title: Therapeutic responses of Plasmodium vivax malaria to chloroquine and primaquine treatment in northeastern Myanmar.
abstract: Chloroquine-primaquine (CQ-PQ) continues to be the frontline therapy for radical cure of Plasmodium vivax malaria. Emergence of CQ-resistant (CQR) P. vivax parasites requires a shift to artemisinin combination therapies (ACTs), which imposes a significant financial, logistical, and safety burden. Monitoring the therapeutic efficacy of CQ is thus important. Here, we evaluated the therapeutic efficacy of CQ-PQ for P. vivax malaria in northeast Myanmar. We recruited 587 patients with P. vivax monoinfection attending local malaria clinics during 2012 to 2013. These patients received three daily doses of CQ at a total dose of 24 mg of base/kg of body weight and an 8-day PQ treatment (0.375 mg/kg/day) commencing at the same time as the first CQ dose. Of the 401 patients who finished the 28-day follow-up, the cumulative incidence of recurrent parasitemia was 5.20% (95% confidence interval [CI], 3.04% to 7.36%). Among 361 (61%) patients finishing a 42-day follow-up, the cumulative incidence of recurrent blood-stage infection reached 7.98% (95% CI, 5.20% to 10.76%). The cumulative risk of gametocyte carriage at days 28 and 42 was 2.21% (95% CI, 0.78% to 3.64%) and 3.93% (95% CI, 1.94% to 5.92%), respectively. Interestingly, for all 15 patients with recurrent gametocytemia, this was associated with concurrent asexual stages. Genotyping of recurrent parasites at the merozoite surface protein 3α gene locus from 12 patients with recurrent parasitemia within 28 days revealed that 10 of these were the same genotype as at day 0, suggesting recrudescence or relapse. Similar studies in 70 patients in the same area in 2007 showed no recurrent parasitemias within 28 days. The sensitivity to chloroquine of P. vivax in northeastern Myanmar may be deteriorating.
authors.affiliation: Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, China Department of Entomology, Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Institute of Tropical Medicine, Third Military Medical University, Chongqing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Entomology, Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Parker
authors.affiliation: Department of Entomology, Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Bhavna
authors.initials: B
authors.lastname: Gupta
authors.affiliation: Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, China.
authors.forename: Zhaoqing
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, China.
authors.forename: Huaie
authors.initials: H
authors.lastname: Liu
authors.affiliation: Dalian Institute of Biotechnology, Dalian, Liaoning, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Department of Immunology, China Medical University, Shenyang, China.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Immunology, China Medical University, Shenyang, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Program in Public Health, University of California at Irvine, Irvine, California, USA.
authors.forename: Ming-chieh
authors.initials: MC
authors.lastname: Lee
authors.affiliation: Program in Public Health, University of California at Irvine, Irvine, California, USA.
authors.forename: Guofa
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Program in Public Health, University of California at Irvine, Irvine, California, USA.
authors.forename: Guiyun
authors.initials: G
authors.lastname: Yan
authors.affiliation: Eijkman-Oxford Clinical Research Unit, Jakarta, Indonesia Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Baird
authors.affiliation: Department of Entomology, Pennsylvania State University, University Park, Pennsylvania, USA luc2@psu.edu.
authors.forename: Liwang
authors.initials: L
authors.lastname: Cui
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D016780:Malaria, Vivax / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010966:Plasmodium vivax / Q000187:drug effects* / Q000472:pathogenicity*; D011319:Primaquine / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000962:Antimalarials; D002738:Chloroquine; D011319:Primaquine