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

Wangchuk, Sonam, Drukpa, Tobgyel, Penjor, Kinley, Peldon, Tashi, Dorjey, Yeshey, Dorji, Kunzang, Chhetri, Vishal, Trimarsanto, Hidayat, To, Sheren, Murphy, Amanda, von Seidlein, Lorenz, Price, Ric N., Thriemer, Kamala and Auburn, Sarah (2016) Where chloroquine still works: the genetic make-up and susceptibility of Plasmodium vivax to chloroquine plus primaquine in Bhutan. Malaria Journal, 15 277: 1-11. doi:10.1186/s12936-016-1320-8


Author Wangchuk, Sonam
Drukpa, Tobgyel
Penjor, Kinley
Peldon, Tashi
Dorjey, Yeshey
Dorji, Kunzang
Chhetri, Vishal
Trimarsanto, Hidayat
To, Sheren
Murphy, Amanda
von Seidlein, Lorenz
Price, Ric N.
Thriemer, Kamala
Auburn, Sarah
Title Where chloroquine still works: the genetic make-up and susceptibility of Plasmodium vivax to chloroquine plus primaquine in Bhutan
Formatted title
Where chloroquine still works: the genetic make-up and susceptibility of Plasmodium vivax to chloroquine plus primaquine in Bhutan
Journal name Malaria Journal   Check publisher's open access policy
ISSN 1475-2875
Publication date 2016-05-12
Year available 2016
Sub-type Article (original research)
DOI 10.1186/s12936-016-1320-8
Open Access Status DOI
Volume 15
Issue 277
Start page 1
End page 11
Total pages 11
Place of publication London, United Kingdom
Publisher BioMed Central
Collection year 2017
Language eng
Formatted abstract
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 (HE 0.87 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.
Keyword Malaria
Plasmodium vivax
Chloroquine
Primaquine
Bhutan
India
Population genetics
Imported malaria
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
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