Tuberculosis meningitis (TBM) is the most severe form of extra-pulmonary tuberculosis and is particularly intense in small children; there is no universally accepted algorithm for the diagnosis and substantiation of TB infection, which can lead to delayed intervention, a high risk factor for morbidity and mortality. In this study a proton magnetic resonance (1H NMR)-based metabolomics analysis and several chemometric methods were applied to data generated from lumber cerebrospinal fluid (CSF) samples from three experimental groups: (1) South African infants and children with confirmed TBM, (2) non-meningitis South African infants and children as controls, and (3) neurological controls from the Netherlands. A total of 16 NMR-derived CSF metabolites were identified, which clearly differentiated between the controls and TBM cases under investigation. The defining metabolites were the combination of perturbed glucose and highly elevated lactate, common to some other neurological disorders. The remaining 14 metabolites of the host's response to TBM were likewise mainly energy-associated indicators. We subsequently generated a hypothesis expressed as an "astrocyte-microglia lactate shuttle" (AMLS) based on the host's response, which emerged from the NMR-metabolomics information. Activation of microglia, as implied by the AMLS hypothesis, does not, however, present a uniform process and involves intricate interactions and feedback loops between the microglia, astrocytes and neurons that hamper attempts to construct basic and linear cascades of cause and effect; TBM involves a complex integration of the responses from the various cell types present within the CNS, with microglia and the astrocytes as main players.

BACKGROUND

Coagulation disorders remain barriers to successful pig-to-primate organ xenotransplantation. In vitro, we investigated the impact of pig genetic modifications on human platelet aggregation in response to pig aortic endothelial cells (pAEC).

METHODS

In comparison to human (h)AEC and wild-type (WT) pAEC, the expression of human complement- (CD46, CD55) or coagulation (thrombomodulin [TBM], endothelial protein C receptor [EPCR]) -regulatory proteins on pAEC from WT or α1,3-galactosyltransferase gene-knockout (GTKO) pigs was studied by flow cytometry. Using platelet-aggregometry, human whole blood platelet aggregation was evaluated after co-incubation with various AEC. Further, the inhibitory effect on aggregation of heparin, low molecular weight heparin, and hirudin was assessed.

RESULTS

Heparin, low molecular weight heparin and hirudin almost completely prevented platelet aggregation induced by WT pAEC. The level of expression of human CD46, CD55, TBM and EPCR on pAEC was comparable to that on hAEC. Platelet aggregation induced by all genetically modified pAEC was significantly less (P < 0.05) than that by WT pAEC (which was 54%). GTKO/CD46/TBM pAEC induced the least platelet aggregation (27%)-a reduction of almost 50%-but this remained significantly greater (P < 0.01) than aggregation induced by hAEC (4%). There was significant positive correlation between reduction of aggregation and TBM or EPCR expression on pAEC (r = 0.89 and r = 0.86, respectively; P < 0.05). Platelet aggregation induced by GTKO/CD46/TBM pAEC in the presence of hirudin (1 IU/ml) was comparable to platelet aggregation induced by hAEC.

CONCLUSIONS

Genetic modification of pAEC is associated with significant reduction of human platelet aggregation in vitro. With concomitant thrombin inhibition, platelet aggregation was comparable to that stimulated by hAEC.

Tuberculous meningitis (TBM), the most severe form of Mycobacterium tuberculosis infection in humans, is associated with significant morbidity and mortality despite successful treatment with antituberculous drugs. This is due to the irreversible brain damage subsequent to the local inflammatory response of the host to M. tuberculosis. Corticosteroids have been used in conjunction with antituberculous therapy in an attempt to modulate the inflammatory response, but this strategy has been of limited success. Therefore, we examined whether combining antituberculous drugs with the immunomodulatory drug thalidomide or with a new thalidomide analog, immunomodulatory drug 3 (IMiD3), would be effective in reducing morbidity and mortality in an experimental rabbit model of TBM. Intracisternal inoculation of 5 x 10(4) CFU of Mycobacterium bovis Ravenel in rabbits induced progressive subacute meningitis characterized by high cerebrospinal fluid (CSF) leukocytosis, protein influx, release of tumor necrosis factor (TNF), substantial meningeal inflammation, and mortality by day 28. Treatment with antituberculous drugs or with antituberculous drugs plus thalidomide improved the clinical course of disease somewhat and increased survival to about 50%. In contrast, treatment with antituberculous drugs in combination with IMiD3 limited pathological neurologic changes and resulted in marked improvement (73%) in survival. IMiD3 treatment was also associated with reduced leukocytosis in the CSF and significantly lower levels of TNF in CSF and plasma. Histologically, the meningeal inflammation in animals treated with antituberculous drugs plus IMiD3 was considerably attenuated compared to that of the other treatment groups. These results suggest a potential role for IMiD3 in the management of TBM in patients.

The pathophysiology underlying tuberculous meningitis (TBM), the most prominent extra pulmonary tuberculosis and a serious public health problem in developing countries is still unclear. Whereas, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are cytokines involved in cell-mediated immune response. TNF-alpha and IFN-gamma production has earlier been shown to be associated with tissue necrosis. To see whether these cytokines have any role to play in the pathophysiology of TBM, we measured the levels of serum and cerebrospinal fluid (CSF) TNF-alpha and IFN-gamma in 31 consecutive patients of TBM by ELISA. There was a remarkable rise (P<0.001) in the levels of serum and CSF TNF-alpha and IFN-gamma levels in TBM patients with respect to 20 age and sex-matched control subjects. Furthermore, TNF-alpha and IFN-gamma levels showed a positive correlation with the severity of the disease at the end of 6 months of antibiotic therapy. Elevated TNF-alpha and IFN-gamma levels, especially in CSF, despite of these patients undergoing multidrug therapy suggests the persistence of central nervous system inflammation. We also found an associated rise (P<0.001) in the nitric oxide (NO) levels of serum and CSF but there was no correlation between NO levels and the severity of TBM. The continuous release of cytokines despite these patients undergoing anti-tubercular therapy suggests that TBM severity may result mainly from the immune response rather than the organism itself.

The present study investigated the pattern of longitudinal changes in cognition and anatomy in three variants of primary progressive aphasia (PPA). Eight patients with the non-fluent variant of PPA (nfvPPA), 13 patients with the semantic variant (svPPA), seven patients with the logopenic variant (lvPPA), and 29 age-matched, neurologically healthy controls were included in the study. All participants underwent longitudinal MRI, neuropsychological and language testing at baseline and at a 1-year follow-up. Tenser-based morphometry (TBM) was applied to T1-weighted MRI images in order to map the progression of gray and white matter atrophy over a 1-year period. Results showed that each patient group was characterized by a specific pattern of cognitive and anatomical changes. Specifically, nfvPPA patients showed gray matter atrophy progression in the left frontal and subcortical areas as well as a decline in motor speech and executive functions; svPPA patients presented atrophy progression in the medial and lateral temporal lobe and decline in semantic memory abilities; and lvPPA patients showed atrophy progression in lateral/posterior temporal and medial parietal regions with a decline in memory, sentence repetition and calculations. In addition, in all three variants, the white matter fibers underlying the abovementioned cortical areas underwent significant volume contraction over a 1-year period. Overall, these results indicate that the three PPA variants present distinct patterns of neuroanatomical contraction, which reflect their clinical and cognitive progression.

BACKGROUND

Hydrocephalus can be classified as purely obstructive, purely communicating or due to combinations of pathologies (obstruction in addition to defective absorption). Endoscopic third ventriculostomy (ETV) as an alternative to shunt procedures is an established treatment for obstructive hydrocephalus. However, patients who have combination of pathologies (complex hydrocephalus) could result in failure of ETV in spite of a patent stoma. The aim of this study was to prospectively evaluate the incidence of complex hydrocephalus in patients with obstructive hydrocephalus who failed an endoscopic third ventriculostomy.

RESULTS

Seventy one patients of obstructive hydrocephalus who underwent ETV in our institution were included in this study. Aetiology of hydrocephalus included congenital aqueductal stenosis in 42 and tubercular meningitis (TBM) in 29 patients. Failure of ETV was seen in 15 (21%) patients. These 15 patients included 6 (14.3%) from the congenital group and 9 (31.0%) patients from the TBM group. Iohexol CT ventriculography confirmed a patent stoma (suggesting a complex hydrocephalus) in 10 (66.7%) out of the 15 failed ETV cases. The incidence of complex hydrocephalus was more common in TBM group (8/29 patients, 27.60%) compared to congenital group (2/42 patients, 4.8%). The complex hydrocephalus patients with a patent ETV stoma were successfully managed by a lumbar peritoneal (LP) shunt.

CONCLUSIONS

Ten out of the 71 patients (14%) with obstructive hydrocephalus who underwent an ETV had a complex hydrocephalus, which was the major (66.7%) cause for failure of ETV. Improving methods to detect the exact type of hydrocephalus pre-operatively could increase success rate of ETV and avoid an unnecessary operative procedure (ETV).

BACKGROUND

There are no widely accepted objective criteria to determine the presence of basal enhancement on CT in children with suspected tuberculous meningitis (TBM).

OBJECTIVE

To test nine recently described objective CT criteria for the presence of abnormal basal enhancement in children with suspected TBM against the definite diagnosis as determined by cerebrospinal fluid (CSF) culture.

METHODS

CT scans of patients with a clinical suspicion of TBM who had undergone lumbar puncture for CSF culture spanning a period of 4 years were reviewed for the presence of nine recently described criteria for the presence of abnormal basal enhancement. The radiologists were blinded to the final diagnosis based on CSF culture against which the criteria were tested. The criteria have been named: the 'Y-sign', 'linear enhancement', 'double lines', 'infundibular recess of the third', 'ill-defined edge', 'nodular enhancement', 'join the dots', 'contrast filling the cisterns', and 'asymmetry'.

RESULTS

A total of 65 patients were included in the study, 34 with culture-proven TBM and 31 with other diagnoses. Four individual criteria had a specificity of 100%, but the sensitivities of these criteria ranged from 15% to 53% only. Three other criteria had specificities of 97% and sensitivities ranging from 62% to 82%. The presence of more than one criterion in the same patient showed a specificity of 97% and sensitivity of 91%.

CONCLUSIONS

Very high specificity was demonstrated for all nine criteria, including 100% specificity for four individual criteria. Sensitivity was at best 82%, but improved to 91% when more than one criterion was present. These criteria need to be tested for inter- and intraobserver variability to prove their clinical usefulness.

Antiidiotypic immunity can successfully inhibit the development of antitubular basement membrane (alpha TBM) disease that produces interstitial nephritis. Rats normally immunized to produce disease, however, do not develop this regulatory and protective antiidiotypic effect. The failure to see such a regulatory response is functionally related to the influence of a nonspecific, RT7.1+, OX8-suppressor T cell that appears shortly after immunization. While this suppressor cell system can partially reduce the intensity of disease, it also limits the host's ability to specifically regulate the alpha TBM immune response and, hypothetically, leaves the disease process in an operationally active mode.

Using the model of renal disease induced in guinea pigs by immunization with bovine TBM preparations in adjuvant, the following observations were made. Animals with activity induced disease show bright staining for IgG along the TBM and only faint, inconstant staining along the GBM. Following transfer of serum animals with anti-TBM disease to normal recipients, accumulation of IgG was found predominantly in glomeruli at 4 hours, but at Days 3 and 5, IgG was seen predominantly along the TBM. There was no appreciable accumulation of neutrophils in the kidneys of recipients of anti-TBM serum, even at early intervals (4 and 24 hours) after transfer. However, within 2 days, small numbers of mononuclear cells were found. By Day 3, mononuclear cells were numerous, and multinucleate giant cells and tubular cell damage were present. After that, the lesions increased in severity and by 10 days were indistinguishable from those found in actively immunized animals at 14 to 21 days. Study of frozen section of kidneys obtained from animals with active disease at 14 days, employing sheep cells coated with rabbit antibody (IgG EA) revealed rosettes around many of the mononuclear cells in the infiltrate, indicating that they are mononuclear phagocytes (monocytes or macrophages). IgM complexed with sheep cells and complement (EAC) did not react and thus failed to provide evidence for the presence of B lymphocytes. Transfer of 7 X 10(8) lymph node cells from the TBM-immunized Strain 13 donors to normal Strain 13 recipients failed to result in renal lesions. The findings are interpreted as indicating that anti-TBM antibodies mediate the renal disease without the participation of cell-mediated immunity and further that these antibodies bring about an influx of ciculating mononuclear cells, predominantly monocytes, without attracting appreciable numbers of neutrophils.

The purpose of this study was to compare bone reconstruction using either mesenchymal stem cells (MSCs) or total bone marrow (TBM) in association with biphasic calcium phosphate (BCP) granules after irradiation in a rat model. Three weeks after an external irradiation of the hind limbs of rats, four bone defects were created per animal. The defects were filled with either BCP alone, or with a mixture of BCP and TBM, or with a mixture of BCP and MSCs (adipose-derived or bone marrow-derived MSCs). Three weeks after implantations, new-bone formation was assessed. Histological examination showed osteoconductive and osteointegrative properties of BCP in irradiated tissue. The BCP-TBM mixture significantly improved bone ingrowth (p<0.05). The BCP-MSCs mixtures did not provide new-bone formation over and above that induced by BCP alone. This gives grounds for suspecting that there is a link between this result and the cellular and vascular weakness observed in irradiated bone. The BCP-TBM mixture may have induced an increased vascularization of irradiated bone. This could be due to the presence of all components in TBM that were lacking in the BCP-MSCs mixtures. BCP associated with TBM appears to be the most efficient material for bone substitution in irradiated areas.

Inbred strains of rats differ widely in their susceptibility to interstitial nephritis induced by rabbit renal tubular basement membrane (TBM) preparations. We now report that susceptibility is determined in part by an RT1-linked gene for effector cell responsiveness producing interstitial lesions. Furthermore, we also obtained evidence that the gene determining expression of the target TBM antigen is linked to the gene for albinism on the first linkage group. When non-susceptible rats lacking the TBM antigen but having the gene for cellular responsiveness were mated with non-susceptible rats which had the TBM antigen but lacked the gene for cellular responsiveness, the F1 hybrids were susceptible to the induction of interstitial nephritis. Although strains varied widely in the amount of anti-TBM antibody (alpha TBM-Ab) they produced, this variation does not appear to be controlled by RT1-linked genes, nor does the isotype or amount of antibody appear to be related to the susceptibility to infiltrating cellular lesions.

BACKGROUND

Tuberculous meningitis (TBM) is the most frequent manifestation of central nervous system tuberculosis (TB) and is more common in children than in adults. The diagnosis of TBM in children is difficult because signs and symptoms are vague. Information about drug resistant TB in children is scarce, and there is no published information on drug resistant TBM in children.

METHODS

This is a retrospective review of medical records of children with culture-confirmed multidrug-resistant tuberculous meningitis (MDR-TBM) at King George V Hospital in Durban, South Africa.

RESULTS

Between 1992 and 2003, there were 8 children with MDR-TBM; 6 were HIV infected and 2 were HIV negative. Only one child survived. The diagnosis was made posthumously in almost all the children.

CONCLUSIONS

The changes in the cerebrospinal fluid (CSF) in early TBM can be nonspecific and can change rapidly; therefore, CSF studies should always include culture and susceptibility testing. Factors that contributed to the high mortality were disseminated TB, HIV infection, delay in diagnosis and treatment, the absence of a standardized approach to the management of MDR-TBM and the poor CSF penetration of most MDR-TB drugs. MDR-TB therapy should be considered if there is a history of TB: a MDR-TB contact or a poor clinical response to TB therapy despite adequate adherence to treatment. Early diagnosis is important because TBM in children is often associated with a grave outcome.

Cerebrospinal fluid (CSF) and peripheral blood (PBL) were sampled multiple times from 25 patients with a clinical diagnosis of tuberculous meningitis (TBM) and 49 controls, including 27 patients with other infectious diseases of the central nervous system and 22 patients with other noninfectious neurological diseases. We used an enzyme-linked immunospot assay (ELISPOT) to detect anti-Mycobacterium bovis BCG antibody-secreting cells in CSF and PBL, PCR to detect a repeated insertion sequence (IS6110) specific for Mycobacterium tuberculosis in CSF, and an enzyme-linked immunosorbent assay (ELISA) to detect anti-BCG antibodies in CSF and PBL. In the meantime, culture of CSF from every TBM and control patient was done on Lowenstein-Jensen medium. ELISPOT proved to be the most valuable test, with a sensitivity of 84.0% and a specificity of 91.8%, and showed a sensitivity of 100.0% with the CSF specimens obtained within 4 weeks after the onset of TBM. The numbers of CSF anti-BCG immunoglobulin-secreting cells tested by ELISPOT were even higher in the early phase of TBM and declined while the disease was going on (P = 0.008), which allowed an early diagnosis to be made. The sensitivities of PCR and ELISA were only 75.0% and 52.3%, respectively; and the specificities were 93.7% and 91.6%, respectively. Culture of CSF on Lowenstein-Jensen medium was the least sensitive (16%) compared to the sensitivities of the other three assays. Our results demonstrate that the ELISPOT technique is worthy for routine use in the laboratory to support the clinical diagnosis of TBM.

BACKGROUND

Isolation of Mycobacterium tuberculosis in cerebrospinal fluid (CSF) specimen in patients with tuberculous meningitis (TBM) is infrequent and carries low sensitivity. Thus development of an alternative laboratory diagnostic test is essential for the early diagnosis and treatment of TBM.

OBJECTIVE

A simple, rapid Dot immunobinding assay (Dot-Iba), for the laboratory diagnosis of TBM is devised. This method minimizes the risk of handling infectious material in the laboratory.

METHODS

The Dot-Iba was standardized with heat-inactivated M tuberculosis antigen (PPD). The heat-inactivated CSF from TBM and non-TBM patients was similarly assayed and it can detect antigen upto 1ng/ml in CSF.

RESULTS

A positive result was obtained in all the five culture positive patients with TBM and in 20/25 probable TBM. A negative result was obtained in 38/40 CSF from disease control group. The overall sensitivity and specificity of Dot-Iba was 83.3% and 95% respectively.

CONCLUSIONS

Dot-Iba can be used as an adjunct for the laboratory diagnosis of TBM, particularly in culture negative TBM patients and also in those clinical situations where no laboratory tests are available to distinguish between TBM and partially treated pyogenic meningitis.

OBJECTIVE

A simple and rapid immunological assay method has been developed to demonstrate the presence of IgG antibodies to 30Kd protein antigen (30Kdpa) and culture filtrate protein (CFP) in the CSF of patients with Tuberculous meningitis (TBM).

METHODS

Antibody capturing Enzyme Linked Immunosorbent Assay (ELISA) was standardized with CFP antigen of MTB. The IgG antibodies were assayed in CSF sample from TBM and non-TBM patients against 30 Kdpa.

RESULTS

The sensitivity and specificity of IgG antibodies for the diagnosis of suspected patients of TBM using 30 Kdpa was 80% and 91% respectively and the corresponding figures for CFP were 85% and 94% respectively. The sensitivity and specificity in two confirmed cases of TBM was 100%.

CONCLUSIONS

The presence of this 30Kdpa in the CSF of suspected cases of TBM consistently would indicate that the selected protein band carries the candidate protein marker antigen, which is specific to M. tuberculosis and could be considered as a diagnostic marker for TBM.

The clinical course and serial cranial computerized tomographic (CT) findings of 202 children with tuberculous meningitis (TBM) admitted to Tygerberg Hospital between 1985 and 1994 were reviewed with regard to the incidence, CT appearance and clinical course of associated intracranial tuberculous granulomas. Thirty-four patients (16.85 per cent) had associated intracranial granulomas. Thirty-eight individual lesions were analysed and classified as meningeal, parenchymal or ependymal according to their central nervous system (CNS) location. Twenty-five patients had round to irregular, brain iso-, hypo- or hyperdense meningeal granulomas with variable degrees of enhancement and peri-lesional hypodensities. Four patients had diffusely enhancing, brain isodense, enplaque-like ependymal granulomas associated with the ventricular ependymal lining. Four patients with miliary tuberculosis and TBM showed multiple small diffusely enhancing, brain iso- or hyperdense parenchymal lesions and associated hypodensities on initial CT. Although granulomas in the meningeal and ependymal group had the propensity to paradoxically enlarge or appear on standard four-drug antituberculosis therapy, the majority resolved uneventfully. Rapid resolution of small parenchymal granulomas associated with miliary tuberculosis occurred in all cases. Most granulomas in this series were co-incidental, asymptomatic CT findings. In rare cases, the development or enlargement of a strategically located granuloma may result in complications.

Central nervous system (CNS) tuberculosis, particularly tuberculous meningitis (TBM), is the severest form of Mycobacterium tuberculosis (M.Tb) infection, causing death or severe neurological defects in more than half of those affected, in spite of recent advancements in available anti-tuberculosis treatment. The definitive diagnosis of CNS tuberculosis depends upon the detection of M.Tb bacilli in the cerebrospinal fluid (CSF). At present, the diagnosis of CNS tuberculosis remains a complex issue because the most widely used conventional "gold standard" based on bacteriological detection methods, such as direct smear and culture identification, cannot rapidly detect M.Tb in CSF specimens with sufficient sensitivity in the acute phase of TBM. Recently, instead of the conventional "gold standard", the various molecular-based methods including nucleic acid amplification (NAA) assay technique, particularly polymerase chain reaction (PCR) assay, has emerged as a promising new method for the diagnosis of CNS tuberculosis because of its rapidity, sensitivity and specificity. In addition, the innovation of nested PCR assay technique is worthy of note given its contribution to improve the diagnosis of CNS tuberculosis. In this review, an overview of recent progress of the NAA methods, mainly highlighting the PCR assay technique, was presented.

BACKGROUND

Mustard gas primarily affects the eyes, skin, and particularly the respiratory tract. Tracheobronchomalacia (TBM) and air trapping are often observed in high-resolution computerized tomography (HRCT) scans of the chest of mustard gas-exposed patients.

OBJECTIVE

To examine the frequency and severity of TBM in a group of Iranian wartime mustard gas-exposed victims, and to investigate the correlation between TBM and air trapping in these cases.

METHODS

Chest HRCT films obtained from 300 randomly selected subjects who had been exposed to mustard gas 15.5 yr previously were reviewed to determine the existence of TBM and air trapping. The HRCT films of a healthy control group were also analyzed for comparison.

RESULTS

Out of 300 reviewed cases, 13 had TBM. From these 13 TBM cases, 11 (85%) showed air trapping with mean score of 5.5. In the control group, 5 (25%) of 20 subjects showed air trapping, with mean score of 0.6. The total air trapping was significantly higher in the TBM group (p < 0.001). There was an association between the severity of tracheomalacia and air trapping in the TBM group (p = 0.01, r = 0.69), but no association was observed between severity of bronchomalacia and air trapping.

CONCLUSIONS

The results show that air trapping and TBM are correlated, both as long-term sequelae in mustard gas-exposed cases. Because air trapping is highly suggestive of bronchiolitis obliterans, we conclude that both bronchiolitis obliterans and TBM are caused by a single underlying process affecting small and large airways, respectively, in this group of patients.

The locations of cerebral infarctions were studied in 14 patients with tuberculous meningitis (TBM) and 173 patients with noninflammatory ischemic stroke (IS). In patients with TBM, 75% of infarctions occurred in the "TB zone" supplied by medial striate and thalamoperforating arteries; only 11% occurred in the "IS zone" supplied by lateral striate, anterior choroidal and thalamogeniculate arteries. In patients with IS, 29% of infarctions occurred in the IS zone, 29% in the subcortical white matter, and 24% in (or involving) the cerebral cortex. Only 11% occurred in the TB zone. Bilaterally symmetrical infarctions of the TB zone were common with TBM (71%) but rare with IS (5%).

BACKGROUND

Pediatric meningitis remains a common cause of childhood morbidity and mortality in developing countries. Knowledge of the causative organisms in a region is of importance in guiding empiric antibiotic regimes and immunization schedules assisting decisions on primary health-care interventions.

METHODS

This retrospective review of 557 meningitis cases represents a third pediatric survey conducted over a 3-year period (January 2007 to December 2009) at the same institution and after an interval of 14 years. Cases were identified using cerebrospinal fluid results. Demographic and laboratory variables were collected and meningitis was classified as aseptic/viral, bacterial, septic, tuberculous meningitis (TBM) or fungal.

RESULTS

The commonest form of bacterial meningitis was TBM diagnosed in 22% (n = 126) of children. Streptococcus pneumoniae 4% (n = 23) and Klebsiella pneumoniae 3% (n = 17) were the next commonest causes of bacterial meningitis diagnosed. Haemophilus influenzae meningitis occurred in <1% (n = 3) of cases with a median age of 3 months. Aseptic meningitis remains the commonest category. Human immunodeficiency virus (HIV) testing was requested in 43% (n = 241) of cases; 8% (n = 46) were positive.

CONCLUSIONS

TBM remains the commonest cause of pediatric bacterial meningitis in the Western Cape. It is concerning that the percentage of TBM cases out of the total study population has more than doubled compared with that in previous surveys. The low prevalence and young age of H. influenzae meningitis cases confirm the benefits derived from H. influenzae type b (Hib) vaccination.

A polymerase chain reaction (PCR) method for the rapid diagnosis of tuberculous meningitis (TBM) was used to study prospectively 47 cerebrospinal fluid (CSF) samples from 45 patients. Twenty CSF samples were from patients with clinically suspected TBM and another 27 samples came from patients without clinically suspected TBM. Mycobacterial DNA was detected in 15 CSF samples (14 from patients with clinically suspected TBM and 1 from a patient not suspected of having TBM). Of the PCR-positive samples, 4 were also positive for mycobacterial culture. However, 32 PCR-negative samples were all culture-negative. All samples were negative for the acid-fast bacillus by direct smear. The single PCR-positive patient in the clinically unsuspected TBM group was initially diagnosed as suffering from aseptic meningitis on the basis of his clinical features. The mycobacterial culture of his CSF specimen was also positive and a revised diagnosis of an aseptic type of TBM was made. The estimations of specificity and sensitivity in this study were 100% and 70% respectively. The results showed that using a PCR to detect mycobacterial DNA in CSF for the early diagnosis of TBM is not only a rapid but also an accurate method.

BACKGROUND

The value of CT in the diagnosis of tuberculous meningitis (TBM) in children is well reported. Follow-up CT scanning for these patients is, however, not well described and, in particular, the value of early follow-up CT has not been addressed for children with TBM.

OBJECTIVE

To assess the value of early follow-up CT in children with TBM in identifying diagnostic, prognostic and therapeutically relevant features of TBM.

METHODS

A retrospective 4-year review of CT scans performed within 1 week and 1 month of initial CT in children with proven (CSF culture-positive) and probable TBM (CSF profile-positive but culture-negative) and comparison with initial CT for the diagnostic, prognostic and therapeutic CT features of TBM.

RESULTS

The CT scans of 50 children were included (19 "definite" TBM; 31 "probable" TBM). Of these, 30 had CT scans performed within 1 week of the initial CT. On initial CT, 44 patients had basal enhancement. Only 24 patients had contrast medium-enhanced follow-up scans. Important findings include: 8 of 29 patients (who were not shunted) developed new hydrocephalus. New infarcts developed in 24 patients; 45% of those who did not have infarction initially developed new infarcts. Three of the six patients who did not show basal enhancement on initial scans developed this on the follow-up scans, while in seven patients with pre-existing basal enhancement this became more pronounced. Two patients developed hyperdensity in the cisterns on non-contrast medium scans. Eight patients developed a diagnostic triad of features. Three patients developed CT features of TBM where there was none on the initial scans.

CONCLUSIONS

Early follow-up CT is useful in making a diagnosis of TBM by demonstrating features that were not present initially and by demonstrating more sensitive, obvious or additional features of TBM. In addition, follow-up CT is valuable as a prognostic indicator as it demonstrates additional infarcts which may have developed or become more visible since the initial study. Lastly, follow-up CT has therapeutic value in demonstrating hydrocephalus, which may develop over time and may require drainage. We advise routine follow-up CT in patients with suspected TBM within the first week of initial CT and optionally at 1 month.

Computerized tomography (CT) has the advantage of allowing the isolation of trabecular bone of the axial skeleton, which is the more sensitive to metabolic changes. By means of single-energy X-ray CT we have devised a method for assessing trabecular bone mass (TBM) at L-4 vertebral body, which has an acceptable reproducibility (CV = 2.76%). Normal values where obtained after studying 29 normal individuals from both sexes and different ages. In order to know if the method is accurate, TBM was assessed in 17 patients (6 with creatinine clearance less than 6 ml/min and 11 on chronic hemodialysis), and in all of them the results were compared with the histomorphometry of the iliac crest bone biopsy. TBM assessed by CT correlated with trabecular bone volume (TBV; mineralized bone + osteoid) (r = 0.82; p less than 0.001) and this correlation was not improved after adding the volume of marrow fibrosis to TBV. TBM assessed by CT also correlated with mineralized bone volume but at a lower level of significance (r = 0.72; p = 0.001), and no correlation was found with relative osteoid volume alone. These findings suggest that final CT value is an integral of mineralized bone and osteoid but with a higher influence of mineralized bone. Osteomalacia and osteitis fibrosa were seen in situations of normal, decreased, or increased TBM assessed by CT, although the 2 patients with severe osteosclerosis suffered osteomalacia. We conclude that the assessment of TBM by CT at the axial skeleton of uremic patients has an acceptable reproducibility and accuracy.(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVE

To identify factors associated with HIV-infected status in children admitted with tuberculous meningitis (TBM), and to find out whether HIV co-infection affects in-hospital outcome.

METHODS

This prospective hospital-based study was conducted from May 2000 to August 2003. All consecutive children, aged 1 month to 12 years of age, admitted with a diagnosis of TBM were enrolled. Relationship between 35 features viz., two demographic factors, nine clinical features, 13 neurological features, five laboratory (including cerebrospinal fluid) parameters, six radiological (including computed tomography scan brain) features, and the two outcomes (disabled survivor or death); with HIV-infected status was assessed.

RESULTS

Of a total 123 TBM cases enrolled, eight (6.5%) were HIV-infected. There was no significant difference between the two groups, except that more children in the HIV-infected group had Hb < 8 gm/dl: both on bivariate analysis, (OR, 12.0; 95% CI, 2.6-55.9; P = 0.001) and on multivariate analysis (OR, 12.30; 95% CI, 1.9-79.6; P = 0.008). Outcome was similar in both the groups.

CONCLUSIONS

Only presence of Hb < 8 gm/dl was associated with HIV-infected status. HIV co-infection did not affect the outcome.