Research

Extended high efficacy of the combination sulphadoxine-pyrimethamine with artesunate in children with uncomplicated falciparum malaria on the Benin coast, West Africa

Alain Nahum¹ , Annette Erhart² , Daniel Ahounou¹ , Désiré Bonou¹ , Chantal Van Overmeir² , Joris Menten² , Martin Akogbeto¹ , Marc Coosemans² , Achille Massougbodji³ and Umberto D'Alessandro²

¹  Centre de Recherches Entomologiques de Cotonou, Cotonou, Bénin

²  Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium

³  Laboratoire de Parasitologie, Faculté des Sciences de la Santé, Université Nationale du Bénin, Cotonou, Bénin

author email corresponding author email

Malaria Journal 2009, 8:37doi:10.1186/1475-2875-8-37

Published:	3 March 2009

Abstract

Background

A study carried out in 2003–2005 in Southern Benin showed a day-28 sulphadoxine-pyrimethamine (SP) monotherapy failure rate greater than 40%, while for SP combined with artesunate (SP-AS) the failure rate was 5.3%. Such a large difference could be explained by the relatively short 28-day follow-up period, with a substantial number of recurrent infections possibly occurring after day 28. This paper reports the treatment outcome observed in the same study cohort beyond the initial 28-day follow-up.

Methods

After the 28-day follow-up, children treated with either chloroquine alone (CQ), SP or SP-AS, were visited at home twice a week until day 90 after treatment. A blood sample was collected if the child had fever (axillary temperature ≥37.5°C). Total clinical failure for each treatment group was estimated by combining all the early treatment failures and late clinical failures that occurred over the whole follow-up period, i.e. from day 0 up to day 90. Pre-treatment randomly selected blood samples were genotyped for the dhfr gene (59) and the dhps gene (437 and 540) point mutations related to SP resistance.

Results

The PCR-corrected clinical failure at day 90 was significantly lower in the SP-AS group (SP-AS: 2.7%, SP alone: 38.2%; CQ: 41.1%) (Log-Rank p < 0,001). The most prevalent haplotype was dhfr Arg-59 with the dhps Gly-437 mutant and the dhps 540 wild type (85.5%). The dhps 540 mutation could be found in only three (8.3%) samples.

Conclusion

Combining artesunate to SP dramatically increased the treatment efficacy, even when extending the follow-up to day 90 post-treatment, and despite the high percentage of failures following treatment with SP alone. Such a good performance may be explained by the low prevalence of the dhps 540 mutation, by the rapid parasite clearance with artesunate and by the level of acquired immunity.