title: In vivo and in vitro efficacy of amodiaquine against Plasmodium falciparum in an area of continued use of 4-aminoquinolines in East Africa.
abstract: In light of reports of increasing resistance of parasites to amodiaquine in African countries in which Plasmodium falciparum is endemic as well as the paucity of recent in vitro sensitivity data, we assessed the in vivo and in vitro sensitivity to amodiaquine of P. falciparum isolates from 128 pediatric outpatients (0.5-10 years old) in Pingilikani, Kilifi District, Kenya, who were treated with amodiaquine (10 mg/kg/day for 3 days). The polymerase chain reaction-corrected parasitological cure rate on day 28 (by Kaplan-Meier analysis) was 82% (95% confidence interval [CI], 74%-88%). Twenty-six percent (17/66) of tested pretreatment P. falciparum field isolates had 50% in vitro growth inhibition at concentrations of N-desethyl-amodiaquine (DEAQ)-the major biologically active metabolite of amodiaquine-above the proposed resistance threshold of 60 nmol/L, but baseline median DEAQ 50% inhibitory concentration values were not associated with subsequent risk of asexual parasite recrudescence (29 nmol/L [95% CI, 23-170 nmol/L] and 34 nmol/L [95% CI, 30-46 nmol/L] for patients with and those without recrudescences, respectively). The median absolute neutrophil count dropped by 1.3 X 10(3) cells/microL (95% CI, -1.7 X 10(3) to -0.7 X 10(3) cells/microL) between days 0 and 28. The high prevalence of in vitro and in vivo resistance precludes the use of amodiaquine on its own as second-line treatment. These findings also suggest that the value of amodiaquine combinations as first- or second-line treatment in areas with similar patterns of 4-aminoquinoline resistance should be reassessed.
authors.affiliation: Kenya Medical Research Institute, Center for Geographic Medicine Research-Coast, Kilifi, Kenya.
authors.forename: Philip
authors.initials: P
authors.lastname: Sasi
authors.forename: Abdi
authors.initials: A
authors.lastname: Abdulrahaman
authors.forename: Leah
authors.initials: L
authors.lastname: Mwai
authors.forename: Steven
authors.initials: S
authors.lastname: Muriithi
authors.forename: Judith
authors.initials: J
authors.lastname: Straimer
authors.forename: Elise
authors.initials: E
authors.lastname: Schieck
authors.forename: Anja
authors.initials: A
authors.lastname: Rippert
authors.forename: Mahfudh
authors.initials: M
authors.lastname: Bashraheil
authors.forename: Amina
authors.initials: A
authors.lastname: Salim
authors.forename: Judith
authors.initials: J
authors.lastname: Peshu
authors.forename: Ken
authors.initials: K
authors.lastname: Awuondo
authors.forename: Brett
authors.initials: B
authors.lastname: Lowe
authors.forename: Munir
authors.initials: M
authors.lastname: Pirmohamed
authors.forename: Peter
authors.initials: P
authors.lastname: Winstanley
authors.forename: Steve
authors.initials: S
authors.lastname: Ward
authors.forename: Alexis
authors.initials: A
authors.lastname: Nzila
authors.forename: Steffen
authors.initials: S
authors.lastname: Borrmann
mesh_terms: D000655:Amodiaquine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D007630:Kenya / Q000453:epidemiology; D008288:Malaria / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D010045:Outpatients; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D000655:Amodiaquine