Abstract
SummaryBackgroundChloroquine is the first-line treatment for Plasmodium vivax malaria in most endemic countries, but resistance is increasing. Monitoring of antimalarial efficacy is essential, but in P vivax infections the assessment of treatment efficacy is confounded by relapse from the dormant liver stages. We systematically reviewed P vivax malaria treatment efficacy studies to establish the global extent of chloroquine resistance.MethodsWe searched Medline, Web of Science, Embase, and the Cochrane Database of Systematic Reviews to identify studies published in English between Jan 1, 1960, and April 30, 2014, which investigated antimalarial treatment efficacy in P vivax malaria. We excluded studies that did not include supervised schizonticidal treatment without primaquine. We determined rates of chloroquine resistance according to P vivax malaria recurrence rates by day 28 whole-blood chloroquine concentrations at the time of recurrence and study enrolment criteria.FindingsWe identified 129 eligible clinical trials involving 21 694 patients at 179 study sites and 26 case reports describing 54 patients. Chloroquine resistance was present in 58 (53%) of 113 assessable study sites, spread across most countries that are endemic for P vivax. Clearance of parasitaemia assessed by microscopy in 95% of patients by day 2, or all patients by day 3, was 100% predictive of chloroquine sensitivity.InterpretationHeterogeneity of study design and analysis has confounded global surveillance of chloroquine-resistant P vivax, which is now present across most countries endemic for P vivax. Improved methods for monitoring of drug resistance are needed to inform antimalarial policy in these regions.FundingWellcome Trust (UK).
Highlights
Plasmodium vivax is a major cause of morbidity, causing72–390 million clinical cases of malaria worldwide each year.1,2 Vivax malaria is an important cause of morbidity, especially in young children, with adverse consequences for education, development, and wellbeing
Policy makers and malaria researchers have generally focused on P falciparum, which is the main cause of malaria mortality
Substantial progress has been made in reduction of the global burden of malaria, much of which has been attributed to increases in access to health-care services, early diagnosis, treatment with highly effective antimalarial drug regimens, and deployment of insecticide-treated bednets
Summary
Plasmodium vivax is a major cause of morbidity, causing72–390 million clinical cases of malaria worldwide each year. Vivax malaria is an important cause of morbidity, especially in young children, with adverse consequences for education, development, and wellbeing. Plasmodium vivax is a major cause of morbidity, causing. Plasmodium falciparum malaria, P vivax forms dormant liver stages (hypnozoites), which cause relapses of infection weeks to months after the initial attack. Recurrent infections can occur as often as every 3 weeks, with relapses the main cause of vivax illness. One of the greatest threats to control and elimination efforts is the emergence and spread of antimalarial drug resistance. This recurring problem has plagued malaria therapeutics for more than years. In the early 1950s, chloroquine became established as the best antimalarial drug for all human malarias, but within a decade resistance had emerged
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