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J Clin Microbiol. 2019 Jul 26;57(8). pii: e00415-19. doi: 10.1128/JCM.00415-19. Print 2019 Aug.

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

Author information

1
Department of Pediatric Infectious Diseases and Immunology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
2
Department of Anatomical Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
3
Department of Paediatrics and Child Health, Tygerberg Hospital, Stellenbosch University, Cape Town, South Africa.
4
Division of Molecular Biology and Human Genetics, South African Medical Research Council Centre for Tuberculosis Research, DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
5
Department of Pediatric Infectious Diseases and Immunology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands m.vanderkuip@amsterdamumc.nl.
#
Contributed equally

Abstract

Tuberculous meningitis (TBM), the most severe extrapulmonary manifestation of tuberculosis, is caused by the pathogen Mycobacterium tuberculosis The M. tuberculosis 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 M. tuberculosis 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. M. tuberculosis 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%). M. tuberculosis 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 M. tuberculosis lineage and that even young children with rapid progression of disease can harbor more than one M. tuberculosis lineage in the CNS.

KEYWORDS:

CNS tuberculosis; Mycobacterium tuberculosis lineage; childhood tuberculosis; genomic heterogeneity; genotyping; mixed infection; tuberculous meningitis

PMID:
31189579
PMCID:
PMC6663911
[Available on 2020-01-26]
DOI:
10.1128/JCM.00415-19

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