Abstract
BackgroundDetermining 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.MethodsWe 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.ResultsPatients 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%).ConclusionPre-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.
Highlights
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
Patient characteristics and treatment outcomes Specimens from 261 patients with Rifampicin resistance (RR)/MDR-TB were received at the laboratory during the study period
Our genomic epidemiological study of RR/MDR Mycobacterium tuberculosis complex (MTBC) strains in Cameroon showed that, besides age of 30–50 years, genotypic resistance to high-dose isoniazid, and ethambutol is a strong predictor for molecular clusters, which is a surrogate for recent transmission
Summary
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. The short MDR-TB regimen is recommend for patients infected with a RR/MDR Mycobacterium tuberculosis complex (MTBC) strain who have not been treated for more than 1 month with the above mentioned antibiotics and for whom resistance to fluoroquinolones and second-line injectable drugs has been excluded [4]. Prudent usage with careful follow-up has been recommended when resistance to isoniazid, pyrazinamide or second-line injectable drugs is present at the initiation of the short MDR-TB therapy [10,11,12]. Besides the elevated risks of treatment failure under standardized treatment regimens, pre-existing drug resistances have been linked to increased transmission rates of MDR MTBC strains globally [13,14,15]
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