title: Extended high efficacy of the combination sulphadoxine-pyrimethamine with artesunate in children with uncomplicated falciparum malaria on the Benin coast, West Africa.
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 > 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre de Recherches Entomologiques de Cotonou, Cotonou, Bénin. nahum_alain@yahoo.fr
authors.forename: Alain
authors.initials: A
authors.lastname: Nahum
authors.forename: Annette
authors.initials: A
authors.lastname: Erhart
authors.forename: Daniel
authors.initials: D
authors.lastname: Ahounou
authors.forename: Désiré
authors.initials: D
authors.lastname: Bonou
authors.forename: Chantal
authors.initials: C
authors.lastname: Van Overmeir
authors.forename: Joris
authors.initials: J
authors.lastname: Menten
authors.forename: Martin
authors.initials: M
authors.lastname: Akogbeto
authors.forename: Marc
authors.initials: M
authors.lastname: Coosemans
authors.forename: Achille
authors.initials: A
authors.lastname: Massougbodji
authors.forename: Umberto
authors.initials: U
authors.lastname: D'Alessandro
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D037621:Artemisinins / Q000008:administration & dosage / Q000627:therapeutic use*; D000077332:Artesunate; D001541:Benin; D002675:Child, Preschool; D015331:Cohort Studies; D004338:Drug Combinations; D005260:Female; D005334:Fever / Q000209:etiology / Q000517:prevention & control; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011739:Pyrimethamine / Q000008:administration & dosage / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; D011739:Pyrimethamine