title: Phenotyping clinical resistance to chloroquine in Plasmodium vivax in northeastern Papua, Indonesia.
abstract: Chloroquine (CQ)-resistant Plasmodium vivax was first documented in 1989 and threatens much of eastern Indonesia, with > 50% of therapeutic failure rates. We screened 2236 subjects for malaria infection through active case detection and identified 232 infected cases with 100 subjects carried P. vivax mono infection. We prospectively evaluated therapeutic responses to CQ in 73 subjects infected by P. vivax in northeastern Papua, Indonesia. We phenotyped these infections as susceptible or resistant to CQ using a 28-day in vivo test format. Eighteen subjects (25%) had persistent or recurrent parasitemia during the test and were provisionally classified as resistant. Among the remainder, 46 (63%) subjects had no persistent or recurrent parasitemia and were classified as having infections sensitive to CQ, 4 were lost to follow up, and 5 dropped out. Among the 18 provisionally resistant cases, 1 subject (6%) had persistent parasitemia at Day 3 and was considered as a direct treatment failure, 2 subjects (11%) had recurrent parasitemia by Day 7 and were considered early treatment failures, and 7 (39%) and 8 (44%) had recurrent parasitemia by Days 14 and 28, respectively. Analysis of blood for CQ+N-desethylchloroquine (DCQ) levels on day of recurrence from 15 of the 18 with treatment failures showed 11 subjects having CQ+DCQ blood levels ⩾ 100 ng/ml and 2 with CQ+DCQ blood levels < 100 ng/ml. The 28-day cumulative incidence of therapeutic failure likely due to parasite resistance was 17.5%. These findings affirm P. vivax resistance to CQ in eastern Indonesia, albeit at lower levels than reported elsewhere. This simple means of phenotyping P. vivax infections could be implemented in other malaria endemic areas of Indonesia.
authors.affiliation: Eijkman Institute for Molecular Biology, Jakarta, Indonesia ; Graduate Program in Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
authors.forename: Puji B S
authors.initials: PB
authors.lastname: Asih
authors.affiliation: Eijkman Institute for Molecular Biology, Jakarta, Indonesia ; Department of Parasitology, Faculty of Medicine, Hasanuddin University, Makasar, Indonesia.
authors.forename: Din
authors.initials: D
authors.lastname: Syafruddin
authors.affiliation: Department of Pediatrics, University of California at San Diego, CA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Leake
authors.affiliation: Department of Medicine, University of Cendrawasih, Papua Province, Indonesia.
authors.forename: Yohanna
authors.initials: Y
authors.lastname: Sorontou
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Sadikin
authors.affiliation: Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.affiliation: Department of Internal Medicine, University of California at San Diego, CA, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Vinetz
authors.affiliation: Eijkman-Oxford Clinical Research Unit, Jakarta, Indonesia ; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK.
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Baird
keywords: Indonesia; Papua; Phenotype; Plasmodium vivax