Seasonal malaria chemoprevention drug levels and drug resistance markers in children with or without malaria in Burkina Faso: a case control study

Abstract Background Despite scale-up of seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (SP-AQ) in children <5 years old in Burkina Faso, malaria incidence remains high, raising concerns regarding SMC effectiveness and selection of drug resistance. Using a case-control design, we determined associations between SMC drug levels, drug resistance markers, and presentation with malaria. Methods We enrolled 310 children presenting at health facilities in Bobo-Dioulasso. Cases were SMC-eligible children 6-59 months of age diagnosed with malaria. Two controls were enrolled per case: SMC-eligible children without malaria and older (5-10 years old), SMC-ineligible children with malaria. We measured SP-AQ drug levels among SMC-eligible children and SP-AQ resistance markers among parasitemic children. Conditional logistic regression was used to compute odds ratios (ORs) comparing drug levels between cases and controls. Results Compared to SMC-eligible controls, children with malaria were less likely to have any detectable SP or AQ (OR = 0.33 [95% CI: 0.16-0.67]; p = 0.002) and have lower drug levels (p < 0.05). Prevalences of mutations mediating high-level SP resistance were rare (0-1%) and similar between cases and SMC-ineligible controls (p > 0.05). Conclusion Incident malaria among SMC-eligible children was likely due to suboptimal levels of SP-AQ, resulting from missed cycles, rather than increased antimalarial resistance to SP-AQ.