Seasonal Malaria Chemoprevention Drug Levels and Drug Resistance Markers in Children With or Without Malaria in Burkina Faso: A Case-Control Study

J Infect Dis. 2023 Oct 3;228(7):926-935. doi: 10.1093/infdis/jiad172.

Abstract

Background: Despite scale-up of seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (SP-AQ) in children 3-59 months of age 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% confidence interval, .16-.67]; P = .002) and have lower drug levels (P < .05). Prevalences of mutations mediating high-level SP resistance were rare (0%-1%) and similar between cases and SMC-ineligible controls (P > .05).

Conclusions: 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.

Keywords: amodiaquine; antimalarial resistance; malaria; seasonal malaria chemoprevention; sulfadoxine-pyrimethamine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amodiaquine / therapeutic use
  • Antimalarials* / pharmacology
  • Antimalarials* / therapeutic use
  • Burkina Faso / epidemiology
  • Case-Control Studies
  • Chemoprevention / methods
  • Child
  • Child, Preschool
  • Drug Combinations
  • Drug Resistance
  • Humans
  • Infant
  • Malaria* / drug therapy
  • Malaria* / epidemiology
  • Malaria* / prevention & control
  • Seasons
  • Sulfadoxine / therapeutic use

Substances

  • Antimalarials
  • Sulfadoxine
  • Amodiaquine
  • Drug Combinations