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Tuberculous meningitis (TBM), the most severe extra-pulmonary manifestation of tuberculosis, is caused by the pathogen  The  complex includes seven lineages, all described to harbour a unique geographical dissemination pattern and clinical presentation. In this study, we set out to determine whether a certain  lineage demonstrated tropism to cause TBM in patients from Cape Town, South Africa. DNA was extracted from formalin-fixed paraffin embedded central nervous system (CNS) tissue from a unique neuro-pathological cohort of 83 TBM patients, collected between 1975 and 2012.  lineages 1, 2, 3 and 4 were determined using an allele specific PCR and Sanger sequencing. Of the 83 patient specimen tested, bacterial characterization could be performed on 46 patients (55%).  lineage 4 was present in 26 patients (56%) and non-lineage 4 was identified in 10 cases (22%). Moreover, genomic heterogeneity was detected in the CNS specimens of 7 adults and 3 children. We could show that infection of the CNS is not restricted to a single  lineage and that even young children with rapid progression of disease can harbour more than one  lineage in the CNS.

journal of clinical microbiology

Bacterial Genotyping of Central Nervous System Tuberculosis in South Africa: Heterogenic Mycobacterium tuberculosis Infection and Predominance of Lineage 4