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

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

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.

MeSH terms

  • Adult
  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / therapeutic use
  • Cameroon / epidemiology
  • Epidemiologic Studies
  • Genomics
  • Humans
  • Isoniazid / pharmacology
  • Microbial Sensitivity Tests
  • Middle Aged
  • Mycobacterium tuberculosis* / genetics
  • Rifampin / pharmacology
  • Tuberculosis, Multidrug-Resistant* / drug therapy
  • Tuberculosis, Multidrug-Resistant* / epidemiology

Substances

  • Antitubercular Agents
  • Isoniazid
  • Rifampin