title: Treatment of uncomplicated malaria with artesunate plus sulfadoxine-pyrimethamine is failing in Somalia: evidence from therapeutic efficacy studies and Pfdhfr and Pfdhps mutant alleles.
abstract: OBJECTIVE
  Artesunate plus sulfadoxine-pyrimethamine (AS + SP) has been Somalia's national treatment policy since 2006. Routine monitoring of first-line malaria treatment is needed to ensure appropriate national malaria treatment policy and early detection of drug resistance. For this purpose, we conducted therapeutic efficacy studies of AS + SP for the treatment of uncomplicated malaria in Somalia in 2011.
  
  
  METHODS
  Studies were conducted in three sentinel sites. Eligible patients were evaluated for clinical and parasitological outcomes according to the WHO standard protocol. Molecular surveillance was conducted on resistance conferring mutations in the P.falciparum dihydrofolate reductase (dfhr) and dihydropteroate synthase (dhps) genes.
  
  
  RESULTS
  The proportion of PCR-corrected treatment failures was high in Jamame (22%, 95% CI: 13.7-32.8%) and low (<5%) in Janale and Jowhar. All patients cleared parasites by day 3. Molecular markers associated with SP resistance were detected in all three sites. Treatment failure was associated with the presence of the double mutant dhps A437G/K540E (OR = 22.4, 95% CI: 5.1-98.1), quadruple mutant dhfr N51I/S108N+dhps A437G/K540E (OR = 5.5, 95% CI: 2.3-13.6), quintuple mutant dhfr N51I/C59R/S108N+dhps A437G/K540E (OR = 3.5, 95% CI: 1.4-8.8) and younger age (OR=0.86, 95% CI: 0.76-0.96).
  
  
  CONCLUSIONS
  The high treatment failure rate observed in Jamame, together with the presence of molecular mutations associated with SP resistance, indicates P. falciparum resistance to SP. In Jowhar, high treatment failure rates were absent despite the presence of molecular mutations; signs of resistance in vivo may have been masked by the stronger immunity of the older study population. The study underscores the need to update Somalia's national malaria treatment policy.
authors.affiliation: Global Malaria Programme, World Health Organization, Geneva, Switzerland.
authors.forename: Marian
authors.initials: M
authors.lastname: Warsame
authors.forename: Abdillahi Mohamed
authors.initials: AM
authors.lastname: Hassan
authors.forename: Amy
authors.initials: A
authors.lastname: Barrette
authors.forename: Ali Mohamed
authors.initials: AM
authors.lastname: Jibril
authors.forename: Husein Haji
authors.initials: HH
authors.lastname: Elmi
authors.forename: Abdulkadir Mohamed
authors.initials: AM
authors.lastname: Arale
authors.forename: Hanan El
authors.initials: HE
authors.lastname: Mohammady
authors.forename: Rania A
authors.initials: RA
authors.lastname: Nada
authors.forename: Jamal Ghilan Hefzullah
authors.initials: JG
authors.lastname: Amran
authors.forename: Abdikarim
authors.initials: A
authors.lastname: Muse
authors.forename: Fahmi Essa
authors.initials: FE
authors.lastname: Yusuf
authors.forename: Abdiqani Sheikh
authors.initials: AS
authors.lastname: Omar
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000483:Alleles; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004094:Dihydropteroate Synthase / Q000235:genetics; D018432:Drug Resistance, Multiple; D005260:Female; D005798:Genes, Bacterial; D006291:Health Policy; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010963:Plasmodium falciparum / Q000201:enzymology / Q000235:genetics*; D011739:Pyrimethamine / Q000627:therapeutic use*; D012998:Somalia; D013413:Sulfadoxine / Q000627:therapeutic use*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; C578917:sulfadoxine-pyrimethamine-artesunate; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine
keywords: Malaria; Plasmodium falciparum; Somalia; Somalie; artemisinin-based combination therapy; drug resistance; malaria; paludisme; resistencia a medicamentos; résistance aux médicaments; terapia de combinación basada en artemisinina; thérapie combinée à base d'artémisinine