Transmission patterns of rifampicin resistant Mycobacterium tuberculosis complex strains in Cameroon: a genomic epidemiological study.


Journal

BMC infectious diseases
ISSN: 1471-2334
Titre abrégé: BMC Infect Dis
Pays: England
ID NLM: 100968551

Informations de publication

Date de publication:
31 Aug 2021
Historique:
received: 14 06 2021
accepted: 17 08 2021
entrez: 1 9 2021
pubmed: 2 9 2021
medline: 25 9 2021
Statut: epublish

Résumé

Determining factors affecting the transmission of rifampicin (RR) and multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains under standardized tuberculosis (TB) treatment is key to control TB and prevent the evolution of drug resistance. We combined bacterial whole genome sequencing (WGS) and epidemiological investigations for 37% (n = 195) of all RR/MDR-TB patients in Cameroon (2012-2015) to identify factors associated with recent transmission. Patients infected with a strain resistant to high-dose isoniazid, and ethambutol had 7.4 (95% CI 2.6-21.4), and 2.4 (95% CI 1.2-4.8) times increased odds of being in a WGS-cluster, a surrogate for recent transmission. Furthermore, age between 30 and 50 was positively correlated with recent transmission (adjusted OR 3.8, 95% CI 1.3-11.4). We found high drug-resistance proportions against three drugs used in the short standardized MDR-TB regimen in Cameroon, i.e. high-dose isoniazid (77.4%), ethambutol (56.9%), and pyrazinamide (43.1%). Virtually all strains were susceptible to fluoroquinolones, kanamycin, and clofazimine, and treatment outcomes were mostly favourable (87.5%). Pre-existing resistance to high-dose isoniazid, and ethambutol is associated with recent transmission of RR/MDR strains in our study. A possible contributing factor for this observation is the absence of universal drug susceptibility testing in Cameroon, likely resulting in prolonged exposure of new RR/MDR-TB patients to sub-optimal or failing first-line drug regimens.

Sections du résumé

BACKGROUND BACKGROUND
Determining factors affecting the transmission of rifampicin (RR) and multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains under standardized tuberculosis (TB) treatment is key to control TB and prevent the evolution of drug resistance.
METHODS METHODS
We combined bacterial whole genome sequencing (WGS) and epidemiological investigations for 37% (n = 195) of all RR/MDR-TB patients in Cameroon (2012-2015) to identify factors associated with recent transmission.
RESULTS RESULTS
Patients infected with a strain resistant to high-dose isoniazid, and ethambutol had 7.4 (95% CI 2.6-21.4), and 2.4 (95% CI 1.2-4.8) times increased odds of being in a WGS-cluster, a surrogate for recent transmission. Furthermore, age between 30 and 50 was positively correlated with recent transmission (adjusted OR 3.8, 95% CI 1.3-11.4). We found high drug-resistance proportions against three drugs used in the short standardized MDR-TB regimen in Cameroon, i.e. high-dose isoniazid (77.4%), ethambutol (56.9%), and pyrazinamide (43.1%). Virtually all strains were susceptible to fluoroquinolones, kanamycin, and clofazimine, and treatment outcomes were mostly favourable (87.5%).
CONCLUSION CONCLUSIONS
Pre-existing resistance to high-dose isoniazid, and ethambutol is associated with recent transmission of RR/MDR strains in our study. A possible contributing factor for this observation is the absence of universal drug susceptibility testing in Cameroon, likely resulting in prolonged exposure of new RR/MDR-TB patients to sub-optimal or failing first-line drug regimens.

Identifiants

pubmed: 34465301
doi: 10.1186/s12879-021-06593-8
pii: 10.1186/s12879-021-06593-8
pmc: PMC8406724
doi:

Substances chimiques

Antitubercular Agents 0
Isoniazid V83O1VOZ8L
Rifampin VJT6J7R4TR

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

891

Subventions

Organisme : German Research Foundation
ID : EXC 2167
Organisme : German Research Foundation
ID : EXC 2167

Informations de copyright

© 2021. The Author(s).

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Auteurs

Matthias Merker (M)

Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany. mmerker@fz-borstel.de.
Evolution of the Resistome, Research Center Borstel, Borstel, Germany. mmerker@fz-borstel.de.
German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Borstel, Germany. mmerker@fz-borstel.de.

Nkongho F Egbe (NF)

Tuberculosis Reference Laboratory Bamenda, Center for Health Promotion and Research, Bamenda, Cameroon.
School of Life Sciences, College of Science, University of Lincoln, Lincoln, England, UK.

Yannick R Ngangue (YR)

Tuberculosis Reference Laboratory Bamenda, Center for Health Promotion and Research, Bamenda, Cameroon.

Comfort Vuchas (C)

Tuberculosis Reference Laboratory Bamenda, Center for Health Promotion and Research, Bamenda, Cameroon.

Thomas A Kohl (TA)

Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany.

Viola Dreyer (V)

Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany.

Christopher Kuaban (C)

Faculty of Health Sciences, University of Bamenda, Bamenda, Cameroon.

Jürgen Noeske (J)

, Bamenda, Cameroon.

Stefan Niemann (S)

Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany.
German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Borstel, Germany.

Melissa S Sander (MS)

Tuberculosis Reference Laboratory Bamenda, Center for Health Promotion and Research, Bamenda, Cameroon.

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Classifications MeSH