Where chloroquine still works: the genetic make-up and susceptibility of Plasmodium vivax to chloroquine plus primaquine in Bhutan

Malaria Journal

Research

Hidayat Trimarsanto¹  Vishal Chhetri²  Tashi Peldon²  Sarah Auburn³  Kamala Thriemer³  Sheren To³  Ric N. Price⁴  Amanda Murphy⁵  Lorenz von Seidlein⁶  Sonam Wangchuk⁷  Kunzang Dorji⁷  Kinley Penjor⁸  Tobgyel Drukpa⁹  Yeshey Dorjey^1,10 

[1] Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, 10430, Jakarta Pusat, Indonesia;The Ministry of Research and Technology (RISTEK), Jakarta, Indonesia;Agency for Assessment and Application of Technology, Jl. MH Thamrin 8, 10340, Jakarta, Indonesia;Gelephu Regional Referral Hospital, Ministry of Health, Gelephu, Bhutan;Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, 0810, Darwin, NT, Australia;Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, 0810, Darwin, NT, Australia;Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research Building, University of Oxford Old Road Campus, Oxford, UK;Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, 0810, Darwin, NT, Australia;Faculty of Medicine and Biomedical Sciences, School of Population Health, The University of Queensland, Brisbane, Australia;Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research Building, University of Oxford Old Road Campus, Oxford, UK;Public Health Laboratory, Department of Public Health, Ministry of Health, Thimphu, Bhutan;Sarpang District Hospital, Ministry of Health, Sarpang District, Bhutan;Vector Borne Disease Control Programme in Gelephu, Communicable Disease Division, Department of Public Health, Ministry of Health, Thimphu, Bhutan;Yebilaptsa Hospital, Ministry of Health, Zhemgang District, Bhutan;

关键词: Malaria;    Plasmodium vivax;    Chloroquine;    Primaquine;    Bhutan;    India;    Population genetics;    Imported malaria;   

DOI  :  10.1186/s12936-016-1320-8

 received in 2016-01-29, accepted in 2016-04-30,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundBhutan 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.MethodsPatients 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.ResultsA 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 (HE 0.87 and 0.90) in both populations. There was no notable differentiation between the autochthonous and imported populations.ConclusionsCQ 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.

【 授权许可】

CC BY   
© The Author(s). 2016

【 图 表 】

Fig. 9