title: Efficacy of sulfadoxine-pyrimethamine in Tanzania after two years as first-line drug for uncomplicated malaria: assessment protocol and implication for treatment policy strategies.
abstract: BACKGROUND
  Systematic surveillance for resistant malaria shows high level of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine (SP) across eastern and southern parts of Africa. This study assessed in vivo SP efficacy after two years of use as an interim first-line drug in Tanzania, and determined the rates of treatment failures obtained after 14 and 28 days of follow-up.
  
  
  METHODS
  The study was conducted in the Ipinda, Mlimba and Mkuranga health facilities in Tanzania. Children aged 6-59 months presenting with raised temperature associated exclusively with P. falciparum (1,000-100,000 parasites per microl) were treated with standard dose of SP. Treatment responses were classified according to the World Health Organization (WHO) definition as Adequate Clinical and Parasitological Response (ACPR), Early Treatment Failure (ETF), Late Clinical Failure (LCF) and Late Parasitological Failure (LPF) on day 14 and day 28.
  
  
  RESULTS
  Overall 196 (85.2%) of 230 patients had ACPR on day 14 but only 116 (50.9%) on day 28 (57.7% after excluding new infections by parasite genotyping). Altogether 21 (9.1%) and 13 (5.7%) of the 230 patients assessed up to day 14 and 39 (17.1%) and 55 (24.1%) of the 228 followed up to day 28 had clinical and parasitological failure, respectively.
  
  
  CONCLUSIONS
  These findings indicate that SP has low therapeutic value in Tanzania. The recommendation of changing first line treatment to artemether + lumefantrine combination therapy from early next year is, therefore, highly justified. These findings further stress that, for long half-life drugs such as SP, establishment of cut-off points for policy change in high transmission areas should consider both clinical and parasitological responses beyond day 14.
authors.affiliation: Ifakara Health Research and Development Centre, PO Box 53, Ifakara, Tanzania. kefas.mugittu@unibas.ch
authors.forename: Kefas
authors.initials: K
authors.lastname: Mugittu
authors.forename: Salim
authors.initials: S
authors.lastname: Abdulla
authors.forename: Nicole
authors.initials: N
authors.lastname: Falk
authors.forename: Honorati
authors.initials: H
authors.lastname: Masanja
authors.forename: Ingrid
authors.initials: I
authors.lastname: Felger
authors.forename: Hassan
authors.initials: H
authors.lastname: Mshinda
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Beck
authors.forename: Blaise
authors.initials: B
authors.lastname: Genton
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics; D000962:Antimalarials / Q000627:therapeutic use*; D001831:Body Temperature; D002675:Child, Preschool; D004338:Drug Combinations; D004341:Drug Evaluation / Q000379:methods; D004359:Drug Therapy, Combination; D005838:Genotype; D006291:Health Policy / Q000639:trends*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D018512:Parasitemia / Q000097:blood; D010963:Plasmodium falciparum / Q000145:classification / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics; D011739:Pyrimethamine / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*; D013636:Tanzania; D016896:Treatment Outcome
chemical_list: D000953:Antigens, Protozoan; D000962:Antimalarials; D004338:Drug Combinations; D006454:Hemoglobins; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine