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Title: Where chloroquine still works: The genetic make-up and susceptibility of Plasmodium vivax to chloroquine plus primaquine in Bhutan
Authors: Sonam Wangchuk
Tobgyel Drukpa
Kinley Penjor
Tashi Peldon
Yeshey Dorjey
Kunzang Dorji
Vishal Chhetri
Hidayat Trimarsanto
Sheren To
Amanda Murphy
Lorenz Von Seidlein
Ric N. Price
Kamala Thriemer
Sarah Auburn
Ministry of Health
Sarpang District Hospital
Gelephu Regional Referral Hospital
Yebilaptsa Hospital
Eijkman Institute for Molecular Biology
Kementerian Riset Teknologi Dan Pendidikan Tinggi Republik Indonesia
Badan Pengkajian dan Penerapan Teknologi
Menzies School of Health Research
University of Queensland
Mahidol University
Nuffield Department of Clinical Medicine
Keywords: Immunology and Microbiology
Issue Date: 12-May-2016
Citation: Malaria Journal. Vol.15, No.1 (2016)
Abstract: © 2016 The Author(s). Background: Bhutan has made substantial progress in reducing malaria incidence. The national guidelines recommend chloroquine (CQ) and primaquine (PQ) for radical cure of uncomplicated Plasmodium vivax, but the local efficacy has not been assessed. The impact of cases imported from India on the genetic make-up of the local vivax populations is currently unknown. Methods: Patients over 4 years of age with uncomplicated P. vivax mono-infection were enrolled into a clinical efficacy study and molecular survey. Study participants received a standard dose of CQ (25 mg/kg over 3 days) followed by weekly review until day 28. On day 28 a 14-day regimen of PQ (0.25 mg/kg/day) was commenced under direct observation. After day 42, patients were followed up monthly for a year. The primary and secondary endpoints were risk of treatment failure at day 28 and at 1 year. Parasite genotyping was undertaken at nine tandem repeat markers, and standard population genetic metrics were applied to examine population diversity and structure in infections thought to be acquired inside or outside of Bhutan. Results: A total of 24 patients were enrolled in the clinical study between April 2013 and October 2015. Eight patients (33.3 %) were lost to follow-up in the first 6 months and another eight patients lost between 6 and 12 months. No (0/24) treatment failures occurred by day 28 and no (0/8) parasitaemia was detected following PQ treatment. Some 95.8 % (23/24) of patients were aparasitaemic by day 2. There were no haemolytic or serious events. Genotyping was undertaken on parasites from 12 autochthonous cases and 16 suspected imported cases. Diversity was high (HE0.87 and 0.90) in both populations. There was no notable differentiation between the autochthonous and imported populations. Conclusions: CQ and PQ remains effective for radical cure of P. vivax in Bhutan. The genetic analyses indicate that imported infections are sustaining the local vivax population, with concomitant risk of introducing drug-resistant strains.
ISSN: 14752875
Appears in Collections:Scopus 2016-2017

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