Multidrug-resistant tuberculosis control in Rwanda overcomes a successful clone that causes most disease over a quarter century.

Autor:	Ngabonziza JCS; National Reference Laboratory Division, Department of Biomedical Services, Rwanda Biomedical Center, Kigali, Rwanda.; Mycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.; Department of Clinical Biology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda., Rigouts L; Mycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium., Torrea G; Mycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium., Decroo T; Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.; Research Foundation Flanders, Brussels, Belgium., Kamanzi E; National Reference Laboratory Division, Department of Biomedical Services, Rwanda Biomedical Center, Kigali, Rwanda., Lempens P; Mycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium., Rucogoza A; National Reference Laboratory Division, Department of Biomedical Services, Rwanda Biomedical Center, Kigali, Rwanda., Habimana YM; Tuberculosis and Other Respiratory Diseases Division, Institute of HIV/AIDS Disease Prevention and Control, Rwanda Biomedical Center, Kigali, Rwanda., Laenen L; Clinical Department of Laboratory Medicine and National Reference Center for Respiratory Pathogens, University Hospitals Leuven, Leuven, Belgium., Niyigena BE; National Reference Laboratory Division, Department of Biomedical Services, Rwanda Biomedical Center, Kigali, Rwanda., Uwizeye C; Mycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium., Ushizimpumu B; National Reference Laboratory Division, Department of Biomedical Services, Rwanda Biomedical Center, Kigali, Rwanda., Mulders W; Mycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium., Ivan E; National Reference Laboratory Division, Department of Biomedical Services, Rwanda Biomedical Center, Kigali, Rwanda., Tzfadia O; Mycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium., Muvunyi CM; Department of Clinical Biology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda., Migambi P; Research Foundation Flanders, Brussels, Belgium., Andre E; Mycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.; Clinical Department of Laboratory Medicine and National Reference Center for Respiratory Pathogens, University Hospitals Leuven, Leuven, Belgium.; KU Leuven, Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical Bacteriology and Mycology, Leuven, Belgium., Mazarati JB; Department of Biomedical Services, Rwanda Biomedical Center, Kigali, Rwanda., Affolabi D; Laboratoire de Référence des Mycobactéries, Cotonou, Benin., Umubyeyi AN; Management Sciences for Health, Pretoria, South Africa., Nsanzimana S; Rwanda Biomedical Center, Kigali, Rwanda., Portaels F; Mycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium., Gasana M; Tuberculosis and Other Respiratory Diseases Division, Institute of HIV/AIDS Disease Prevention and Control, Rwanda Biomedical Center, Kigali, Rwanda., de Jong BC; Mycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium., Meehan CJ; Mycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.; School of Chemistry and Biosciences, University of Bradford, UK.
Jazyk:	angličtina
Zdroj:	Journal of clinical tuberculosis and other mycobacterial diseases [J Clin Tuberc Other Mycobact Dis] 2022 Jan 24; Vol. 27, pp. 100299. Date of Electronic Publication: 2022 Jan 24 (Print Publication: 2022).
DOI:	10.1016/j.jctube.2022.100299
Abstrakt:	Summary Background: Multidrug-resistant (MDR) tuberculosis (TB) poses an important challenge in TB management and control. Rifampicin resistance (RR) is a solid surrogate marker of MDR-TB. We investigated the RR-TB clustering rates, bacterial population dynamics to infer transmission dynamics, and the impact of changes to patient management on these dynamics over 27 years in Rwanda. Methods: We analysed whole genome sequences of a longitudinal collection of nationwide RR-TB isolates. The collection covered three important periods: before programmatic management of MDR-TB (PMDT; 1991-2005), the early PMDT phase (2006-2013), in which rifampicin drug-susceptibility testing (DST) was offered to retreatment patients only, and the consolidated phase (2014-2018), in which all bacteriologically confirmed TB patients had rifampicin DST done mostly via Xpert MTB/RIF assay. We constructed clusters based on a 5 SNP cut-off and resistance conferring SNPs. We used Bayesian modelling for dating and population size estimations, TransPhylo to estimate the number of secondary cases infected by each patient, and multivariable logistic regression to assess predictors of being infected by the dominant clone. Results: Of 308 baseline RR-TB isolates considered for transmission analysis, the clustering analysis grouped 259 (84.1%) isolates into 13 clusters. Within these clusters, a single dominant clone was discovered containing 213 isolates (82.2% of clustered and 69.1% of all RR-TB), which we named the "Rwanda Rifampicin-Resistant clone" (R3clone). R3clone isolates belonged to Ugandan sub-lineage 4.6.1.2 and its rifampicin and isoniazid resistance were conferred by the Ser450Leu mutation in rpoB and Ser315Thr in katG genes, respectively. All R3clone isolates had Pro481Thr, a putative compensatory mutation in the rpoC gene that likely restored its fitness. The R3clone was estimated to first arise in 1987 and its population size increased exponentially through the 1990s', reaching maximum size (∼84%) in early 2000 s', with a declining trend since 2014. Indeed, the highest proportion of R3clone (129/157; 82·2%, 95%CI: 75·3-87·8%) occurred between 2000 and 13, declining to 64·4% (95%CI: 55·1-73·0%) from 2014 onward. We showed that patients with R3clone detected after an unsuccessful category 2 treatment were more likely to generate secondary cases than patients with R3clone detected after an unsuccessful category 1 treatment regimen. Conclusions: RR-TB in Rwanda is largely transmitted. Xpert MTB/RIF assay as first diagnostic test avoids unnecessary rounds of rifampicin-based TB treatment, thus preventing ongoing transmission of the dominant R3clone. As PMDT was intensified and all TB patients accessed rifampicin-resistance testing, the nationwide R3clone burden declined. To our knowledge, our findings provide the first evidence supporting the impact of universal DST on the transmission of RR-TB. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2022 The Authors.)
Databáze:	MEDLINE
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