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

• Published in: Malaria journal 2009-03, Vol.8 (1), p.37-37, Article 37
• Main Authors: Nahum, Alain, Erhart, Annette, Ahounou, Daniel, Bonou, Désiré, Van Overmeir, Chantal, Menten, Joris, Akogbeto, Martin, Coosemans, Marc, Massougbodji, Achille, D'Alessandro, Umberto
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Antimalarials; Antimalarials - administration & dosage; Antimalarials - therapeutic use; Artemisinins - administration & dosage; Artemisinins - therapeutic use; Benin; Care and treatment; Child, Preschool; Children; Cohort Studies; Demographic aspects; Diseases; Dosage and administration; Drug Combinations; Drug therapy; Female; Fever - etiology; Fever - prevention & control; Follow-Up Studies; Genotype; Health aspects; Humans; Infant; Kaplan-Meier Estimate; Malaria; Malaria, Falciparum - drug therapy; Malaria, Falciparum - epidemiology; Malaria, Falciparum - parasitology; Male; Plasmodium falciparum - drug effects; Plasmodium falciparum - isolation & purification; Polymerase Chain Reaction; Pyrimethamine; Pyrimethamine - administration & dosage; Pyrimethamine - therapeutic use; Sulfadoxine - administration & dosage; Sulfadoxine - therapeutic use; Treatment Outcome
• ISSN: 1475-2875; 1475-2875
• DOI: 10.1186/1475-2875-8-37

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. 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 > or =37.5 degrees 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. 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. 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.