Fourth National Anti-Tuberculosis Drug Resistance Survey in Côte d'Ivoire Incorporating Sequencing

Drug-resistant tuberculosis (TB) hinders global TB control. Rifampicin-resistant TB (RR-TB) prevalence, in Côte d'Ivoire, was 4.6% (95% confidence interval [95% CI]: 2.4-6.7) for new cases and 22% (95% CI: 13.7-30.3) with retreatment cases in 2016. The TB drug resistance survey (DRS) conducted in 2023 aimed to determine the updated prevalence of resistance among new, previously treated TB cases and to characterize the genotypes of circulating Mycobacterium tuberculosis strains.

A nationwide, cluster-based cross-sectional DRS was conducted in a 6-month timeframe in 44 health facilities across the country, grouped into 45 clusters according to the World Health Organization guidance. Bacteriologically confirmed pulmonary TB cases were recruited after giving informed consent. Xpert ® MTB/RIF Ultra, Hain MTBDR plus and MTBDR sl were carried out on sputum samples. All samples with resistance detected and 10% of rifampicin (RIF) susceptible TB cases were cultured in liquid medium with Mycobacterium growth incubator tube (MGIT) (MGIT 960). Phenotypic drug susceptibility testing was performed for isoniazid (INH), RIF, amikacin (AMK), moxifloxacin, levofloxacin, clofazimine, bedaquiline, and linezolid. Whole-genome or targeted next-generation sequencing was conducted on 120 selected drug-resistant and susceptible strains. KoboCollect v2013.1.2 was used for data collection and storage. For statistical and cluster analysis, STATA 19.5 and core genome multilocus sequence typing in Ridom SeqSphere + were used, respectively.

1024 participants were enrolled, 947 (92.5%) were new cases. INH monoresistant TB prevalence was 4.8% (95% CI: 3.6-6.4) in new cases and 5.6% (95% CI: 1.5-18.8) in retreatment cases. Multidrug-resistant TB (MDR-TB) prevalence was 2.5% (95% CI: 1.7%-3.8%) in new and 14.1% (95% CI: 7.0%-26.5%) in previous treated cases. Among RR-TB, MDR-TB prevalence was 89.5% (95% CI: 73.8-96.3), of whom 2 pre-extensively drug-resistant (XDR) TB and 1 XDR-TB were detected. Sequencing revealed a predominant circulation of lineage 4.6.2.2 and 4.1 (28% each) following by lineage 6 (11%).

Progress has been made in combating TB drug resistance in Côte d'Ivoire compared to the previous DRS. Molecular tools have permitted to detect heteroresistance or mixed infection and the existence of circulating virulent strains associated with alarming rates of drug resistance.