title: Efficacy and effectiveness of the combination of sulfadoxine/pyrimethamine and a 3-day course of artesunate for the treatment of uncomplicated falciparum malaria in a refugee settlement in Zambia.
abstract: In the Maheba Refugee Settlement, in the clinics supported by Medecins Sans Frontieres, all children aged up to 5 years with a confirmed diagnosis of uncomplicated falciparum malaria are treated with the combination of sulfadoxine/pyrimethamine (SP) and artesunate (AS). We compared the treatment's efficacy and effectiveness. Patients were randomized in order to receive the treatment supervised (efficacy) or unsupervised (effectiveness). Therapeutic response was determined after 28 days of follow up. The difference between recrudescence and re-infection was ascertained by polymerase chain reaction (PCR). We also assessed genetic markers associated to SP resistance (dhfr and dhps). Eighty-five patients received treatment under supervision and 84 received it unsupervised. On day 28, and after PCR adjustment, efficacy was found to be 83.5% (95% CI: 74.1-90.5), and effectiveness 63.4% (95% CI: 52.6-73.3) (P < 0.01). Point mutations on dhfr (108) and dhps (437) were found for 92.0% and 44.2% respectively of the PCR samples analysed. The significant difference in therapeutic response after supervised and unsupervised treatment intake can only be explained by insufficient patient adherence. When implementing new malaria treatment policies, serious investment in ensuring patient adherence is essential to ascertain the effectiveness of the new treatment schedules.
authors.affiliation: Epicentre, 8 rue Saint Sabin, 75011 Paris, France. evelyn.depootere@brussels.msf.org
authors.forename: Evelyn
authors.initials: E
authors.lastname: Depoortere
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Guthmann
authors.forename: Jacinthe
authors.initials: J
authors.lastname: Pressé
authors.forename: Naawa
authors.initials: N
authors.lastname: Sipilanyambe
authors.forename: Esther
authors.initials: E
authors.lastname: Nkandu
authors.forename: Suna
authors.initials: S
authors.lastname: Balkan
authors.forename: Philippe Eldin
authors.initials: PE
authors.lastname: de Pécoulas
authors.forename: Dominique
authors.initials: D
authors.lastname: Legros
mesh_terms: D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D002675:Child, Preschool; D003906:Developing Countries; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005819:Genetic Markers; D023281:Genomics; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000235:genetics / Q000523:psychology; D008297:Male; D010349:Patient Compliance; D011739:Pyrimethamine / Q000627:therapeutic use*; D012036:Refugees; D012717:Sesquiterpenes / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*; D016896:Treatment Outcome; D015024:Zambia
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D005819:Genetic Markers; D012717:Sesquiterpenes; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; D011739:Pyrimethamine