Parasitological efficacy of sulfadoxine-pyrimethamine and amodiaquine for seasonal malaria chemoprevention in Africa
Abstract
Seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine (SPAQ) protects millions of African children, yet the contribution of each drug to preventive efficacy remains unclear. We pooled individual-level data on drug concentrations and malaria infection in 934 children from Uganda (NCT05323721), Mozambique (NCT05186363), and Burkina Faso (NCT05478954). The primary outcome was malaria infection by day 28, and the secondary outcome was the day 28 qPCR cycle threshold value. From natural variation in drug exposure, desethylamodiaquine, the active amodiaquine metabolite, was the primary determinant of malaria infection (OR 0.55, 95% CI 0.44–0.68 per standard deviation increase in log concentration). Children with low day 28 desethylamodiaquine exposure (<24 ng/mL) had nearly twice the risk of malaria infection (RR 1.9, 95% CI 1.5–2.4). Sulfadoxine and pyrimethamine showed only weak associations, consistent across countries despite varying resistance haplotypes. SPAQ efficacy appears primarily amodiaquine-driven and the role of single-dose sulfadoxine–pyrimethamine merits further evaluation.
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BibTeX
@article{sararat2026parasitological,
title = {{Parasitological efficacy of sulfadoxine-pyrimethamine and amodiaquine for seasonal malaria chemoprevention in Africa}},
author = {Chayanin Sararat and Paul Sondo and Craig Bonnington and Jane Achan and Chukwudi A. Nnaji and Anna Y. Burkhard and Gauthier Tougri and Adama Traore and Aimé Parfait Korou Yaro and Anthony Nuwa and Richard Kajubi and Kanokon Suwannasin and Stephane Proux and Urairat Koesukwiwat and Sonia Enosse and Ivan Alejandro Pulido Tarquino and Stije J. Leopold and Arjen M. Dondorp and Halidou Tinto and James K. Tibenderana and Joel Tarning and Mallika Imwong and Francois H. Nosten and James A. Watson and Nicholas J. White},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78189-2},
url = {https://www.nature.com/articles/s41467-026-78189-2},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Parasitological efficacy of sulfadoxine-pyrimethamine and amodiaquine for seasonal malaria chemoprevention in Africa
AU - Chayanin Sararat
AU - Paul Sondo
AU - Craig Bonnington
AU - Jane Achan
AU - Chukwudi A. Nnaji
AU - Anna Y. Burkhard
AU - Gauthier Tougri
AU - Adama Traore
AU - Aimé Parfait Korou Yaro
AU - Anthony Nuwa
AU - Richard Kajubi
AU - Kanokon Suwannasin
AU - Stephane Proux
AU - Urairat Koesukwiwat
AU - Sonia Enosse
AU - Ivan Alejandro Pulido Tarquino
AU - Stije J. Leopold
AU - Arjen M. Dondorp
AU - Halidou Tinto
AU - James K. Tibenderana
AU - Joel Tarning
AU - Mallika Imwong
AU - Francois H. Nosten
AU - James A. Watson
AU - Nicholas J. White
PY - 2026
DA - 2026/10/01
JO - Nature Communications
DO - 10.1038/s41467-026-78189-2
UR - https://www.nature.com/articles/s41467-026-78189-2
AB - Seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine (SPAQ) protects millions of African children, yet the contribution of each drug to preventive efficacy remains unclear. We pooled individual-level data on drug concentrations and malaria infection in 934 children from Uganda (NCT05323721), Mozambique (NCT05186363), and Burkina Faso (NCT05478954). The primary outcome was malaria infection by day 28, and the secondary outcome was the day 28 qPCR cycle threshold value. From natural variation in drug exposure, desethylamodiaquine, the active amodiaquine metabolite, was the primary determinant of malaria infection (OR 0.55, 95% CI 0.44–0.68 per standard deviation increase in log concentration). Children with low day 28 desethylamodiaquine exposure (<24 ng/mL) had nearly twice the risk of malaria infection (RR 1.9, 95% CI 1.5–2.4). Sulfadoxine and pyrimethamine showed only weak associations, consistent across countries despite varying resistance haplotypes. SPAQ efficacy appears primarily amodiaquine-driven and the role of single-dose sulfadoxine–pyrimethamine merits further evaluation.
SN - 2041-1723
ER -