Role of the BACTEC radiometric method in the evaluation of patients with clinically probable tuberculous meningitis.

BACKGROUND: Confirmation of tuberculous meningitis (TBM) and initiation of treatment are often delayed due to limitations in isolating Mycobacterium tuberculosis from cerebrospinal fluid (CSF). OBJECTIVES: To evaluate the role of the BACTEC radiometric method in a clinical setting for the early diagnosis of TBM. MATERIALS AND METHODS: Patients meeting criteria for clinically probable TBM over a 3 year period were included. Clinical features, results of CSF investigations (protein, glucose, cell count, Ziehl-Neelsen staining, culture in Löwenstein-Jensen (LJ) medium and BACTEC) and brain CT imaging were reviewed. Drug sensitivity was tested using BACTEC. Patients were started on standard treatment and functional outcome, and response at discharge and follow-up were assessed. Patients were divided according to whether or not M. tuberculosis was isolated by BACTEC and the clinical, radiological, and laboratory features compared. RESULTS: Sixty patients were evaluated. The mean age was 30 years +/- 11.7 years. Headache and fever were the most common symptoms and the mean duration was 26 days. CT findings were hydrocephalus (n=21), basal exudates (n=16), and tuberculoma (n=14). In 40 patients, M. tuberculosis was isolated by BACTEC and average 15 days was required for detection, whereas it was 30 days in LJ medium. Results of drug-sensitivity testing (n=32) were obtained average 7 days after isolation. Patients from whom M. tuberculosis had been isolated by BACTEC more often had tuberculomas in CT imaging (P=0.018). CONCLUSION: Use of the BACTEC method allows early confirmation in patients with clinically probable TBM. It can guide clinicians in the rational use of anti-tuberculosis treatment by confirming diagnosis and identifying drug- sensitivity.

Clinicopathological study of tuberculous brain abscess.

Central nervous system tuberculosis is still one of the leading causes of morbidity in the developing world, and tuberculous abscess is one of its uncommon manifesting forms. It closely mimics a pyogenic abscess clinically, radiologically, and histologically. An accurate diagnosis is imperative due to therapeutic implications. In this study, 21 cases of tuberculous abscesses encountered over a period of 13 years (1995-2007) were reviewed to study the clinical, radiological, and histopathological spectrum of the disease. The presence of palisading epithelioid cells and sheets of foamy histiocytes, enclosing a neutrophillic exudate rich in fibrin with nuclear debris, were clues as to suspicion of a tuberculous abscess. The demonstration of acid fast bacilli in the wall of the abscess or necrotic contents by microscopy or culture is essential to confirm the diagnosis of tuberculous abscess. A high index of clinical suspicion is necessary particularly in countries endemic for tuberculosis to ensure an accurate diagnosis and application of an appropriate therapy.

Nocardial brain abscess in an immunocompetent host.

Nocardial infection of the central nervous system is rare and usually manifests as brain abscess. Here we describe an elderly gentleman who presented with signs and symptoms of an intracranial mass lesion localising to the frontal lobe. Clinical examination and CT scan suggested neoplasia as the probable diagnosis. A biloculated abscess was seen at surgery. Aspiration of the contents and examination of pus revealed Nocardia asteroides . Treatment included total excision and prolonged antibiotic therapy which resulted in an excellent outcome.

Investigation of an outbreak of device-related postoperative ventriculitis: a lesson learnt.

Pseudomonas aeruginosa (P aeruginosa) is one of the most common nosocomial pathogens. We report our experience of a device-related outbreak of postoperative ventriculitis caused by P aeruginosa thus initiating investigation of the unusual occurrence. Five neurosurgical patients were affected, postoperatively. The investigations entailed extensive screening of the common sources of contamination for colonization of P aeruginosa. Sterilized instruments used for surgery, including the ultrasonic aspirator (USA) sets and other hollow devices, were randomly sampled and cultured. Conventional culture methods yielded P aeruginosa, with almost similar antibiotic sensitivity pattern in all the patients and the ultrasonic aspirator, clinching the source of contamination. Routine surveillance, identification of unusual patterns, molecular epidemiological typing would be helpful in quick control of outbreaks of postoperative infections.

Symptomatic seizures in neurosyphilis: an experience from a university hospital in south India.

PURPOSE: Neurosyphilis has protean clinical manifestations, including epilepsy. However, there is paucity of literature providing details regarding seizures. The aim of the study was to analyze the clinical profile and brain imaging features of 30 patients of neurosyphilis, and to evaluate the predictors and the outcome of seizures in this subgroup. PATIENT AND METHODS: Among the 119 patients (M:F:: 84:35) of neurosyphilis, evaluated over 6 years, 30 patients (M:W::23:7, age: 37.5+/-10.1 years, duration of illness: 11.9+/-20.1 months) were reported to have seizures. CSF-VDRL was positive in all. In addition, HIV serology was positive in 2/20. RESULTS: Seizure was the dominant symptom in all and lone manifestation in two patients. None had history of epilepsy. Their seizure profile was: generalized (17), partial (8), and status epilepticus (5). Concomitant manifestations were encephalopathy (7), meningitis (7), dementia (6), behavioral disturbances (4), stroke (2), and optic atrophy (1). CSF study revealed pleocytosis in 24 (34.6+/-51.5/cu mm) and raised protein in 20 (67+/-33.3mg%). CT scan was abnormal in 26 patients and revealed diffuse atrophy in all and focal hypodensities in 5 patients. MRI of brain (6) showed features of ischemia (2), meningeal enhancement (1) and white matter (1) and medial temporal (2) signal changes. Three patients had reversible periodic lateralized epileptiform discharges (PLEDs), without structural lesion. Nineteen patients received penicillin and/or ceftriaxone. At a mean follow up of 6.7+/-9.4 months, 13/17 had variable improvement. Nine patients required polytherapy and seizures remained uncontrolled in five patients. CONCLUSIONS: Symptomatic seizures due to neurosyphilis are frequent, may have diverse underlying mechanism(s) and rarely can be the lone manifestation. In view of availability of specific therapy for syphilis, a high index of suspicion is recommended.

Drug susceptibility profiling of tuberculous meningitis.

Drug-resistant tuberculosis is an increasing problem worldwide. There are few reports of drug susceptibility patterns of Mycobacterium tuberculosis isolated from cases of tuberculous meningitis. A 5-year retrospective study aimed at analysing the drug susceptibility profile of M. tuberculosis isolated from tuberculous meningitis cases was conducted. A total of 366 isolates were analysed. Among these, 301 (82.2%) were sensitive to all the four primary drugs tested, while 65 (17.8%) showed resistance. There were 46 (12.5%) isolates resistant to isoniazid (INH), while 9 (2.4%) demonstrated multidrug resistance. These data suggest that multidrug resistance in tuberculous meningitis is not yet a serious problem. However, a periodic review is required to ascertain the global incidence of drug-resistant tuberculous meningitis.

Central nervous system cladosporiosis: an account of ten culture-proven cases.

BACKGROUND: Central nervous system (CNS) cladosporiosis is a rare infection caused by Cladophialophora bantiana. It has varied presentation and poor outcome. Most of the available data in the literature are reviews of individual case reports. OBJECTIVE: To describe the clinical, radiological and mycological features of 10 cases of C. bantiana managed at a single tertiary center. To analyze the various treatment options, factors associated with outcome and to review the relevant literature. MATERIALS AND METHODS: This is a retrospective study of 10 patients with CNS cladosporiosis managed at National Institute of Mental Health and Neurosciences from 1979 to 2006. It is a descriptive study. The case records were reviewed for clinical presentation, radiological features, management and outcome. Only those patients in whom the fungus could be isolated on culture were included in the study. RESULTS: The age of the patients ranged from three to 42 years. Nine patients presented with features of space-occupying lesion and one patient with chronic meningitis. There were no specific clinical or radiological features. None of patients had impaired immune status. This infection presented as two pathomorphological forms - diffuse meningoencephalitis and focal abscesses. Burr hole tapping and excision are the surgical options. Both patients with burr hole tapping required excision of abscess subsequently. Two out of seven patients with abscess expired compared to all three patients with diffuse meningoencephalitis who expired. Recurrences occurred in four of the five patients following excision of the abscess. Combination antifungal treatment had better result than monotherapy. The outcome was poor with survival of only 50%. CONCLUSIONS: Thorough microbiological examination is required to diagnose CNS infection caused by C. bantiana. The outcome is better in patients with abscess. Excision of the abscess followed by combination antifungal therapy results in better outcome. Close follow-up is required due to high risk of recurrence.

Comparative evaluation of BACTEC 460TB system and Lowenstein-Jensen medium for the isolation of M. tuberculosis from cerebrospinal fluid samples of tuberculous meningitis patients.

PURPOSE: To evaluate the role of the radiometric BACTEC 460TB system and the conventional Lowenstein-Jensen (LJ) medium for isolation of M. tuberculosis from cerebrospinal fluid (CSF) samples of tuberculous meningitis (TBM) patients. METHODS: CSF specimens (n=2325) from suspected TBM patients were processed for isolation of mycobacteria by inoculating BACTEC 12B medium and the LJ medium. The isolation of mycobacteria in both media was confirmed by microscopy and biochemical identification. Drug sensitivity testing for the anti-TB drugs was carried out by BACTEC radiometric method. RESULTS: Among the total 2325 CSF specimens processed by both methods, M. tuberculosis was isolated from 256 specimens. The isolation rates were 93% and 39% for the BACTEC system and LJ medium respectively. Both the media supported growth in 32% of the culture-positive specimens. BACTEC system alone yielded growth in 61% and LJ alone in 7%, of the culture-positive specimens. Among 205 isolates tested for drug susceptibility 81% were sensitive to all the drugs tested and 19% were resistant. CONCLUSIONS: The BACTEC 460TB system provides a highly sensitive and rapid tool for the isolation and drug susceptibility testing of M. tuberculosis, from CSF of TBM patients. Use of a solid medium in conjunction with the BACTEC 12B medium is essential for optimal recovery for M. tuberculosis from CSF specimens.

Bacteriological profile of community acquired acute bacterial meningitis: a ten-year retrospective study in a tertiary neurocare centre in South India.

PURPOSE: Ten years retrospective study to evaluate the bacteriological spectrum of community acquired acute bacterial meningitis (CAABM). METHODS: Cerebrospinal fluid (CSF) samples from 385 clinically suspected cases of pyogenic meningitis were processed for cell counts, cytospin Gram stain, culture, antigen detection by latex agglutination (LAT) and antibiotic susceptibility test. Eighteen of these CSF samples were also subjected to a polymerase chain reaction (PCR) assay for detection of pneumococcal DNA. RESULTS: The etiological agent could be identified in 284 (73.8%) of the total 385 cases by culture and/or smear and /or LAT. Streptococcus pneumoniae was the predominant pathogen accounting for 238 (61.8%) cases. Haemophilus influenzae and Neisseria meningitidis accounted for 7 (1.8%) and 4 (1%) cases respectively. Other gram negative bacilli, Streptococcus spp. and Staphylococcus aureus were isolated from 19 (4.9%), 9 (2.3%) and 7 (1.8%) cases respectively. CONCLUSIONS: Streptococcus pneumoniae remains the major aetiological agent of CAABM both in adults and children in our set-up. No penicillin resistance was detected among the isolates. Further research should focus on preventable aspects of CAABM, especially pneumococcal vaccines, to help reduce the disease burden.

Fatal Group A Streptococcal meningitis in an adult.

Despite the recent resurgence in reports of invasive Group A Streptococcal (GAS) infections worldwide, it remains a rare cause of pyogenic meningitis both in children and adults. We report a case of fatal GAS meningitis in a healthy adult emphasizing the need for clinicians to be aware of its fulminant course, prompting early diagnosis and treatment. There is also a need to consider postexposure chemoprophylaxis in close contacts of such cases.

Role of IS6110 uniplex PCR in the diagnosis of tuberculous meningitis: experience at a tertiary neurocentre.

SETTING: Tuberculous meningitis (TBM) is the commonest form of neurotuberculosis in the Indian subcontinent. Rapid laboratory confirmation of TBM is important for the institution of early treatment and to avoid associated morbidity and mortality. The polymerase chain reaction (PCR) is the most widely applied alternative rapid diagnostic technique for TBM. OBJECTIVE: To evaluate the efficacy of an in-house developed IS6110 uniplex PCR (uPCR) in the diagnosis of TBM. DESIGN: A prospective, blinded study was conducted in a large sample base of 677 cerebrospinal fluid samples from 677 patients with clinically suspected TBM. RESULTS: All culture-positive samples (n = 136) were positive (100%) by the PCR assay. The assay was found to be positive in 70% (n = 541) of the samples with a clinical diagnosis of TBM. The assay had an observed sensitivity of 76.37% (negative predictive value 59.90%) and a specificity of 89.18% (positive predictive value 94.69%). A diagnostic accuracy of 80% (kappa 0.57) was seen in patients with a clinical diagnosis of TBM. Statistical significance was observed, as patients with a clinical diagnosis of TBM were found to be 9.38 times more likely to be PCR-positive (OR 9.38, chi2 = 149.94, P < 0.001). CONCLUSION: The performance of the in-house IS6110 uPCR assay merits its use as a sensitive and specific tool for the rapid diagnosis of TBM.

Antimicrobial resistance pattern among aerobic gram-negative bacilli of lower respiratory tract specimens of intensive care unit patients in a neurocentre.

BACKGROUND: Analysis of the tracheal and bronchial isolates from the lower respiratory tract specimens of the intensive care unit (ICU)-admitted patients, was carried out for the year 2002 with a perspective of looking at the antibiotic resistance pattern. METHODS: Lower respiratory tract secretions (tracheal or bronchoscopic aspirates) of 370 patients were cultured, identified and antimicrobial susceptibility performed by standard methods. RESULTS: Out of samples obtained from 370 patients, 274 (74%) were culture positive. A total of 489 bacterial isolates were recovered from 270 patients; 451 were gram-negative bacilli (GNB) and 38 were Staphylococcus aureus. In four of the patients, Candida spp was isolated. The common GNB isolates were non-fermentative gram-negative bacilli (NFGNB, 31.9%), followed by Pseudomonas aeruginosa (21.5%) and Klebsiella spp (19%). Elderly (24.8%) and adults (19.2%) showed increased rate of GNB isolation. In both tracheal and bronchial GNB isolates, the highest mean resistance was to cefazolin (98.8%) and ampicillin (97.6%) while the lowest mean resistance was to amikacin (48.5%). Isolation of two organisms per specimen (41.4%) was commonly seen. Multidrug resistance to the tested antimicrobials was more frequent in NFGNB (6.6%) and Pseudomonas aeruginosa (5%). There were no remarkable differences in the overall mean drug resistance among tracheal and bronchial GNB isolates. CONCLUSIONS: Isolation practices, antibiotic policies, effective surveillance, maintenance of epidemiological trends of infections and, rapid molecular diagnosis are the need of hour in improved and speedy management of lung infections with resistant organisms.

Neuropathology of HIV/AIDS with an overview of the Indian scene.

Neurological manifestations of HIV infection and AIDS are being recognized with a frequency that parallels the increasing number of AIDS cases. Next to sub-Saharan Africa, India has the second largest burden of HIV related pathology, essentially caused by HIV-1 clade C in both the geographic locales, in contrast to USA and Europe. But the true prevalence of HIV related neuroinfections and pathology is not available due to inadequate medical facilities, social stigma and ignorance that lead to underdiagnosis. Neurotuberculosis, followed by cryptococcosis and toxoplasmosis in various combinations are the major neuropathologies reflecting the endemicity and manifesting clinically by reactivation of latent infection. Discordance in the clinical prevalence of various infections, when compared to pathological studies highlight similarities in clinical, radiological modalities of diagnosis and inherent problems in establishing definitive diagnosis. Viral infections appear to be relatively rare. Inspite of heavy burden of HIV/AIDS, HIV associated neoplasia is infrequent, including primary CNS lymphomas. HIV encephalitis and HIV associated dementia are considered infrequent, though systematic studies have just been initiated in various centres. Peripheral neuropathy characteristically manifests with vasculitic neuropathy while diffuse infiltrative lymphocytosis syndrome (DILS) involving nerves has not been reported from India. Spinal cord pathology including vacuolar myelopathy is rare, even in asymptomatic cases. Till now the AIDS cases in India were drug naive but a new cohort of cases following initiation of HAART therapy as a national policy is soon emerging, altering the biology and evolution of HIV/AIDS in India. Lacunae in the epidemiology, diagnosis and study of biology of HIV/AIDS are outlined for future research.

Brain abscess due to Cladophialophora bantiana.

Cladophialophora bantiana (Xylohypha bantiana) is a dematiaceous fungus with distinct neurotropism. CNS phaeohyphomycosis due to C. bantiana is an uncommon infectious condition and is associated with high mortality. We report this rare clinical entity in a 22-year-old male, presenting as brain abscess. Etiological diagnosis was made based on fungal culture and histopathological examination. Complete surgical resection of the lesion and treatment with antifungal agents could not save the patient from this frequently fatal infection.

T helper responses to Japanese encephalitis virus infection are dependent on the route of inoculation and the strain of mouse used.

T helper cytokine and IgG subtype responses were studied in three strains of mice (C57BL/6J, Swiss albino, BALB/c; n=90 per strain) immunized with live Japanese encephalitis virus (JEV) by intraperitoneal (IP), subcutaneous (SC) and peroral (PO) routes. Lymphocytes obtained from the spleens of immunized and control mice were stimulated in vitro with JEV for 48 h and the supernatants were assayed for the presence of the cytokines IL-4 and IFN-gamma. JEV-specific IgG isotypes were also measured in the sera of immunized mice. T helper cytokine responses in mice immunized with JEV were found to be strain- and route-specific in the three species tested. Moreover, they were also dependent on the type of immunogen used (live vs killed virus), as well as the number of doses administered. C57BL/6J and BALB/c mice were more uniform in their T helper responses compared with the outbred Swiss albino mice and induced a good Th1 response (P<0.001). Among the three routes evaluated, the IP and SC routes consistently elicited a Th1 response compared with the PO route (P<0.001), where an initial Th2-type response reverted to a Th1 response after repeated immunization. Live JEV induced a Th1 response while the commercial killed vaccine induced a predominant Th2 profile.

Profile of neurologic disorders associated with HIV/AIDS from Bangalore, south India (1989-96).

One hundred patients (95 males, 5 females, mean age at presentation 31.6 +/- 9.4 yr) with various neurological disorders associated with HIV infection during 1989-1996 were evaluated at NIMHANS, Bangalore. Eighty patients belonged to group I associated with opportunistic neuroinfections and 20 to group II--non infectious neurological disorders. Cryptococcal meningitis either alone (n = 31) or associated with tuberculous meningitis (n = 6) was the most common (46.3%) followed by neurotuberculosis either alone (n = 24) or with cerebral toxoplasmosis (n = 4) accounting for 35 per cent. Other opportunistic neuroinfections included cerebral toxoplasmosis, herpes zoster, fulminant pyogenic meningitis and neurosyphilis. Clinical characteristics, diagnostic clues, their laboratory and radiological profiles and problems encountered in diagnosis and management of these opportunistic infections are highlighted. In group II (19 males and one female; mean age of 32.6 +/- 9.4 yr), two patients had cortical dementia, three acute brain stem involvement, two epilepsy and one had features suggestive of progressive multifocal leukoencephalopathy. Two patients of group I during follow up developed cortical dementia. Six had peripheral nervous system involvement similar to Guillain-Barre syndrome. Sixty six patients (63 of group I and 3 of group II) progressed to AIDS, 33 patients from group I and one patient from group II succumbed to the disease. With the rapid increase in the incidence of HIV/AIDS and an increase in the neurological manifestations of HIV/AIDS it is important to recognise the magnitude of the problem for health planning in India.