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 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
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:1098-660X, 1098-660X
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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.
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ISSN:1098-660X
1098-660X
DOI:10.1128/JCM.00415-19