, total PSA determination, and transrectal prostate biopsy. RESULTS: Ten patients were eligible for regular follow-up. All the patients were symptom free during follow-up. The median length of follow-up was 3.4 years (range 1 to 9). The average number of follow-up transrectal prostate biopsies was 2.4 (range 2 to 3). The follow-up histologic findings showed nodular hyperplasia in 7 patients and chronic inflammatory cell infiltration in 3 patients. No acid-fast bacillus was found in any follow-up specimen. Similarly, subsequent transrectal biopsy showed no relapse after a median length of 3.4 years of follow-up. Of the 6 patients with elevated PSA levels, the post-treatment PSA returned to normal in 3 patients. CONCLUSIONS: Our results suggest that a triple-drug regimen of 6 months' duration can successfully control prostatic tuberculosis. Histologic follow-up is a good method for monitoring the efficacy of treatment. Transrectal prostate biopsy is an important tool for the diagnosis and follow-up of prostatic tuberculosis.


2960.  Marques MA.  Ant nio VL.  Sarno EN.  Brennan PJ.  Pessolani MC. Binding of alpha2-laminins by pathogenic and non-pathogenic mycobacteria and adherence to Schwann cells.   Journal of Medical Microbiology.  50(1):23-8, 2001 Jan.


  The ability of Mycobacterium leprae to specifically bind alpha2-laminins of Schwann cells has been described recently as being an important property of the leprosy bacillus, which could explain the neural tropism of M. leprae. Therefore, the extent of the expression of alpha2-laminin-binding properties among mycobacteria was investigated. In an ELISA-based assay, all three species of Mycobacterium tested (M. tuberculosis, M. chelonae and M. smegmatis) expressed laminin-binding capacity, suggesting that the ability to bind alpha2-laminins is conserved within the genus Mycobacterium. This report also demonstrated that not only M. leprae but all the mycobacterial species tested readily interacted with the ST88-14 cells, a human schwannoma cell line, and that the addition of soluble alpha2-laminins significantly increased their adherence to these cells. These results failed to demonstrate the presence in M. leprae of a unique system based on alpha2-laminins for adherence to Schwann cells.


2961.  Marsman WA.  Jie C.  van Meyel JJ.  Dysphagia caused by esophageal tuberculosis. Netherlands Journal of Medicine.  58(2):82-5, 2001 Feb.


  This report describes two patients with dysphagia who appeared to have esophageal tuberculosis. One patient had a fistula draining into a mediastinal mass. Both patients responded promptly to treatment with tuberculostatics. Surgery was not required. Esophageal tuberculosis is a rare entity.


2962.  McMurray DN.  Disease model: pulmonary tuberculosis. [Review] [10 refs] Trends Mol Med.  7(3):135-7, 2001 Mar.


  In spite of a massive effort to apply the tools currently available for tuberculosis (TB) control, both in this country and abroad, it is clear that complicating factors [for example, HIV co-infection, drug resistance, lack of patient compliance with chemotherapy, variable efficacy of Bacille Calmette-Guerin (BCG) vaccine] will prevent disease control unless new drugs, vaccines and diagnostic tests are developed (1). The publication of the complete genome sequence of Mycobacterium tuberculosis in 1998 (2) has facilitated a directed search for virulence genes, new drug targets, and vaccine antigens. This research effort has been made possible by the availability of highly biologically relevant animal models of pulmonary TB ((3)). [References: 10]


2963.  Meddows-Taylor S.  Pendle S.  Tiemessen CT.  Altered expression of CD88 and associated impairment of complement 5a-induced neutrophil responses in human immunodeficiency virus type 1-infected patients with and without pulmonary tuberculosis.  Journal of Infectious Diseases.  183(4):662-5, 2001 Feb 15.


  The effect of infection with human immunodeficiency virus type 1 (HIV patient group), infection with Mycobacterium tuberculosis (TB patient group), and coinfection with both of these organisms (HIV/TB patient group) on the expression of CD88 on polymorphonuclear leukocytes (PMNL) was determined by using a receptor-specific monoclonal antibody and flow cytometry. A significant reduction in the fluorescence intensity of CD88 on PMNL was observed in the HIV and HIV/TB groups, compared with both the healthy donor (HD) and TB groups. Furthermore, when degranulation of PMNL was induced by ligation of CD88 by complement 5a (C5a), a large proportion of patients in the HIV and the HIV/TB groups was found to have reciprocal degranulation responses. Patients in the 2 HIV groups also were found to have significantly reduced C5a-induced chemotactic responses and significantly elevated peripheral levels of C5a des Arg, compared with the HD and TB groups. These differences may contribute to the increased susceptibility of HIV-1-infected individuals to secondary microbial infections.


2964.  Melzer M.  Warley A.  Chrystie I.  Milburn H.  O'Sullivan D. Anonymous testing for HIV in tuberculosis cases and contacts.   Lancet.  357(9259):888, 2001 Mar 17.


2965.      O'Brien RJ.  Nunn PP.The need for new drugs against tuberculosis. Obstacles, opportunities, and next steps. American Journal of Respiratory & Critical Care Medicine.  163(5):1055-8, 2001 Apr.

2966.      Olobo JO.  Geletu M.  Demissie A.  Eguale T.  Hiwot K.  Aderaye G.  Britton S. Circulating TNF-alpha, TGF-beta, and IL-10 in tuberculosis patients and healthy contacts.  Scandinavian Journal of Immunology.  53(1):85-91, 2001 Jan.


  Levels of tumour necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, and interleukin (IL)-10 in plasma of pulmonary tuberculosis (TB) patients and healthy contacts and plasma and pleural fluid of patients with tuberculous pleuritis were examined by enzyme immunoassay. Plasma TNF-alpha and IL-10 were elevated to significant levels in healthy contacts. High levels of TGF-beta and IL-10 were also detected in plasma from TB patients and healthy contacts. Pleural fluid contained all three cytokines with the level of IL-10 being highest followed by TGF-beta and TNF-alpha. Plasma of tuberculous pleuritis patients also had detectable levels of the three cytokines. Increased levels of TNF-alpha in plasma of contacts and to some extent pleural fluid of pleuritis patients, is perhaps to limit the infection, while elevated IL-10 in plasma of TB patients and contacts and pleural fluid would perhaps modulate excess proinflammation. Elevated TGF-beta in TB patients suggests its role in the immunopathogenesis.


2967.  Orlovic D.  Kularatne R.  Ferraz V.  Smego RA Jr.  Dual pulmonary infection with Mycobacterium tuberculosis and Pneumocystis carinii in patients infected with human immunodeficiency virus. Clinical Infectious Diseases.  32(2):289-94, 2001 Jan 15.


  During a 22-month period, we identified 39 patients with human immunodeficiency virus (HIV) infection (mean CD4(+) count, 90 cells/mm(3)) who were hospitalized with pneumonia and who had sputum and/or other specimens that tested concurrently positive for both Mycobacterium tuberculosis and Pneumocystis carinii. The most common chest x-ray abnormality was a reticulonodular pattern or bilateral infiltrates (n=26). Serum lactate dehydrogenase levels were elevated in 17 (85%) of 20 of patients tested (mean value, 2208 U/L). Mean O(2) saturation and PO(2) were 89% and 64 mm Hg, respectively. A majority (24 patients [62%]) received both antituberculous and anti-PCP therapy (17 with steroids), and 22 improved. All ten patients who received no treatment for PCP improved and were discharged from the hospital, whereas 4 (80%) of the 5 persons who received no antituberculous treatment had a poor outcome (P<.001; OR=43). Patients with HIV or acquired immune deficiency syndrome may present with both TB and PCP; of the 2, TB seems to account for the most severe features of disease.


2968.  Otieno MW.  Remick SC.  Whalen C. Adult Burkitt's lymphoma in patients with and without human immunodeficiency virus infection in Kenya. International Journal of Cancer.  92(5):687-91, 2001 Jun 1.


  Prior to the acquired immunodeficiency syndrome (AIDS) epidemic, one or two cases of adult Burkitt's lymphoma (BL) were seen annually at the Kenyatta National Hospital, the national referral medical center in Nairobi, Kenya. To investigate the influence of human immunodeficiency virus (HIV) infection in adult BL in Kenya, we conducted a national prevalence survey of all patients 16 years of age and older with BL. A systematic review of medical records of all patients diagnosed with BL between 1992 and 1996 was performed. The diagnosis of BL was based and confirmed on review of pathological material from time of original diagnosis. HIV serology was confirmed by enzyme-linked immunosorbent assay (ELISA). Twenty-nine adult patients with BL were identified during the 5-year study period. Of these patients, 17 (59%) were males, 12 (41%) were females, and the median age was 26 years. Nineteen patients (66%) with BL were HIV-seropositive. The proportion of men was similar in HIV-seropositive and -seronegative patients (58% vs 60%). HIV-seropositive BL patients were significantly older than seronegatives (median 35 vs 19.5 years, p < 0.001). HIV-seropositive patients uniformly presented with constitutional or B symptoms and advanced BL accompanied by diffuse lymph node involvement, whereas the clinical presentation of HIV-seronegative patients during this time period was reminiscent of the "typical" endemic pattern of disease with complete sparing of peripheral lymph nodes. The overall survival of HIV-seropositive cases was significantly worse than that of the HIV-seronegative cases; median survival in the HIV-seropositive patients was 15 weeks. There is an approximate 3-fold increase in the incidence of adult BL during the time period of this study, which is attributable to the AIDS epidemic. In this setting, patients often present with disseminated disease, diffuse peripheral lymphadenopathy and fever, the latter two of which heretofore have been commonly associated with non-lymphoproliferative disorders such as Mycobacterium tuberculosis and sexually transmitted diseases in Kenya. These observations warrant inclusion of AIDS-related BL in the differential diagnosis of the adult patient with unexplained fever and lymphadenopathy in Kenya. The corollary is that HIV infection is virtually excluded in an adult patient without peripheral lymphadenopathy and biopsy-proven BL. Copyright 2001 Wiley-Liss, Inc.



2969.  Patnaik M.  Liegmann K.  Peter JB.  Rapid detection of smear-negative Mycobacterium tuberculosis by PCR and sequencing for rifampin resistance with DNA extracted directly from slides.  Journal of Clinical Microbiology.  39(1):51-2, 2001 Jan.


  Conventional methods for identification of Mycobacterium tuberculosis from culture can take 6 weeks. To facilitate the rapid detection of M. tuberculosis and to assess the risks of drug resistance, we developed a technique of eluting DNA directly from sputum slides and performing PCR for the detection of M. tuberculosis DNA, followed by sequencing the rpoB gene to detect rifampin resistance. This entire process requires only 48 h. Forty-seven sputum specimens submitted for microscopy for detection of acid-fast bacilli (AFB) and for mycobacterial culture and susceptibility testing were assessed after elution from the slides and extraction. M. tuberculosis-specific DNA was amplified in a nested PCR with previously described primers (primers rpo95-rpo293 and rpo105-rpo273), followed by analysis on a 4% agarose gel for a 168-bp product. Automated sequencing was performed, and the sequences were aligned against a database for detection of anomalies in the rpoB gene (codons 511 to 533) which indicate rifampin resistance. Of the 47 sputum specimens tested, 51% (24 of 47) were culture positive (time to positive culture, 2 to 6 weeks). Smears for AFB were positive for 58% (14 of 24) of the specimens and were negative for 42% (10 of 24) of the specimens. All 24 culture-positive sputum specimens (14 microscopy-positive and 10 microscopy-negative sputum specimens) were positive by PCR with eluates from the smears. Forty-nine percent (23 of 47) of the sputum specimens were negative for M. tuberculosis by smear, culture, and PCR. Of the isolates from the culture-positive samples, five were rifampin resistant by sequencing; all five were also rifampin resistant by in vitro susceptibility testing. Of these rifampin-resistant M. tuberculosis isolates, two were microscopy negative for AFB. Patients who are negative for AFB and culture positive for M. tuberculosis can now be identified within a day, allowing institution of therapy and reducing isolation time and medical costs.



2970.    Pene F.  Papo T.  Brudy-Gulphe L.  Cariou A.  Piette JC.  Vinsonneau C. Septic shock and thrombotic microangiopathy due to Mycobacterium tuberculosis in a nonimmunocompromised patient. Archives of Internal Medicine.  161(10):1347-8, 2001 May 28.


2971.  Price NM.  Farrar J.  Tran TT.  Nguyen TH.  Tran TH.  Friedland JS.  Identification of a matrix-degrading phenotype in human tuberculosis in vitro and in vivo.   Journal of Immunology.  166(6):4223-30, 2001 Mar 15.


  Tuberculous meningitis is characterized by cerebral tissue destruction. Monocytes, pivotal in immune responses to Mycobacterium tuberculosis, secrete matrix metalloproteinase-9 (MMP-9), which facilitates leukocyte migration across the blood-brain barrier, but may cause cerebral injury. In vitro, human monocytic (THP-1) cells infected by live, virulent M. tuberculosis secreted MMP-9 in a dose-dependent manner. At 24 h, MMP-9 concentrations increased 10-fold to 239 +/- 75 ng/ml (p = 0.001 vs controls). MMP-9 mRNA became detectable at 24--48 h. In contrast, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) gene expression and secretion were similar to constitutive levels from controls at 24 h and increased just 5-fold by 48 h. In vivo investigation revealed MMP-9 concentration per leukocyte in cerebrospinal fluid (CSF) from tuberculous meningitis patients (n = 23; median (range), 3.19 (0.19--31.00) ng/ml/cell) to be higher than that in bacterial (n = 12; 0.23 (0.01--18.37) ng/ml/cell) or viral meningitis (n = 20; 0.20 (0.04--31.00) ng/ml/cell; p < 0.01). TIMP-1, which was constitutively secreted into CSF, was not elevated in tuberculous compared with bacterial meningitis or controls. Thus, a phenotype in which MMP-9 activity is relatively unrestricted by TIMP-1 developed both in vitro and in vivo. This is functionally significant, since MMP-9 concentrations per CSF leukocyte (but not TIMP-1 concentrations) were elevated in fatal tuberculous meningitis and in patients with signs of cerebral tissue damage (unconsciousness, confusion, or neurological deficit; p < 0.05). However, MMP-9 activity was unrelated to the severity of systemic illness. In summary, M. tuberculosis-infected monocytic cells develop a matrix-degrading phenotype, which was observed in vivo and relates to clinical signs reflecting cerebral injury in tuberculous meningitis.


2972.  Ray M.  Goraya JS.  Basu S.  Parmar V. Perinatal tuberculosis. Indian Journal of Pediatrics.  68(4):343-5, 2001 Apr.


  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. We hereby report a baby with perinatal tuberculosis who was not offered any prophylactic therapy inspite of the mother being diagnosed to have pulmonary tuberculosis.


2973.  Rodriguez JC.  Ruiz M.  Climent A.  Royo G. In vitro activity of four fluoroquinolones against Mycobacterium tuberculosis. International Journal of Antimicrobial Agents.  17(3):229-31, 2001 Mar.


  The in vitro activity of ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin against strains of Mycobacterium tuberculosis was studied. Moxifloxacin and levofloxacin showed the greatest activity having an MIC(90) of 1 mg/l. The MIC(90) for ofloxacin was 2 mg/l and for ciprofloxacin 4 mg/l. Further studies should be made to determine the role played by these compounds in the treatment of tuberculosis.


2974.  Ruhul A.  Suzuki Y.  Takatorige T.  Tatara K.  Shirakura R.  [Usefulness of self ligation mediated polymerase chain reaction: a rapid method for fingerprinting in molecular epidemiology of tuberculosis].  Kekkaku.  76(1):9-18, 2001 Jan.


  Restriction fragment length polymorphism (RFLP) analysis based on the insertion sequence IS 6110 has been used as one of the powerful tools for epidemiological study of tuberculosis. However this technique requires more than 1 micro-gram of DNA and two days for completion. To overcome these inconvenience, we have modified a PCR-based method, self ligation mediated PCR (SL-PCR) on the molecular epidemiological study. This method uses a pair of primers whose orientations are from inside to outside of IS 6110. The DNA fragments flanking IS 6110 are amplified by the PCR by using the Sau 3A I digested and ligated chromosomal DNA of Mycobacterium tuberculosis strains. By using this method, M. tuberculosis strains can be differentiated within 8 hours.


2975.  Sahly HM.  Adams GJ.  Soini H.  Teeter L.  Musser JM. Epidemiologic differences between United States- and foreign-born tuberculosis patients in Houston, Texas. Journal of Infectious Diseases.  183(3):461-468, 2001 Feb 1.


  The proportion of foreign-born tuberculosis patients in the United States is increasing. To analyze the epidemiology of tuberculosis in foreign-born people, culture-positive patients with tuberculosis in Houston, Texas, were interviewed from October 1995 through September 1998, and their isolates were molecularly characterized. Of the 1131 patients included in the study, 795 (70.3%) were US born and 336 (29.7%) were foreign born. The decrease in tuberculosis case rate among US-born people was 3.5 times that of foreign-born people. Significantly more US-born than foreign-born patients belonged to strain clusters (71.3% vs. 29.5%; P<.001). Risk factors associated with strain clustering were as follows: black ethnicity, low income, and homelessness in US-born patients and homelessness in foreign-born patients. Isolates from foreign-born patients were more likely to be resistant to >/=1 drug (15.4% vs. 8.4%; P=.001) and to be multidrug resistant (2.4% vs. 0.7%; P=.027) than isolates from US-born patients. These observations warrant increased emphasis on this distinct subpopulation of tuberculosis patients.


2976.  Sarlak AY.  Gundes H.  Gundes S.  Alp M. Primary sternal tuberculosis: a rare unhealed case treated by resection and local rotational flap.  Thoracic & Cardiovascular Surgeon.  49(1):58-9, 2001 Feb.


  Primary sternal tuberculosis is very rare. Only few cases have been reported in the English-language literature. We present a case of primary sternal tuberculosis that had intractable drainage for 18 months. Diagnosis was confirmed with biopsy, and there were no other tuberculous foci. No improvement was achieved in the status of the wound despite 4 months of chemotherapy. We applied the principles as in bacterial osteomyelitis of sternum, resected the wound and covered it with a pectoralis major musculocutaneous rotational flap. The wound healed, and there was no recurrence 24 months after surgery.



2977.  Schwebach JR.  Jacobs WR Jr.  Casadevall A.  Sterilization of Mycobacterium tuberculosis Erdman samples by antimicrobial fixation in a biosafety level 3 laboratory.   Journal of Clinical Microbiology.  39(2):769-71, 2001 Feb.


  Incomplete sterilization of Mycobacterium tuberculosis Erdman cultures followed 1 h of incubation in low concentrations of glutaraldehyde (0.5 and 1.0%) or azide. In contrast, 2.5% glutaraldehyde, paraformaldehyde (2 or 4%), Vesphine IIse or 5% formalin sterilized these samples after 1 h. These results suggest caution in removing fixed M. tuberculosis samples from biosafety level 3.


2978.  Sessler R.  Konyar H.  Hasche G.  Olbricht CJ. The haemodialysis patient with night sweats, ascites, and increased CA 125. Nephrology, Dialysis, Transplantation.  16(1):175-7, 2001 Jan.


2979.  Sigurdarson ST.  Field FJ.  Schlesinger LS.  Esophageal tuberculosis: a rare but not to be forgotten entity.  American Journal of Medicine.  110(5):415-6, 2001 Apr 1.


2980.  Sirgel F.  Venter A.  Mitchison D. Sources of variation in studies of the early bactericidal activity of antituberculosis drugs.  Journal of Antimicrobial Chemotherapy.  47(2):177-82, 2001 Feb.


  The early bactericidal activity (EBA) of antituberculosis drugs can be measured as the daily fall in cfu counts of Mycobacterium tuberculosis in sputum, usually during the first 2 days of treatment. In studies of low potency drugs, it is necessary to compare the treated group of patients with a group who receives no chemotherapy (Nil group). Over the past 10 years, five Nil groups of between five and 13 patients have been studied in Cape Town and two Nil groups in Hong Kong. There was a suggestion of an increase in variation within the Cape Town groups, as shown by a regression of variance size against study date (P = 0.06), which could not be attributed to technical causes. It might indicate increasing host resistance in the Western Cape epidemic of tuberculosis. Since the weighted mean of all Nil groups at Cape Town was 0.00036, very close to zero, it would seem safe to test means of treated groups against zero thus increasing precision and avoiding ethical problems in delaying treatment. In contrast to Nil groups, the variation found in five groups who received 300 mg isoniazid daily (INH 300) was uniform and homoscedastic, possibly because the additional variation was caused mainly by individual differences in plasma isoniazid concentrations and patient body weights. The mean EBA in the INH 300 series was 0.575 with 95% confidence limits of 0.515 and 0.636.


2981.    Soini H.  Musser JM. Molecular diagnosis of mycobacteria. [Review] [37 refs] Clinical Chemistry.  47(5):809-14, 2001 May.


  Tuberculosis is one of the leading infectious diseases in the world and is responsible for more than 2 million deaths and 8 million new cases annually. Because of the slow growth rate of the causative agent Mycobacterium tuberculosis, isolation, identification, and drug susceptibility testing of this organism and other clinically important mycobacteria can take several weeks or longer. During the past several years, many molecular methods have been developed for direct detection, species identification, and drug susceptibility testing of mycobacteria. These methods can potentially reduce the diagnostic time from weeks to days. Currently, two nucleic acid amplification methods, the Enhanced Mycobacterium tuberculosis Direct Test (Gen-Probe) and the Amplicor Mycobacterium tuberculosis Test (Roche Diagnostic Systems), have been approved by the Food and Drug Administration for direct detection of M. tuberculosis from clinical specimens. PCR-based sequencing has become commonly used to identify many mycobacterial species. DNA probes have been widely used for species determination of the most commonly encountered mycobacteria. High-density oligonucleotide arrays (DNA microarrays) also have been applied to simultaneous species identification and detection of mutations that confer rifampin resistance in mycobacteria. [References: 37]


2982.  Soini H.  Pan X.  Teeter L.  Musser JM.  Graviss EA. Transmission dynamics and molecular characterization of Mycobacterium tuberculosis isolates with low copy numbers of IS6110.  Journal of Clinical Microbiology.  39(1):217-21, 2001 Jan.


  Population-based analysis of Mycobacterium tuberculosis transmission in Houston, Tex., over 5 years identified 377 patients infected with an isolate containing one to four copies of IS6110. The isolates were analyzed by spoligotyping and assigned to one of three major genetic groups based on nucleotide polymorphisms in codons katG 463 and gyrA 95. Prospectively obtained patient interviews were reviewed to assess epidemiologic links between apparently clustered patients. A total of 13 groups of isolates with the same IS6110 profile were identified, representing 326 of the 377 patients (86.5%; range 2 to 113 patients). In contrast, 28 groups of isolates containing 334 patients (88.6%) had the same spoligotype (range, 2 to 143 patients). Combination of IS6110 profile and spoligotype data identified 31 clusters with 300 patients (79.6%; range, 2 to 82 patients). All 377 isolates belonged to major genetic group 1 (77 patients) or genetic group 2 (300 patients); no major genetic group 3 isolates were identified. Among the 228 patients interviewed, 33 patients (14.5%) were directly linked to another patient in the same cluster. Possible epidemiologic links were also found among 11 patients. Moreover, many clusters consisted of individuals with the same ethnicity. In conclusion, we confirmed that IS6110 profiling and spoligotyping together provide enhanced molecular discrimination of M. tuberculosis isolates with low copy numbers of IS6110. Identification of epidemiologic links among some of the patients verified that the combination of these two methods reliably indexes tuberculosis transmission.


2983.  Solomon A. Silicosis and tuberculosis: Part 2--a radiographic presentation of nodular tuberculosis and silicosis. International Journal of Occupational & Environmental Health.  7(1):54-7, 2001 Jan-Mar.


  Indolent nodular pulmonary tuberculosis (TB) in workers exposed to silica dust may go undetected clinically and radiographically, especially in the absence of identification of tubercle bacilli in sputum. Illustrative cases demonstrating the radiographic manifestations of coexistent pulmonary silicosis and the indolent form of nodular TB are presented. Alterations in the usual chronologic progress, a rapid advance in nodular profusion or size outside the expected time frame, and distinct pattern alterations are features indicating the presence of TB associated with silicosis.


2984.  Southwick KL.  Hoffmann K.  Ferree K.  Matthews J.  Salfinger M.  Cluster of tuberculosis cases in North Carolina: possible association with atomizer reuse. American Journal of Infection Control.  29(1):1-6, 2001 Feb.


  BACKGROUND: Three patients with identical strains of M tuberculosis (TB) underwent bronchoscopy on the same day at hospital A. METHODS: We reviewed each patient's clinical history, hospital A's infection control practices for bronchoscopies, and specimen and isolate handling at each of 3 laboratories involved. We searched for possible community links between patients. Restriction fragment length polymorphism was performed on TB isolates. RESULTS: The first patient who underwent bronchoscopy had biopsy-confirmed granulomatous pulmonary TB. A sputum sample collected from the third patient 6 weeks after the bronchoscopy produced an isolate with an identical restriction fragment length polymorphism pattern to isolates collected during the bronchoscopies. No evidence existed for community transmission or laboratory contamination; the only common link was the bronchoscopy. Different bronchoscopes were used for each patient. Hospital ventilation and wall-suctioning were functioning well. Respiratory technicians reported sometimes reusing the nozzles of atomizers on more than one patient. A possible mechanism for transmission was contamination from the first patient of the atomizer if it was used to apply lidocaine to the pharynx and nasal passages of other patients. CONCLUSIONS: A contaminated atomizer may have caused TB transmission during bronchoscopy. Hospital A changed to single-use atomizers after this investigation.


2985.  Spindola de Miranda S.  Kritski A.  Filliol I.  Mabilat C.  Panteix G.  Drouet E. Mutations in the rpoB gene of rifampicin-resistant Mycobacterium tuberculosis strains isolated in Brazil and France. Memorias do Instituto Oswaldo Cruz.  96(2):247-50, 2001 Feb.


  We evaluated the mutations in a 193bp of the rpoB gene by automated sequencing of rifampicin (RMP)-resistant and susceptible Mycobacterium tuberculosis strains isolated from Brazil (25 strains) and France (37 strains). In RMP-resistant strains, mutations were identified in 100% (16/16) from France and 89% (16/18) from Brazil. No mutation was detected in the 28 RMP-susceptible strains. Among RMP-resistant or RMP-susceptible strains deletion was observed. A double point mutation which had not been reported before was detected in one strain from France. Among French resistant strains mutations were found in codons 531 (31.2%), 526, 513 and 533 (18.7% each). In Brazilian strains the most common mutations were in codons 531 (72.2%), 526 (11.1%) and 513 (5.5%). The heterogeneity found in French strains may be related to the fact that most of those strains were from African or Asian patients.


2986.  Stratta P.  Messuerotti A.  Canavese C.  Coen M.  Luccoli L.  Bussolati B.  Giorda L.  Malavenda P.  Cacciabue M.  Bugiani M.  Bo M.  Ventura M.  Camussi G.  Fubini B. The role of metals in autoimmune vasculitis: epidemiological and pathogenic study. Science of the Total Environment.  270(1-