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3401            . Akpede GO.  Akenzua GI. Management of children with prolonged fever of unknown origin and difficulties in the management of fever of unknown origin in children in developing countries. [Review] [90 refs] Paediatric Drugs.  3(4):247-62, 2001.


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

3402.          Berkley JA.  Mwangi I.  Ngetsa CJ.  Mwarumba S.  Lowe BS.  Marsh K.  Newton CR. Diagnosis of acute bacterial meningitis in children at a district hospital in sub-Saharan Africa. Lancet.  357(9270):1753-7, 2001 Jun 2.


  BACKGROUND: The diagnosis of acute bacterial meningitis in children is difficult in sub-Saharan Africa, because the clinical features overlap with those of other common diseases, and laboratory facilities are inadequate in many areas. We have assessed the value of non-laboratory tests and incomplete laboratory data in diagnosing childhood acute bacterial meningitis in this setting. METHODS: We prospectively studied 905 children undergoing lumbar puncture at a rural district hospital in Kenya over 1 year. We related microbiological findings and cerebrospinal-fluid (CSF) laboratory measurements to tests that would typically be available at such a hospital. FINDINGS: Acute bacterial meningitis was proven in 45 children (5.0% [95% CI 3.7-6.6]) and probable in 26 (2.9% [1.9-4.2]). 21 of the 71 cases of proven or probable acute bacterial meningitis had neither neck stiffness nor turbid CSF. In eight of 45 children with proven disease the CSF leucocyte count was less than 10x10(6)/L or leucocyte counting was not possible because of blood-staining. The presence of either a leucocyte count of 50x10(6)/L or more or a CSF/blood glucose ratio of 0.10 or less detected all but two of the 45 children with proven acute bacterial meningitis; these two samples were grossly blood-stained. INTERPRETATION: The diagnosis of childhood acute bacterial meningitis is likely to be missed in a third of cases at district hospitals in sub-Saharan Africa without adequate and reliable laboratory resources. CSF culture facilities are expensive and difficult to maintain, and greater gains could be achieved with facilities for accurate leucocyte counting and glucose measurement.

3403.          Breukels MA.  Spanjaard L.  Sanders LA.  Rijkers GT. Immunological characterization of conjugated Haemophilus influenzae type b vaccine failure in infants. Clinical Infectious Diseases.  32(12):1700-5, 2001 Jun 15.


  Infant vaccination with conjugated Haemophilus influenzae type b (Hib) vaccine is highly effective in protecting against invasive Hib infections, but vaccine failures do occur. Twenty-one vaccine failures are reported since the introduction of the Hib conjugate vaccine in The Netherlands. Of the 14 evaluable patients, 6 children showed no antibody response to Hib polysaccharide in convalescent-phase serum (immunoglobulin [Ig] G anti-Hib level <1.0 microg/mL), including 1 child with hypogammaglobulinemia and 1 child with IgG2 deficiency. After revaccination, almost all children developed anti-Hib antibodies. In case of Hib vaccine failure, case investigation should be performed, including measurement of serum Ig concentrations as well as specific anti-Hib antibodies. Invasive Hib disease after infant conjugate Hib vaccination may be the presentation of an underlying immunodeficiency, but more often, only a decreased antibody response to Hib is found; revaccination with conjugated Hib vaccine is advised.

3404.          Burkhard PR.  Sanchez  JC.  Landis T.  Hochstrasser DF. CSF detection of the 14-3-3 protein in unselected patients with dementia.  Neurology.  56(11):1528-33, 2001 Jun 12.


  OBJECTIVE: To determine the usefulness of the 14-3-3 test in patients with dementia of various causes. BACKGROUND: Recent reports have suggested that the detection of the 14-3-3 protein in the CSF of patients with Creutzfeldt--Jakob disease is a highly sensitive and specific marker of the disease that might be used as a diagnostic criterion. We examined the validity of this test when applied to a cohort of unselected patients prospectively examined for an ongoing dementing process. METHODS: One hundred patients underwent an extensive neurologic examination for dementia, including a CSF 14-3-3 protein immunoblotting assay. Final clinical diagnoses were compared with the qualitative results of the test, and statistical measures of test validity were carried out. RESULTS: We found a positive test in 14 of 100 patients, only two of whom had definite Creutzfeldt--Jakob disease. Positive results were found in patients with various degenerative dementias, including AD (4), frontotemporal dementia (2), and dementia with Lewy body (1), and in patients with vascular dementia (1), carcinomatous meningitis (1), and anoxic encephalopathy (1). In two other positive patients, the dementia could not be confidently classified. Sensitivity, specificity, and negative predictive value were fairly good, but positive predictive value was poor. Similar results were found independently of the disease duration. There was no correlation between intensity nor pattern of the 14-3-3 protein expression and diagnosis. CONCLUSIONS: The 14-3-3 test is not valid for discriminating between Creutzfeldt--Jakob disease and non-Creutzfeldt--Jakob disease in unselected patients with dementia. Positive results are found in various degenerative and secondary, prion-unrelated dementias.


3405.          Jedrzejas MJ. Pneumococcal virulence factors: structure and function. [Review] [167 refs]  Microbiology & Molecular Biology Review (Washington, DC).  65(2):187-207 ; first page, table of contents, 2001 Jun.


  The overall goal for this review is to summarize the current body of knowledge about the structure and function of major known antigens of Streptococcus pneumoniae, a major gram-positive bacterial pathogen of humans. This information is then related to the role of these proteins in pneumococcal pathogenesis and in the development of new vaccines and/or other antimicrobial agents. S. pneumoniae is the most common cause of fatal community-acquired pneumonia in the elderly and is also one of the most common causes of middle ear infections and meningitis in children. The present vaccine for the pneumococcus consists of a mixture of 23 different capsular polysaccharides. While this vaccine is very effective in young adults, who are normally at low risk of serious disease, it is only about 60% effective in the elderly. In children younger than 2 years the vaccine is ineffective and is not recommended due to the inability of this age group to mount an antibody response to the pneumococcal polysaccharides. Antimicrobial drugs such as penicillin have diminished the risk from pneumococcal disease. Several pneumococcal proteins including pneumococcal surface proteins A and C, hyaluronate lyase, pneumolysin, autolysin, pneumococcal surface antigen A, choline binding protein A, and two neuraminidase enzymes are being investigated as potential vaccine or drug targets. Essentially all of these antigens have been or are being investigated on a structural level in addition to being characterized biochemically. Recently, three-dimensional structures for hyaluronate lyase and pneumococcal surface antigen A became available from X-ray crystallography determinations. Also, modeling studies based on biophysical measurements provided more information about the structures of pneumolysin and pneumococcal surface protein A. Structural and biochemical studies of these pneumococcal virulence factors have facilitated the development of novel antibiotics or protein antigen-based vaccines as an alternative to polysaccharide-based vaccines for the treatment of pneumococcal disease. [References: 167]

3406.          John MA.  Coovadia YM. Shortfalls in the use of adenosine deaminase in tuberculous meningitis.  Tropical Doctor.  31(3):138-9, 2001 Jul.

3407.          Jolly K.  Stewart G. Epidemiology and diagnosis of meningitis: results of a five-year prospective, population-based study. Communicable Disease & Public Health.  4(2):124-9, 2001 Jun.


  Implementation of the advice to give penicillin prior to admission, a fall in the lumbar puncture rate and the introduction into routine use of the meningococcal polymerase chain reaction (PCR) test are factors that have led us to reassess the way meningitis is diagnosed. We examined data for the period 1994-98 from a health district of 800,000 population. Of the 355 cases of meningitis reported, 258 (73%) had either confirmed, probable or possible meningococcal disease. Only 28% of meningococcal cases had received pre-admission benzylpenicillin. The proportion of suspected meningitis cases undergoing lumbar puncture fell over the period. It was 79% in 1994 and 61% in 1998 (p < 0.001). After meningococcal PCR was introduced in 1996, 73 (68%) meningococcal cases were microbiologically confirmed, compared to 72 (48%) before 1996 (p = 0.001). In all cases, age was an independent predictor of meningitis mortality, and for meningococcal cases, age and serogroup were independent predictors. Advice to general practitioners (GPs) to give preadmission benzylpenicillin to any suspected case of meningitis or meningococcal septicaemia should be reinforced regardless of age or whether a rash is present.


3408.          Kenyon G. ... and funds meningitis vaccine work. Nature Medicine.  7(7):758, 2001 Jul.

3409.          Kotnis R.  Simo R. Tuberculous meningitis presenting as sensorineural hearing loss. Journal of Laryngology & Otology.  115(6):491-2, 2001 Jun.


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

3410.          Lauby G. Carcinomatous meningitis in a patient with metastatic breast cancer. Clinical Laboratory Science.  14(3):141-4, 2001 Summer.


  Metastases are defined as the appearance of neoplasms in parts of the body remote from the site of the primary tumor. Metastasis can occur through one of three processes: direct seeding of body cavities or surfaces, lymphatic spread, and hematogenous spread. The importance of laboratory utilization in the diagnosis of metastasis is explored using a case study of a 39-year-old female with metastatic breast carcinoma to the brain. This case study was carried out using clinical records, laboratory results, pathology reports, and physician interviews. Cerebrospinal fluid was obtained and examined in hematology, chemistry, and microbiology. Tissue from the breast was examined both before and after chemotherapy. Morphologic comparisons of both primary and metastatic tumor cells were carried out. The breast tissue showed infiltrating mammary carcinoma, ductal type, with 8/11 auxiliary lymph nodes showing metastasis. Evaluations of cerebrospinal fluid cell count results revealed the presence of malignant cells in remarkable numbers. Based on cytological and hematological results, a diagnosis of meningeal carcinomatosis was determined and treatment was started. Following the intrathecal chemotherapy, serial cerebrospinal fluid examinations showed the percentage of malignant cells decreased and no cells were detected 11 days after treatment. Metastasis, including meningeal carcinomatosis is a common occurrence with breast carcinoma. An effective chemotherapeutic treatment is evaluated for this disease when an accurate diagnosis is made. As demonstrated by this case study, proper use of the laboratory can help establish the diagnosis of metastasis.




3411.          Lewis R.  Nathan N.  Diarra L.  Belanger F.  Paquet C. Timely detection of meningococcal meningitis epidemics in Africa. [see comments]. [Review] [32 refs] Lancet.  358(9278):287-93, 2001 Jul 28.


  BACKGROUND: Epidemics of meningococcal disease in Africa are commonly detected too late to prevent many cases. We assessed weekly meningitis incidence as a tool to detect epidemics in time to implement mass vaccination. METHODS: Meningitis incidence for 41 subdistricts in Mali was determined from cases recorded in health centres (1989-98) and from surveillance data (1996-98). For incidence thresholds of 5 to 20 cases per 100000 inhabitants per week, we calculated sensitivity and specificity for detecting epidemics, and determined the time lapse between threshold and epidemic peak. FINDINGS: We recorded 9084 meningitis cases. Clinic-based weekly incidence of 5 and 10 cases per 100000 inhabitants detected all meningitis epidemics (sensitivity 100%, 95% CI 93-100), with median threshold-to-peak time of 5 and 3 weeks. Under-reporting reduced sensitivity: only surveillance thresholds of 5 or 7 cases per 100000 inhabitants per week detected all epidemics. Crossing the lower threshold before the 10th calendar week doubled epidemic risk relative to crossing it later (relative risk 2.1, 95% CI 1.4-3.2). At 10 cases per 100000 inhabitants per week, specificity for outbreak prediction was 88%, 95% CI 83-91). For populations under 30000, 3 to 5 cases in one or two weeks predicted epidemics with 85% to 97% specificity. INTERPRETATION: Low meningitis thresholds improve timely detection of epidemics. Ten cases per 100000 inhabitants per week in one area confirm epidemic activity in a region, with few false alarms. An alert threshold of 5 cases per 100000 inhabitants per week allows time to investigate, prepare for an epidemic, and initiate mass vaccination where appropriate. For populations under 30000, the alert threshold is two cases in a week. High quality surveillance is essential. [References: 32]

3412.            Marx RD.  Baer ST. Spontaneous recovery of profound post-meningitic hearing loss. Journal of Laryngology & Otology.  115(5):412-4, 2001 May.


  The timing of insertion of a cochlear implant (CI) in post-meningitic sensorineural hearing loss is, in spite of recent advances in the understanding of the pathogenesis of the condition, still controversial. The danger of labyrinthitis ossificans allows only a little time to decide whether to implant a CI or not. On the other hand the clinician needs to be certain that no residual hearing is present and whether or not the patient will benefit from conventional amplification. A well-documented case of early spontaneous recovery of a profound post-meningitic sensorineural hearing loss in a child is presented and the relevant literature reviewed.

3413.          Mathai A.  Radhakrishnan VV.  George SM.  Sarada C. A newer approach for the laboratory diagnosis of tuberculous meningitis. Diagnostic Microbiology & Infectious Disease.  39(4):225-8, 2001 Apr.


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


3414.          Mitra S.  Ghosh D.  Pathak A.  Kumar L.  Bilateral subdural effusion and subcutaneous swelling with normally functioning csf shunt. Neurology India.  49(2):178-81, 2001 Jun.


  We report a child with hydrocephalus due to tuberculous meningitis who developed a subcutaneous fluid collection around the ventriculoperitoneal shunt tube entry point, after one month of shunting. On investigation, he had decompressed ventricles with bilateral fronto parietal subdural hygroma. Bifrontal burr hole drainage helped resolution of both subdural effusion and subcutaneous scalp swelling. This complication is unique and its pathogenesis has been postulated.

3415.          Panicker JN.  Mammachan R.  Jayakumar RV. Primary neuroleptospirosis. Postgraduate Medical Journal.  77(911):589-90, 2001 Sep.


  Leptospirosis is an important zoonosis of worldwide distribution. It is uncommon for leptospirosis to present as a primary neurological disease. In this study of patients who presented with an acute neurological disease, and who were subsequently found to have leptospirosis, aseptic meningitis was the commonest manifestation. The other presentations were myeloradiculopathy, myelopathy, Guillain-Barré syndrome-like presentation, meningoencephalitis, intracerebral bleed, cerebellar dysfunction, iridocyclitis, and tremor/rigidity. Treatment consists of antibiotics, crystalline penicillin being the drug of choice, which reduces the course of illness if given early. The role of steroids is controversial. The prognosis after primary neuroleptospirosis is generally good but altered sensorium and seizures herald a worse prognosis.

3416.          Perkins BA. Prospects for prevention of meningococcal meningitis. [letter; comment]. Lancet.  358(9278):255-6, 2001 Jul 28.

3417.          Polin RA.  Harris MC. Neonatal bacterial meningitis. [Review] [102 refs] Seminars in Neonatology.  6(2):157-72, 2001 Apr.


  Despite major improvements in infant intensive care, neonatal meningitis remains a devastating disease. Survivors of bacterial meningitis are at high-risk for life-long neurological handicaps, and despite a reduction in mortality, the morbidity of neonatal meningitis has not changed substantially over the last thirty years. A substantial improvement in outcome is unlikely to result from further refinements in ICU technology or new antibiotics. However, recent advancements in our understanding of the pathogenesis of meningitis and the pathophysiology of brain injury in meningitis may provide the opportunity to interrupt the mechanisms that allow bacteria to enter the central nervous system and initiate the inflammatory response. Strategies aimed at modulating the inflammatory response must be chosen carefully, so as not to disrupt normal host responses needed for the infant to recover from the infectious episode. Copyright 2001 Harcourt Publishers Ltd. [References: 102]


3418.          Rappuoli R. Conjugates and reverse vaccinology to eliminate bacterial meningitis. [Review] [22 refs] Vaccine.  19(17-19):2319-22, 2001 Mar 21.


  Bacterial meningitis is caused mainly by Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis. Haemophilus influenzae type b vaccines have been extremely successful in eradicating the disease from those countries where the vaccine has been introduced. The recent licensure of the conjugated pneumococcal vaccine suggests that this pathogen also will be soon controlled. Consequently, if we succeed in developing effective vaccines against meningococcus, this will enable us to eliminate bacterial meningitis. The global elimination of bacterial meningitis is a goal which, if appropriate resources are applied, can be reached within the first fifteen years of the 21st century. [References: 22]


3419.          Rushing EJ.  Burns DK. Infections of the nervous system. [Review] [76 refs] Neuroimaging Clinics of North America.  11(1):vii, 1-13, 2001 Feb.


  This article surveys common causes and pathologic features of nervous system infections within the general population. Special consideration is given to infections in people with the HIV virus. [References: 76]


3420.          Sheldon T. Dutch consider following UK on vaccines after meningitis scare. BMJ.  323(7311):470, 2001 Sep 1.

3421.          No Abstract.

3422.          Tarafdar K.  Rao S.  Recco RA.  Zaman MM. Lack of sensitivity of the latex agglutination test to detect bacterial antigen in the cerebrospinal fluid of patients with culture-negative meningitis. Clinical Infectious Diseases.  33(3):406-8, 2001 Aug 1.


  For culture-negative meningitis, use of the latex agglutination test for detection of bacterial antigen in the CSF has a sensitivity of only 7%. Routine use of the latex agglutination test may not contribute to the management of suspected acute bacterial meningitis, since patients are treated on the basis of their clinical presentations and CSF findings.

3423.            Zimmerman RK.Pneumococcal conjugate vaccine for young children. [see comments]. [Review] [17 refs] American Family Physician.  63(10):1991-8, 2001 May 15.


  Streptococcus pneumoniae causes approximately 3,300 cases of meningitis, 100,000 to 135,000 cases of pneumonia requiring hospitalization and 6 million cases of otitis media annually in the United States. Pneumococcal conjugate vaccine, approved in 2000 for use in the United States, was designed to cover the seven serotypes that account for about 80 percent of invasive infections in children younger than six years. This vaccine demonstrated 100 percent efficacy against invasive pneumococcal disease in the primary analysis of a large randomized, double-blind, controlled trial. In the follow-up analysis, performed eight months after the trial ended, efficacy against invasive disease was found to be 94 percent for the included serotypes. When initiated during infancy, the four-dose vaccination schedule is set at two, four, six and 12 to 15 months of age. The American Academy of Family Physicians recommends routine vaccination of infants, catch-up vaccination of children younger than 24 months and catch-up vaccination of children 24 to 59 months of age with high-risk medical conditions such as sickle cell disease and congenital heart disease. [References: 17]

Apr 02

4120.          Alessio M. Cytoadherence of Plasmodium falciparum-infected erythrocytes is mediated by a redox-dependent conformational fraction of CD36. J Immunol  2001 Dec 1;167(11):6510-7


The adherence of Plasmodium falciparum-infected RBC (IRBC) to postcapillary venular endothelium is an important determinant of the pathogenesis of severe malaria complications. Cytoadherence of IRBC to endothelial cells involves specific receptor/ligand interactions. The glycoprotein CD36 expressed on endothelial cells is the major receptor involved in this interaction. Treatment of CD36-expressing cells with reducing agents, such as DTT and N-acetylcysteine, was followed by CD36 conformational change monitorable by the appearance of the Mo91 mAb epitope. Only a fraction of the surface expressed CD36 molecules became Mo91 positive, suggesting the presence of two subpopulations of molecules with different sensitivities to reduction. The Mo91 epitope has been localized on a peptide (residues 260-279) of the C-terminal, cysteine-rich region of CD36. Treatment with reducing agents inhibited the CD36-dependent cytoadherence of IRBC to CD36-expressing cells and dissolved pre-existent CD36-mediated IRBC/CD36-expressing cell aggregates. CD36 reduction did not impair the functionality of CD36, since the reactivity of other anti-CD36 mAbs as well as the binding of oxidized low density lipoprotein, a CD36 ligand, were maintained. The modifications induced by reduction were reversible. After 14 h CD36 was reoxidized, the cells did not express the Mo91 epitope, and cytoadherence to IRBC was restored. The results indicate that IRBCs bind only to a redox-modulated fraction of CD36 molecules expressed on the cell surface. The present data indicate the therapeutic potential of reducing agents, such as the nontoxic drug N-acetylcysteine, to prevent or treat malaria complications due to IRBC cytoadhesion.


4121.          Amaral L, Viveiros M, Kristiansen JE. Phenothiazines: potential alternatives for the management of antibiotic resistant infections of tuberculosis and malaria in developing countries. Trop Med Int Health  2001 Dec;6(12):1016-22


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


4122.          Arevalo-Herrera M, Herrera S. Plasmodium  vivax malaria vaccine development. Mol Immunol  2001 Dec;38(6):443-55


Plasmodium vivax represents the most widespread malaria parasite worldwide. Although it does not result in as high a mortality rate as P. falciparum, it inflicts debilitating morbidity and consequent economic impact in endemic communities. In addition, the relapsing behavior of this malaria parasite and the recent resistance to anti-malarials contribute to making its control more difficult. Although the biology of P. vivax is different from that of P. falciparum and the human immune response to this parasite species has been rather poorly studied, significant progress is being made to develop a P. vivax-specific vaccine based on the information and experience gained in the search for a P. falciparum vaccine. We have devoted great effort to antigenically characterize the P. vivax CS protein and to test its immunogenicity using the Aotus monkey model. Together with other groups we are also assessing the immunogenicity and protective efficacy of the asexual blood stage vaccine candidates MSP-1 and DBP in the monkey model, as well as the immunogenicity of Pvs25 and Pvs28 ookinete surface proteins. The transmission-blocking efficacy of the responses induced by these latter antigens is being assessed using Anopheles albimanus mosquitoes. The current status of these vaccine candidates and other antigens currently being studied is described.

4123.          B, Gay F, Looareesuwan S. Association of splenomegaly with cerebral malaria and decreased concentrations of reactive nitrogen intermediates in Thailand. Am J Trop Med Hyg  2001 Nov;65(5):639-43


The role of the spleen during Plasmodium falciparum malaria in humans is unclear. In Thailand, malaria transmission is low and splenomegaly is rarer than in high transmission areas. We compared the prevalence of splenomegaly between 52 cerebral malaria patients and 191 patients without complications despite a high parasite biomass. We also measured concentrations of reactive nitrogen intermediates (RNIs) in a fraction of these cases recruited in 1998 (24 cerebral malaria and 56 controls). Splenomegaly was significantly associated with cerebral malaria (adjusted odds ratio = 2.07 [95% confidence interval = 1-4.2]; P = 0.048). There was a linear trend for this association (P = 0.0003). After adjusting for potential confounders, concentrations of RNIs were significantly lower in the presence of splenomegaly (P = 0.01). These results suggest that in humans, as in animal models, the spleen may be involved in the pathogenesis of cerebral malaria. The relationship between RNI concentrations and the spleen suggest that nitric oxide may have a regulating role in the complex physiology of the spleen during malaria.


4124.          Basco LK, Ringwald P. Molecular epidemiology of malaria in Yaounde, Cameroon. VIII. Multiple Plasmodium falciparum infections in symptomatic patients. Am J Trop Med Hyg  2001 Dec;65(6):798-803


The extent of genetically distinct parasite populations coinfecting individual human hosts (i.e., multiplicity) was studied by polymerase chain reaction amplification of 3 polymorphic genetic markers, circumsporozoite protein and merozoite surface antigens (MSA) 1 and 2, in symptomatic children and adults and analyzed in relation with age and initial parasitemia. Of the total of 177 DNA samples analyzed (of which 115 were paired pre- and posttreatment samples), 101 (57%) were composed of multiclonal infections, with up to 7 distinguishable parasite populations. Among the 3 polymorphic markers, msa-2 yielded the highest proportion of clinical isolates with multiclonal populations. Patients with multiclonal infections before treatment had, on average, 2.9 genetically distinct parasite populations. The extent of multiplicity decreased significantly (P < 0.05) in recrudescent parasites, but not with reinfections, as compared with the pretreatment samples. Neither age (5-60 years) nor initial parasitemia was correlated with multiplicity. Further studies in different epidemiological settings are required to understand the role of multiclonal Plasmodium falciparum infections in influencing malaria transmission.


4125.          Bhat GP, Surolia N. In vitro antimalarial activity of extracts of three plants used in the traditional medicine of India. Am J Trop Med Hyg  2001 Oct;65(4):304-8 


In an attempt to search for new antimalarial drugs, we studied plants used by traditional healers of southwest India to treat malaria. Aqueous and organic solvent extracts obtained from specific parts of the plants Swertia chirata, Carica papaya, and Citrus sinensis were tested on malaria strain Plasmodium falciparum FCK 2 in vitro. The temperatures of extraction were the same as that used by the traditional healers in their plant preparations. Visual evaluation of the antimalarial activity of the plant extracts on thin blood smears was followed by quantification of the activity by use of [35S]-methionine incorporation into parasite proteins to determine the value that inhibits 50% (IC50). Among the 3 plants tested, 2 had significant inhibitory effect on P. falciparum in vitro.

4126.          Biswas R, Sengupta G, Mundle M: Controlled study  on haemograms of  malaria patients in Calcutta. Indian J Malar 1999, 36(1-2), 42-8. (015287) Aug 1, 2023

Study was carried out at the Urban Health Centre, Chetla, Calcutta to evaluate the efficacy of quantitative buffy coat (QBC) analysis of haemograms in malaria patients suffering from fever with bodyahe and chill and /or rigour attending the Fever Treatment Depot during a three months period (March-June 1996) who had undergone both malaria parasite study and haematological investigation by the QBC method, from blood samples collected finger prick. To avoid bias, malaria parasite studies and haemograms were done separately, and investigators were kept ‘blind’ about the results of other investigation. The haematological dinfings obtained of 180 slide negative malaria cases were compared with a sample of 177 age- and sex-matched slide-negative controls selected random smpling. The results revealed that haemoglobin levels (g%), haematocrit values (%)., WBC and platelet counts of malaria cases were significantly lower than in the matched controls. Thus, QBC estimation correlates well with existing knowledge about malarial haematology. This relatively easier, quicker and reliable method of taking haemograms may be recommended for filed testing for assessing haematological parameters of malaria cases under field condition, before its introduction for large-scale use.

4127.          Bradbury J. Haemoglobin C protection against  malaria. Lancet  2001 Nov 17;358(9294):1702  No Abstract.

4128.          Brice GT, Graber NL, Hoffman SL, Doolan DL. Expression of the chemokine MIG is a sensitive and predictive marker for antigen-specific, genetically restricted IFN-gamma production and IFN-gamma-secreting cells. J Immunol Methods  2001 Nov 1;257(1-2):55-69


The evaluation of antigen-specific immune responses is critical for understanding the mechanisms of immune protection and for establishing the efficacy of candidate vaccines. Here, we describe a novel assay for IFN-gamma activity which is based on the flow cytometric detection of the chemokine, monokine induced by gamma interferon (MIG) as a sensitive and predictive measure of IFN-gamma-mediated effector function, and a surrogate marker for IFN-gamma-producing cells. Upregulation of MIG expression was demonstrated following in vitro activation of peripheral blood mononuclear cells (PBMCs) with defined CD8+ T-cell epitopes derived from influenza virus, cytomegalovirus (CMV), or Epstein-Barr virus (EBV) and was antigen-specific, genetically restricted and dependent on both CD8+ T cells and IFN-gamma. Furthermore, antigen-specific MIG expression was also demonstrated with Plasmodium falciparum circumsporozoite protein (CSP) peptides, using PBMCs from volunteers immunized with irradiated P. falciparum sporozoites. In multiple parallel experiments, the MIG assay was compared to conventional IFN-gamma ELISPOT, IFN-gamma ELISA, MIG ELISA and intracellular cytokine staining assays. The level of MIG expression was shown to be directly associated with the number of IFN-gamma spot-forming cells (SFCs) detected by ELISPOT (r2=0.94). Moreover, in all instances where cultures were considered positive by ELISPOT, a higher stimulation index was noted with the MIG assay as compared with the ELISPOT assay (on average at least threefold higher) and, in some cases, responses as detected by the MIG assay were significant, but the corresponding response as measured by ELISPOT was not significant. Finally, the flow-based MIG assay offers a number of practical and technical advantages over the ELISPOT assay. Our data validate this novel method for the detection of low as well as high levels of antigen-specific and genetically restricted IFN-gamma activity.

4129.          Brower V. Tackling the most difficult diseases. Genetics and genomics open new strategies to fight vector-borne diseases. EMBO Rep  2001 Oct;2(10):875-7 No Abstract.

4130.          Bryceson A. A policy for leishmaniasis with respect to the prevention and control of drug resistance. Trop Med Int Health  2001 Nov;6(11):928-34


At the moment no country has a policy designed to control or prevent drug resistance in leishmaniasis. The risk of resistance is high in areas of anthroponotic visceral leishmaniasis, for example North Bihar, India, where the rate in some areas is 60%. Post-epidemic Sudan is also at risk. Zoonotic areas in which HIV co-infection is common could also be at risk as sandflies can become infected from co-infected individuals. Many factors determine the choice of drug for the treatment of visceral leishmaniasis, and drug resistance may not be the over-riding priority. In anthroponotic areas reduction in transmission through public health measures will be important, but the use of two drugs in combination should be seriously considered. Pharmacokinetic and other features of the drugs available, relevant to their use in combination are discussed and tentative suggestions made concerning trials of possible combinations. These include miltefosine plus paromomycin and allopurinol plus an azole. Lessons may be learnt from the experiences of similar problems in malaria, leprosy and tuberculosis. Guidelines are offered for the introduction of policies to use drugs in combination, which differ between anthroponotic and zoonotic areas of transmission.

4131.          Burgess DC, Kain KC. The performance and utility of rapid diagnostic assays for Plasmodium falciparum malaria in a field setting in the Lao People's Democratic Republic. Ann Trop Med Parasitol  2001 Oct;95(7):671-7


Rapid diagnostic assays for malaria have the potential to improve the management and control of the disease in developing countries. The objectives of the present study were to evaluate, in a field setting, the performance of several such assays for Plasmodium falciparum infection and to examine the usefulness of these assays in identifying subjects for treatment trials in rural field sites. Residents of 12 villages in Laos who presented with fever were eligible for inclusion. Blood was collected by fingerprick for a dipstick assay, developed by the Program for Appropriate Technology in Health (PATH), performed and interpreted in the field by local healthcare workers. Compared with 'blinded' reference microscopy (N =196), the sensitivity and specificity of the PATH assay were 96.2% and 93.0%, respectively. Two rapid diagnostic assays (PATH and OptiMAL) were also performed on the subset of subjects eligible to participate in an in-vivo treatment trial (N = 97), and the results again compared with those of 'blinded' reference microscopy. In this subset, a subject was considered a 'true positive' if found positive by microscopy or the alternate rapid assay. Using this modified reference standard, the sensitivity and specificity of the PATH assay were 96.7% and 94.4%, and those of the OptiMAL assay were 91.8% and 100%, respectively. Both of the rapid assays tested therefore appear suitable for use in rural field settings by local healthcare providers and can accurately identify participants for treatment trials.

4132.          Chongsuphajaisiddhi T, White NJ. Factors contributing to anemia after uncomplicated falciparum malaria. Am J Trop Med Hyg  2001 Nov;65(5):614-22


The factors contributing to anemia in falciparum malaria were characterized in 4,007 prospectively studied patients on the western border of Thailand. Of these, 727 patients (18%) presented with anemia (haematocrit < 30%), and 1% (55 of 5,253) required blood transfusion. The following were found to be independent risk factors for anemia at admission: age < 5 years, a palpable spleen, a palpable liver, recrudescent infections, being female, a prolonged history of illness (> 2 days) before admission, and pure Plasmodium falciparum infections rather than mixed P. falciparum and Plasmodium vivax infections. The mean maximum fractional fall in hematocrit after antimalarial treatment was 14.1% of the baseline value (95% confidence interval [CI], 13.6-14.6). This reduction was significantly greater in young children (aged < 5 years) and in patients with a prolonged illness, high parasitemia, or delayed parasite clearance. Loss of parasitized erythrocytes accounted for < 10% of overall red blood cell loss. Hematological recovery was usually complete within 6 weeks, but it was slower in patients who were anemic at admission (adjusted hazards ratio [AHR], 1.9, 95% CI, 1.5-2.3), and those whose infections recrudesced (AHR, 1.2, 95% CI, 1.01-1.5). Half the patients with treatment failure were anemic at 6 weeks compared with 19% of successfully treated patients (relative risk, 2.8, 95% CI, 2.0-3.8). Patients coinfected with P. vivax (16% of the total) were 1.8 (95% CI, 1.2-2.6) times less likely to become anemic and recovered 1.3 (95% CI, 1.0-1.5) times faster than those with P. falciparum only. Anemia is related to drug resistance and treatment failure in uncomplicated malaria. Children aged < 5 years of age were more likely than older children or adults to become anemic. Coinfection with P. vivax attenuates the anemia of falciparum malaria, presumably by modifying the severity of the infection.

4133.          Cian F, Declich S. HIV, malaria parasites, and acute febrile episodes in Ugandan adults: a case-control study. AIDS  2001 Dec 7;15(18):2445-50


BACKGROUND: In sub-Saharan Africa, co-infection with HIV and malaria is probably very common. Although an interaction between the two infections is biologically plausible, it has not been investigated thoroughly. OBJECTIVES: To evaluate the association firstly between co-infection with HIV and malaria parasites and the occurrence of acute fever, and secondly between HIV infection and clinical malaria, defined as the presence of acute fever and malaria parasites. METHODS: A hospital-based case-control study was conducted in Gulu District (northern Uganda), an area endemic for malaria and with a high HIV prevalence. HIV testing and malaria parasite quantification were performed on 167 consecutive adult out-patients with acute fever and no signs or symptoms of localized infection, and on 134 consecutive adult in-patients without fever who were admitted for non-HIV-related trauma or elective surgery. RESULTS: No significant association with acute fever was observed for single infection with either malaria parasites [adjusted odds ratio (AOR), 1.75; 95% confidence interval (CI), 0.73 4.21] or HIV (AOR, 1.01; 95% CI, 0.51-2.03), whereas a significant association was observed for co-infection (AOR, 9.75; 95% CI, 1.19 80.00). An association was found between HIV infection and clinical malaria (AOR, 2.34; 95% CI, 0.89-6.17); the association became statistically significant when the definition of clinical malaria included a cut-off for parasite density (50th percentile; i.e., 586 parasites/microl; AOR, 3.61; 95% CI, 1.04-12.52). CONCLUSIONS: Despite the limited statistical power, the results of our study show an association between HIV infection and clinical malaria; if confirmed, this finding could be important for public health in sub-Saharan Africa.

4134.          Corbellino M. Subacute malaria due to Plasmodium falciparum and the role of polymerase chain reaction. Clin Infect Dis  2001 Nov 1;33(9):1614-5  No Abstract.

4135.          Cunha MG, Rodrigues MM, Soares IS. Comparison of the immunogenic properties of recombinant proteins representing the Plasmodium vivax vaccine candidate MSP1(19) expressed in distinct bacterial vectors. Vaccine  2001 Nov 12;20(3-4):385-96


The 19kDa C-terminal region of the merozoite surface protein 1 (MSP1(19)) is one of the most promising vaccine candidates against the erythrocytic forms of malaria. In the present study, we used three different Escherichia coli expression vectors to generate five recombinant proteins representing the MSP1(19) of Plasmodium vivax. These proteins were compared for reactivity with a panel of sera from individuals naturally exposed to P. vivax and for their immunogenicity in mice. Among the proteins studied, MSP1(19) expressed by the vector pET (His(6)-MSP1(19)) was better recognized by the antibodies of several individuals exposed to P. vivax. The addition of the T-cell Pan-allelic DR epitope (PADRE) did not alter the recognition of this recombinant protein by human antibodies. Although recombinant proteins were immunogenic to mice, immunization with MSP1(19) expressed by the pET or pGEX vectors induced significantly higher antibody titers than a protein produced by the pMAL vector. The antibody immune response elicited by His(6)-MSP1(19) containing the PADRE epitope was compared using different adjuvant formulations. After only two immunizing doses, antibody titers induced in the presence of the adjuvants TiterMax, MPL/TDM/CWS or alum plus CpG ODN 1826 were as high as titers generated by complete Freund's adjuvant. We concluded that, among the bacterial recombinant proteins, MSP1(19) expressed by the vector pET should be selected for further evaluation in pre-clinical immunizations against P. vivax.


4136.          D'Alessandro U, Buttiens H. History and importance of antimalarial drug resistance. Trop Med Int Health  2001 Nov;6(11):845-8


The emergence of Plasmodium falciparum resistance to widely used antimalarial drugs such as chloroquine (CQ) has made malaria control and treatment much more difficult. This is particularly dramatic for Africa, as few affordable alternatives are available. Drug pressure has been identified as one of the key factors for the emergence and spread of resistance. The contribution of the extensive use and misuse of antimalarial drugs to the selection of resistant parasites became particularly evident during the Global Malaria Eradication campaign, launched by World Health Organization (WHO) in 1955. The first reports confirming P. falciparum resistance to CQ came almost simultaneously in the early 1960s from South America and South-East Asia, where direct or indirect (through use of medicated cooking salt) mass drug administration (MDA) had been implemented. Similar approaches were very limited in Africa, where P. falciparum resistance to CQ was first reported from the eastern region in the late 1970s and spread progressively west. Most African countries still rely heavily on CQ as first-line treatment despite various levels of resistance, although some states have changed to sulphadoxine-pyrimethamine (SP) as the first-line drug. Unfortunately, the predicted SP useful therapeutic life might be very short, probably because of its prolonged half-life, causing a higher probability of selecting resistant strains and a consequent fast development of resistance. CQ resistance is not evenly distributed and important differences can be found within and between countries. It seems to have spread more rapidly in East than in West Africa. Considering the high level of CQ use in West Africa, other factors such as intensity of transmission, population immunity or population movements should be considered when explaining the different levels of resistance. Understanding such factors may help us in devising strategies to contain the spread of drug resistance.


4137.          Foca A, Matera G, Barreca GS, Gagliardi F, Apuzzo G, Guaglianone L. Imported malaria in pregnancy due to Plasmodium falciparum. J Travel Med  2001 Nov-Dec;8(6):331-2 No Abstract.

4138.          Goodman CA, Coleman PG, Mills AJ. Changing the first line drug for malaria treatment--cost-effectiveness analysis with highly uncertain inter-temporal trade-offs. Health Econ  2001 Dec;10(8):731-49


Access to effective treatment would substantially reduce the burden of malaria in sub-Saharan Africa, but resistance to chloroquine, the most commonly used first line drug, is now widespread. There has been considerable debate over the level of chloroquine resistance at which a new first line drug should be adopted. Two issues make this an extremely complex decision: it involves trade-offs in costs and health outcomes over time; and many of the parameters are uncertain. A modelling approach was identified as appropriate for addressing these issues. The costs and effects of changing from chloroquine to sulphadoxine-pyrimethamine (SP) as the first line drug were modelled over 10 years, allowing for growth in drug resistance. Probabilistic sensitivity analysis was used to allow for the high levels of parameter uncertainty. The optimal year of switch was highly dependent on both empirical values, such as initial resistance and resistance growth rates, and on subjective values, such as the time preferences of policy-makers. It was not possible to provide policy-makers with a definitive threshold resistance level at which to switch, but the model can be used as an analytical tool to structure the problem, explore trade-offs, and identify areas for which data are lacking. Copyright 2001 John Wiley & Sons, Ltd.


4139.          Gupta D, Chugh K, Sachdev A, Soni A. ICU management of  severe malaria. Indian J Pediatr  2001 Nov;68(11):1057-61


Malaria is very common in India. First step in management of malaria is to establish the diagnosis. It is established by using traditional smear or method like dipstick antigen captures assay which is simpler, accurate and doesn't require expertise. Next step is to look for signs and symptoms, which help cases of severe malaria should be admitted in intensive care unit (ICU) and antimalarial chemotherapy should be started through parenteral route. Complications like coma, anemia, renal failure, pulmonary edema, disseminated intravascular coagulation are not very uncommon. These complications should be anticipated and treated in time. There is no role of corticosteroids, mannitol in the treatment of cerebral edema. Therapeutic monitoring of severe malaria should involve quantitative estimation of parasite load.


4140.          Haldar K, Samuel BU, Mohandas N, Harrison T, Hiller NL. Transport mechanisms in Plasmodium-infected erythrocytes: lipid rafts and a tubovesicular network. Int J Parasitol  2001 Oct;31(12):1393-401


The mature human erythrocyte is a simple cell that is devoid of intracellular organelles and does not show endocytic or phagocytic activity at the plasma membrane. However, following infection by Plasmodium, the erythrocyte undergoes several morphological and functional changes. Parasite-derived proteins are exported into the erythrocyte cytoplasm and to the membrane, while several proteins are localised to the parasitophorous vacuolar membrane and to the tubovesicular membranous network structures surrounding the parasite. Recent evidence indicates that multiple host proteins, independent of the type of their membrane anchor, that exist in detergent-resistant membrane (DRM) rafts or microdomains enter this apicomplexan vacuole. The internalised host components along with the parasite-encoded transmembrane protein PfEXP1 can be detected as DRM rafts in the vacuole. It appears that in Plasmodium-infected erythrocytes lipid rafts may play a role in endovacuolation and macromolecular transport.


4141.          Hemingway J. Identification of a novel class of insect glutathione S-transferases involved in resistance to DDT in the malaria vector Anopheles gambiae. Biochem J  2001 Oct 15;359(Pt 2):295-304


The sequence and cytological location of five Anopheles gambiae glutathione S-transferase (GST) genes are described. Three of these genes, aggst1-8, aggst1-9 and aggst1-10, belong to the insect class I family and are located on chromosome 2R, in close proximity to previously described members of this gene family. The remaining two genes, aggst3-1 and aggst3-2, have a low sequence similarity to either of the two previously recognized classes of insect GSTs and this prompted a re-evaluation of the classification of insect GST enzymes. We provide evidence for seven possible classes of insect protein with GST-like subunits. Four of these contain sequences with significant similarities to mammalian GSTs. The largest novel insect GST class, class III, contains functional GST enzymes including two of the A. gambiae GSTs described in this report and GSTs from Drosophila melanogaster, Musca domestica, Manduca sexta and Plutella xylostella. The genes encoding the class III GST of A. gambiae map to a region of the genome on chromosome 3R that contains a major DDT [1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane] resistance gene, suggesting that this gene family is involved in GST-based resistance in this important malaria vector. In further support of their role in resistance, we show that the mRNA levels of aggst3-2 are approx. 5-fold higher in a DDT resistant strain than in the susceptible strain and demonstrate that recombinant AgGST3-2 has very high DDT dehydrochlorinase activity.


4142.          Kaushik A, Gahlot S, Kaushik  S, Verma B L. Rapid manual test for falciparum malaria. Indian Pediat 2001, 38(6), 650-4. (017313).1 Sept 2001. No Abstract.

4143.          Kawamoto F. Detection of Plasmodium ovale by the ICT malaria P.f/P.v. immunochromatographic test. Acta Trop  2001 Dec 21;80(3):283-4  No Abstract.

4144.          Kirk K.  Malaria. A voracious creature. Lancet  2001 Dec;358 Suppl:S41 No Abstract.

4145.          Krettli AU, Andrade-Neto VF, Brandao MG, Ferrari WM. The search for new antimalarial drugs from plants used to treat fever and malaria or plants ramdomly selected: a review. Mem Inst Oswaldo Cruz  2001 Nov;96(8):1033-42


In this review we discuss the ongoing situation of human malaria in the Brazilian Amazon, where it is endemic causing over 610,000 new acute cases yearly, a number which is on the increase. This is partly a result of drug resistant parasites and new antimalarial drugs are urgently needed. The approaches we have used in the search of new drugs during decades are now reviewed and include ethnopharmocology, plants randomly selected, extracts or isolated substances from plants shown to be active against the blood stage parasites in our previous studies. Emphasis is given on the medicinal plant Bidens pilosa, proven to be active against the parasite blood stages in tests using freshly prepared plant extracts. The anti-sporozoite activity of one plant used in the Brazilian endemic area to prevent malaria is also described, the so called "Indian beer" (Ampelozizyphus amazonicus, Rhamnaceae). Freshly prepared extracts from the roots of this plant were totally inactive against blood stage parasites, but active against sporozoites of Plasmodium gallinaceum or the primary exoerythrocytic stages reducing tissue parasitism in inoculated chickens. This result will be of practical importance if confirmed in mammalian malaria. Problems and perspectives in the search for antimalarial drugs are discussed as well as the toxicological and clinical trials to validate some of the active plants for public health use in Brazil.


4146.          L, Sergheraert C, Grellier P, Schirmer RH, Becker K. A prodrug form of a Plasmodium falciparum glutathione reductase inhibitor conjugated with a 4-anilinoquinoline. J Med Chem  2001 Nov 22;44(24):4268-76


Glutathione (GSH), which is known to guard Plasmodium falciparum from oxidative damage, may have an additional protective role by promoting heme catabolism. An elevation of GSH content in parasites leads to increased resistance to chloroquine (CQ), while GSH depletion in resistant P. falciparum strains is expected to restore the sensitivity to CQ. High intracellular GSH levels depend inter alia on the efficient reduction of GSSG by glutathione reductase (GR). On the basis of this hypothesis, we have developed a new strategy for overcoming glutathione-dependent 4-aminoquinoline resistance. To direct both a 4-aminoquinoline and a GR inhibitor to the parasite, double-drugs were designed and synthesized. Quinoline-based alcohols (with known antimalarial activity) were combined with a GR inhibitor via a metabolically labile ester bond to give double-headed prodrugs. The biochemically most active double-drug 7 of this series was then evaluated as a growth inhibitor against six Plasmodium falciparum strains that differed in their degree of resistance to CQ; the ED(50) values for CQ ranged from 14 to 183 nM. While the inhibitory activity of the original 4-aminoquinoline-based alcohol followed that of CQ in these tests, the double-drug exhibited similar efficiency against all strains, the ED(50) being as low as 28 nM. For the ester 7, a dose-dependent decrease in glutathione content and GR activity and an increase in glutathione-S-transferase activity were determined in treated parasites. The drug was subsequently tested for its antimalarial action in vivo using murine malaria models infected with P. berghei. A 178% excess mean survival time was determined for the animals treated with 40 mg/kg 7 for 4 days. No cytotoxicity due to this compound was observed. Work is in progress to extend and validate the strategy outlined here.

4147.          Leke RG. The state of immunology in Africa: HIV/AIDS and malaria. Curr Opin Immunol  2001 Oct;13(5):523-7


HIV and malaria are two major infections that are responsible for the greatest burden of diseases, morbidity and mortality in the African population. Successful research has been undertaken in Africa into novel means of monitoring HIV disease progression and in identifying vaccine candidates. The role of IgG isotypes in malaria has been investigated, as have parasite adhesion molecules important for pathogenesis. It is hoped that vaccines for malaria will soon prove successful. However, many problems still face immunology research in Africa.

4148.          Mayxay M, Chotivanich K, Pukrittayakamee S, Newton P, Looareesuwan S, White NJ. Contribution of humoral immunity to the therapeutic response in falciparum malaria. Am J Trop Med Hyg  2001 Dec;65(6):918-23


The contribution of humoral immunity to the therapeutic response in acute falciparum malaria was assessed in a case-control study. Forty adult Thai patients with acute falciparum malaria who had subsequent recrudescent infections and 40 patients matched for age, therapeutic regimen, and disease severity who were cured by Day 28 were studied. All cured patients had positive immunoglobulin (Ig) G to ring-infected erythrocyte surface antigen (RESA) in their admission plasma, compared with only 60% of patients who failed to respond to treatment (P < 0.001). The proportion of IgM-positive cases at admission was also higher in the successfully treated group than in the group with failure (70% versus 30%) (P < 0.001). The geometric mean (95% confidence interval) reciprocal IgG titer at admission was significantly higher in cured patients (187.0 [83.5-418.3]) compared with those who experienced treatment failure (11.6 [5.1-26.5]) (P < 0.001). The patients with uncomplicated malaria who were both IgG and IgM positive at admission had significantly shorter fever clearance times and lower admission parasitemia levels compared with those who were negative (P = 0.01 and P = 0.02, respectively). The median (range) in vitro parasite multiplication rate was significantly lower in cultures containing positive anti-RESA antibody plasma compared with those containing normal plasma (0.7 [0.1-3.5] versus 2.6 [0.1-12.1]; P < 0.001). These results suggest that antimalarial antibodies may play an important supportive role in the therapeutic response to antimalarial drugs during acute falciparum malaria.


4149.          Merten M, Thiagarajan P. Role for sulfatides  in platelet aggregation. Circulation  2001 Dec 11;104(24):2955-60


BACKGROUND: Sulfatides are sulfated glycosphingolipids present on the surface of oligodendrocytes, renal tubular cells, and certain tumor cells. They appear to be involved in nerve conduction and cell adhesion, but their precise physiological function is not known. METHODS AND RESULTS: Here, we show a novel role for sulfatides as a major ligand for P-selectin in platelet adhesion and aggregation. Sulfatides are expressed on the platelet surface, and platelets expressing sulfatides adhere to P-selectin. Both sulfatide micelles and sulfatide-binding recombinant malaria circumsporozoite protein (MCSP) inhibit this adhesion. In parallel, platelets and CHO cells expressing P-selectin adhere to sulfatides, and anti-P-selectin antibodies inhibit this adhesion. Furthermore, both anti-P-selectin antibodies and sulfatide antagonist MCSP significantly reverse platelet aggregation induced by ADP, collagen, or thrombin receptor-activating peptide, suggesting that sulfatide-P-selectin interactions are necessary for the formation of stable platelet aggregates. CONCLUSIONS: These results show that sulfatide interactions with P-selectin are important in platelet adhesion and platelet aggregation. The sulfatide interactions with P-selectin stabilize platelet aggregates, representing a new mechanism of platelet aggregation that may play a significant role in hemostasis and thrombosis.

4150.          Modiano D. Antimalarial  antibody levels and IL4 polymorphism in the Fulani of West Africa. Genes Immun  2001 Nov;2(7):411-4


The Fulani are less clinically susceptible and more immunologically responsive to malaria than neighbouring ethnic groups. Here we report that anti-malarial antibody levels show a wide distribution amongst the Fulani themselves, raising the possibility that quantitative analysis within the Fulani may be an efficient way of screening for important genetic factors. The Th2 cytokine interleukin-4 is an obvious candidate: in Fulani, the IL4-524 T allele is at high frequency and is associated with elevated antibody levels against malaria antigens. These data highlight the possibility of combining inter- and intra-ethnic comparisons to characterize critical determinants of malarial immunity in a natural setting.

4151.          Nacer A, Berry L, Slomianny C, Mattei D. Plasmodium falciparum signal sequences: simply sequences or special signals? Int J Parasitol  2001 Oct;31(12):1371-9


The malaria parasite, Plasmodium falciparum, synthesises and exports several proteins inducing morphological and biochemical modifications of erythrocytes during the erythrocytic cycle. The protein trafficking machinery of the parasite is similar to that of other eukaryotic cells in several ways. However, some unusual features are also observed. The secretion of various polypeptides was inhibited when P. falciparum infected erythrocytes were incubated with Brefeldin A. Immunoelectron microscopy studies revealed substantial morphological changes in the endoplasmic reticulum following exposure of parasitised erythrocytes to the drug. Immunofluorescence studies of Brefeldin A-treated parasites suggest that polypeptide sorting to different intracellular destinations begins at the endoplasmic reticulum. The parasite also secretes polypeptides by a Brefeldin A-insensitive route that bypasses the classical endoplasmic reticulum-Golgi complex pathway.

4152.          Oguariri RM, Borrmann S, Klinkert MQ, Kremsner PG, Kun JF. High prevalence of human antibodies to recombinant Duffy binding-like alpha domains of the Plasmodium falciparum-infected erythrocyte membrane protein 1 in semi-immune adults compared to that in nonimmune children. Infect Immun  2001 Dec;69(12):7603-9


We used a panel of nine fusion proteins that contain different Duffy binding-like alpha (DBL-alpha) domains of Plasmodium falciparum infected erythrocyte membrane protein 1 to assess the levels of antibody activity in serum samples obtained from semi-immune or nonimmune individuals from Lambarene, Gabon. Recognition was measured in terms of either the prevalence or the magnitude of the response. A strong correlation between the immune status of the patients and reactivity with recombinant proteins was observed, which was interpreted as a reflection of the number of infections acquired over time. The antibody responses were predominantly directed toward variable epitopes of the DBL-alpha domain. Antibody responses could be reduced by preincubation of the sera with various fusion proteins. A portion of individuals who exhibited high-level responses to all fusion proteins also had antibodies which recognized conserved epitopes. The possibility that a synergizing effect of anti-DBL-alpha domain antibodies could support chemotherapy is discussed.

4153.          Okech BA, Nalunkuma A, Okello D, Pang XL, Suzue K, Li J, Horii T, Egwang TG. Natural human immunoglobulin G subclass responses to Plasmodium falciparum serine repeat antigen in Uganda. Am J Trop Med Hyg  2001 Dec;65(6):912-7


Serum samples from Ugandan residents of a malaria-hyperendemic region were tested by enzyme-linked immunosorbent assay for reactivity against recombinant constructs of the 47 (SE47')- and 50 (SE50A)-kDa fragments of Plasmodium falciparum serine repeat antigen (SERA). Immunoglobulin (Ig) G3 and IgG1 were the predominant subclass responses to SE47' and SE50A, respectively. The geometric mean optical density (OD) for IgG3 anti-SE47' was significantly lower in children < 15 years compared with adults > or = 15 years (P < 0.0001). By contrast, the geometric mean IgG1 anti-SE50A was slightly higher in children compared with adults (P < 0.01). The proportion of high responders (ODs > 0.5) to SE47' was significantly lower in children compared with adults (P < 0.001), whereas the proportion of high responders to SE50A was comparable in children and adults (P = 0.07). This first detailed study of SERA in a malaria-hyperendemic region suggests that natural human IgG3 anti-SE47' might be associated with immunity to malaria.


4154.          Olliaro P, Taylor WR, Rigal J. Controlling malaria: challenges and solutions. Trop Med Int Health  2001 Nov;6(11):922-7


Antimalarial drug resistance is a major public health challenge and the principal reason for the erosion of efficacious treatments. Cost and the limited number of antimalarial drugs in current use impose considerable constraints on malaria control, especially in sub-Saharan Africa. The paper describes a multilateral, multidisciplinary research project on artemisinin-based combination therapy, which offers a new and potentially highly effective way to prevent or retard the development of drug resistance.


4155.          Ouellette M. Biochemical and molecular mechanisms of drug  resistance in parasites. Trop Med Int Health  2001 Nov;6(11):874-82


Drug resistance is complicating the treatment of parasitic diseases. We review here the basic mechanisms of parasite resistance in malaria, sleeping sickness, leishmaniasis and common helminthiases. Parasites resort to multiple biochemical means to achieve resistance and we have begun to isolate and characterize the genes/proteins implicated in resistance. Understanding drug resistance is essential for the control of parasitic diseases.


4156.          Pennisi E. Genes and disease. Genetic change wards off malaria. Science  2001 Nov 16;294(5546):1439  No Abstract.

4157.          Pinder M, Hill AV, Plebanski M.  Unique T cell effector functions elicited by Plasmodium falciparum epitopes in malaria-exposed Africans tested by three T cell assays. J Immunol  2001 Oct 15;167(8):4729-37


Natural immunity to malaria is characterized by low level CD4 T cell reactivity detected by either lymphoproliferation or IFN-gamma secretion. Here we show a doubling in the detection rate of responders to the carboxyl terminus of circumsporozoite protein (CS) of Plasmodium falciparum by employing three T cell assays simultaneously: rapid IFN-gamma secretion (ex vivo ELISPOT), IFN-gamma secretion after reactivation of memory T cells and expansion in vitro (cultured ELISPOT), and lymphoproliferation. Remarkably, for no individual peptide did a positive response for one T cell effector function correlate with any other. Thus these CS epitopes elicited unique T cell response patterns in malaria-exposed donors. Novel or important epitope responses may therefore be missed if only one T cell assay is employed. A borderline correlation was found between anti-CS Ab levels and proliferative responses, but no correlation was found with ex vivo or cultured IFN-gamma responses. This suggested that the proliferating population, but not the IFN-gamma-secreting cells, contained cells that provide help for Ab production. The data suggest that natural immunity to malaria is a complex function of T cell subgroups with different effector functions and has important implications for future studies of natural T cell immunity.

4158.          Rajagopal  V, Appavoon N C, Sarangapani T D, Mani S: Comparative study on microscopic detection of malaria parasites under conventional thick film and concentration by saponin haemolysis.Indian J Malar 1999, 36(1-2), 49-51. (015249), Aug 1, 2023 No Abstract.

4159.          Rajesh Kumar: Study of consequences of malaria among sicklers. Proc Indian Sci Congr Ass- Pt II, Sect- II 1999, 28-9. (016449). Aug 16, 2001.


Except tribals and African black people, other population group also possesses the gene of Sickle Cell. In other words the genes of Sickle Cell transmitting from one population group to other or its occurrence by mutation is still continue due to its selective advantages. It provides protection against the severe consequences of Malaria. Indian continent and its people are sensitive in connection with Malaria as well as Sickle Cell gene. Madhya Pradesh Statw and Mandla district is heart place of the country. 43 percent people of Mehra (Jharia) caste fo Mandla district possess sickle cell gene, frequency of genes (Sickle Cell gene) is 0.2450 in this population. It is concluded from the investigation that 44.18 percent Sicklers and 47.37 percent normal individuals are affected by the malarial parasite before the recent year, either once or twice. The Sicklers (23.25 per cent ) more affected once in last one year, as compared to normal individuals (17.54 percent). The percentage of never affected  individuals found more among normal individuals (17.54 per cent) as compared to Sicklers (9.30 percent). The investigation shows that there are not any selective advantages for Sicklers against the parasite of Plasmodium malarialii, plasmodium ovale and plasmodium vivex but they hardly suffer from plasmodium falsiparum.

4160.          Rhee MS, Akanmori BD, Waterfall M, Riley EM. Changes in cytokine production associated with acquired immunity to Plasmodium falciparum malaria. Clin Exp Immunol  2001 Dec;126(3):503-10


Individuals living in malaria-endemic areas eventually develop clinical immunity to Plasmodium falciparum. That is, they are able to limit blood parasite densities to extremely low levels and fail to show symptoms of infection. As the clinical symptoms of malaria infection are mediated in part by pro-inflammatory cytokines it is not clear whether the acquisition of clinical immunity is due simply to the development of antiparasitic mechanisms or whether the ability to regulate inflammatory cytokine production is also involved. We hypothesize that there is a correlation between risk of developing clinical malaria and the tendency to produce high levels of proinflammatory cytokines in response to malaria infection. In order to test this hypothesis, we have compared the ability of peripheral blood mononuclear cells from malaria-naive and malaria-exposed adult donors to proliferate and to secrete IFN-gamma in response to P. falciparum schizont extract (PfSE). In order to determine how PfSE-induced IFN-gamma production is regulated, we have also measured production of IL-12p40 and IL-10 from PfSE-stimulated PBMC and investigated the role of neutralizing antibody to IL-12 in modulating IFN-gamma production. We find that cells from naive donors produce moderate amounts of IFN-gamma in response to PfSE and that IFN-gamma production is strongly IL-12 dependent. Cells from malaria-exposed donors living in an area of low malaria endemicity produce much higher levels of IFN-gamma and this response is also at least partially IL-12 dependent. In complete contrast, cells from donors living in an area of very high endemicity produce minimal amounts of IFN-gamma. No significant differences were detected between the groups in IL-10 production, suggesting that this cytokine does not play a major role in regulating malaria-induced IFN-gamma production. The data from this study thus strongly support the hypothesis that down-regulation of inflammatory cytokine production may be a component of acquired clinical immunity to malaria but the mechanism by which this is achieved remains to be elucidated.


4161.          Rowe AK, Onikpo F, Lama M, Cokou F, Deming MS. Management of childhood illness at health facilities in Benin: problems and their causes. Am J Public Health  2001 Oct;91(10):1625-35


OBJECTIVES: To prepare for the implementation of Integrated Management of Childhood Illness (IMCI) in Benin, we studied the management of ill children younger than 5 years at outpatient health facilities. METHODS: We observed a representative sample of consultations; after each consultation, we interviewed caregivers and reexamined children. Health workers' performance was evaluated against IMCI guidelines. To identify determinants of performance, statistical modeling was performed and 6 focus groups with health workers were conducted to solicit their opinions. RESULTS: Altogether, 584 children were enrolled and 101 health workers were observed; 130 health workers participated in focus group discussions. Many serious deficiencies were found: incomplete assessment of children's signs and symptoms, incorrect diagnosis and treatment of potentially life-threatening illnesses, inappropriate prescription of dangerous sedatives, missed opportunities to vaccinate, and failure to refer severely ill children for hospitalization. Quantitative and qualitative analyses showed various health facility-, health worker-, caregiver-, and child-related factors as possible determinants of health worker performance. CONCLUSIONS: Action is urgently needed. Our results suggest that to improve health care delivery, interventions should target both the health system and the community level.

4162.          Rubio JM, Berzosa PJ, Benito A. Amplified fragment length polymorphism (AFLP) protocol for genotyping the malarial parasite Plasmodium falciparum. Parasitology  2001 Oct;123(Pt 4):331-6


We have established an amplified fragment length polymorphism (AFLP) protocol for identifying anonymous polymorphic loci of the malarial parasite, Plasmodium falciparum. The method consists of the following steps (i) digestion and ligation in one reaction; (ii) selective fluorescence forward primers labelled; (iii) PCR products resolved in polyacrylamide gels using the ABIPRISM 377 XL DNA sequencer and, (iv) the use of Genescan software to size the fragments. This standardized protocol distinguished between 2 standard reference clones of P. falciparum from West African and Southeast Asian and 2 Central African isolates from patients with clinical malaria. The AFLP protocol resulted in evenly distributed and reproducible band patterns for amplified fragments ranking from 163 to 489 bp long +/-0.5 S.D. The primer Tru ACA labelled with the phosphoramidite 6-carboxifluorescein (FAM-blue) was easy to interpret, with a maximum of 53 bands per clone and of 81 per isolate (mixed falciparum populations) whereas the primer Tru AG labelled with the hexachlorinated analogue (HEX-green) showed a less clear pattern of bands and reproducibility than Tru ACA.


4163.          Saito-Ito A, Akai Y, He S, Kimura M, Kawabata M. A rapid, simple and sensitive flow cytometric system for detection of Plasmodium falciparum. Parasitol Int  2001 Nov;50(4):249-57


We have established a rapid, simple and sensitive flow cytometric system for the detection of Plasmodium falciparum that involves lysing erythrocytes and staining parasites at the same time using a newly developed hemolysing and staining solution containing dodecyl methyl ammonium chloride and acridine orange. In this system, freed parasites of P. falciparum could be plotted separately from erythrocyte ghosts, white blood cells and platelets on the two-dimensional scattergram of forward-angle light scatter and green fluorescence by flow cytometry with an argon laser. It took only 2-3 min per sample to obtain the scattergram and analyze the data, including the time of sample preparation for flow cytometric analysis. Sample preparation with this method does not require any difficult handling procedures. The threshold of parasite detection was almost equal to that of microscopic examination for cultured P. falciparum. The results of drug-susceptibility assays using this system were also almost identical to those obtained using microscopic examination. In this system, parasites at different erythrocytic stages could be easily distinguished. This system must prove useful and practical for basic laboratory studies of P. falciparum including those requiring the differential measurement of parasites at specific erythrocytic stages.


4164.          Senior K. "Imperfect" vaccines may encourage more potent pathogens, model suggests. Lancet  2001 Dec 15;358(9298):2055  No Abstract.

4165.          Snounou G. Association of genetic mutations in Plasmodium vivax dhfr with resistance to sulfadoxine-pyrimethamine: geographical and clinical correlates. Antimicrob Agents Chemother  2001 Nov;45(11):3122-7


Mutations in the Plasmodium falciparum gene (dhfr) encoding dihydrofolate reductase are associated with resistance to antifols. Plasmodium vivax, the more prevalent malaria parasite in Asia and the Americas, is considered antifol resistant. Functional polymorphisms in the dhfr gene of P. vivax (pvdhfr) were assessed by PCR-restriction fragment length polymorphism using blood samples taken from 125 patients with acute vivax malaria from three widely separated locations, Thailand (n = 100), India (n = 16), and Madagascar and the Comoros Islands (n = 9). Upon evaluation of the three important codons (encoding residues 57, 58, and 117) of P. vivax dhfr (pvdhfr), double- or triple-mutation genotypes were found in all but one case from Thailand (99%), in only three cases from India (19%) and in no cases from Madagascar or the Comoros Islands (P < 0.0001). The dhfr PCR products of P. vivax from 32 Thai patients treated with the antifolate sulfadoxine-pyrimethamine (S-P) were investigated. All samples showed either double (53%) or triple (47%) mutations. Following treatment, 34% of the patients had early treatment failures and only 10 (31%) of the patients cleared their parasitemias for 28 days. There were no significant differences in cure rates, but parasite reduction ratios at 48 h were significantly lower for patients whose samples showed triple mutations than for those whose samples showed double mutations (P = 0.01). The three mutations at the pvdhfr codons for residues 57, 58, and 117 are associated with high levels of S-P resistance in P. vivax. These mutations presumably arose from selection pressure.


4166.          Tarimo DS, Minjas JN, Bygbjerg IC. Perception of chloroquine efficacy and alternative treatments for uncomplicated malaria in children in a holoendemic area of Tanzania: implications for the change of treatment policy. Trop Med Int Health  2001 Dec;6(12):992-7

Prior to policy change from chloroquine (CQ) to sulphadoxine/pyrimethamine (S/P; Fansidar) we assessed the perception of CQ efficacy and the alternative treatment options for malaria in children among parents/guardians (N=527) of under-fives attending first level health facilities on account of fever. It was hypothesized that the long experience with CQ and its antipyretic effect (lacking in S/P) might impede acceptance of S/P for wider use as first-line drug. Malarial fevers in children were most commonly treated with CQ (92.8%), followed by quinine (60.7%) and S/P (28.7%). A 63.2% knew the reasons for non-response to antimalarial treatment, and only 50% were aware that CQ could fail to treat malaria, and 57.1% knew alternative treatment options, namely quinine (52.2%) and S/P (20.5%). Generally, decreased efficacy of CQ had been noticed, and quinine was prescribed for both suspected and proven CQ failures in first level health facilities and the district hospital. S/P was judged to be more effective than quinine, but too strong for children, and was the least known drug in the study area. All formulations of S/P cost more per dose for a child and an adult than CQ. The implications of these findings on the change of malaria treatment policy are discussed.


4167.          Tjitra E, Suprianto S, Currie BJ, Morris PS, Saunders JR, Anstey NM. Therapy of uncomplicated falciparum malaria: a randomized trial comparing artesunate plus sulfadoxine-pyrimethamine versus sulfadoxine-pyrimethamine alone in Irian Jaya, Indonesia. Am J Trop Med Hyg  2001 Oct;65(4):309-17


Combining artesunate with existing antimalarial drugs may improve cure rates, delay emergence of resistance, and reduce transmission. We performed a randomized comparative trial to quantify the effect of adding artesunate to sulfadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria in Indonesia. Using a modified 1997 World Health Organization protocol for assessment of therapeutic efficacy of antimalarial drugs, 105 patients (stratified by age/ethnic group) were randomized: 53 received artesunate orally, 4 mg/kg of body weight, a single daily dose for three days, plus sulfadoxine pyrimethamine orally (1.25 mg of pyrimethamine/kg of body weight), a single dose on day 0, and 52 patients received sulfadoxine-pyrimethamine alone. Six from the combination group were withdrawn from analysis, as were six of the sulfadoxine-pyrimethamine group. Treatment failure rates on day 14 were 0% in the artesunate plus sulfadoxine-pyrimethamine group and 8.7% in the sulfadoxine-pyrimethamine group (P = 0.12). Treatment failure rates on day 28 were 4.4% and 15.2%, respectively (P = 0.16). Relative risk of treatment failure at 28 days was 0.3 (95% confidence interval [CI] = 0.1-1.3). Mean fever clearance time (1.3 versus 1.7 days) and mean parasite clearance time (1.4 versus 2.0 days) were both faster in the artesunate plus sulfadoxine-pyrimethamine group than in the sulfadoxine-pyrimethamine group (P = 0.08 and P < 0.0001, respectively). Only 20 (39.2%) of 51 patients treated with artesunate plus sulfadoxine-pyrimethamine were still parasitemic on day 1 compared with 45 (86.5%) of 52 patients treated with sulfadoxine-pyrimethamine alone (P = 0.000001, relative risk [RR] = 0.4, 95% CI = 0.3-0.6). Gametocyte carriage was lower following artesunate plus sulfadoxine-pyrimethamine than following sulfadoxine-pyrimethamine (RR = 0.5, 95% CI = 0.2-1.0 on day 7 and RR = 0.5, 95% CI = 0.2-1.1 on day 14). Mild diarrhea, rash, and itching resolved without treatment. Combined artesunate plus sulfadoxine-pyrimethamine resulted in more rapid fever and parasiteclearance, was well tolerated, reduced risk of treatment failure, and lowered gametocyte carriage.

4168.          Tjitra E, Suprianto S, Dyer ME, Currie BJ, Anstey NM. Detection of histidine rich protein 2 and panmalarial ICT Malaria Pf/Pv test antigens after chloroquine treatment of uncomplicated falciparum malaria does not reliably predict treatment outcome in eastern Indonesia. Am J Trop Med Hyg  2001 Nov;65(5):593-8


In regions with drug-resistant malaria, the ability to rapidly detect or predict treatment failure (TF) soon after a course of standard therapy for Plasmodium falciparum malaria would facilitate the prompt institution of second-line therapy. We thus evaluated longitudinally the ability of the ICT Malaria Pf/Pv immunochromatographic test to predict treatment outcome. Sixty-six Sumbanese Indonesians with uncomplicated falciparum malaria were treated with chloroquine and followed for 28 days by use of 1997 World Health Organization criteria for assessment of therapeutic efficacy of antimalarial drugs. The ICT Pf/Pv testing could be compared with microscopy in approximately half of the patients on each day of follow-up. Although strongly positive histidine rich protein 2 (HRP2) line intensities (equal to or greater than the control band) in convalescence were highly predictive of TF, any degree of positivity for the HRP2 and panmalarial antigens in convalescence was only moderately predictive of TE Positive predictive values of the HRP2 and panmalarial antigens for TF were 76.9% and 87.0%, respectively, on Day 3, 82.4% and 87.5% on Day 7, and 78.9% and 78.9% on Day 14. Negative HRP2 and panmalarial antigen results in convalescence were even less predictive of an adequate clinical response, and false-negative HRP2 and panmalarial antigen test results were found in one-sixth (6 of 37) of recrudescent infections diagnosed by microscopy among patients with late treatment failure. To reliably predict treatment outcome with rapid antigen tests, further development appears necessary to improve sensitivity for viable asexual parasites while avoiding detection of both gametocytes and persistent antigen in convalescence.

4169.          Toure FS, Mavoungou E, Ndong JM, Tshipamba P, Deloron P. Erythrocyte binding antigen (EBA-175) of Plasmodium falciparum: improved genotype determination by nested polymerase chain reaction. Trop Med Int Health  2001 Oct;6(10):767-9


We have designed primers to the conserved region of the erythrocyte binding antigen (EBA)-175 gene which amplify specifically the two alleles by polymerase chain reaction (PCR) and by nested PCR. This approach provides a specific, sensitive and rapid method for genotype determination in a large number of Plasmodium falciparum field isolates.


4170.          Trial Team. Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial. Lancet  2001 Dec 8;358(9297):1927-34


BACKGROUND: RTS,S/AS02 is a pre-erythrocytic malaria vaccine based on the circumsporozoite surface protein of Plasmodium falciparum fused to HBsAg, incorporating a new adjuvant (AS02). We did a randomised trial of the efficacy of RTS,S/AS02 against natural P. falciparum infection in semi-immune adult men in The Gambia. METHODS: 306 men aged 18-45 years were randomly assigned three doses of either RTS,S/AS02 or rabies vaccine (control). Volunteers were given sulfadoxine/pyrimethamine 2 weeks before dose 3, and kept under surveillance throughout the malaria transmission season. Blood smears were collected once a week and whenever a volunteer developed symptoms compatible with malaria. The primary endpoint was time to first infection with P. falciparum. Analysis was per protocol. FINDINGS: 250 men (131 in the RTS,S/AS02 group and 119 in the control group) received three doses of vaccine and were followed up for 15 weeks. RTS,S/AS02 was safe and well tolerated. P. falciparum infections occurred significantly earlier in the control group than the RTS,S/AS02 group (Wilcoxon's test p=0.018). Vaccine efficacy, adjusted for confounders, was 34% (95% CI 8.0-53, p=0.014). Protection seemed to wane: estimated efficacy during the first 9 weeks of follow-up was 71% (46-85), but decreased to 0% (-52 to 34) in the last 6 weeks. Vaccination induced strong antibody responses to circumsporozoite protein and strong T-cell responses. Protection was not limited to the NF54 parasite genotype from which the vaccine was derived. 158 men received a fourth dose the next year and were followed up for 9 weeks; during this time, vaccine efficacy was 47% (4-71, p=0.037). INTERPRETATION: RTS,S/AS02 is safe, immunogenic, and is the first pre-erythrocytic vaccine to show significant protection against natural P. falciparum infection.

4171.          Tsuji M, Zavala F. Peptide-based subunit vaccines against pre-erythrocytic stages of malaria parasites. Mol Immunol  2001 Dec;38(6):433-42


Malaria currently ranks among the most prevalent infections in tropical and sub-tropical areas throughout the world with relatively high morbidity and mortality particularly in young children. The widespread occurrence and the increased incidence of malaria in many countries, caused by drug-resistant parasites (Plasmodium falciparum and P. vivax) and insecticide-resistant vectors (Anopheles mosquitoes), indicate the need to develop new methods of controlling this disease. Experimental vaccination with radiation-attenuated sporozoites can protect animals and humans against the disease, demonstrating the feasibility of developing an effective malaria vaccine. However, vaccines based on radiation-attenuated sporozoites are not feasible for large scale application due to lack of in vitro culture system. Therefore, the development of peptide-based subunit vaccines has been undertaken as an alternative approach. Synthetic peptides containing defined B- and T-cell epitopes of different antigens expressed in sporozoites and/or liver stages have been used as subunit vaccines in experimental animal models. They have been shown to be highly immunogenic and capable of inducing protective immunity mediated by antibodies, as well as CD4+ and CD8+ T-cells.

4172.          Urquiza M, Ocampo M, Patarroyo ME, Patarroyo MA. Plasmodium vivax: functional analysis of a highly conserved PvRBP-1 protein region. Mol Biochem Parasitol  2001 Oct;117(2):229-34 No Abstract.

4173.          Yapabandara AM, Curtis CF, Wickramasinghe MB, Fernando WP. Control of malaria vectors with the insect growth regulator pyriproxyfen in a gem-mining area in Sri Lanka. Acta Trop  2001 Dec 21;80(3):265-76


The study was conducted in eight adjacent villages in central Sri Lanka where there are many shallow pits dug by gem miners that fill with water. These become breeding places of the main malarial vector Anopheles culicifacies, and of the second most important vector Anopheles subpictus, but not of Anopheles varuna, the third most important vector. With the help of local volunteers, data on the adult populations of these three species was collected by various standard methods, and data on the incidence of malaria cases was collected by two clinics set up for the project and through the existing hospitals. Prevalence of malaria infection in symptom-less people was investigated by mass blood surveys. On the basis of a year's pre-intervention data the villages were stratified into four with high levels of malaria transmission and four with lower transmission. Within each stratum two villages were randomly assigned for mosquito control by treating all the gem pits, as well as river bed pools, with a granular formulation of the insect growth regulator pyriproxyfen at a target dose of 0.01 mg a.i./litre. The intervention caused significant reductions in the adult populations of An. culicifacies and An. subpictus. Similarly, incidence of malaria was reduced in the intervention villages to about 24% (95% c.l. 20-29%) of that in the controls. Prevalence of parasitaemia also declined significantly. It is concluded that in this situation where, with active community participation, the breeding sites of the main vectors could be located; vector control by a highly active and persistent insect growth regulator can be a very effective means of malaria control.



July 02


4752.          Ahlawat S, Kumar R, Roy P, Varma S, Sharma BKS. Meningococcal meningitis outbreak control strategies. J Commun Dis 2000, 32(4), 264-74.

Abstract : Meningococcal meningitis has been occurring worldwide in both endemic and epidemic forms. Serogroup A accounts for majority of cases of epidemic as well as endemic Meningococcal meningitis in developing nations, whereas group C and group B cases epidemic and endemic meningococcal meningitis in developed countries. Preventive strategies include vaccination, chemoprophylaxis and early detection and treatment. Mass vaccination campaign, if appropriately carried out, has been documented to halt an epidemic of meningococcal disease due to serogroup A or C. Discussed the available evidence with regards to prevention at primary, secondary and tertiary level. Public health approach to an outbreak of meningococcal meningitis  In a community or an organization is also outlined. 49 ref.


4753.          Bakardjiev A, Glaser C, Schuster F, Visvesvara GS. Three-year-old girl with fever and coma. Pediatr Infect Dis J. 2002 Jan;21(1):75, 85-6..

No Abstract

4754.          Berger RP, Pierce MC, Wisniewski SR, Adelson PD, Clark RS, Ruppel RA, Kochanek PM.  Neuron-specific enolase and S100B in cerebrospinal fluid after severe traumatic brain innjury in infants and children Pediatrics. 2002 Feb;109(2):E31.


BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability in children. Considerable insight into the mechanisms involved in secondary injury after TBI has resulted from analysis of ventricular cerebrospinal fluid (CSF) obtained in children with severe noninflicted and inflicted TBI (nTBI and iTBI, respectively). Neuron-specific enolase (NSE) is a glycolytic enzyme that is localized primarily to the neuronal cytoplasm. S100B is a calcium-binding protein localized to astroglial cells. In adults, CSF and serum concentrations of NSE and S100B have served as markers of neuronal damage after TBI. Neither NSE nor S100B has previously been studied in CSF after TBI in infants or children. OBJECTIVE: To compare the time course and magnitude of neuronal and astroglial death after nTBI and iTBI by measuring CSF concentrations of NSE and S100B using a rapid enzyme-linked immunosorbent assay. METHODS: Severe nTBI and iTBI were defined by strict clinical criteria. Serial ventricular CSF samples (n = 35) were obtained from children 1.5 to 9 years with severe nTBI (n = 5) and children 0.2 to 1.5 years (n = 5) with severe iTBI. Lumbar CSF samples from 5 children 0.1 to 2.3 years evaluated for meningitis were used as a comparison group. CSF NSE and S100B concentrations were quantified by an enzyme-linked immunosorbent assay (SynX Pharma Inc, Ontario, Canada). RESULTS: There was no difference in age between patients with iTBI (median [range]: 0.2 years [0.2-1.8]), nTBI (2.0 years [1.5-9]), and the comparison group (0.2 years [0.2-1.8]). The initial Glasgow Coma Scale score was higher in the iTBI group (9 [4-14]) versus the nTBI group (3 [3-7]). NSE was increased in TBI versus the comparison group in 34 of 35 samples. Mean NSE was markedly increased (mean +/- SEM, 117.1 +/- 12.0 ng/mL vs 3.5 +/- 1.4 ng/mL). After nTBI, a transient peak in NSE was seen at a median of 11 hours after injury (range: 5-20 hours). After iTBI, an increase in admission NSE was followed by a sustained and delayed peak at a median of 63 hours after injury (range: 7-94). The magnitude of peak NSE was similar in nTBI and iTBI. S100B was increased versus the comparison group in 35 of 35 samples. Mean S100B was markedly increased in TBI versus the comparison group (1.67 +/- 0.2 ng/mL vs 0.02 +/- 0.0 ng/mL). S100B showed a single peak at 27 hours (range: 5-63 hours)

after both nTBI and iTBI. The mean S100B concentration, peak S100B concentration, and the time to peak were not associated with mechanism of injury. CONCLUSIONS: Markers of neuronal and astroglial death are markedly increased in CSF after severe nTBI and iTBI. ITBI produces a unique time course of NSE, characterized by both an early and late peak, presumably representing 2 waves of neuronal death, the second of which may represent apoptosis. Delayed neuronal death may represent an important therapeutic target in iTBI. NSE and S100B may also be useful as markers to identify occult iTBI, help differentiate nTBI and iTBI, and assist in determining the time of injury in cases of iTBI.


4755.          Black M, Graham DI.  Sudden unexplained death in adults caused by intracranial pathology. J Clin Pathol. 2002 Jan;55(1):44-50. Review.

Sudden unexplained deaths as a result of intracranial lesions in adults are an important component of medicolegal practice and are best examined as a combined effort by a forensic pathologist, or a histopathologist experienced in coroner's necropsies, and a neuropathologist. Analysis of case material on file in the University of Glasgow's departments of forensic medicine and science, and neuropathology showed that the principal causes were sudden unexplained death in epilepsy (SUDEP), intracranial haemorrhage, either natural or after trauma, purulent meningitis or an abscess, and tumours. The mechanisms of death are

 considered to be the rapid increase of intracranial pressure caused by bleeding into the various compartments of the brain, or an acute obstructive hydrocephalus, and in cases where death is very rapid, autonomic and/or neurochemical dysfunction.


4756.          Brown EM, de Louvois J, Bayston R, Lees PD, Pople IK. Distinguishing between chemical and bacterial meningitis in patients who have undergone neurosurgery. Clin Infect Dis. 2002 Feb 15;34(4):556-8.

No Abstract

4757.          Caksen H, Uzum K, Kurtoglu S, Sungurlu I, Gulec M.  Imaging of an atypical case of congenital toxoplasmosis. Comput Med Imaging Graph. 2002 Jan-Feb;26(1):49-53.

In this article we describe the cranial computerized tomography findings of an infant with congenital toxoplasmosis, which was performed because she showed an atypical clinical course consisting of meningitis and multiple cerebral abscesses. In this case the cranial computerized tomography allowed the diagnosis of hydrocephalus and multiple cerebral abscesses, and guided the therapeutic approach.


4758.          Choi SH, Kim YS, Bae IG, Chung JW, Lee MS, Kang JM, Ryu J, Woo JH. The possible role of cerebrospinal fluid adenosine deaminase activity in the diagnosis of tuberculous meningitis in adults. Clin Neurol Neurosurg. 2002 Jan;104(1):10-5.

We studied an adenosine deaminase (ADA) activity in the cerebrospinal fluid (CSF) of 182 patients with meningitis. The patients were subdivided into four groups, (1) 36 cases of tuberculous meningitis; (2) 130 cases of viral or aseptic meningitis; (3) nine cases of bacterial meningitis; (4) seven cases of cryptococcal meningitis. Mean+/-S.D. ADA activity was 12.76+/-7.53 U/l in group 1; 2.58+/-2.37 U/l in group 2; 7.38+/-3.27 U/l in group 3; 7.42+/-4.38 U/l in group 4. Comparing the ADA activity in each group with the other groups, the difference is significant (P<0.001), except between groups 3 and 4. The sensitivity of the test for group 1 compared with group 2 was 0.83 and the specificity was 0.95 when a cut-off value of 7 U/l was used. When group 1 was compared with groups 3 and 4, the sensitivity was 0.58 and the specificity was 0.89 and 0.71 with groups 3 and 4, respectively, when a cut-off value of 10 U/l was used. Values >15 U/l were not observed  in any of the non-tuberculou meningitis patients; therefore, ADA activity >15 U/l could be a strong indication of tuberculous meningitis. We conclude that a determination of CSF ADA can aid in the early differential diagnosis of tuberculous meningitis.


4759.          Das S, Mahajan RC, Ganguly NK, Sawhney IM, Dhawan V, Malla N.  Detection of antigen B of Cysticercus cellulosae in cerebrospinal fluid for the diagnosis of human neurocysticercosis. Trop Med Int Health. 2002 Jan;7(1):53-8.


Neurocysticercosis (NCC) is a major cause of morbidity and mortality in developed and developing countries. The diagnosis of this disease remains a problem. We report the detection of specific antigenic fraction (antigen B) of Cysticercus cellulosae by enzyme-linked immunosorbent assay (ELISA) in various fractions of cerebrospinal fluid (CSF) obtained by high performance liquid chromatographic (HPLC) separation, for the diagnosis of human NCC. Forty patients attending or admitted to Nehru Hospital, Chandigarh were included in the study: 10 with suspected NCC, 20 with other neurological diseases and 10 undergoing surgery under spinal anaesthesia for non-neurological conditions, who served as controls. CSF samples collected from all patients and controls were subjected to chromatographic separation on an HPLC system. Antigen B (AgB) was detected in separated fractions by an ELISA test and compared with the detection of antibody response in CSF samples by indirect haemagglutination (IHA) technique. Antigen B was detected in 9 out of 10 patients with suspected NCC

based on clinical symptoms and radioimaging reports, but in none of the control subjects. However, antigen B was also detected in 9 out of 20 patients with other neurological disorders, mostly tubercular meningitis. Antibody response by IHA was found positive in only 2 of 10 cases clinically suspected of NCC. In conclusion, antigen B detection in CSF samples may be a useful adjunct to clinical suspicion and radiological reports for the diagnosis of NCC as there is no gold standard criteria to confirm this disease. However, the test needs to be evaluated on more patients in countries where tuberculosis and cysticercosis are endemic due to the high cross reactivity with samples from tubercular meningitis patients.


4760.          Deshpande R, Soni M.   Tuberculous meningitis. Gujarat med J 2000, 57(3), 93-4.

No Abstract

4761.          Domingo P, Muniz-Diaz E, Baraldes MA, Arilla M, Barquet N, Pericas R, Juarez C, Madoz P, Vazquez G.  Associations between Fc gamma receptor IIA polymorphisms and the risk and prognosis of meningococcal disease. Am J Med. 2002 Jan;112(1):19-25.

BACKGROUND: In vitro studies have shown that the neutrophil Fc gamma receptor IIA (FcgammaRIIA) polymorphism influences the phagocytic capacity of neutrophils and the removal of encapsulated bacteria from the bloodstream. In particular,

the R/R131 allotype is associated with less phagocytic activity. SUBJECTS AND METHODS: We performed a case-control study to determine the influence of the FcgammaRIIA polymorphism (R/R131, R/H131, H/H131) on the risk and outcome of

meningococcal disease. The polymorphisms were measured in 130 patients with microbiologically proven meningococcal disease diagnosed from 1987 to 1998 (cases) and 260 asymptomatic sex-matched blood donors (controls). Clinical manifestations and complications of meningococcal disease were recorded, and a prognostic score (based on age, hemorrhagic diathesis, neurologic signs, and the absence of preadmission antibiotic) therapy was calculated. RESULTS: The

distributions of FcgammaRIIA allotypes were similar in cases and controls. However, among patients with meningococcal infection, fulminant meningococcal disease (odds ratio [OR] = 3.9; 95% confidence interval [CI]: 1.0 to 16; P = 0.04) and meningococcemia without meningitis (OR = 3.0; 95% CI: 1.4 to 7.8; P = 0.004) were more common in those with the FcgammaRIIA-R/R131 allotype. Complications were also significantly more frequent in these patients. Of the 42 patients with the R/R131 allotype, 31 (74%) had an adverse prognostic score, compared with 7% (4 of 59) of those with the R/H131 allotype and 3% (1 of 29) of those with the H/H131 allotype (P <0.0001). CONCLUSION: The FcgammaRIIA-R/R131

allotype is associated with more severe forms of meningococcal disease.

4762.          Florakis D, Kontogeorgos G, Anapliotou M, Mazarakis N, Richter E, Bruck W, Piaditis G.  Isolated pituitary granuloma by atypical Mycobacterium in a nonimmunosuppressed woman. Clin Endocrinol (Oxf). 2002 Jan;56(1):123-6.


A 32-year-old woman presented with a 10-day history of fever (38.0 degrees C), headaches, nausea, vomiting and a 6-month history of diabetes insipidus and amenorrhoea. Two months previously she had undergone a surgical drilling of the right mastoid area because of mastoiditis. Endocrine investigation showed elevated serum prolactin levels, secondary adrenal and gonadal failure and a normal thyroid function. Cranial MRI scan revealed a contrast enhancing intrasellar mass (approximately 2 cm) of heterogeneous appearance with suprasellar extension and thickening of the pituitaary stalk. Lumbar puncture wa suggestive of aseptic meningitis. The Ziehl-Neelsen stain of cerebrospinal fluid (CSF) and the tuberculin skin test were both negative. The pituitary mass was removed with a transsphenoidal approach. Histological examination demonstrated destruction of the adenohypophysis by epithelioid granulomas with partial caseous necrosis and microabscess formation, suggestive of a mycobacterial infection. A polymerase chain reaction analysis performed on paraffin-embedded tissue was positive for mycobacterial DNA. According to the individual 16S sequence, it was identified as Mycobacterium malmoense, an atypical nontuberculous mycobacterium (NTM). In conclusion, this is the first case of an isolated pituitary granuloma caused by an NTM infection in a nonimmunosuppressed patient.


4763.          Gumbo T, Kadzirange G, Mielke J, Gangaidzo IT, Hakim JG.  Cryptococcus neoformans meningoencephalitis in African children with acquired immunodeficiency syndrome. Pediatr Infect Dis J. 2002 Jan;21(1):54-6.

BACKGROUND: The number of children with AIDS in Africa is high. Such children may be at risk for cryptococcal meningoencephalitis, but data are scarce regarding this disease in our population. METHODS: We examined records of HIV-infected children (< or =16 years) diagnosed with cryptococcal meningoencephalitis in Harare, Zimbabwe, between 1995 and 2000. To elucidate features unique to pediatric disease, the children were compared with adult patients with HIV-associated cryptococcal meningoencephalitis. RESULTS: Thirteen children presented to our institution with headache (85%), nuchal rigidity (69%), vomiting (46%), impaired mental status (38%), convulsions (38%) and focal neurologic signs (23%). The mean duration of symptoms before diagnosis was 9 days. Cerebrospinal fluid examination revealed normal white blood cell counts in

64%, protein value in 67% and glucose concentration in 57% of patients. Children were more likely than adults to have seizures (38% vs. 11%, P = 0.02) and normal cerebrospinal fluid protein (67% vs. 10%, P < 0.01). The in-hospital mortality was 43%. Convulsions (P = 0.05) and impaired mental status (P < 0.01) were associated with increased mortality CONCLUSIONS: Cryptococcal meningoencephalitis in African children presents acutely or subacutely, can have a fulminant picture and is consistent with progressive meningoencephalitis.

4764.          Hunziker L,  Klenerman P, Zinkernagel RM, Ehl S. Exhaustion of cytotoxic T cells during adoptive immunotherapy of virus carrier mice can be prevented by B cells or CD4+ T cells. Eur J Immunol. 2002 Feb;32(2):374-82.


Rapid disappearance of antiviral CTL after transfusion into persistently infected individuals is a serious limitation of adoptive immunotherapy protocols. In the mouse model of persistent infection with lymphocytic choriomeningitis virus (LCMV) naive or immune virus-specific donor CD8+ T cells are exhausted after transfusion into carrier recipients with similar kinetics. Here we show that cotransfusion of immune CD4+ T cells prevents exhaustion of immune CD8+ T cells. Interestingly, cotransfer of primed B cells also prevented CD8+ T cell exhaustion in carriers even in the absence of T helper cells. This effect required the presence of immune B cells as repetitive treatment with hyperimmune serum led to the generation of antibody escape mutants. A combination of primed CD4+ T cells and primed B cells enhanced antiviral effects and prevented exhaustion also of naive CD8+ T cells. One key factor for prevention of CD8+ T cell exhaustion was the antiviral effect of the cotransfused cells thus reducing the time that CD8+ T cells are confronted with a high systemic viral load. These findings have implications for improving adoptive immunotherapy for persistent human viral infections.

4765.          Ibsen LM.  Radiological case of the month. Intracranial hypertension and reduced cerebral blood flow in meningococcal meningitis. Arch Pediatr Adolesc Med. 2002 Mar;156(3):293-4.

  No Abstract

4766.          Jarva H, Janulczyk R, Hellwage J, Zipfel PF, Bjorck L, Meri S.  Streptococcus pneumoniae evades complement attack and opsonophagocytosis by expressing the pspC locus-encoded Hic protein that binds to short consensus repeats 8-11 of factor H. J Immunol. 2002 Feb 15;168(4):1886-94.


Streptococcus pneumoniae is an important cause of upper and lower respiratory tract infections, meningitis, peritonitis, bacterial arthritis, and sepsis. Here we have studied a novel immune evasion mechanism of serotype 3 pneumococci, which are particularly resistant to phagocytosis. On their surfaces the bacteria express the factor H-binding inhibitor of complement (Hic), a protein of the pneumococcal surface protein C family. Using radioligand binding, microtiter plate assays, surface plasmon resonance analysis, and recombinant constructs of factor H, we located the binding site of Hic to short consensus repeats (SCRs) 8-11 in the middle part of factor H. This represents a novel microbial interaction region on factor H. The only other ligand known so far for SCRs 8-11 of factor H is C-reactive protein (CRP), an acute phase protein that binds to the pneumococcal C-polysaccharide. The binding sites of Hic and CRP within the SCR8-11 region were different, however, because CRP did not inhibit the binding of Hic and required calcium for binding. Binding of factor H to Hic-expressing pneumococci promoted factor I-mediated cleavage of C3b and restricted phagocytosis of pneumococci. Thus, virulent pneumococci avoid complement attack and opsonophagocytosis by recruiting functionally active factor H with the Hic surface protein. Hic binds to a previously unrecognized microbial interaction site in the middle part of factor H.

4767.          Jones NS, Walker JL, Bassi S, Jones T, Punt J.  The intracranial complications of rhinosinusitis: can they be prevented? Laryngoscope. 2002 Jan;112(1):59-63.


OBJECTIVES/HYPOTHESIS: Reference textbooks on the intracranial complications of rhinosinusitis imply that many of the intracranial complications of rhinosinusitis can be prevented. We sought to examine whether or not this is true. STUDY DESIGN: A retrospective case series. METHODS: The study included 47 consecutive patients presenting with intracranial complications secondary to rhinosinusitis between 1992 to 1999 with a mean follow-up of 5 years and 1 month. RESULTS: The most common presenting symptoms of intracranial involvement were an altered mental state, headache, fever, seizure, vomiting, a unilateral weakness or hemiparesis, or a cranial nerve sign. These justify an urgent magnetic resonance imaging or computed tomography scan. The importance of imaging before a lumbar puncture cannot be overemphasized. Of particular note was the finding that 21 patients (45%) presented with a periorbital cellulites or frontal swelling. Therefore, it does not follow that because a collection of pus presents anteriorly it precludes any intracranial involvement. More than half of our patients (55%) had visited their primary care physician with an upper respiratory tract infection and had been treated appropriately. Once any central symptoms or signs developed, there was little evidence of any significant delay in referral to our unit. Only six patients had a history of nasal disease, three having had recent sinus surgery and three having had nasal polyps. Nine patients had significant long-term morbidity, seven patients had epilepsy, one patient had dysphasia, and one patient had right arm weakness. The single death in our series was associated with a cavernous sinus thrombosis. CONCLUSIONS: The report emphasizes the need for surgeons to be alert to the diagnosis, particularly in patients with a periorbital abscess or frontal swelling. Sinus surgery has a role in obtaining pus for culture, as well as draining the sinus if it is in continuity with an intracranial collection. Intracranial infections secondary to rhinosinusitis occur sporadically and, although it appears that this cannot be prevented, early recognition and treatment are essential to reduce any subsequent morbidity or mortality.


4768.          Kastenbauer S, Koedel U, Becker BF, Pfister HW. Oxidative stress in bacterial meningitis in humans. Neurology. 2002 Jan 22;58(2):186-91.

OBJECTIVE: To study reactive nitrogen species-mediated oxidative brain damage and antioxidant defenses in patients with acute bacterial meningitis. METHODS: Nitrotyrosine (a widely used marker for the formation of reactive nitrogen species, such as peroxynitrite) and the lipid peroxidation product 4-hydroxynonenal were detected by immunohistochemistry in brain specimens obtained at autopsy. CSF concentrations of nitrotyrosine were quantified by ELISA. CSF and serum concentrations of ascorbic acid, uric acid, and its oxidation product allantoin were determined by high-pressure liquid chromatography. RESULTS: Tyrosine nitration was strongly increased during meningitis. It was most evident in inflammatory cells and blood vessels in the subarachnoid space. The same cell types stained positive for the lipid peroxidation marker 4-hydroxynonenal, suggesting that reactive nitrogen species contribute to oxidative brain damage during meningitis. High CSF nitrotyrosine concentrations were associated with an unfavorable outcome according to the Glasgow Outcome Score. In the CSF, the increase of nitrotyrosine was accompanied by a depletion of the antioxidant ascorbic acid and an increased oxidation of the natural peroxynitrite scavenger uric acid to allantoin. CONCLUSION: These findings indicate that oxidative stress due to reactive nitrogen species and altered antioxidant defenses are involved in the pathophysiology of bacterial meningitis in humans.

4769.          Katial RK, Brandt BL, Moran EE, Marks S, Agnello V, Zollinger WD.  Immunogenicity and safety testing of a group B intranasal meningococcal native outer membrane vesicle vaccine. Infect Immun. 2002 Feb;70(2):702-7.


The presently licensed meningococcal vaccine is a tetravalent capsular polysaccharide vaccine that induces immunity to serogroups A, C, Y, and W-135 but not to group B, which causes nearly half of the meningitis cases in the United States. The purpose of this study was to evaluate the safety and immunogenicity of an intranasal native outer membrane vesicle (NOMV) vaccine prepared from a capsule negative strain of group B of Neisseria meningitidis. In this study all volunteers received the same dose of vaccine, but we evaluated two different immunization schedules and the oropharyngeal and intranasal routes of vaccine delivery, assessed nasal cytology for cellular infiltration, and measured antibody-secreting cells (enzyme-linked immunospot assay [ELISPOT]) as an early marker for systemic immune response. Additionally, both intranasal and serum vaccine-specific antibodies were measured as well as serum bactericidal activity. Four groups with a total of 42 subjects were immunized on days 0, 28, and 56. Group 3 received an additional dose on day 7. Group 2 subjects were immunized both intranasally and oropharyngeally. Group 4 received a different lot of vaccine. All groups received approximately 1,200 microg of vaccine per subject. Patients were evaluated for side effects. The vaccine was well tolerated without evidence of inflammation on nasal cytology. The group receiving the extra vaccine dose showed the maximum increase in bactericidal activity. Thirty of 42 subjects demonstrated an increase in meningococcus-specific intranasal immunoglobulin A (IgA) titers, while 23 of 42 demonstrated an increase in specific IgG titers. The group receiving vaccine intranasally and oropharyngeally showed the highest rise in intranasal titers for both IgA and IgG. Groups 1, 3, and 4 showed a significant increase in antibody-secreting cells on ELISPOT. Eighteen of 42 volunteers demonstrated a fourfold or greater rise in bactericidal titers, with 81% showing an increase over baseline. We have demonstrated the immunogenicity and safety of a group B lipopolysaccharide-containing, intranasal, NOMV vaccine.

4770.          Kihara T, Miyata M.  Brain abscess formed in the cavum septi pellucidi. J Neurol Neurosurg Psychiatry. 2002 Mar;72(3):411.

      No Abstract

4771.          Kleinschmidt-DeMasters BK.  Central nervous system aspergillosis: a 20-year retrospective series. Hum Pathol. 2002 Jan;33(1):116-24.

Over the past 20 years at my institution, 71 patients with invasive necrotizing aspergillosis have been encountered; 42 have shown central nervous system (CNS) involvement by autopsy (40) or surgical biopsy (2). Most non-CNS aspergillosis patients had invasive disease confined to the lung, and only 2 with dissemination to 3 or more organs did not have spread to the CNS. In addition to the expected post-transplantation and hematologic malignancy cases, other risk groups identified included those with chronic asthma and steroid use, acquired immunodeficiency syndrome, thermal burn, hepatic failure, and postoperative infection. Unusual cases manifested with basilar meningitis, myelitis, proptosis caused by sino-orbital disease, or epidural and subdural Aspergillus abscesses. The extent of gross neuropathologic disease ranged from subtle abscesses to massive hemorrhagic necrosis causing herniation and death. In addition to the expected hemorrhagic necrosis, extensive hemorrhage, focal purulent meningitis, and subtle bland infarctions were also seen. Distinctive microscopic findings encountered included 1 case with numerous meningeal granulomas and multinucleated giant cells and 4 cases showing the Splendore-Hoeppli phenomenon. During the same period, single cases of cerebritis caused by morphologically similar fungi (Pseudoallescheria boydii [Scedosporium apiospermum], Scedosporium inflatum, Chaetomium sp) were identified and were indistinguishable from CNS aspergillosis clinically and pathologically. Copyright 2002 by W.B. Saunders Company

4772.          Knausz M, Niederland T, Dosa E, Rozgonyi F. Meningo-encephalitis in a neonate caused by maternal Mycoplasma hominis treated successfully with chloramphenicol. J Med Microbiol  2002 Feb;51(2):187-8

  No Abstract

4773.          Kovoor JM, Mahadevan A, Narayan JP, Govindappa SS, Satishchandra P, Taly AV, Shankar SK.  Cryptococcal choroid plexitis as a mass lesion: MR imaging and histopathologic correlation. AJNR Am J Neuroradiol. 2002 Feb;23(2):273-6.

Cryptococcosis is a relatively common mycotic infection of the CNS caused by a ubiquitous saprophytic fungus. We present an unusual case of CNS cryptococcosis in an immunocompetent patient. Florid choroid plexitis resulted in the formation of intraventricular enhancing mass lesions that filled the ventricles and were hyperintense to associated periventricular edema on T2-weighted MR images. We also noted lesions corresponding to microcystic, dilated Virchow-Robin spaces in the basal ganglia that were characteristic of cryptococcal infection.


4774.        Larner AJ, Muqit MM, Glickman S. Concurrent syrinx and inflammatory central nervous system disease detected by magnetic resonance imaging: an illustrative case and review of the literature. Medicine (Baltimore)  2002 Jan;81(1):41-50


4775.          Mahapatra AK, Pawar SJ, Sharma RR.  Intracranial Salmonella infections: meningitis, subdural collections and brain abscess. A series of six surgically managed cases with follow-up results. Pediatr Neurosurg. 2002 Jan;36(1):8-13. Review.

Focal intracranial infections due to Salmonella are rare. So far, around 80 cases have been reported in the world literature. The authors present their experience of 6 cases of intracranial Salmonella infections, mainly subdural empyema in 5 and effusion in 1. In 1 case, subdural empyema was bilateral, and in another case, there was an associated brain abscess. Positive blood cultures and positive Widal tests were noticed in 2 patients each. Early diagnosis and prompt evacuation of subdural collections and brain abscess and antibiotic therapy lead to satisfactory results. This study suggests that a high index of suspicion, early diagnosis and quick evacuation lead to success; this point is highlighted with the help of a review of the literature. Copyright 2002 S. Karger AG, Basel


4776.          Memish ZA. Meningococcal disease and travel. Clin Infect Dis  2002 Jan 1;34(1):84-90.


Invasive meningococcal disease, in both endemic and epidemic forms, is the cause of significant morbidity and mortality worldwide. Despite all advances in therapy, the fatality rate of meningococcal meningitis remains unacceptably high, between 5% and 10%, and a similar proportion suffers long-term neurological sequalae. Prevention of this rapidly fatal disease is of paramount importance. The use of the available internationally licensed meningococcal vaccines would be indicated for individuals with medical conditions that increase the risk of the disease and for travelers to high-risk countries. In the last 2 years, there has been a shift in the epidemic pattern of meningococcal disease during the Hajj (pilgrimage) season, with predominance of Neisseria meningitidis serogroup W135. Recent changes have been made in the policy issued by the Saudi Ministry of Health (Riyadh, Saudi Arabia), which requires visitors from all over the world arriving for purposes of umra and Hajj to show evidence of vaccination against meningitis with the quadrivalent meningococcal vaccine.


4777.          Meqdam MM, Khalousi MM, Al-Shurman A.  Enteroviral meningitis in Northern Jordan: prevalence and association with clinical findings. J Med Virol. 2002 Feb;66(2):224-8.


During the summer-autumn of 1999, 390 specimens of cerebrospinal fluid were taken from infants and children younger than 15 years of age. They were suspected of having meningitis and were admitted to Princess Rahma Hospital, Northern Jordan. They were investigated for the presence of enteroviruses using shell vial culture and indirect immunofluorescence assays. Most cases (46.9%) occurred in children younger than 1 year of age in which males represented 71.9%. The common symptoms were fever, vomiting, and headache. Enteroviruses were isolated from 32 (8.2%) cases, coxsackievirus B types 2, 4, and 5 from 15 (46.9%) cases, and echovirus 9 (31.3%) was the most common identified serotype. The virus isolation rate was directly proportional to the number of leukocytes in the cerebrospinal fluid. However, enteroviral isolation was demonstrated in 4 (12.5%) of 32 cerebrospinal fluid specimens without pleocytosis. Leukocyte differential count revealed a predominance of polymorphonuclear cells in 71.4% of the cases. Hospitalization ranged from 1 day to 25 days with a mean of 7 days. The majority of enterovirus-infected patients (88.9%) were treated with at least one type of antibiotic. These results emphasize the importance of shell vial culture assay for diagnosing enteroviruses, especially in laboratories that do not have access to advanced techniques such as polymerase chain reaction.


4778.          Moellering Jr RC.  The continuing challenge of lower respiratory tract infections. Clin Infect Dis. 2002 Mar 1;34 Suppl 1:S1-3.

Lower respiratory tract infections have been a major cause of morbidity and mortality among humans since the dawn of history. The initial hope that the era of antibiotics would remove this scourge has been replaced by the more realistic view that although antimicrobial agents represent a major therapeutic advance, they have not yet solved all of the problems of lower respiratory tract infections. The pneumococcus, for example, causes mortality in a certain number of patients despite antimicrobial therapy. An even greater challenge is being imposed by the emergence of antimicrobial resistance among important bacterial pathogens, especially Streptococcus pneumoniae.


4779.          Moller K, Skinhoj P.  Guidelines for managing acute bacterial meningitis. Selections BMJ - South Asia Edn 2000, 16(6), 407.

No Abstract

4780.          Nau R, Bruck W.  Neuronal injury in bacterial meningitis: mechanisms and implications for therapy. Trends Neurosci. 2002 Jan;25(1):38-45. Review.

In bacterial meningitis, long-term neurological sequelae and death are caused jointly by several factors: (1) the systemic inflammatory response of the host, leading to leukocyte extravasation into the subarachnoid space, vasculitis, brain edema and secondary ischemia; (2) stimulation of resident microglia within the CNS by bacterial compounds; and (3) possible direct toxicity of bacterial compounds on neurons. Neuronal injury is mediated by the release of reactive oxygen intermediates, proteases, cytokines and excitatory amino acids, and is executed by the activation of transcription factors, caspases and other proteases. In experimental meningitis, dexamethasone as an adjunct to antibiotic treatment leads to an aggravation of neuronal damage in the hippocampal formation, suggesting that corticosteroids might not be the ideal adjunctive therapy. Several approaches that interfere selectively with the mechanisms of neuronal injury are effective in animal models, including the use of nonbacteriolytic protein synthesis-inhibiting antibiotics, antioxidants and inhibitors of transcription factors, matrix metalloproteinases, and caspases.


4781.          Nau R, Eiffert H.  Modulation of release of proinflammatory bacterial compounds by antibacterials: potential impact on course of inflammation and outcome in sepsis and meningitis. Clin Microbiol Rev. 2002 Jan;15(1):95-110. Review.


Several bacterial components (endotoxin, teichoic and lipoteichoic acids, peptidoglycan, DNA, and others) can induce or enhance inflammation and may be directly toxic for eukaryotic cells. Bactericidal antibiotics which inhibit bacterial protein synthesis release smaller quantities of proinflammatory/toxic bacterial compounds than B-lactams and other cell wall-active drugs. Among the B-lactams, compounds binding to penicillin-binding protein 2 (PBP-2) release smaller amounts of bacterial substances than antibacterials inhibiting PBP-3. Generally, high antibiotic concentrations (more than 10 times the MIC) induce the release of fewer bacterial proinflammatory/toxic compounds than concentrations close to the MIC. In several in vitro and in vivo systems, bacteria treated with protein synthesis inhibitors or B-lactams inhibiting PBP-2 induce less inflammation than bacteria treated with PBP-3-active B-lactams. In mouse models of Escherichia coli peritonitis sepsis and of Streptococcus pneumoniae meningitis, lower release of proinflammatory bacterial compounds was associated with reduced mortality. In conclusion, sufficient evidence for the validity of the concept of modulating the release of proinflammatory bacterial compounds by antibacterials has been accumulated in vitro and in animal experiments to justify clinical trials in sepsis and meningitis. A properly conducted study addressing the potential benefit of bacterial protein synthesis inhibitors versus B-lactam antibiotics will require both strict selection and inclusion of a large number of patients. The benefit of this approach should be greatest in patients with a high bacterial load.


4782.          Okten A, Ahmetoglu A, Dilber E, Dinc H, Kalyoncu M, Ciftcibais K, Yaris N. Cranial Doppler ultrasonography as a predictor of neurologic sequelae in infants with bacterial meningitis. Invest Radiol. 2002 Feb;37(2):86-90.


OBJECTIVE: To perform transcranial Doppler sonography in newborns and infants with bacterial meningitis to evaluate predictive value of neurologic sequelae. MATERIALS AND METHODS: Thirty-three patients (15 newborn, 18 infant patients) with bacterial meningitis underwent cranial Doppler ultrasonography during acute phase and 3rd and 6th months after disease. Patients were examined regularly for neurologic outcome with electroencephalography and magnetic resonance imaging. The age-matched control group consisted of 20 healthy children underwent cranial Doppler sonography only. RESULTS: To compare with the healthy controls, the mean blood flow velocity was significantly increased (P < 0.001), and pulsatility index was higher than those control group (P < 0.05) during acute bacterial meningitis. None of the patients were diagnosed with stenosis of cerebral artery. According to neurologic outcome, 14 of 33 patients had neurologic sequelae. The mean cerebral blood flow was significantly higher   (P < 0.01) in patients without neurologic sequelae; pulsatility index was significantly higher (P < 0.05) in patients with neurologic sequelae when compared with the healthy controls. There was no significant difference between mean cerebral blood flow velocities and mean pulsatility index values of newborn and infant patients, regarding to neurologic outcome (P < 0.05). CONCLUSION: Cranial Doppler ultrasonography is useful for prediction of neurologic sequelae in infants with bacterial meningitis.


4783.          Pashenkov M, Teleshova N, Kouwenhoven M, Smirnova T, Jin YP, Kostulas V, Huang YM, Pinegin B, Boiko A, Link H.  Recruitment of dendritic cells to the cerebrospinal fluid in bacterial neuroinfections. J Neuroimmunol. 2002 Jan;122(1-2):106-16.


Dendritic cells (DC) accumulate in the CNS during inflammation and may contribute to local immune responses. Two DC subsets present in human cerebrospinal fluid (CSF) are probably recruited from myeloid (CD11c(+)CD123(dim)) and plasmacytoid (CD11c(-)CD123(high)) blood DC. In bacterial meningitis and especially in Lyme meningoencephalitis, numbers of myeloid and plasmacytoid DC in CSF were increased, compared to non-inflammatory  neurological diseases, and correlated with chemotactic activity of CSF for immature monocyte-derived DC (moDC). Multiple DC chemoattractants, including macrophage inflammatory protein (MIP)-1beta, monocyte chemotactic protein (MCP)-1, MCP-3, RANTES and stromal cell-derived factor (SDF)-1alpha were elevated in CSF in these two neuroinfections. Chemotaxis of immature moDC induced by these CSFs could be partially inhibited by mAbs against CXCR4, the receptor for SDF-1alpha, and CD88, the receptor for C5a. SDF-1alpha present in CSF also chemoattracted mature moDC, which in vivo could correspond to a diminished migration of antigen-bearing DC from the CSF to secondary lymphoid organs. Regulation of DC trafficking to and from the CSF may represent a mechanism of controlling the CNS inflammation.


4784.          Rajs G, Finzi-Yeheskel Z, Rajs A, Mayer M.  C-reactive protein concentrations in cerebral spinal fluid in gram-positive and gram-negative bacterial meningitis. Clin Chem. 2002 Mar;48(3):591-2.

No Abstract

4785.          Reis JN, Cordeiro SM, Coppola SJ, Salgado K, Carvalho MG, Teixeira LM, Thompson TA, Facklam RR, Reis MG, Ko AI.  Population-based survey of antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae from meningitis patients in Salvador, Brazil. J Clin Microbiol. 2002 Jan;40(1):275-7.


Penicillin-nonsusceptible strains were isolated from 15% of 303 individuals with pneumococcal meningitis identified during a 4-year surveillance study in Salvador, Brazil. The estimated rate of coverage of the seven-valent conjugate vaccine was 74% among patients <5 years of age and 94% among those infected with nonsusceptible isolates, indicating that the use of conjugate vaccines may be an approach to the control of emerging penicillin resistance in Brazil.


4786.          Reuter D, Brownstein D.  Common emergent pediatric neurologic problems. Emerg Med Clin North Am. 2002 Feb;20(1):155-76. Review.


Although there are a variety of neurologic disease processes that the emergency physician should be aware of the most common of these include seizures, closed head injury, headache, and syncope. When one is evaluating a patient who has had a seizure, differentiating between febrile seizures, afebrile seizures, and SE helps to determine the extent of the work-up. Febrile seizures are typically benign, although a diagnosis of meningitis must not be missed. Educating parents regarding the likelihood of future seizures, and precautions to be taken should a subsequent seizure be witnessed, is important. The etiology of a first-time afebrile seizure varies with the patient's age at presentation, and this age-specific differential drives the diagnostic work-up. A follow-up EEG is often indicated, and imaging studies can appropriate on a nonurgent basis. Appropriate management of SE requires a paradigm of escalating pharmacologic therapy, and early consideration of transport for pediatric intensive care services if the seizure cannot be controlled with conventional three-tiered therapy. Closed head injury frequently is seen in the pediatric emergency care setting. The absence of specific clinical criteria to guide the need for imaging makes management of these children more difficult. A thorough history and physical examination is important to uncover risk factors that prompt emergent imaging. Headaches are best approached by assessing the temporal course, associated symptoms, and the presence of persistent neurologic signs. Most patients ultimately are diagnosed with either a tension or migraine headache;

however, in those patients with a chronic progressive headache course, an intracranial process must be addressed and pursued with appropriate imaging. Syncope has multiple causes but can generally be categorized as autonomic, cardiac, or noncardiac. Although vasovagal syncope is the most common cause of syncope, vigilance is required to identify those patients with a potentially fatal arrhythmia or with heart disease that predisposes to hypoperfusion. As such, all patients who present with syncope should have an ECG. Additional work-up studies are guided by the results of individual history and physical examination.


4787.          Saez-Llorens X, McCoig C, Feris JM, Vargas SL, Klugman KP, Hussey GD, Frenck RW, Falleiros-Carvalho LH, Arguedas AG, Bradley J, Arrieta AC, Wald ER, Pancorbo S, McCracken GH Jr.  Quinolone treatment for pediatric bacterial meningitis: a comparative study of trovafloxacin and ceftriaxone with or without vancomycin. Pediatr Infect Dis J. 2002 Jan;21(1):14-22.

BACKGROUND: Trovafloxacin is a new fluoroquinolone that exhibits good penetration into the central nervous system and excellent antimicrobial activity against common meningeal pathogens, including beta-lactam-resistant pneumococci. PURPOSE AND DESIGN: A multicenter, randomized clinical trial was conducted in children with bacterial meningitis to compare the safety and efficacy of trovafloxacin with that of ceftriaxone with or without vancomycin therapy. RESULTS: A total of 311 patients, ages 3 months to 12 years, were enrolled, of whom 203 were fully evaluable, 108 treated with trovafloxacin and 95 with the conventional regimen. Both groups were comparable with regard to baseline characteristics: age; cerebrospinal fluid findings; u


4788.        Shenoy S, Wilson G, Prashanth HV, Vidyalakshmi K, Dhanashree B, Bharath R.  Primary meningoencephalitis by Naegleria fowleri: first reported case from Mangalore, South India. J Clin Microbiol. 2002 Jan;40(1):309-10.


A fatal case of primary amebic meningoencephalitis (PAM) in a 5-month-old infant is described. The disease may have been contracted during bathing. The source of water was from an artificial well. The clinical presentation, the isolation of the ameba from the cerebrospinal fluid, the poor response to amphotericin B, and the ultimate fatal outcome are all consistent with the diagnosis of PAM. On the basis of its ability to grow at temperatures above 30 degrees C, the morphology of the trophozoite, and the presence of flagellate forms, the ameba was identified as Naegleria fowleri. Pathogenic N. fowleri amebae were recovered from samples of water from the well. To our knowledge this case represents the second case of PAM in an infant in the absence of the history of swimming.


4789.        Simon RP, Beckman JS.  Why pus is bad for the brain. Neurology. 2002 Jan 22;58(2):167-8.

No Abstract


4790.          Sudha K; Rao AV; Rao SN; Rao A. Oxidative stress and antioxidants in tubercular meningitis Indian Journal of Clinical Biochemistry 2002 Jan; 17(1): 34-41


ABSTRACT: Oxidative stress is implicated in etiopathogenesis of a variety of human diseases. Therefore, in the present study, erythrocyte lipid peroxidation, percentage hemolysis, antioxidant enzymes viz., glutathione reductase, glutathione peroxidase, superoxide dismutase and plasma antioxidants viz., ceruloplasmin, vitamins A,E and C have been determined in 19 patients with tubercular meningitis (TBM) and 50 normals. Six patients who were treated with antibiotics were considered for the follow up. The statistical analysis was carried out be Mann Whitney U test and Wilcoxon rank sum test. Lipid peroxidation (P<0.02), percentage hemolysis (P<0.001) and plasma ceruloplasmin (P<0.0001) of TBM patients were significantly higher, whereas erythrocyte glutathione reductase (P<0.05) and plasma antioxidant vitamins A,E and C (P<0.01, P<0.05 respectively) were significantly lower than those of the controls. In the follow up patients the glutathione reductase and catalase levels were significantly high (P<0.05) compared to their pre-treated condition. Vitamin C and E levels have attained normal range. This study indicated that the blood antioxidant status of TBM patients which was low compared to controls improved after treatment, suggesting the role of free radicals in TBM.


4791.          Tecle T, Mickiene A, Johansson B, Lindquist L, Orvell C.  Molecular characterisation of two mumps virus genotypes circulating during an epidemic in Lithuania from 1998 to 2000. Arch Virol. 2002;147(2):243-53.


An epidemic of mumps in Lithuania started in December 1998 and continued until May 2000. The total registered number of cases was about 11.000 of a total of 3,7 million inhabitants in Lithuania (29,7 cases/10,000). Virus-containing samples were collected from 80 patients treated at the hospital of Kaunas from October 1999 until the end of the epidemic. Out of the 80 patients with parotitis, meningitis was observed in 11 patients and orchitis in 22 of 69 male patients. Twenty-seven virus strains were genotyped by nucleotide sequencing of the small hydrophobic (SH) protein gene, and the 57 amino acid sequences of the gene were deduced. Twenty-five virus strains belonged to the C genotype and two were of the D genotype. By phylogenetic analysis the virus strains causing meningitis grouped in a separate cluster, designated C1, within the C genotype. Another group of ten of the 25 genotype C strains exhibited an amino acid triplet at amino acid positions 28 to 30 of the protein, consisting of valine, alanine and serine, instead of the previously recognised valine, valine and serine combination of genotype C. The amino acid alanine at position 29 was found in combination with the amino acid serine at position 48. This variant was designated C2 and it was associated with parotitis. The amino acid alanine at position 29 and serine in position 48 of the C2 genotype may constitute a marker of low neurovirulence compared to other genotype C strains.


4792.          Totan M, Kucukoduk S, Dagdemir A, Dilber C.  Meningitis due to Salmonella in preterm neonates. Turk J Pediatr. 2002 Jan-Mar;44(1):45-8.


Meningitis due to Salmonella is a rare condition. Here we report seven cases with neonatal Salmonella meningitis diagnosed and treated in the Pediatric Neonatology Unit of Ondokuz Mayis University Faculty of Medicine between January 1985-February 2001. Five cases were cured with appropriate treatment; in two of them no neurological sequelae were seen. Of the remaining three, reversible hydrocephalus occurred in two cases and subdural empyema was found in one. Two patients died on the 30th and 40th days of hospitalization: one of them had hydrocephalus and the other ventriculitis. In this report we point out the importance of neonatal meningitis due to Salmonella serotypes, though it rarely occurs.


4793.          Tsirpouchtsidis A, Hurwitz R, Brinkmann V, Meyer TF, Haas G.  Neisserial immunoglobulin A1 protease induces specific T-cell responses in humans. Infect Immun. 2002 Jan;70(1):335-44.


We have previously shown that immunoglobulin A1 (IgA1) protease, an exoenzyme of pathogenic neisseriae, can trigger the release of proinflammatory cytokines from human monocytic subpopulations. Here, we demonstrate a dose-dependent T-cell response to recombinant gonococcal IgA1 protease (strain MS11) in healthy human blood donors. This response was delayed in comparison to the immune response against tetanus toxoid. Stimulation with IgA1 protease led to the activation of CD4(+) and CD8(+) T cells, as well as CD19(+) B cells and CD56(+) NK cells, indicated by de novo expression of CD69. Only CD4(+) T cells proliferated and stained positive for intracellular gamma interferon (IFN-gamma). Both proliferation and IFN-gamma production were dependent on antigen presentation via major histocompatibility complex class II. Peripheral blood mononuclear cells stimulated with IgA1 protease produce IFN-gamma and tumor necrosis factor alpha but no, or very low amounts of, interleukin-10 (IL-10) or IL-4, indicating a Th1-based proinflammatory immune response. These findings support the significance of IgA1 protease as a virulence determinant of bacterial meningitis and its function as a dominant proinflammatory T-cell antigen.


4794.          Vaispapir V, Blum A, Soboh S, Ashkenazi H.  West Nile virus meningoencephalitis with optic neuritis. Arch Intern Med. 2002 Mar 11;162(5):606-7.

No Abstract


4795.          Williamson JC, Glazier SS, Peacock JE Jr.  Successful treatment of ventriculostomy-related meningitis caused by vancomycin-resistant Enterococcus with intravenous and intraventricular quinupristin/dalfopristin. Clin Neurol Neurosurg. 2002 Jan;104(1):54-6.


We report a case of ventriculostomy-related meningitis caused by vancomycin-resistant Enterococcus faecium (VRE). The patient was successfully treated with administration of quinupristin/dalfopristin by both intravenous and intraventricular routes. A brief review of the literature is provided, which indicates that optimal management with quinupristin/dalfopristin should include daily intraventricular doses of at least 2 mg.


Oct 2002


5551.          Bhojo AK, Akhter N, Bakshi R, Wasay M. Thoracic myelopathy complicating acute meningococcal meningitis: MRI findings. Am J Med Sci. 2002 May;323(5):263-5.


Spinal cord dysfunction is a rare complication of Neisseria meningitidis (meningococcal) meningitis. We report a 17-year-old patient who had a 3-day history of fever, headache and vomiting, agitation, and unresponsiveness. Cerebrospinal fluid showed a marked polymorphonuclear pleocytosis. Latex particle agglutination was positive for meningococci. The patient was given intravenous antibiotics and intravenous dexamethasone. Over the next 4 days, he developed weakness of the lower extremities, with areflexia and extensor plantar responses. MRI revealed contiguous hyperintensities on T2-weighted images involving the thoracic spinal cord from T4 to T9 and 4 brain abscesses. Five months later, he recovered brain function, but the paraparesis remained. This case illustrates that myelopathy may complicate acute meningococcal meningitis, possibly due to a vasculitis, stroke, autoimmune myelopathy, or direct infection of the spinal cord. Patients with myelopathy associated with acute meningitis should receive spinal MRI. In addition, meningitis should be considered in patients presenting with acute myelopathy.


5552.          Brandtzaeg P, van Deuren M. Current concepts in the role of the host response in Neisseria meningitidis septic shock. Curr Opin Infect Dis. 2002 Jun;15(3):247-52. Review.


Lipopolysaccharides in the outer membrane of Neisseria meningitidis are key molecules that induce inflammation and cause meningitis and shock. Mutant strains, with altered lipid A, the toxic moiety of lipopolysaccharide, or completely lacking lipopolysaccharide, induce significantly less inflammation than wild-type strains. Polymorphism of the Fc gamma receptors and interleukin-10 gene but not of the Toll-like receptor 4 may influence the development of meningococcal infection. Mannan-binding lectin is involved in complement activation, the regulation of adhesion molecules and cytokine production induced by meningococci. The activation of protein C by the thrombomodulin protein C receptor complex on the endothelial cell surface appears to be reduced in meningococcal sepsis but is still sufficient to convert protein C to activated protein C in patients treated with concentrated protein C.

5553.          Fellick JM, Thomson AP. Long-term outcomes of childhood meningitis. Hosp Med. 2002 May;63(5):274-7. Review.


Meningitis and meningococcal disease remain a major source of anxiety to paediatricians and parents alike. Survival rates have improved with rapid diagnosis and appropriate management. However, survivors remain at risk of long-term neurodevelopmental sequelae.

5554.          Kalita J, Mista UK. Effect of methyl prednisolone on sensory motor functions in tuberculous meningitis. Neurol India. 2001; 49(3), 267-71.
Prospective hospital based study was undertaken to study the effect of methyl prednisolone therapy on sensory and motor functions in tuberculosis meningitis (TBM). The patients with TB meningitis seen during 1994-1998 were studied. CT scan, motor evoked potentials (SEP) were carried out in all the patients. Outcome was defined at the end of 3 months into poor, partial or complete recovery on the basis of Barthel index score. Inj methyl prednisolone (MPS) 500 mg IV was given to 21 patients followed by oral tapering dose of prednisolone over one month in addition to 4 drug anti-tubercular treatment. The control group comprised of 16 patients who received 4 drugs anti-tubercular therapy without any corticosteroid. These groups were comparable with respect to their age, stage of meningitis, Glasgow coma scale score and radiological findings. In the control group, these were abnormal in 9 and 5 patients respectively. Three months after the therapy the frequency of improvement, deterioration and stationary evoked potential changes were also noted. Evoked potential changes were neither significantly different between the groups nor there was any beneficial effect shown in MPS group at 3 months.

5555.          Kastenbauer S, Winkler F, Pfister HW. Cranial CT before lumbar puncture in suspected meningitis. N Engl J Med. 2002 Apr 18;346(16):1248-51; discussion 1248-51.  No Abstract.

5556.          Kitoh A, Arima Y, Nishigori C, Kikuta K, Miyachi Y. Tissue adhesive and postoperative allergic meningitis. Lancet. 2002 May 11;359(9318):1668-70.


Adhesives containing cyanoacrylate are used in many surgical procedures, including closure of skin wounds and reinforcement of intracranial aneurysm repairs. A 61-year-old woman developed fever, neck stiffness, and cerebrospinal fluid eosinophilia after an operation for an intracranial aneurysm. We suspected allergic meningitis due to a foreign substance. To detect the cause of this disorder, we did 2-day closed patch testing with the substances thought to be possible allergens. We recorded a positive reaction to methyl-2-cyanoacrylate, the main ingredient of Biobond, the tissue adhesive used in the surgery. This substance could have caused postoperative allergic meningitis.

5557.          Leonard MK, Murrow JR, Jurado R, Gaynes R. Salmonella meningitis in adults infected with HIV: case report and review of the literature. Am J Med Sci. 2002 May;323(5):266-8. Review.

We report a case of Salmonella infantis meningitis in a patient infected with HIV who was successfully treated with 4 weeks of therapy and has had no relapses after 12 months of follow-up. Only 10 episodes of Salmonella species meningitis in patients infected with HIV are reported in the literature.

5558.          Meli DN, Christen S, Leib SL, Tauber MG. Current concepts in the pathogenesis of meningitis caused by Streptococcus pneumoniae. Curr Opin Infect Dis. 2002 Jun;15(3):253-7. Review.


In spite of improved antimicrobial therapy, bacterial meningitis still results in brain damage leading to significant long-term neurological sequelae in a substantial number of survivors, as confirmed by several recent studies. Meningitis caused by Streptococcus pneumoniae is associated with a particularly severe outcome. Experimental studies over the past few years have increased our understanding of the molecular mechanisms underlying the events that ultimately lead to brain damage during meningitis. Necrotic damage to the cerebral cortex is at least partly mediated by ischemia and oxygen radicals and therefore offers a promising target for adjunctive therapeutic intervention. Neuronal apoptosis in the hippocampus may represent the major pathological process responsible for cognitive impairment and learning disabilities in survivors. However, the mechanisms involved in causing this damage remain largely unknown. Anti-inflammatory treatment with corticosteroids aggravates hippocampal damage, thus underlining the potential shortcomings of current adjuvant strategies. In contrast, the combined inhibition of matrix metalloproteinase and tumour necrosis factor-alpha converting enzyme protected both the cortex and hippocampus in experimental meningitis, and may represent a promising new approach to adjunctive therapy. It is the hope that a more refined molecular understanding of the pathogenesis of brain damage during bacterial meningitis will lead to new adjunctive therapies.

5559.          Sahai SN, Mahadevan S, Srinivasan S, Kanungo R. Childhood bacterial meningitis in Pondicherry, South India. Indian J Paediat. 2001; 68(9), 839-41. Identifies causative bacteria from cerebrospinal fluid (CSF) of children with meningitis and analyse various clinical and laboratory parameters. Over a 20 months period, September 1994 to April 1996, one hundred episodes of acute bacterial meningitis in children aged 1 month-12 years were studied in a tertiary urban hospital in South India. Organisms were isolated from the cerebrospinal fluid (CSF) in 35% of cases. Among infants and children, the two major pathogens were H. Influenzae (17%) and S. pneumoniae (12%). The illness at presentation was mild in 13% and severe in 36% of cases. The association of subdural effusion in children with Salmonella Gp B meningitis merits attention. The overall case fatality rate was 25%. S. pneumonia had a higher case fatality rate than Salmonella Gp B and H. influenza (50% vs 17%vs 12%). All the three infants below 3 months of age with S. pneumonia meningitis died. On analysis of selected clinical and laboratory features by discriminant analysis, CSF culture was the significant (p=0.02) variable in relation to outcome. In relation to outcome. In pneumococcal meningitis. CSF WBC count was a highly significant variable in relation to outcome (Wilk’s Lambda 0.15, f=24.64, p=0.0002).

5560.          Seth R, Sharma U. Diagnostic criteria for Tuberculous Meningitis. Indian J Pediatr. 2002 Apr;69(4):299-303.OBJECTIVE: Tuberculous Meningitis is associated with a high morbidity and mortality if there is a delay in diagnosis. The diagnosis is based on clinical evaluation since the bacteriological diagnosis takes time and has a low yield. This study attempts to validate these criteria in children with TBM. METHODS: Forty-two children clinically suspected to have TBM were enrolled in the study. History, examination, CT scan and CSF findings were utilized to categorize patients into "definite", "highly probable", "probable" and "possible" TBM based on the criteria laid down by Ahuja et al. The validity of these criteria was tested against bacterial isolation and response to treatment. RESULTS: Thirty one children, with complete data, were included for analysis. Using "improvement on therapy as a criterion for definite TBM, we analyzed the sensitivity and specificity of the Ahuja criteria in diagnosing TBM. Using the criteria of "highly probable" TBM, the sensitivity was 65% with a specificity of 75%. When the criteria of "probable" TBM were used, the sensitivity increased to 96% while the specificity dropped to 38%. In an attempt to make these criteria more appropriate for children, we modified the criteria by including mantoux reaction, and family history of exposure in the criteria. The modified criteria gave a sensitivity of 83% and a specificity of 63%. DISCUSSION: A sensitivity of 65% (highly probable group) implies that 35% of TBM patients will be missed, while the probable criteria gave a 63% false positive rate suggesting that the trade-off for a higher sensitivity makes the criteria very unreliable. Our modification of the criteria gave us a reasonable sensitivity of 83% with a higher specificity of 63%. The false positive rate was also reduced to 38%. Thus the modified Ahuja criteria worked better for children with TBM. CONCLUSION: The modified Ahuja criteria are better applicable for use in pediatric patients with TBM . Since the number of patients was small in this study, the study needs to be validated with a larger sample size.

5561.          Singhi S, Singhi P, Paranwal AK. Baterial meningitis in children; critical care needs. Indian J Pediat. 2001; 68(8), 737-47. Abstract:  Acute bacterial meningitis (ABM) in children is associated with a high rate of acute complications and mortality, particularly in the developing countries. Most of the deaths occur during first 48 hrs of hospitalization. Coma, raised intracranial pressure  (ICP), siezures, shock have been identified as significant predictors of death and morbidity. Reviews issues in critical care with reference to our experience of managing 88 children with ABM in PICU. Attention should first be directed toward basic ABCs of life-support. Children with Glasgow Coma Scale (GSC) score <8 need intubation and supplemental oxygen. Antibiotics should be started, even without LP (contraindicated if focal neuro-deficit, papilledema, or signs of raised (ICP). Raised ICP is present in most of patients ; GCS <8 and high blood pressure are good guides. Mannitol (0.25 gm/Kg) should be used in such patients. If there are signs of (impending) heriation short-term hyperventilation is recommended; prolonged hyperventilation (>1 hour) must be avoided. Any evidence of poor perfusion, hypovolemia and/ or hypotension needs aggressive treatment with normal saline boluses and inotropes, if necessary, to maintain normal blood pressure. Empiric fluid restriction is not justified. Seizures may be controlled with intravenous diazepam or lorazepam.


5562.          Sukumaran SK, Prasadarao NV. Regulation of protein kinase C in Escherichia coli K1 invasion of human brain microvascular endothelial cells. J Biol Chem. 2002 Apr 5;277(14):12253-62.


Escherichia coli is one of the most important pathogens involved in the development of neonatal meningitis in many parts of the world. Traversal of E. coli across the blood-brain barrier is a crucial event in the pathogenesis of E. coli meningitis. Our previous studies have shown that outer membrane protein A (OmpA) expression is necessary in E. coli for a mechanism involving actin filaments in its passage through the endothelial cells. Focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K) have also been activated in host cells during the process of invasion. In an attempt to elucidate the mechanisms leading to actin filament condensation, we have focused our attention on protein kinase C (PKC), an enzyme central to many signaling events, including actin rearrangement. In the current study, specific PKC inhibitors, bisindolmaleimide and a PKC-inhibitory peptide, inhibited E. coli invasion of human brain microvascular endothelial cells (HBMEC) by more than 75% in a dose-dependent manner, indicating a significant role played by this enzyme in the invasion process. Our results further showed that OmpA+ E. coli induces significant activation of PKC in HBMEC as measured by the PepTag nonradioactive assay. In addition, we identified that the PKC isoform activated in E. coli invasion is a member of the conventional family of PKC, PKC-alpha, which requires calcium for activation. Immunocytochemical studies have indicated that the activated PKC-alpha is associated with actin condensation beneath the bacterial entry site. Overexpression of a dominant negative mutant of PKC-alpha in HBMEC abolished the E. coli invasion without significant changes in FAK phosphorylation or PI3K activity patterns. In contrast, in HBMEC overexpressing the mutant forms of either FAK or PI3K, E. coli-induced PKC activation was significantly blocked. Furthermore, our studies showed that activation of PKC-alpha induces the translocation of myristoylated alanine-rich protein kinase C substrate, an actin cross-linking protein and a substrate for PKC-alpha, from the membrane to cytosol. This is the first report of FAK- and PI3K-dependent PKC-alpha activation in bacterial invasion related to cytoskeletal reorganization.

5563.          Tattevin P, Bruneel F, Regnier B. Cranial CT before lumbar puncture in suspected meningitis. N Engl J Med. 2002 Apr 18;346(16):1248-51; discussion 1248-51. No Abstract.






5564.          Hostetler MA, Suara RO, Denison MR. Unilateral facial paralysis occurring in an infant with enteroviral otitis media and aseptic meningitis. J Emerg Med. 2002 Apr;22(3):267-71.


We report the case of a four month old infant presenting to the Emergency Department (ED) with irritability and facial asymmetry following a recent bout of gastroenteritis. Physical examination revealed a unilateral peripheral facial nerve paralysis. Common in older children and adults, facial nerve palsy has rarely been described in infancy. Although historically associated with a variety of inflammatory and infectious causes, the pathogenesis remains unclear. In this infant we were able to successfully identify an underlying acute enteroviral infection. Coxsackie B5 was isolated from the middle ear fluid, cerebrospinal fluid (CSF), nasopharyngeal and rectal swabs. After myringotomy drainage of the middle ear fluid and placement of pneumatic equalization tubes, there was rapid and complete resolution of facial paralysis.

5565.          Inder T, Mocatta T, Darlow B, Spencer C, Senthilmohan R, Winterbourn CC, Volpe JJ. Markers of oxidative injury in the cerebrospinal fluid of a premature infant with meningitis and periventricular leukomalacia. J Pediatr. 2002 May;140(5):617-21.


Free radicals have been hypothesized to play a key role in the evolution of periventricular leukomalacia, although direct evidence of oxidative injury in the human infant is lacking. This case report is the first to demonstrate a marked elevation in the levels of lipid and protein oxidative products in the cerebrospinal fluid during the evolution of periventricular leukomalacia in a premature infant with meningitis.


5566.          Kashyap AS, Kashyap S. Infliximab-induced aseptic meningitis. Lancet. 2002 Apr 6;359(9313):1252.  No Abstract.

5567.          Khan NA, Wang Y, Kim KJ, Chung JW, Wass CA, Kim KS. Cytotoxic necrotizing factor-1 contributes to Escherichia coli K1 invasion of the central nervous system. J Biol Chem. 2002 May 3;277(18):15607-12.


Escherichia coli K1 invasion of brain microvascular endothelial cells (BMECs) is a prerequisite for penetration into the central nervous system and requires actin cytoskeletal rearrangements. Here, we demonstrate that E. coli K1 invasion of BMECs requires RhoA activation. In addition, we show that cytotoxic necrotizing factor-1 (CNF1) contributes to E. coli K1 invasion of brain endothelial cells in vitro and traversal of the blood-brain barrier in the experimental hematogenous meningitis animal model. These in vitro and in vivo effects of CNF1 were dependent upon RhoA activation as shown by (a) decreased invasion and RhoA activation with the Delta cnf1 mutant of E. coli K1 and (b) restoration of invasion frequency of the Delta cnf1 mutant to the level of the parent E. coli K1 strain in BMECs with constitutively active RhoA. In addition, CNF1-enhanced E. coli invasion of brain endothelial cells and stress fiber formation were independent of focal adhesion kinase and phosphatidylinositol 3-kinase activation. This is the first demonstration that CNF1 contributes to E. coli K1 invasion of BMECs.


5568.          Palacios G, Casas I, Cisterna D, Trallero G, Tenorio A, Freire C. Molecular epidemiology of echovirus 30: temporal circulation and prevalence of single lineages. J Virol. 2002 May;76(10):4940-9.


Echovirus 30 (EV30) is one of the most frequently isolated EVs, causing extensive outbreaks of EV30 aseptic meningitis in temperate climates. EV30 is antigenically heterogeneous, and three major antigenic groups have been defined, although the basis for the antigenic differences is unknown. A reverse transcription-nested PCR which amplifies the 3'-terminal region of the VP1 gene directly from clinical samples was selected for studying EV30 molecular epidemiology, since the major antigenic sites in this region reflect the serotypic pattern of this virus. The different previous approaches to the genetic classification of EV30 were analyzed. A complete study of the EV30 strains was performed by analyzing the sequences from the 112 EV30 strains amplified in this work and the complete set of EV30 strains previously published. A total of 318 strains of EV30 were divided into two broad genotypes (I and II). This classification was supported by the phylogenetic trees obtained from amino acid sequences, and it correlated with the antigenic heterogeneity of the reference strains described in earlier studies. The genotypes could be further divided into subgroups, and these subgroups could be divided into lineages based on their nucleotide distances and levels of bootstrapping. On the other hand, the subgroups and lineages did not result in the same correlation between amino acid and nucleotide differentiation. The molecular epidemiology of EV30 can be compared to influenza virus epidemiology, where prevailing lineages displace the less established lineages on the basis of immune escape. This pattern of evolution is clearly different from that of other enteroviruses. A single lineage at a time appears to be circulating worldwide. This behavior may be related to the epidemic activity of EV30.


5569.          Pashenkov M, Soderstrom M, Huang YM, Link H. Cerebrospinal fluid affects phenotype and functions of myeloid dendritic cells. Clin Exp Immunol. 2002 May;128(2):379-87.


Myeloid (CD11c+) dendritic cells (DC) are present in cerebrospinal fluid (CSF), as well as in the meninges and choroid plexus. Functional studies of these DC are hindered or impossible. To obviate this problem, we investigated the effects of CSF supernatants from patients with non-inflammatory neurological diseases (NIND), multiple sclerosis (MS), bacterial meningitis (BM) and Lyme meningoencephalitis (LM) on immature monocyte-derived DC (moDC) from healthy donors. CSF supernatants caused maturation of moDC (MS > LM > NIND > BM), as reflected by a decrease in CD1a, and an increase in HLA-DR, CD80 and CD86 expression. The maturation effect of MS CSF and LM CSF could be blocked by anti-TNF-alpha MoAb or recombinant human IL-10. moDC cultured with BM CSF either remained immature or turned into CD14+ macrophage-like cells and were relatively inefficient at inducing T cell responses in vitro. In contrast, moDC cultured with LM CSF induced strong Th1 responses. Both BM CSF and LM CSF contained IFN-gamma, a cytokine that augments IL-12 production by moDC and hence should confer an ability to induce a Th1 response. However, BM CSF also contained high levels of IL-10, which could antagonize the effects of IFN-gamma on moDC. MoDC cultured with MS CSF induced a higher production of IFN-gamma from T cells compared to moDC cultured with NIND CSF or BM CSF. In summary, soluble factors present in the CSF may influence the phenotype and functions of meningeal, choroid plexus and CSF DC which, in turn, may have an impact on the character of intrathecal T cell responses.

5570.          Sharma A, Kaur R, Ganguly NK, Singh PD, Chakraborti A. Subtype distribution of Haemophilus influenzae isolates from north India. J Med Microbiol. 2002 May;51(5):399-404.


A total of 120 Haemophilus influenzae isolates from blood, cerebrospinal fluid, sputum and throat swabs of patients and carriers in North India was characterised by biotyping, ribotyping and random amplification of polymorphic DNA (RAPD)-PCR. Of these, 77 isolates (64%) were serotype b; the other 43 (36%) were non-typable. Biotype I was the most predominant among the typable strains and biotype II among the non-typable strains. Ribotyping with restriction endonucleases HaeIII and EcoRI differentiated the isolates into three and six ribotypes, respectively. However, RAPD fingerprints generated by the application of arbitrary primers AP1 and AP2 provided a higher level of discrimination. RAPD typing revealed distinct polymorphism among the serologically typable isolates. This study is the first report that stratifies the subtypes of H. influenzae strains from India by molecular techniques.


5571.          Comanducci M, Bambini S, Brunelli B, Adu-Bobie J, Arico B, Capecchi B, Giuliani MM, Masignani V, Santini L, Savino S, Granoff DM, Caugant DA, Pizza M, Rappuoli R, Mora M.  NadA, a novel vaccine candidate of Neisseria meningitidis. J Exp Med. 2002 Jun 3;195(11):1445-54.


Neisseria meningitidis is a human pathogen, which, in spite of antibiotic therapy, is still a major cause of mortality due to sepsis and meningitis. Here we describe NadA, a novel surface antigen of N. meningitidis that is present in 52 out of 53 strains of hypervirulent lineages electrophoretic types (ET) ET37, ET5, and cluster A4. The gene is absent in the hypervirulent lineage III, in N. gonorrhoeae and in the commensal species N. lactamica and N. cinerea. The guanine/cytosine content, lower than the chromosome, suggests acquisition by horizontal gene transfer and subsequent limited evolution to generate three well-conserved alleles. NadA has a predicted molecular structure strikingly similar to a novel class of adhesins (YadA and UspA2), forms high molecular weight oligomers, and binds to epithelial cells in vitro supporting the hypothesis that NadA is important for host cell interaction. NadA induces strong bactericidal antibodies and is protective in the infant rat model suggesting that this protein may represent a novel antigen for a vaccine able to control meningococcal disease caused by three hypervirulent lineages.


5572.          Jodar L, Feavers IM, Salisbury D, Granoff DM. Development of vaccines against meningococcal disease. Lancet. 2002 Apr 27;359(9316):1499-508. Review.


Neisseria meningitidis is a major cause of bacterial meningitis and sepsis. Polysaccharide-protein conjugate vaccines for prevention of group C disease have been licensed in Europe. Such vaccines for prevention of disease caused by groups A (which is associated with the greatest disease burden worldwide), Y, and W135 are being developed. However, conventional approaches to develop a vaccine for group B strains, which are responsible for most cases in Europe and the USA, have been largely unsuccessful. Capsular polysaccharide-based vaccines can elicit autoantibodies to host polysialic acid, whereas the ability of most non-capsular antigens to elicit broad-based immunity is limited by their antigenic diversity. Many new membrane proteins have been discovered during analyses of genomic sequencing data. These antigens are highly conserved and, in mice, elicit serum bactericidal antibodies, which are the serological hallmark of protective immunity in man. Therefore, there are many promising new vaccine candidates, and improved prospects for development of a broadly protective vaccine for group B disease, and for control of all meningococcal disease.


5573.          Liliang PC, Liang CL, Chang WN, Lu K, Lu CH. Use of ventriculoperitoneal shunts to treat uncontrollable intracranial hypertension in patients who have cryptococcal meningitis without hydrocephalus. Clin Infect Dis. 2002 Jun 15;34(12):E64-8.


Between 1997 and 2000, 4 human immunodeficiency virus-negative patients in our institution had cryptococcal meningitis with uncontrollable intracranial hypertension. All 4 patients were treated with antifungal drugs as well as ventriculoperitoneal (VP) shunts for intracranial hypertension. Neurological deficits that were unresponsive to pharmacologic treatment were resolved by use of the VP shunt. Uncontrollable elevation of intracranial pressure associated with cryptococcal meningitis can be resolved by use of a VP shunt, even when imaging studies do not reveal hydrocephalus.


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