Severe Form Of Extrapulmonary Tuberculosis Research Articles

CANDIDATE OF MEDICINE, SENIOR RESEARCHER OF THE DEPARTMENT OF NEUROINFECTIONS OF L. HROMASHEVSKYI INSTITUTE OF EPIDEMIOLOGY AND INFECTION DISEASES OF THE NATIONAL ACADEMY OF MEDICAL SCIENCES OF UKRAINE

Background. Central nervous system tuberculosis is one of the most severe forms of extra-pulmonary tuberculosis. Tuberculous meningoencephalitis (TBM) is highly prevalent globally in resource-limited countries and in patients with immunosuppression. We present here a case of meningoencephalitis with proved acute Herpes simplex virus infection. However, our patient responded to antituberculosis therapy. This raises the possibility that some cases of “idiopathic” (cryptogenic) meningoencephalitis may represent occult tuberculosis disease.
 Result. A 22-year-old woman was admitted to our hospital because of fever, headache and hallucinations. Neck stiffness and other meningeal symptoms were present. CSF examination showed lymphocyte-dominant pleocytosis and a decreased level of glucose. Both Herpes simplex virus type 1 (HSV-1) DNA and IgG antibodies to the virus were found in the CSF sample. Although antibiotics and acyclovir were administered, fever, disturbance of consciousness, hallucinations and meningeal signs intensified. A second CSF sample obtained a week after the collection of the first one contained higher level of cytosis and so called “spider-web” cloth (SWC). As a result, the diagnosis was revised: tuberculosis was regarded as the most likely cause of the disease. The patient started receiving antituberculous treatment. Soon after the medications were changed, the meningoencephalitis started to subside and was finally cured. Judging from the clinical features, the CSF and MRI findings, the effectiveness of antituberculous drugs, the final diagnosis was made as tuberculous meningoencephalitis. From all these things, we conclude when even antibodies for Herpes viruses and viral DNA are present in the CSF of the patient with sterile meningoencephalitis the possibility of latent involvement in the process of Koch bacteria (KB) should be kept in mind.
 Conclusion. The patient’s symptoms and signs began to resolve with antituberculous therapy. Resolution of the lesions was confirmed by magnetic resonance imaging. We conclude that this case represented occult tuberculous disease. An empiric trial of antituberculous therapy may be used in other cases of apparently idiopathic meningoencephalitis.

Diagnostic scoring system for tuberculous meningitis among adult patients with non-suppurative and non-bacterial meningitis.

Tuberculous meningitis (TBM) is the most severe form of extra-pulmonary tuberculosis. The definite diagnosis of this disease is difficult and can result in delayed treatment. Conventional culture yields low sensitivity while high-sensitivity diagnostic techniques are costly and unpractical. Adenosine deaminase (ADA) is used to diagnose several settings of extra-pulmonary tuberculosis but it is limited in TBM especially among HIV-infected patients. We retrospectively reviewed the data of patients with non-suppurative meningitis and compared the patient data with TBM and other causes including carcinomatous, lymphomatous, lymphocytic and fungal meningitis. We found that HIV infection, diabetes mellitus, duration of symptoms <14 days, radiologic findings of hydrocephalus, and CSF ADA level >10 IU were associated with TBM. The scoring system based on these parameters and their coefficients in the final model achieved an area under the receiver operating characteristic curve of 0.95,625. The indices were HIV infection=5, diabetes mellitus=3, duration of symptoms <14 days=5, hydrocephalus=4, and ADA in CSF >10 IU=5. Based on the assumed costs of the patients with false negative and false positive, an appropriate cut off value of 10 was selected and the sensitivity was 92% and specificity was 89%.

COMPLICATED LUMBAR TUBERCULOUS SPONDYLODISCITIS IN DISSEMINATED TUBERCULOSIS, TREATED USING A NON-CONVENTIONAL ANTERIOR SUPPORT SYSTEM FOR HYDROSTATIC DISTRACTION: A CASE REPORT.

ABSTRACTObjective:To describe a case of disseminated tuberculosis affecting the lumbar spine that was treated using a non-conventional anterior support system.Background:Tuberculous spondylodiscitis is the most common and most severe form of extrapulmonary tuberculosis. Although antibiotic therapy is the most frequently used treatment, surgery is necessary in cases of neurological deficit, spinal instability, significant deformity, severe sepsis, paravertebral and epidural abscesses or in cases wherein clinical treatment has failed. A surgical procedure is also indicated when a biopsy is required. With the development of new methods for reconstruction and fixation of the spine, complete debridement of the tuberculous foci has become an increasingly common approach, but there is a lack consensus on the best technique.Methods and results:The patient suffered from disseminated tuberculosis affecting the lumbar region of the spine, with an abscess in the psoas muscle. He underwent extensive debridement via both anterior and posterior approaches, using a non-conventional anterior support system that promotes hydrostatic distraction.Conclusions:Treatment using the hydrostatic distraction system was able to reestablish both the stability and anatomy of the lumbar curve. Level of evidence IV, Case report.

Prognostic Models for 9-Month Mortality in Tuberculous Meningitis.

Tuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis. We developed and validated prognostic models for 9-month mortality in adults with TBM, with or without human immunodeficiency virus (HIV) infection. We included 1699 subjects from 4 randomized clinical trials and 1 prospective observational study conducted at 2 major referral hospitals in Southern Vietnam from 2001-2015. Modeling was based on multivariable Cox proportional hazards regression. The final prognostic models were validated internally and temporally and were displayed using nomograms and a Web-based app (https://thaole.shinyapps.io/tbmapp/). 951 HIV-uninfected and 748 HIV-infected subjects with TBM were included; 219 of 951 (23.0%) and 384 of 748 (51.3%) died during 9-month follow-up. Common predictors for increased mortality in both populations were higher Medical Research Council (MRC) disease severity grade and lower cerebrospinal fluid lymphocyte cell count. In HIV-uninfected subjects, older age, previous tuberculosis, not receiving adjunctive dexamethasone, and focal neurological signs were additional risk factors; in HIV-infected subjects, lower weight, lower peripheral blood CD4 cell count, and abnormal plasma sodium were additional risk factors. The areas under the receiver operating characteristic curves (AUCs) for the final prognostic models were 0.77 (HIV-uninfected population) and 0.78 (HIV-infected population), demonstrating better discrimination than the MRC grade (AUC, 0.66 and 0.70) or Glasgow Coma Scale score (AUC, 0.68 and 0.71) alone. The developed models showed good performance and could be used in clinical practice to assist physicians in identifying patients with TBM at high risk of death and with increased need of supportive care.

Diagnostic usefulness of Xpert MTB/RIF assay for detection of tuberculous meningitis using cerebrospinal fluid

Tuberculous meningitis (TBM) is the most severe form of extra-pulmonary tuberculosis (TB) due to association of diseases with high rates of mortality and morbidity. Diagnosis continues to be a clinical challenge as microbiological confirmation is rare and time consuming resulting in delayed treatment. Xpert MTB/RIF assay is a rapid and simple test, which has been endorsed by World Health Organization as an initial diagnostic test for the diagnosis of TBM. However, evidence still lacks for its performance on cerebrospinal fluid (CSF) for the diagnosis of TBM especially from India. A total of 267 CSF samples from patients with high clinico-radiological suspicion of TBM were included in this study. Ziehl-Neelsen (ZN) staining, BACTEC Mycobacterial Growth Indicator Tube (MGIT-960) culture system, and Xpert MTB/RIF assay (using cartridge version G4) were tested on all samples. Of total 267 samples, all were negative for smear AFB and 52 (19.5%) were culture positive by MGIT-960 culture system. However, out of 52 (19.5%) cultures detected positive by MGIT-960, 5 (9.6%) were detected as resistant to rifampicin. Xpert MTB/RIF assay was positive in 38 (14.2%) samples and negative in 223 (83.5%) samples. Cartridge error was detected in 6 (2.2%) samples, which could not be repeated due to insufficient sample volume. The sensitivity and specificity of Xpert MTB/RIF assay in comparison to MGIT-960 was 55.1% (95%, CI: 40.2-69.3) and 94.8% (95%, CI: 90.9-97.4) respectively. Overall, Xpert MTB/RIF assay detected 38 (14.2%) as positive for MTB of which 4 (10.5%), 31 (81.6%) and 3 (7.9%) were found to be rifampicin resistant, sensitive and indeterminate respectively. Xpert MTB/RIF assay showed lower sensitivity as compared to MGIT 960 culture for the diagnosis of TBM from CSF samples.

Compound palmar ganglion causing compressive neuropathy of the median nerve

Tuberculosis (TB) of synovial sheath of tendon is uncommon, it is a severe form of extrapulmonary TB, diagnosis is obvious on clinical grounds in later stages, but is always confirmed by histopathology. Here, we are presenting a case of a 50-year-old female, who presented to us with gradual increasing swelling in her left hand and wrist and numbness over left thenar eminence. The patient was successfully treated with debulking operation and anti-tubercular drugs. Tubercular tenosynovitis of wrist and hand is a severe form of extrapulmonary TB. Intraoperatively, the presence of rice body or melon seed bodies is pathognomonic for confirming the diagnosis. Early diagnosis and intervention give good prognosis.

Comparison of DNA Extraction Protocols and Molecular Targets to Diagnose Tuberculous Meningitis.

Tuberculous meningitis (TBM) is a severe form of extrapulmonary tuberculosis. The aims of this study were to evaluate in-house molecular diagnostic protocols of DNA extraction directly from CSF samples and the targets amplified by qPCR as an accurate and fast diagnosis of TBM. One hundred CSF samples from 68 patients suspected of TBM were studied. Four DNA extraction techniques (phenol-chloroform-thiocyanate guanidine, silica thiocyanate guanidine, resin, and resin with ethanol) were compared and CSF samples were used to determine the best target (IS6110, MPB64, and hsp65 KDa) by qPCR. The extraction protocol using the phenol-chloroform-thiocyanate guanidine showed the best results in terms of quantification and sensitivity of PCR amplification, presenting up to 10 times more DNA than the second best protocol, the silica guanidine thiocyanate. The target that showed the best result for TBM diagnosis was the IS6110. This target showed 91% sensitivity and 97% specificity when we analyzed the results by sample and showed 100% sensitivity and 98% specificity when we analyzed the results by patient. The DNA extraction with phenol-chloroform-thiocyanate guanidine followed by IS6110 target amplification has been shown to be suitable for diagnosis of TBM in our clinical setting.

Modelling of cerebral tuberculosis in BALB/c mice using clinical strain from patients with CNS tuberculosis infection

Background & objectives:Central nervous system (CNS) infection caused by Mycobacterium tuberculosis (MTB) is the most severe form of extrapulmonary tuberculosis (EPTB) due to a high level of mortality and morbidity. Limited studies are available on CNS-TB animal model development. The present study describes the development of a murine model of CNS-TB using a clinical strain (C3) isolated from the cerebrospinal fluid (CSF) of CNS-TB patients.Methods:Groups of mice were infected by the intravenous route with MTB C3 strain isolated from the CSF of CNS-TB patients. Brain and lung tissue were evaluated for bacterial burden, histopathology and surrogate markers of TB infection at 30 and 50 days post-infection.Results:Mice infected intravenously with MTB C3 strains showed progressive development of CNS disease with high bacillary burden in lungs at the initial stage (30 days), which eventually disseminated to the brain at a later stage (50 days). Similarly, high mortality (60%) was associated in mice infected with C3 strain compared to control.Interpretation & conclusions:The study showed development of a novel murine model of CNS-TB using the C3 strain of MTB that replicated events of extrapulmonary dissemination. The developed model would be helpful in understanding the pathogenesis of CNS-TB infection for the development of improved therapeutic interventions in future.

Microglia activation in a pediatric rabbit model of tuberculous meningitis.

ABSTRACTCentral nervous system (CNS) tuberculosis (TB) is the most severe form of extra-pulmonary TB and disproportionately affects young children where the developing brain has a unique host response. New Zealand white rabbits were infected with Mycobacterium tuberculosis via subarachnoid inoculation at postnatal day 4-8 and evaluated until 4-6 weeks post-infection. Control and infected rabbit kits were assessed for the development of neurological deficits, bacterial burden, and postmortem microbiologic and pathologic changes. The presence of meningitis and tuberculomas was demonstrated histologically and by in vivo magnetic resonance imaging (MRI). The extent of microglial activation was quantified by in vitro immunohistochemistry as well as non-invasive in vivo imaging of activated microglia/macrophages with positron emission tomography (PET). Subarachnoid infection induced characteristic leptomeningeal and perivascular inflammation and TB lesions with central necrosis, a cellular rim and numerous bacilli on pathologic examination. Meningeal and rim enhancement was visible on MRI. An intense microglial activation was noted in M. tuberculosis-infected animals in the white matter and around the TB lesions, as evidenced by a significant increase in uptake of the tracer 124I-DPA-713, which is specific for activated microglia/macrophages, and confirmed by quantification of Iba-1 immunohistochemistry. Neurobehavioral analyses demonstrated signs similar to those noted in children with delayed maturation and development of neurological deficits resulting in significantly worse composite behavior scores in M. tuberculosis-infected animals. We have established a rabbit model that mimics features of TB meningitis in young children. This model could provide a platform for evaluating novel therapies, including host-directed therapies, against TB meningitis relevant to a young child's developing brain.

Analysis of glutathione levels in the brain tissue samples from HIV-1-positive individuals and subject with Alzheimer's disease and its implication in the pathophysiology of the disease process

HIV-1 positive individuals are at high risk for susceptibility to both pulmonary tuberculosis (TB) and extra-pulmonary TB, including TB meningitis (TBM) which is an extreme form of TB. The goals of this study are to determine the mechanisms responsible for compromised levels of glutathione (GSH) in the brain tissue samples derived from HIV-1-infected individuals and individuals with Alzheimer's disease (AD), investigate the possible underlying mechanisms responsible for GSH deficiency in these pathological conditions, and establish a link between GSH levels and pathophysiology of the disease processes. We demonstrated in the autopsied human brain tissues that the levels of total and reduced forms of GSH were significantly compromised in HIV-1 infected individuals compared to in healthy subjects and individuals with AD. Brain tissue samples derived from HIV-1-positive individuals had substantially higher levels of free radicals than that derived from healthy and AD individuals. Enzymes that are responsible for the de novo synthesis of GSH such as γ-glutamate cysteine-ligase catalytic subunit (GCLC-rate limiting step enzyme) and glutathione synthetase (GSS-enzyme involved in the second step reaction) were significantly decreased in the brain tissue samples derived from HIV-1-positive individuals with low CD4+ T-cells (<200cells/mm3) compared to healthy and AD individuals. Levels of glutathione reductase (GSR) were also decreased in the brain tissue samples derived from HIV-1 infected individuals. Overall, our findings demonstrate causes for GSH deficiency in the brain tissue from HIV-1 infected individuals explaining the possible reasons for increased susceptibility to the most severe form of extra-pulmonary TB, TBM.

Are the Present Doses of Anti Tubercular Drugs Adequate for Severe Disease?

Are the Present Doses of Anti Tubercular Drugs Adequate for Severe Disease?

A hypothetical astrocyte-microglia lactate shuttle derived from a 1H NMR metabolomics analysis of cerebrospinal fluid from a cohort of South African children with tuberculous meningitis.

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.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-014-0741-z) contains supplementary material, which is available to authorized users.

ESTUDO EPIDEMIOLÓGICO DA COINFECÇÃO TUBERCULOSE-HIV NO NORDESTE DO BRASIL

The study aimed to analyze the epidemiology of TB-HIV co-infection in northeastern Brazil. This is a descriptive study of TB-HIV co-infected patients, occurring from 2002 to 2011 and recorded in the Diseases Information System Notifications. We recorded 12,405 cases of TB-HIV co-infection, of which 596 died (4.8% mortality). Pernambuco, Sergipe and Paraíba States recorded the highest percentage of co-infection. Co-infection was reported in 53% of municipalities in the Northeast. Males were the most affected (70%). The pulmonary form was presented in 70% of individuals; 6% of co-infected individuals were institutionalized, the cure rate for TB in the period was 39% and the dropout rate from treatment was 14%. 83.95% of co-infected individuals developed the clinical manifestations of AIDS. The low cure rate, high percentage of noncompliance, occurrence of severe forms of extrapulmonary tuberculosis and high mortality rate reflects the challenge in patient care and surveillance of TB cases co-infected with HIV in northeastern Brazil.

Presentation of Tuberculous Meningitis Patients : Study of 30 Cases

Tuberculosis is creating immense adverse social and economic burden in Bangladesh. Tuberculous Meningitis results from the haematogenous spread of primary or postprimary pulmonary disease or from the rupture of a subependymal tubercle into the subarachnoid space. Infection of the CNS is one of the most devastating clinical manifestations of tuberculosis This study aimed to see the presentation of tuberculous meningitis patients in tertiary level hospital of Bangladesh. This cross sectional study was carried out in the Department of Neurology, SSMC, Dhaka from June 2011 to July 2012. In the present study, thirty meningitis patients were enrolled, among the subjects 11.7 % were aged below 20 years, 53.3% were aged between 20 - 39 years, 16.7% were aged between 40 - 49 years and 18.3% were aged above 50 years. Regarding sex 56.7% were male and 43.3% were female. Most prevalent symptom was fever (91.7%). Among others, headache (70%), altered consciousness (45%), vomiting (43.3%) and neck stiffness (28.9%) were notable. The distribution of the study subjects by physical sign 55.0% had anemia, 95.0% had neck rigidity, 10.0% had cranial nerve palsy, 46.7% had kernig's sign and 20.0% had long tract sign. Regarding GCS score 10.0 % had GCS score less than 8, 18.3 % had between 9 – 12 and 71.7% had over&gt; 12.The Laboratory finding among the study subjects 3.3% showed positive gram stain and 43.7% showed MT over 10 mm. In response to treatment 93.3% responded to anti TB out of 30 TBM subjects. This study demonstrated that presentation of tubercular meningitis is different in different patient.TBM is the severe form of extra-pulmonary tuberculosis occurring in 7.0- 12.0% of TB patients in developing countries with high rate of mortality due to delay in diagnosis and proper treatment. DOI: http://dx.doi.org/10.3329/medtoday.v25i1.16069 Medicine Today 2013 Vol.25(1): 32-35

Drug therapy in spinal tuberculosis.

Although the discovery of effective anti-tuberculosis drugs has made uncomplicated spinal tuberculosis a medical disease, the advent of multi-drug-resistant Mycobacterium tuberculosis and the co-infection of HIV with tuberculosis have led to a resurgence of the disease recently. The principles of drug treatment of spinal tuberculosis are derived from our experience in treating pulmonary tuberculosis. Spinal tuberculosis is classified to be a severe form of extrapulmonary tuberculosis and hence is included in Category I of the WHO classification. The tuberculosis bacilli isolated from patients are of four different types with different growth kinetics and metabolic characteristics. Hence multiple drugs, which act on the different groups of the mycobacteria, are included in each anti-tuberculosis drug regimen. Prolonged and uninterrupted chemotherapy (which may be 'short course' and 'intermittent' but preferably 'directly observed') is effective in controlling the infection. Spinal Multi-drug-resistant TB and spinal TB in HIV-positive patients present unique problems in management and have much poorer prognosis. Failure of chemotherapy and emergence of drug resistance are frequent due to the failure of compliance hence all efforts must be made to improve patient compliance to the prescribed drug regimen.

Site of Extrapulmonary Tuberculosis is Associated with HIV Infection

In the United States, the proportion of patients with extrapulmonary tuberculosis (EPTB) has increased relative to cases of pulmonary tuberculosis. Patients with central nervous system (CNS)/meningeal and disseminated EPTB and those with human immunodeficiency virus (HIV)/AIDS have increased mortality. The purpose of our study was to determine risk factors associated with particular types of EPTB. We retrospectively reviewed 320 cases of EPTB from 1995-2007 at a single urban US public hospital. Medical records were reviewed to determine site of EPTB and patient demographic and clinical characteristics. Multivariable logistic regression analyses were performed to determine independent associations between patient characteristics and site of disease. Patients were predominantly male (67%), African American (82%), and US-born (76%). Mean age was 40 years (range 18-89). The most common sites of EPTB were lymphatic (28%), disseminated (23%), and CNS/meningeal (22%) disease. One hundred fifty-four (48.1%) were HIV-infected, 40% had concomitant pulmonary tuberculosis, and 14.7% died within 12 months of EPTB diagnosis. Multivariable analysis demonstrated that HIV-infected patients were less likely to have pleural (adjusted odds ratio [AOR] 0.3; 95% confidence interval [CI] .2, .6) as site of EPTB disease than HIV-uninfected patients. Among patients with EPTB and HIV-infection, patients with CD4 lymphocyte cell count <100 were more likely to have severe forms of EPTB (CNS/meningeal and/or disseminated) (AOR 1.6; 95% CI, 1.0, 2.4). Among patients hospitalized with EPTB, patients coinfected with HIV and low CD4 counts were more likely to have CNS/meningeal and disseminated disease. Care for similar patients should include consideration of these forms of EPTB since they carry a high risk of death.

Molecular Profile of Drug Resistance in Tuberculous Meningitis From Southwest China

Tuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis and causes high mortality and morbidity. Isoniazid resistance is strongly predictive of death in patients with TBM. In the present study, using polymerase chain reaction (PCR) and Genotype MTBDRplus line-probe assay, we investigated the drug resistance in patients with TBM living in Southwest China. Our results showed that only one-third of patients with TBM had a positive result for Mycobacterium tuberculosis culture from cerebrospinal fluid (CSF). PCR-based detection of M. tuberculosis DNA in CSF is not only an alternative diagnostic approach for TBM but also can be further used for the detection of drug resistance when combined with the MTBDRplus assay, the results of which were consistent with the classic drug susceptibility test. However, it further provided the molecular profile of the mutations can be conducted much faster than the classic drug susceptibility test can (1 day vs 30-40 days, respectively). In the studied 30 CSF samples from patients with TMB, we found a rate of 64.29% for isoniazid resistance, 39.29% for rifampicin resistance, and 32.14% for multidrug-resistant tuberculosis, which is relatively higher than the reported resistance in pulmonary tuberculosis. However, the molecular profile indicated that the most frequently observed mutations in the rpoB and katG genes are also responsible for drug resistance in TBM. Our data suggest that the MTBDRplus line-probe assay is capable of detecting drug resistance for the CSF samples that have a PCR-positive result. We recommend PCR-based diagnosis and drug resistance test as routine assays for patients with suspected TBM.

Tuberculous meningitis

Tuberculous meningitis is a severe form of extrapulmonary tuberculosis. The exact incidence and prevalence are not known. In countries with high burden of pulmonary tuberculosis, the incidence is expected to be proportionately high. Children are much more vulnerable. Human immunodeficiency virus-infected patients have a high incidence of tuberculous meningitis. The hallmark pathological processes are meningeal inflammation, basal exudates, vasculitis and hydrocephalus. Headache, vomiting, meningeal signs, focal deficits, vision loss, cranial nerve palsies and raised intracranial pressure are dominant clinical features. Diagnosis is based on the characteristic clinical picture, neuroimaging abnormalities and cerebrospinal fluid changes (increased protein, low glucose and mononuclear cell pleocytosis). Cerebrospinal fluid smear examination, mycobacterial culture or polymerase chain reaction is mandatory for bacteriological confirmation. The mortality and morbidity of tuberculous meningitis are exceptionally high. Prompt diagnosis and early treatment are crucial. Decision to start antituberculous treatment is often empirical. WHO guidelines recommend a 6 months course of antituberculous treatment; however, other guidelines recommend a prolonged treatment extended to 9 or 12 months. Corticosteroids reduce the number of deaths. Resistance to antituberculous drugs is associated with a high mortality. Patients with hydrocephalus may need ventriculo-peritoneal shunting. Bacillus Calmette-Guérin vaccination protects to some degree against tuberculous meningitis in children.

Meningitis tuberculosa en adultos: Análisis de 53 casos

Tuberculous Meningitis (TBM) is the most severe form of extrapulmonary tuberculosis. The clinical spectrum is broad and may be non-specific making early diagnosis difficult. This increases the incidence of mortality. We describe the clinical characteristics of patients with TBM in Dr. Lucio Córdova's Infectious Disease Hospital in Santiago, Chile, between 1995 and 2002. We review 53 adult cases of TBM, with a median age of 39 years. At admission 66% of the patients had some mental status deterioration, and the classic triad of symptoms of meningeal irritation was present only in 30%. The cerebrospinal fluid (CSF) examination showed increased protein level, low glucose level and lymphocytic pleocytosis in most. Thirty percent of the patients were coinfected with HIV. The mortality in the later group was greater than in the TBM population as a whole (31 vs 17%). TBM is still a present diagnostic problem, in spite of the new diagnostic methods. A high index of suspicion is required in order to make an early diagnosis.

EAU Guidelines for the Management of Genitourinary Tuberculosis

Nearly one third of the world's population is estimated to be infected with Mycobacterium tuberculosis. Moreover, tuberculosis is the most common opportunistic infection in AIDS patients. Genitourinary tuberculosis is not very common but it is considered as a severe form of extra-pulmonary tuberculosis The diagnosis of genitourinary tuberculosis is made based on culture studies by isolation of the causative organism; however, biopsy material on conventional solid media may occasionally be required. Drug treatment is the first line therapy in genitourinary tuberculosis. Treatment regimens of 6 months are effective in most of the patients. Although chemotherapy is the mainstay of treatment, surgery in the form of ablation or reconstruction may be unavoidable. Both radical and reconstructive surgery should be carried out in the first 2 months of intensive chemotherapy.