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

• Published in: Journal of clinical microbiology Vol. 57; no. 8
• Main Authors: van Leeuwen, L M, Versteegen, P, Zaharie, S D, van Elsland, S L, Jordaan, A, Streicher, E M, Warren, R M, van der Kuip, M, van Furth, A M
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01-08-2019
• Subjects: Adolescent; Adult; Brain - microbiology; Brain - pathology; Child; Child, Preschool; Cohort Studies; DNA, Bacterial - genetics; Female; Genetic Heterogeneity; Genotype; Genotyping Techniques; Humans; Male; Meningitis, Bacterial - epidemiology; Mycobacteriology and Aerobic Actinomycetes; Mycobacterium tuberculosis - classification; Mycobacterium tuberculosis - genetics; South Africa - epidemiology; Tuberculosis, Central Nervous System - epidemiology; Tuberculosis, Central Nervous System - microbiology; Young Adult; South Africa; genomic heterogeneity; mixed infection; tuberculous meningitis; genotyping; Mycobacterium tuberculosis lineage; CNS tuberculosis; childhood tuberculosis
• ISSN: 0095-1137; 1098-660X; 1098-660X
• DOI: 10.1128/JCM.00415-19

Tuberculous meningitis (TBM), the most severe extrapulmonary manifestation of tuberculosis, is caused by the pathogen
The
complex includes seven lineages, all described to harbor 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 neuropathological 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 specimens tested, bacterial characterization could be performed on 46 specimens (55%).
lineage 4 was present in 26 patient specimens (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 harbor more than one
lineage in the CNS.