Utility of GenoType MTBDRPlus Assay for Direct Detection and Drug Susceptibility Testing of Mycobacterium tuberculosis from Probable Tuberculous Meningitis Patients.

Aims: To evaluate GenoType® MTBDRplus line probe assay as a diagnostic tool for detection of Mycobacterium tuberculosis and drug susceptibility testing from cerebrospinal fluid of probable tuberculous meningitis patients. Study Design: A prospective, double blind study. Place and Duration of study: Dept. of Microbiology and Neurology, Institute of Human Behavior and Allied sciences, Delhi, India between February 2014 to October 2014. Methodology: Cerebrospinal fluid collected from 107 probable meningitis patients with diagnostic score >10 were subjected to smear microscopy, automated liquid culture (BACTEC MGIT 960) and Polymerase chain reaction (IS6110). All the samples were also subjected to GenoType® MTBDRplus line probe assay for detecting M. tuberculosis and drug susceptibility. Drug susceptibility testing of all the M. tuberculosis isolates was done by BACTEC MGIT 960 and GenoType® MTBDRplus line probe assay. Results: The sensitivity, specificity of the assay for M. tuberculosis detection was 49.5%, 100% against clinical diagnosis as reference standard and 68.9%, 100% against definitive diagnosis as reference standard. A diagnostic accuracy of 56.8% (kappa 0.22), 75% (kappa 0.46), were seen in patients with probable and confirmed diagnosis respectively. The drug susceptibility results for Isoniazid and Rifampicin could be delineated in only 39.2% of patients. Conclusion: This assay proved to have better sensitivity, diagnostic accuracy than smear microscopy and automated liquid culture for early detection of M. tuberculosis from probable tuberculous meningitis patients and has comparable sensitivity to culture (39.2%) for detection of drug susceptibility (though on different isolates). Rapid turnaround time and user friendliness makes it an acceptable assay for simultaneous early detection of M. tuberculosis and its drug susceptibility for better patient management.

Prevalence of HIV-associated cryptococcal meningitis and utility of microbiological determinants for its diagnosis in a tertiary care center.

CONTEXT: Human immunodeficiency virus (HIV) infection continues to be the most important risk factor for the development of central nervous system (CNS) cryptococcosis, which in turn is an important contributor to morbidity and mortality in HIV-infected patients. Early diagnosis of such patients is the key to their therapeutic success. AIMS: This study was undertaken to find out the prevalence of CNS cryptococcosis and to assess the role of microbiological parameters for its specific diagnosis in HIV-reactive hospitalized patients admitted with meningeal signs in a tertiary care setting. MATERIALS AND METHODS: A total of 104 patients suspected to be suffering from meningitis/meningoencephalitis were subjected to cerebrospinal fluid (CSF) analysis (including India ink preparation, culture by conventional methods and Bactec MGIT 960 system, antigen detection) and tests for HIV antibodies by standard laboratory operating procedures. RESULTS: The prevalence of HIV infection in our study group was 12.5% (13/104), while the prevalence of cryptococcal CNS infection in HIV-reactive cohort was 46% (6/13). Additionally, 15.3% (2/13) of the patients from this cohort were positive for Mycobacterium tuberculosis. CONCLUSIONS: High prevalence of cryptococcal CNS infections in HIV-infected patients underscores the importance of precise and early microbiological diagnosis for better management of such patients.

Neuropathology of schizophrenia--a review.

Despite clinical evidence of brain dysfunction in schizophrenia, little progress was made for most of the last century in determining its organic parameters. Neuropathology, over the past few decades, has made a substantial contribution to the understanding of cellular and molecular mechanisms of schizophrenia. During the last 10-15 years the concept of schizophrenia as a 'functional' psychosis has changed to the current paradigm of schizophrenia as a neurodevelopmental disorder. Much still has to be unravelled and learnt. This review gives a brief account of the relevant neuroanatomy, viral hypotheses of schizophrenia etiology, pathologic findings reported, concept of neurodevelopmental model and avenues for the future.

Human prion diseases.

Prion diseases is another name for a group of 'transmissible spongiform encephalopathies'. Creutzfeldt-Jakob disease, the first prion disease described in humans, occurs in sporadic, familial or iatrogenic form. Other transmissible spongiform encephalopathies in humans such as familial Creutzfeldt-]akob disease, Gerstmann-Sträussler-Scheinker disease and fatal familial Insomnia have been shown to be associated with specific prion protein gene mutations. In 1996, a new variant of Creutzfeldt-Jakob disease was reported in the United Kingdom among young patients with unusual clinical features and unique neuropathological findings. This new form could be due to transmission to humans of the agent causing bovine spongiform encephalopathy. While examination of brain tissue is the key to making a diagnosis, it is not always possible antemortem. Immunological tests such as ELISA or western blot assays along with tests for 1 4-3-3 protein in the cerebrospinal fluid remain the main tools of diagnosis. Conventional disinfection and sterilization practices are Ineffective for these agents. The unusual properties of prions pose a challenge for treatment, surveillance and control of these diseases.