This study examines the relative contribution of age-specific total IgE levels, eosinophils and water contact behavior to the prevalence and intensity (geometric mean egg counts) of Schistosoma mansoni infection in the poor rural population of Virgem das Graças in northern Minas Gerais State. In bivariate analysis, age was strongly correlated with both prevalence and intensity of infection, while eosinophil levels with prevalence only (p<0.0001); IgE levels and 5 demographic and socioeconomic variables were moderately correlated with prevalence (p<0.05), as were number of persons per room and TBM (total body minutes) with egg counts. In multivariate analysis, after controlling for demographic and socioeconomic factors, only total IgE levels were significantly correlated with both prevalence (p=0.248, 95% CI=1.01-1.11) and intensity (p=0.0217, 95% CI=0.01-0.14) of infection and eosinophil levels with prevalence (p=0.0005, 95% CI=1.07-1.24). Although any causal relationship cannot be confirmed by a cross-sectional study, we demonstrated an associated decrease in prevalence and intensity of S. mansoni infection with increased IgE levels.

We used tensor-based morphometry (TBM) to: 1) map gray matter (GM) volume changes associated with motor learning in young healthy individuals; 2) evaluate if GM changes persist three months after cessation of motor training; and 3) assess whether the use of different schemes of motor training during the learning phase could lead to volume modifications of specific GM structures. From 31 healthy subjects, motor functional assessment and brain 3D T1-weighted sequence were obtained: before motor training (time 0), at the end of training (two weeks) (time 2), and three months later (time 3). Fifteen subjects (group A) were trained with goal-directed motor sequences, and 16 (group B) with non purposeful motor actions of the right hand. At time 1 vs. time 0, the whole sample of subjects had GM volume increase in regions of the temporo-occipital lobes, inferior parietal lobule (IPL) and middle frontal gyrus, while at time 2 vs. time 1, an increased GM volume in the middle temporal gyrus was seen. At time 1 vs. time 0, compared to group B, group A had a GM volume increase of the hippocampi, while the opposite comparison showed greater GM volume increase in the IPL and insula in group B vs. group A. Motor learning results in structural GM changes of different brain areas which are part of specific neuronal networks and tend to persist after training is stopped. The scheme applied during the learning phase influences the pattern of such structural changes.

(1) AIN is the most frequent pattern of drug-induced immunologically mediated renal injury. A number of drugs may be responsible for AIN, namely methicillin and other penicillin derivatives, rifampicin, phenindione and sulfonamides. Particular clinical and pathological features often suggest an immune pathogenetic mechanism. IgG anti-TBM and IgE antibodies have been found in only a few cases and it is likely that antibody-mediated and cell-mediated injury may operate in the same patient. (2) Only few examples of drug-induced vasculitis and glomerulonephritis are known, and the pathophysiology of this kind of renal damage is poorly understood.

Light-chain deposition disease (LCDD) of the kidney is defined as deposition of monotypic light chains (LC) within glomerular (GBM) and tubular (TBM) basement membranes. The morphologic features of pure renal LCDD have been presented only in case reports or small series. The aim of this study was to perform a comprehensive evaluation of the light (LM), immunofluorescence (IF), and electron microscopic (EM) features of pure renal LCDD in a large series of biopsies. Out of 46 cases assembled, 42 had multiple myeloma, 2 had monoclonal gammopathy of unknown significance, and in 2 patients no lymphoproliferative disease was identified. The most common LM lesion of LCDD, nodular glomerulosclerosis, was present in only 14 (30%) cases. GBM and/or TBM thickening was found in 3 (6%), mild to moderate mesangial matrix increase in 12 (23%), and unremarkable glomeruli and tubules were seen in 15 (32%) cases. Forty-two had IF and 40 (92%) showed characteristic linear LC immunoreactivity (24 kappa, 16 lambda) along GBM and/or TBM. Among 39 cases in which IF and EM was available, 25 (64%) were positive by both. Two (6%) were negative by IF, but had deposits by EM. In 12 (30%) with immunoreactivity to LC (4 kappa, 8 lambda), no deposits were identified ultrastructurally. This study shows heterogeneous LM lesions in pure LCDD cases. LM alone may be suspicious but not diagnostic of LCDD. Immunofluorescence is more sensitive than EM for detection of LC for the definitive diagnosis of LCDD. This study supports the importance of utilizing kappa and lambda stains in the routine IF panel for diagnosis of LCDD.

Two patients with Ig deposition disease presented with acute renal failure, moderate proteinuria, and hematuria. A plasmacytoid lymphocytic infiltrate was identified in bone marrow that produced IgG4 lambda and free lambda light chains. One patient developed an anaplastic plasmacytoma (secreting only lambda light chains) 1 yr after renal biopsy. Renal biopsy in both patients demonstrated a nodular intercapillary glomerulopathy and electron dense granular deposits, associated with a linear pattern of IgG4 heavy chain deposition in vascular, tubular, and glomerular basement membranes (VBM, TBM, and GBM). In one patient this entrapped IgG4 was unassociated with detectable kappa or lambda light chains. In the second patient, lambda light chains (1+) were detected only in the GBM, but IgG4 (4+) was identified in GBM/TBM. Neither circulating (peripheral blood and bone marrow serum) nor cellular free gamma chains were present. We propose the term "pseudo-gamma heavy chain deposition disease" for the process.

Twelve of 767 renal allograft recipients developed linear fixation of IgG along the glomerular basement membrane (GBM) by direct immunofluorescence technique. This was associated with linear fixation along the tubular basement membrane in 7 of them. Circulating anti-GBM antibodies were not detected by indirect immunofluorescence or radioimmunoassay in any patient whereas anti-TBM antibodies were found in 2 of 4 with linear TBM fixation. Among the 12 patients with linear GBM fixation, 5 had Alport's syndrome; the 7 others had various renal diseases, excluding anti-GBM nephritis. Among the 767 patients, 34 had Alport's syndrome or variants (i.e., 4.5%). The incidence of linear GBM fixation is much higher in Alport's syndrome than in other renal diseases. Linear GBM fixation was not clearly related to anti-GBM antibodies and was not accompanied by significant deterioration of graft function. These findings may be relevant, however, to the missing GBM antigen in Alport's syndrome.

Polycystic renal disease was induced in rats by feeding 2-amino-4,5-diphenylthiazole. Tubular (TBM) and glomerular basement membranes (GBM) were purified and analyzed for possible structural changes that may be a factor in the development of the tubular dilations and cysts. Changes in the relative quantities of TBM polypeptides were detected by sodium dodecylsulfate polyacrylamide gel electrophoresis. An overall increase in the concentration of high molecular weight components and a decrease in concentration of those of low molecular weight components were observed. Changes which were particularly notable included a twofold increase in a component of Mr = 380,000 and a decrease in one of Mr = 55,000 as analyzed without reduction of disulfide bonds. With reduction of disulfide bonds, the Mr = 380,000 component dissociates, whereas the Mr = 55,000 polypeptide does not, and polypeptides of Mr = 245,000 and 145,000 are observed to does not, and polypeptides of Mr = 245,000 and 145,000 are observed to increase about twofold in concentration (approximate molecular weights were determined using globular protein standards). These changes take place most rapidly from 4 to 8 weeks of drug administration and remain relatively constant between 8 and 16 weeks. If feeding of the drug is discontinued, the distribution of TBM polypeptides returns to normal. These results indicate that tubular basement membrane from animals with 2-amino-4,5-diphenylthiazole-induced polycystic renal disease is abnormal, and this should be considered as a possible contributing factor in the formation of cysts.

We aimed to provide data on the diagnosis of tuberculous meningitis (TBM) in this largest case series ever reported. The Haydarpasa-1 study involved patients with microbiologically confirmed TBM in Albania, Croatia, Denmark, Egypt, France, Hungary, Iraq, Italy, Macedonia, Romania, Serbia, Slovenia, Syria and Turkey between 2000 and 2012. A positive culture, PCR or Ehrlich-Ziehl-Neelsen staining (EZNs) from the cerebrospinal fluid (CSF) was mandatory for inclusion of meningitis patients. A total of 506 TBM patients were included. The sensitivities of the tests were as follows: interferon-γ release assay (Quantiferon TB gold in tube) 90.2%, automated culture systems (ACS) 81.8%, Löwenstein Jensen medium (L-J) 72.7%, adenosine deaminase (ADA) 29.9% and EZNs 27.3%. CSF-ACS was superior to CSF L-J culture and CSF-PCR (p <0.05 for both). Accordingly, CSF L-J culture was superior to CSF-PCR (p <0.05). Combination of L-J and ACS was superior to using these tests alone (p <0.05). There were poor and inverse agreements between EZNs and L-J culture (κ = -0.189); ACS and L-J culture (κ = -0.172) (p <0.05 for both). Fair and inverse agreement was detected for CSF-ADA and CSF-PCR (κ = -0.299, p <0.05). Diagnostic accuracy of TBM was increased when both ACS and L-J cultures were used together. Non-culture tests contributed to TBM diagnosis to a degree. However, due to the delays in the diagnosis with any of the cultures, combined use of non-culture tests appears to contribute early diagnosis. Hence, the diagnostic approach to TBM should be individualized according to the technical capacities of medical institutions particularly in those with poor resources.

For 15 to 20 years, electron microscopy studies have shown that some hereditary renal diseases are characterized by various abnormalities of the basement membranes. In the nail-patella syndrome, in Alport's syndrome and variants, and in benign familial hematuria, the changes involve the glomerular basement membrane (GBM). In nephronophthisis, the tubular basement membrane (TBM) is affected. These histopathologic features are not uniform. The progress afforded by biochemistry, immunology, and molecular biology allows us to compare these various lesions, to analyze their biochemical characteristics and their antigenicity, and to hypothesize as to the mechanisms involved.

Autoimmune tubulointerstitial nephritis was induced in Brown-Norway (BN) rats by immunization with bovine (Bov) tubular basement membrane (TBM) in complete Freund's adjuvant. Serum antibodies thus produced reacted to a greater extent with Bov than BN TBM antigens by indirect immunofluorescence and by radioimmunoassay with particulate (P) and collagenase-solubilized (CS) TBM. The quantities of antibodies reactive with CS TBM correlated with the intensity of tubulointerstitial pathologic changes. Antibodies eluted from kidneys reactive with BN TBM by indirect immunofluorescence were 508 times more concentrated in the kidney than in the serum, compared with 15 times for Bov TBM-reactive antibodies. The reactivity of eluted antibodies to P BN TBM was inhibited by 70% after absorption with BN CS TBM. A major CS TBM antigen of 42,000 m.w. was identified by polyacrylamide gel electrophoresis. This antigen was present in both Bov and BN TBM, and may be important in triggering autoantibody formation in this model. Lewis rats immunized under the same conditions produced antibodies reactive with BN TBM by immunofluorescence but failed to develop immune deposits in TBM of their own kidneys. Analysis of serum anti-TBM antibodies in Lewis rats revealed a selective lack of reactivity with either homologous or autologous CS TBM. These results suggest that the ability to make an immune response to one or more elements of CS TBM plays a major role in the development of autoimmune tubulointerstitial nephritis in rats.

Glomerular basement membrane (GBM) and tubular basement membrane (TBM) were prepared from human kidneys of diabetics and non-diabetics, and their chemical composition was compared. GBM from diabetics contained a larger amount of hydroxyproline than that from non-diabetics, and smaller amounts of half-cystine, glucose, mannose and sialic acid. On the other hand, TBM from diabetics contained larger amounts of hydroxylysine, methionine, galactose, hexosamine and phospholipid phosphorus than non-diabetics, and smaller amounts of half-cystine, valine, leucine, lysine and histidine. No significant difference was observed in the contents of other components examined in this study between the corresponding membrane obtained from diabetics and non-diabetics. The observed changes may be due to alteration of the tissues in diabetes mellitus.

OBJECTIVE

To evaluate predictors of mortality in 160 patients with tuberculous meningitis (TBM).

METHODS

One hundred and sixty patients with TBM who had been followed for 11 years in a tertiary referral centre hospital were assessed retrospectively. Features considered as predictors of mortality in TBM were studied by multivariate logistic regression to develop a prognostic rule.

RESULTS

Of 160 patients, 84% were in Stages II and III; 27 (17%) died. In univariate analysis, age, stage, altered sensorium, underlying comorbidities, pulmonary tuberculosis, leukocytosis and cerebrospinal fluid (CSF)/blood glucose < 0.30 and rise in CSF protein were associated with an increased risk of death. In multivariable analysis, age (OR 4.64, 95%CI 1.03-24.74, P = 0.046), altered sensorium (OR 8.62, 95%CI 1.25-110.0, P = 0.036), underlying comorbidity (OR 9.75, 95%CI 1.58-59.95, P = 0.014) and leukocytosis (OR 9.74, 95%CI 1.67-56.7, P = 0.011) were shown to be the best predictors of mortality in TBM.

CONCLUSIONS

We observed that TBM patients who died were more likely to be older and have altered mental status on admission, underlying comorbidities and leukocytosis than TBM patients who survived. These factors were the most important predictors of mortality from TBM.

A simple immunocytochemical method was standardized for the direct demonstration of mycobacterial antigen in cerebrospinal fluid (CSF) specimens of patients with tuberculous meningitis (TBM). CSF-cytospin smears were prepared from 22 patients with a clinical diagnosis of TBM and also from an equal number of patients with nontuberculous neurological diseases (disease control). Immunocytological demonstration of mycobacterial antigens in the cytoplasm of monocytoid cells was attempted, by using rabbit immunoglobulin G to Mycobacterium tuberculosis as the primary antibody. Of the 22 CSF-cytospin smears from TBM patients, 16 showed positive immunostaining, while all of the CSF-cytospin smears from the disease control showed negative immunostaining for mycobacterial antigen. The technical aspects of this immunocytological method for the demonstration of mycobacterial antigens are simple, rapid, and reproducible, as well as specific, and therefore can be applied for the early diagnosis of TBM, particularly in patients in whom bacteriological methods did not demonstrate the presence of M. tuberculosis in the CSF.

During the 9 years 1985-1993 a prospective survey of all cases of meningitis in children < 13 years of age presenting to our hospital in the Western Cape Province of South Africa was carried out. Two-thousand-nine-hundred-and-twenty cases of meningitis were identified. The commonest form of bacterial meningitis was tuberculous meningitis (TBM) diagnosed in 282 children (mean age 2.94 years). N. meningitidis identified in 220 children (mean age 2.87 years), Haemophilus influenzae in 156 children (mean age 1.15 years) and S. pneumoniae in 106 children (mean age 2.14) were the next commonest causes of bacterial meningitis diagnosed. One-hundred-and-eighteen cases of bacterial meningitis were confirmed in infants < 1 month of age and the commonest bacteria identified were group B beta-haemolytic Streptococcus in 27, E. coli in 21, Klebsiella species in 11, and Candida species in 15 neonates. The emergence of TBM as the predominant cause of bacterial meningitis in childhood at our hospital is probably a reflection of the worsening tuberculosis situation in the Western Cape Province of South Africa.

Diabetic nephropathy (DN) is one the most prevalent chronic complications of diabetes mellitus that affects as much as one-third of diabetic patients irrespective of the type of diabetes. Hyperglycemia is the key trigger for DN that initiates a number of microscopic and ultramicroscopic changes in kidney architecture. Microscopic changes include thickening of the glomerular basement membrane (GBM), tubular basement membrane (TBM), mesangial proliferation, arteriosclerosis, and glomerulotubular junction abnormalities (GTJA). Among the ultramicroscopic changes, effacement of podocytes and decrease in their density seem to be the centerpiece of DN pathogenesis. These changes in kidney architecture then produce functional deficits, such as microalbuminuria and decreased glomerular filtration rate (GFR). Among several mechanisms involved in inflicting damage to podocytes, injuries sustained by increased oxidative stress turns out to be the most important mechanism. Different variables that are included in increased production of reactive oxygen species (ROS) include a hyperglycemia-induced reduction in glutathione (GSH), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation via hyperglycemia, advanced glycation end products (AGEs), protein kinase C (PKC), and renin-angiotensin-aldosterone system (RAAS). Unfortunately, control of podocyte injury hasn't received much attention as a treatment approach for DN. Therefore, this review article is mainly concerned with the exploration of various treatment options that might help in decreasing the podocyte injury, mainly by reducing the level of NADPH oxidase-mediated generation of ROS. This article concludes with a view that certain NADPH oxidase inhibitors, RAAS inhibitors, statins, antidiabetic drugs, and antioxidant vitamins might be useful in decreasing podocyte injury and resultant structural and functional kidney impairments in DN.

The bioassay-guided fractionation of dried flowers of Butea monosperma (BM) was carried out to isolate the active principle responsible for its anticonvulsant activity. The petroleum ether extract was fractionated by column chromatography using solvents of varying polarity such as n-hexane, n-hexane:ethyl acetate, ethyl acetate, and methanol. The anticonvulsive principle of B. monosperma was found to be a triterpene (TBM) present in the n-hexane:ethyl acetate (1:1) fraction of the petroleum ether extract. TBM exhibited anticonvulsant activity against seizures induced by maximum electroshock (MES) and its PD(50) was found to be 34.2+/-18.1 mg/kg. TBM also inhibited seizures induced by pentylenetetrazol (PTZ), electrical kindling, and the combination of lithium sulfate and pilocarpine nitrate (Li-Pilo). However, TBM was not effective against seizures induced by strychnine and picrotoxin. TBM exhibited depressant effect on the central nervous system. After repeated use for 7 days, the PD(50) (MES) of TBM increased to 51.5+/-12.1 mg/kg. Similarly, after repeated use of TBM, the duration of sleep induced by pentobarbital was not reduced significantly. Further studies are required to investigate its usefulness in the treatment of epilepsy.

This study examines the functional morphology of the olecranon process in hominoids and fossil hominins. The length of the bony lever of the triceps brachii muscle (TBM) is measured as the distance between the trochlear articular center and the most distant insertion site of the TBM, and olecranon orientation is measured as the angle that this bony lever makes with the long axis of the ulna. Results show that Homo, Pan, Gorilla, most monkeys, and the Australopithecus fossils studied have similar relative olecranon lengths. Suspensory hominoids and Ateles have shorter olecranons, suggesting, in some instances, selection for greater speed in extension. The orientation that the lever arm of the TBM makes with the long axis of the ulna varies with preferred locomotor mode. Terrestrial primates have olecranons that are more posteriorly oriented as body size increases, fitting general models of terrestrial mammalian posture. Arboreal quadrupeds have more proximally oriented lever arms than any terrestrial quadrupeds, which suggests use of the TBM with the elbow in a more flexed position. Olecranon orientation is not consistent in suspensory hominoids, although they are all characterized by orientations that are either similar or more posterior than those observed in quadrupeds. Homo and the fossils have olecranons that are clearly more proximally oriented than expected for a quadruped of their size. This suggests that Homo and Australopithecus used their TBM in a flexed position, a position most consistent with manipulatory activities.

To further investigate mechanisms of cell-mediated tissue destruction in an organ-specific autoimmune disease, we have established and characterized a nephritogenic CD8+ T cell line. This target antigen-specific effector T cell line, M52, was derived from bulk populations of CD8+ T cells isolated from susceptible animals immunized to produce anti-tubular basement membrane (alpha TBM) disease. Our studies show that M52 retains the phenotypic and functional characteristics of nephritogenic T cells induced in vivo. M52 mediates antigen-specific delayed-type hypersensitivity (DTH) responses to the target antigen 3M-1, it is cytotoxic to 3M-1-expressing renal tubular epithelial cells in vitro, and it adoptively transfers interstitial nephritis to naive syngeneic recipients. Clonal analysis of these nephritogenic CD8+ T cells reveals distinct functional phenotypes within the M52 cell line. We have isolated a cytotoxic CD8+ clone, M52.26, which is not DTH-reactive to 3M-1, and multiple DTH-reactive clones which mediate less efficient cytotoxicity to 3M-1-expressing target cells. Cytofluorographic analysis of four randomly selected clones reveals alpha beta T cell receptor expression. Further characterization of these functionally distinct CD8+ T cell clones will help to define their respective roles in mediating tubular epithelial cell injury and the inflammatory lesion of autoimmune interstitial nephritis.

Experimental anti-tubular basement membrane (anti-TBM) disease is an autoimmune interstitial nephritis elicited in susceptible rodents after immunization with renal tubular antigen. The nephritogenic antigen in the immunizing preparation is 3M-1, a 48,000 Mr noncollagenous glycoprotein. The hallmarks of the renal lesion are the presence of anti-TBM antibodies (anti-TBM-Ab) and a dense mononuclear cell infiltrate. The anti-TBM B cell repertoire in this disease was analyzed using a library of 22 anti-TBM mAbs generated in a prototypically susceptible Brown Norway rat. These anti-TBM mAbs were all demonstrated to be 3M-1 specific and their characterization formed the basis for the following observations: (a) The size of the anti-TBM B cell population is estimated at 58 distinct clones; (b) by competitive inhibition criteria, all anti-TBM mAbs recognize the same (or spatially close) epitope(s) on 3M-1. This focused recognition was maintained in spite of considerable variability in affinity. Epitopic dominance could also be demonstrated in human polyclonal anti-TBM antisera from a patient with anti-TBM disease; and (c) a crossreactive idiotype was documented, and antisera directed toward this set of variable region determinants was shown to be effective as a prophylactic regimen to abrogate disease, and as a therapeutic modality to arrest the progression of disease; (d) analysis of VH gene families suggested biased usage of Q52- and 7183-like families, although at least three gene families are used in the anti-TBM-Ab response. Thus, the anti-TBM B cell compartment in BN rats is moderately large, but is primarily focused to a single epitope on the nephritogenic antigen and is associated with a disease-modifying crossreactive idiotype.

Proximal renal tubule cell volume increases in ouabain but cell swelling is limited by the tubule basement membrane (TBM) and the colloid osmotic pressure from the bath protein. We compared the effect of ouabain, external protein concentration, and TBM on cell volume of proximal convoluted (PCT), proximal straight (PST), and cortical collecting tubules (CCT). We blocked active solute transport with ouabain and evaluated cell size by measuring the outer diameter of nonperfused tubules. Proximal tubules in ouabain swelled 35-40% in isoncotic medium and 20-25% further in hyponcotic medium (0.3 g/100 ml albumin), but PCT swelled faster than PST. The CCT swelled minimally in similar mediums, indicating pronounced heterogeneity in the response of cortical nephron segments to ouabain. In the presence of ouabain, all tubules swelled extensively when we removed the TBM with collagenase. In the hyponcotic medium fluid flux across the peritubular membrane was 0.081, 0.049, and 0.030 nl/min per mm tubule length for PCT, PST, and CCT, respectively. The rates of fluid flux in PCT and PST were proportional to estimates of the respective basolateral surface areas. We suggest that differences in swelling rates between proximal segments reflect variations in surface area rather than intrinsic peritubular membrane permeability to solute and water.

BACKGROUND

Neurologic infections are an important cause of morbidity and mortality especially worldwide but much more in the African continent. The frequency of the different types of neurologic infections and their mortality in this part of Nigeria is not known.

OBJECTIVE

To review cases admitted into the main tertiary referral center in Rivers State of Nigeria with neurologic infections over a 10-year period and to determine the types of infections, their frequency and the mortality.

METHODS

Case notes of all admissions into the medical wards of UPTH, Port Harcourt between April 1993 and March 2003 were reviewed. Cases admitted with neurologic infections were extracted and analyzed for the study.

RESULTS

Of the 1,395 patients admitted with neurologic disorders during the study period, 311 (22.3%) had neurological infections. The M:F ratio and mean age of patients with neurologic infections were 1.7:1 and 34.1 years respectively. The most common infections identified were meningitis 136(43.7%), tetanus 90(28.9%), Pott's disease with cord compression 30(9.6%), viral meningoencephalitis 27(8.7%) and tuberculous meningitis (TBM) 19(6.1%). The case fatality was high: meningitis 49.3%, tetanus 47.8%, Pott's disease 23.3%, meningoencephalitis 44.4% and TBM 68.4%.

CONCLUSIONS

Preventable neurologic infections are a very important cause of morbidity and mortality in this environment. Cases presenting with suspicious neurologic infections should be referred to centers where specialized care can be instituted.

The simultaneous determination of cerebrospinal fluid (CSF) and plasma adenosine deaminase (ADA) activity was evaluated as a diagnostic aid in tuberculous meningitis (TBM). CSF and plasma ADA activity were determined in four groups of patients: (i) a 'no meningitis' group of 174 children investigated for possible meningitis, but found to be uninfected; (ii) an aseptic meningitis group of 40 children; (iii) a bacterial meningitis group of 31 children; and (iv) a TBM group of 27 patients (24 children and 3 adults). CSF ADA alone was determined in a further 23 children with aseptic meningitis, 19 with bacterial meningitis and 13 children and 7 adults with TBM. Both the CSF/plasma ADA ratio and the absolute CSF ADA activity were raised in TBM (mean values 0,24 and 12,61 U/I respectively) and bacterial meningitis (mean values 0,59 and 15,43 U/I respectively), but not in the aseptic meningitis group (mean values 0,06 and 2,00 U/I) or the 'no meningitis' group (mean values 0,04 and 1,51 U/I). Both values will distinguish TBM from aseptic meningitis, but do not appear to hold any marked advantages over conventional CSF criteria in the diagnosis of TBM.

OBJECTIVE

To calculate cut-off point for the adenosine deaminase (ADA) activity in the CSF of patients with tuberculous meningitis (TBM).

METHODS

The ADA assay was based on the automatic indirect method in which ADA catalyzes adenosine to inosine. ADA activity in the CSF was calculated based on ammonia liberated from adenosine and quantified spectrophotometrically. Arithmetic mean values and standard deviation of each variable were measured. Mann-Whitney U and Fisher exact tests were applied to compare continuous and dichotomous variables between tuberculous and non-tuberculous groups. A receiver operating characteristic curve was plotted to identify various cut-off points to determine the best level for ADA activity.

RESULTS

Totally 42 patients were enrolled into the study. The median of ADA activity in the TBM group was 22 and in the non-TBM group was 8.0. The mean CSF-ADA activity was found to be significantly higher in TBM group (23.05+/-13.1IU/L) than in the CSF from non-TBM patients (9.39+/-5.18IU/L). The highest accuracy is at the cut-off value of 10.5IU/L. The sensitivity and specificity of the test at this cut-off to differentiate TBM from non-tuberculous meningitis is 81% and 86% respectively.

CONCLUSIONS

Considering that a high positive value of ADA activity cannot confirm TBM, however, in suspected patients it may lead the physician to treat patient earlier before the confirmatory diagnostic reports will be received. The suggested cut-off value in this pilot study is 10.5IU/L with high sensitivity and specificity.

BACKGROUND

Tuberculous meningitis (TBM) the most fatal presentation of tuberculosis (TB) especially in HIV-infected patients is a real diagnostic and therapeutic challenge worldwide. In Cameroon where HIV and TB are amongst the leading public health problems, the magnitude of TBM has not been defined. Therefore, the objective of this cross sectional study was to describe the presentation and in-hospital outcome of TBM among HIV patients in Douala as well as its diagnostic difficulties.

METHODS

We did a clinical case note analysis of all HIV-1 infected patients treated for TBM in the Internal medicine unit of the Douala General Hospital, between January 1st 2004 and December 31st 2009. The diagnosis of TBM was made using clinical, laboratory [cerebrospinal fluid (CSF) analysis] and/or brain computerised tomographic (CT) scan features.

RESULTS

During the study period, 8% (54/672) of HIV-infected patients had TBM. Their mean age was 40.3 ± 12.7 years. The main presenting complaint was headache in 74.1% (40/54) of patients. Their median CD4 cell count was 16 cells/mm3 (IQR: 10 - 34). CSF analysis showed median protein levels of 1.7 g/l (IQR: 1.3 - 2.2), median glucose level of 0.4 g/l (IQR: 0.3 - 0.5) and median white cell count (WCC) count of 21 cells/ml (IQR: 12 - 45) of which mononuclear cells were predominant in 74% of CSF. Acid fast bacilli were found in 1.9% (1/54) of CSF samples. On CT scan hydrocephalus was the main finding in 70.6% (24/34) of patients. In hospital case fatality was 79.6% (43/54).

CONCLUSIONS

TBM is a common complication in HIV-infected patients in Douala with high case fatality. Its presumptive diagnosis reposes mostly on CSF analysis, so clinicians caring for HIV patients should not hesitate to do lumbar taps in the presence of symptoms of central nervous system disease.