A pilot randomized controlled trial to compare the effectiveness of two 14-day primaquine regimens for the radical cure of vivax malaria in South India

Kavitha Saravu,Krishnamurthy Bhat,Shashikiran Umakanth,Abdul Vahab Saadi,Jagadish Puralae Channabasavaiah,Vasudev Guddattu,Anzil Bava,Gouthami Brahmarouphu,Shrivathsa Kulavalli,Chaitanya Tellapragada,Navyasree Kola Srinivas,Wilbin Xavier,Kapaettu Satyamoorthy

doi:10.1186/s12936-018-2472-5

Kavitha Saravu, Krishnamurthy Bhat + Show 11 more

Open Access

https://doi.org/10.1186/s12936-018-2472-5

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Abstract

BackgroundRadical cure of Plasmodium vivax malaria requires treatment with a blood schizonticide and a hypnozoitocide (primaquine) to eradicate the dormant liver stages. There has been uncertainty about the operational effectiveness and optimum dosing of the currently recommended 14-day primaquine (PQ) course.MethodsA two centre, randomized, open-label, two arm study was conducted in South India. Patients were randomized to receive either high dose (0.5 mg base/kg body weight) or conventional dose (0.25 mg/kg) PQ for 14 days. Plasma concentrations of PQ and carboxyprimaquine (CPQ) on the 7th day of treatment were measured by reverse phase high performance liquid chromatography. Study subjects were followed up for 6 months. Recurrent infections were genotyped using capillary fragment length polymorphism of two PCR-amplified microsatellite markers (MS07 and MS 10).ResultsFifty patients were enrolled. Baseline characteristics and laboratory features did not differ significantly between the groups. Mean age of the study population was 42 ± 16.0 years. Recurrences 80–105 days later occurred in 4 (8%) patients, two in each the groups. All recurrences had the same microsatellite genotype as that causing the index infection suggesting all were relapses. One relapse was associated with low CPQ concentrations suggesting poor adherence.ConclusionsThis small pilot trial supports the effectiveness of the currently recommended lower dose (0.25 mg/kg/day) 14 day PQ regimen for the radical cure of vivax malaria in South India.Trial registration Clinical Trials Registry-India, CTRI/2017/03/007999. Registered 3 March 2017, http://ctri.nic.in/Clinicaltrials/regtrial.php?modid=1&compid=19&EncHid=82755.86366.

Highlights

Radical cure of Plasmodium vivax malaria requires treatment with a blood schizonticide and a hypnozoitocide to eradicate the dormant liver stages
Plasmodium vivax presents a substantial challenge for malaria control and elimination targets because of relapse, resulting from activation of dormant liver stages [4]
PQ radical cure is widely recommended it is often not prescribed because glucose-6-phosphate dehydrogenase (G6PD) testing is seldom available

Summary

Introduction

Radical cure of Plasmodium vivax malaria requires treatment with a blood schizonticide and a hypnozoitocide (primaquine) to eradicate the dormant liver stages. Deployment of rapid diagnostic tests, allowing early diagnosis and treatment, and aggressive vector control measures have both helped to reduce malaria case fatality rates significantly. Plasmodium vivax presents a substantial challenge for malaria control and elimination targets because of relapse, resulting from activation of dormant liver stages (hypnozoites) [4]. Prevention of relapse requires use of 8-aminoquinoline anti-malarials, in addition to schizontocidal treatment of the blood stage infection, with attendant risks of haemolysis in patients who have glucose-6-phosphate dehydrogenase (G6PD) deficiency [5]. PQ radical cure is widely recommended it is often not prescribed because G6PD testing is seldom available

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