title: In vivo and in vitro efficacy of amodiaquine monotherapy for treatment of infection by chloroquine-resistant Plasmodium vivax.
abstract: Amodiaquine retains efficacy against infection by chloroquine-resistant Plasmodium falciparum; however, little information is available on its efficacy against infection by chloroquine-resistant Plasmodium vivax. Patients presenting to a rural clinic with a pure P. vivax infection that recurred after recent antimalarial treatment were retreated, this time with amodiaquine monotherapy, and the risk of further recurrence within 4 weeks was assessed. Of the 87 patients with pure P. vivax infection, 15 patients did not complete a full course of treatment, 4 of whom were intolerant to treatment. In the 72 patients completing treatment, 91% (63 of 69) had cleared their parasitemia within 48 h with no early treatment failure. Follow-up to day 28 or recurrent parasitemia was achieved for 56 patients (78%). The cumulative incidence of treatment failure by day 28 was 22.8% (95% confidence interval, 7.3 to 38%). The in vitro sensitivity profile was determined for a separate set of isolates from outpatients with pure P. vivax infection. The median 50% inhibitory concentration of amodiaquine was 11.3 nM (range, 0.37 to 95.8) and was correlated significantly with that of chloroquine (Spearman rank correlation coefficient, 0.602; P < 0.001). Although amodiaquine results in a rapid clinical response, the risk of recurrence by day 28 is unacceptably high, reducing its suitability as an alternative treatment of infection by chloroquine-resistant P. vivax in this region.
authors.affiliation: National Institute of Health Research and Development, Ministry of Health, Jakarta, Indonesia. rnp@menzies.edu.au
authors.forename: A R
authors.initials: AR
authors.lastname: Hasugian
authors.forename: E
authors.initials: E
authors.lastname: Tjitra
authors.forename: A
authors.initials: A
authors.lastname: Ratcliff
authors.forename: H
authors.initials: H
authors.lastname: Siswantoro
authors.forename: E
authors.initials: E
authors.lastname: Kenangalem
authors.forename: R M
authors.initials: RM
authors.lastname: Wuwung
authors.forename: H L E
authors.initials: HL
authors.lastname: Purba
authors.forename: K A
authors.initials: KA
authors.lastname: Piera
authors.forename: F
authors.initials: F
authors.lastname: Chalfien
authors.forename: J
authors.initials: J
authors.lastname: Marfurt
authors.forename: P M
authors.initials: PM
authors.lastname: Penttinen
authors.forename: B
authors.initials: B
authors.lastname: Russell
authors.forename: N M
authors.initials: NM
authors.lastname: Anstey
authors.forename: R N
authors.initials: RN
authors.lastname: Price
mesh_terms: D000293:Adolescent; D017677:Age Distribution; D000655:Amodiaquine / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D002738:Chloroquine / Q000008:administration & dosage / Q000627:therapeutic use*; D016001:Confidence Intervals; D004351:Drug Resistance; D004361:Drug Tolerance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D010045:Outpatients; D018512:Parasitemia / Q000188:drug therapy*; D010966:Plasmodium vivax / Q000187:drug effects*; D011446:Prospective Studies; D012008:Recurrence; D012423:Rural Health; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D000655:Amodiaquine; D002738:Chloroquine