Assessment of the in vivo effectiveness of sulfadoxine-pyrimethamine plus amodiaquine in children participating in routine Seasonal Malaria Chemoprevention in Békourou health district
Design
Prospective cohort study
Context
Monitoring of molecular markers for the drugs (sulfadoxine-pyrimethamine and amodiaquine, SPAQ) used in the chemoprevention of seasonal malaria in the Moïssala health district, of which Békourou was a part, revealed a substantial increase in the quadruple mutation (dhfr N51I, dhfr C59R, dhfr S108N, dhps A437G), which rose from 28 per cent in 2014 to 48 per cent in 2023. However, the quintuple mutation (including the dhps K540E mutation), a key indicator of resistance, remains low and stable, ranging between 3 per cent and 8 per cent.
This study aims to evaluate the efficacy of SPAQ in vivo, that is, the ability of the drugs to eliminate pre-existing parasitaemia and prevent new infections over a 28-day period.
The study results will enable the efficacy of chemoprophylaxis to be classified according to the method proposed by White et al. (White, 2022; White et al., 2023). The results of this study will provide decision-makers with additional and more precise information to determine whether the SPAQ should be retained as the standard treatment or whether a more effective alternative should be adopted. Currently, the preferred replacement candidate would be the dihydroartemisinin-piperaquine combination (Gutman et al., 2017; Zongo et al., 2015).
Gutman, J., Kovacs, S., Dorsey, G., Stergachis, A., & ter Kuile, F. O. (2017). Safety, tolerability, and efficacy of repeated doses of dihydroartemisinin-piperaquine for prevention and treatment of malaria: A systematic review and meta-analysis. The Lancet Infectious Diseases, 17(2), 184-193. https://doi.org/10.1016/S1473-3099(16)30378-4
White, N. J. (2022). The assessment of antimalarial drug efficacy in vivo. Trends in Parasitology, 38(8), 660-672. https://doi.org/10.1016/j.pt.2022.05.008
White, N. J., Bonnington, C., & Nosten, F. H. (2023). A proposed method of grading malaria chemoprevention efficacy. Transactions of The Royal Society of Tropical Medicine and Hygiene, trad042. https://doi.org/10.1093/trstmh/trad042
Zongo, I., Milligan, P., Compaore, Y. D., Some, A. F., Greenwood, B., Tarning, J., Rosenthal, P. J., Sutherland, C., Nosten, F., & Ouedraogo, J.-B. (2015). Randomized Noninferiority Trial of Dihydroartemisinin-Piperaquine Compared with Sulfadoxine-Pyrimethamine plus Amodiaquine for Seasonal Malaria Chemoprevention in Burkina Faso. Antimicrobial Agents and Chemotherapy, 59(8), 4387-4396. https://doi.org/10.1128/AAC.04923-14
Our role
Coordination
Partners
- Ministry of health, Chad
Methodology
This is a prospective cohort study involving children eligible for Seasonal malaria chemoprevention (SMC) treatment. The asymptomatic children recruited will receive a three-day course of SPAQ under supervision and will be monitored for 28 days following administration of the first dose of SMC, in order to assess their clinical, parasitological and pharmacological status. Parasites extracted from samples taken from infected children will be analysed for genetic markers of resistance to SPAQ.
The target population consists of children eligible for SMC treatment living in the Békourou health district, where SMC has been implemented since 2013.
Children will be recruited for the study during the 2nd, 3rd and 4th rounds of SMC distribution, which are expected to take place between July and September 2026.
The sample size of 203 children was estimated assuming a 95 per cent success rate in eliminating parasites or preventing new infections by the end of the follow-up period, with a precision of 3 per cent and a 95 per cent confidence level. Given that it was anticipated that 25 per cent of the children would not be followed up or would not be eligible for assessment, the sample size was rounded up to 270 (90 children per round).
