Effect of mycobacterium tuberculosis lineage, drug resistance and HIV status on the outcome of patients with tuberculous meningitis

Introduction: Tuberculous Meningitis (TBM) is a devastating disease with high morbidity and mortality. Resistance to anti tubercular drugs, strain variation among M. tuberculosis and HIV status of the host are important factors governing the disease progression in pulmonary tuberculosis and data regarding TBM is lacking. The geographical variations present in these factors necessitate local epidemiological studies. Aim: The present study was conducted to assess the influence of drug resistance and lineage on the outcome of HIV positive and negative cases of TBM. Materials and Methods: Genotypic profiling using 24-loci Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) analysis was retrospectively conducted on 70 (8 HIV positive patients, 62 HIV negative patients) Cerebrospinal Fluid (CSF) culture isolates of M. tuberculosis processed in the Mycobacteriology laboratory of PGIMER during January 2010-December 2015. Drug susceptibility was performed phenotypically by 1% proportion method and genotypically by rpoB and katG gene sequencing. Results: Total 4 (5.7%) out of 70 isolates of M. tuberculosis were multidrug resistant and were associated with higher mortality than the drug sensitive ones. Among the different lineages, the Beijing genotype was uniformly associated with drug resistance and mortality. All HIV positive patients had a poor outcome, irrespective of drug resistance and lineage. Conclusion: Multidrug resistance lineage of M. tuberculosis and HIV status are important determinants of mortality in patients of TBM. Targeting these factors can contribute to a favourable outcome.