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

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 c...

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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
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Citation van Leeuwen LM, Versteegen P, Zaharie SD, van Elsland SL, Jordaan A, Streicher EM, Warren RM, van der Kuip M, van Furth AM. 2019. Bacterial genotyping of central nervous system tuberculosis in South Africa: heterogenic Mycobacterium tuberculosis infection and predominance of lineage 4. J Clin Microbiol 57:e00415-19. https://doi.org/10.1128/JCM.00415-19. L.M.V.L. and P.V. contributed equally to this work.
ISSN:	0095-1137 1098-660X 1098-660X
DOI:	10.1128/JCM.00415-19