title: Efficacy of amodiaquine, sulphadoxine-pyrimethamine and their combination for the treatment of uncomplicated Plasmodium falciparum malaria in children in Cameroon at the time of policy change to artemisinin-based combination therapy.
abstract: BACKGROUND
  The efficacy of amodiaquine (AQ), sulphadoxine-pyrimethamine (SP) and the combination of SP+AQ in the treatment of Cameroonian children with clinical malaria was investigated. The prevalence of molecular markers for resistance to these drugs was studied to set the baseline for surveillance of their evolution with time.
  
  
  METHODS
  Seven hundred and sixty children aged 6-59 months with uncomplicated falciparum malaria were studied in three ecologically different regions of Cameroon - Mutengene (littoral equatorial forest), Yaoundé (forest-savannah mosaic) and Garoua (guinea-savannah). Study children were randomized to receive either AQ, SP or the combination AQ+SP. Clinical outcome was classified according to WHO criteria, as either early treatment failure (ETF), late clinical failure (LCF), late parasitological failure (LPF) or adequate clinical and parasitological response (ACPR). The occurrence of mutations in pfcrt, pfmdr1, dhfr and dhps genes was studied by either RFLP or dot blot techniques and the prevalence of these mutations related to parasitological and therapeutic failures.
  
  
  RESULTS
  After correction for the occurrence of re-infection by PCR, ACPRs on day 28 for AQ, SP and AQ+SP were 71.2%, 70.1% and 80.9%, in Garoua, 79.2%, 62.5%, and 81.9% in Mutengene, and 80.3%, 67.5% and 76.2% in Yaoundé respectively. High levels of Pfcrt 76T (87.11%) and Pfmdr1 86Y mutations (73.83%) were associated with quinoline resistance in the south compared to the north, 31.67% (76T) and 22.08% (86Y). There was a significant variation (p < 0.001) of the prevalence of the SGK haplotype between Garoua in the north (8.33%), Yaoundé (36.29%) in the savannah-forest mosaic and Mutengene (66.41%) in the South of Cameroon and a weak relation between SGK haplotype and SP failure. The 540E mutation on the dhps gene was extremely rare (0.3%) and occurred only in Mutengene while the pfmdr1 1034K and 1040D mutations were not detected in any of the three sites.
  
  
  CONCLUSIONS
  In this study the prevalence of molecular markers for quinoline and anti-folate resistances showed high levels and differed between the south and north of Cameroon. AQ, SP and AQ+SP treatments were well tolerated but with low levels of efficacy that suggested alternative treatments were needed in Cameroon since 2005.
authors.affiliation: Biotechnology Centre, University of Yaoundé I, Yaoundé, Cameroon. wfmbacham@yahoo.com
authors.forename: Wilfred F
authors.initials: WF
authors.lastname: Mbacham
authors.forename: Marie-Solange B
authors.initials: MS
authors.lastname: Evehe
authors.forename: Palmer M
authors.initials: PM
authors.lastname: Netongo
authors.forename: Isabel A
authors.initials: IA
authors.lastname: Ateh
authors.forename: Patrice N
authors.initials: PN
authors.lastname: Mimche
authors.forename: Anthony
authors.initials: A
authors.lastname: Ajua
authors.forename: Akindeh M
authors.initials: AM
authors.lastname: Nji
authors.forename: Domkam
authors.initials: D
authors.lastname: Irenee
authors.forename: Justin B
authors.initials: JB
authors.lastname: Echouffo-Tcheugui
authors.forename: Bantar
authors.initials: B
authors.lastname: Tawe
authors.forename: Rachel
authors.initials: R
authors.lastname: Hallett
authors.forename: Cally
authors.initials: C
authors.lastname: Roper
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Targett
authors.forename: Brian
authors.initials: B
authors.lastname: Greenwood
mesh_terms: D000284:Administration, Oral; D000655:Amodiaquine / Q000627:therapeutic use*; D000962:Antimalarials / Q000627:therapeutic use*; D002163:Cameroon / Q000453:epidemiology; D002675:Child, Preschool; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D016903:Drug Monitoring; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006291:Health Policy; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000302:isolation & purification; D011739:Pyrimethamine / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine