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. 2021 Aug 31;21(1):891.
doi: 10.1186/s12879-021-06593-8.

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

Matthias Merker  1   2   3 , Nkongho F Egbe  4   5 , Yannick R Ngangue  4 , Comfort Vuchas  4 , Thomas A Kohl  6 , Viola Dreyer  6 , Christopher Kuaban  7 , Jürgen Noeske  8 , Stefan Niemann #  6   9 , Melissa S Sander #  4
Affiliations

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

Matthias Merker et al. BMC Infect Dis. .

Abstract

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: 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: 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: 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.

Keywords: Cameroon; MDR-TB; Mycobacterium tuberculosis; Transmission.

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Conflict of interest statement

The authors declare no competing interest.

Figures

Fig. 1
Fig. 1
Drug resistance and molecular clusters of multidrug resistant (MDR) Mycobacterium tuberculosis complex (MTBC) strains in Cameroon. Maximum likelihood phylogeny of 195 rifampicin resistant and MDR-MTBC strains from Cameroon (2012–2015). MTBC lineages are color coded, stronger colours denote closely related strains (≤ 5 SNP pairwise distance) as surrogate for recently transmitted strains. Genotypic resistances to individual drugs are represented by red squares
Fig. 2
Fig. 2
Drug resistance proportions among multidrug resistant (MDR) tuberculosis patients in Cameroon (2012–2015). Annual changes of genotypic drug resistance proportions of 195 rifampicin resistant and MDR Mycobacterium tuberculosis complex strains in Bamenda, Cameroon. Colours code for individual drugs, vertical lines represent 95% confidence interval. INH = isoniazid, EMB = ethambutol, PZA = pyrazinamide, PTH = prothionamide, MFX = moxifloxacin, KM = kanamycin, CFZ = clofazimine
Fig. 3
Fig. 3
Transmission networks among multidrug resistant (MDR) tuberculosis patients in Cameroon. Seven largest molecular clusters of rifampicin resistant and MDR Mycobacterium tuberculosis complex strains in Bamenda, Cameroon. Numbers on connecting lines indicate alelle differences; pink branches connect strains with a maximum distance of five alleles. Boxes indicate strains with identical pncA mutations, and identical node colors represent patients with confirmed epidemiological links
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