Genetic diversity of Mycobacterium tuberculosis strains circulating in Botswana.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2019
Historique:
received: 08 02 2019
accepted: 17 04 2019
entrez: 8 5 2019
pubmed: 8 5 2019
medline: 15 1 2020
Statut: epublish

Résumé

Molecular typing of Mycobacterium tuberculosis (M.tb) isolates can inform Tuberculosis (TB) control programs on the relative proportion of transmission driving the TB epidemic. There is limited data on the M. tb genotypes that are circulating in Botswana. The aim of this study was to generate baseline data on the genetic diversity of M.tb isolates circulating in the country. A total of 461 M.tb isolates received at the Botswana National Tuberculosis Reference Laboratory between March 2012 and October 2013 were included in this study. Drug susceptibility testing was conducted using the BD BACTEC MGIT 960 System. M.tb strains were genotyped using spoligotyping and spoligotype patterns were compared with existing patterns in the SITVIT Web database. A subset of drug resistant isolates which formed spoligo clusters (n = 65) was additionally genotyped with 12-loci MIRU. Factors associated with drug resistance and clustering were evaluated using logistic regression. Of the 461 isolates genotyped, 458 showed 108 distinct spoligotype patterns. The predominant M.tb lineages were Lineage 4 (81.9%), Lineage 2 (9%) and Lineage 1 (7.2%). The predominant spoligotype families within Lineage 4 were LAM (33%), S (14%), T (16%), X (16%). Three hundred and ninety-two (86%) isolates could be grouped into 44 clusters (2-46 isolates per cluster); giving a clustering rate of 76%. We identified 173 (37.8%) drug resistant isolates, 48 (10.5%) of these were multi-drug resistant. MIRU typing of the drug resistant isolates allowed grouping of 46 isolates into 14 clusters, giving a clustering rate of 49.2%. There was no association between age, sex, treatment category, region and clustering. This study highlights the complexity of the TB epidemic in Botswana with multiple strains contributing to disease and provides baseline data on the population structure of M.tb strains in Botswana.

Sections du résumé

BACKGROUND
Molecular typing of Mycobacterium tuberculosis (M.tb) isolates can inform Tuberculosis (TB) control programs on the relative proportion of transmission driving the TB epidemic. There is limited data on the M. tb genotypes that are circulating in Botswana. The aim of this study was to generate baseline data on the genetic diversity of M.tb isolates circulating in the country.
METHODS
A total of 461 M.tb isolates received at the Botswana National Tuberculosis Reference Laboratory between March 2012 and October 2013 were included in this study. Drug susceptibility testing was conducted using the BD BACTEC MGIT 960 System. M.tb strains were genotyped using spoligotyping and spoligotype patterns were compared with existing patterns in the SITVIT Web database. A subset of drug resistant isolates which formed spoligo clusters (n = 65) was additionally genotyped with 12-loci MIRU. Factors associated with drug resistance and clustering were evaluated using logistic regression.
RESULTS
Of the 461 isolates genotyped, 458 showed 108 distinct spoligotype patterns. The predominant M.tb lineages were Lineage 4 (81.9%), Lineage 2 (9%) and Lineage 1 (7.2%). The predominant spoligotype families within Lineage 4 were LAM (33%), S (14%), T (16%), X (16%). Three hundred and ninety-two (86%) isolates could be grouped into 44 clusters (2-46 isolates per cluster); giving a clustering rate of 76%. We identified 173 (37.8%) drug resistant isolates, 48 (10.5%) of these were multi-drug resistant. MIRU typing of the drug resistant isolates allowed grouping of 46 isolates into 14 clusters, giving a clustering rate of 49.2%. There was no association between age, sex, treatment category, region and clustering.
CONCLUSIONS
This study highlights the complexity of the TB epidemic in Botswana with multiple strains contributing to disease and provides baseline data on the population structure of M.tb strains in Botswana.

Identifiants

pubmed: 31063472
doi: 10.1371/journal.pone.0216306
pii: PONE-D-19-03820
pmc: PMC6504092
doi:

Types de publication

Clinical Trial Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0216306

Subventions

Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 107752/Z/15/Z
Pays : United Kingdom

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Tuelo Mogashoa (T)

Department of Medical Laboratory Sciences, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana.
Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.

Pinkie Melamu (P)

Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.

Serej D Ley (SD)

DST-NRF Centre of Excellence in Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Swiss Tropical and Public Health Institute, Basel, Switzerland.

Elizabeth M Streicher (EM)

DST-NRF Centre of Excellence in Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Thato Iketleng (T)

Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
College of Health Sciences, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.

Nametso Kelentse (N)

Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.

Lucy Mupfumi (L)

Department of Medical Laboratory Sciences, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana.
Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.

Margaret Mokomane (M)

National Tuberculosis Reference Laboratory, Ministry of Health and Wellness, Gaborone, Botswana.

Botshelo Kgwaadira (B)

National Tuberculosis Reference Laboratory, Ministry of Health and Wellness, Gaborone, Botswana.

Vladimir Novitsky (V)

Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.

Ishmael Kasvosve (I)

Department of Medical Laboratory Sciences, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana.

Sikhulile Moyo (S)

Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.

Robin M Warren (RM)

DST-NRF Centre of Excellence in Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Simani Gaseitsiwe (S)

Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.

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Classifications MeSH