Abstract

Malaria elimination will be possible only with serious attempts to address asymptomatic infection and chronic infection by both Plasmodium falciparum and Plasmodium vivax. Currently available drugs that can completely clear a human of P. vivax (known as “radical cure”), and that can reduce transmission of malaria parasites, are those in the 8-aminoquinoline drug family, such as primaquine. Unfortunately, people with glucose-6-phosphate dehydrogenase (G6PD) deficiency risk having severe adverse reactions if exposed to these drugs at certain doses. G6PD deficiency is the most common human enzyme defect, affecting approximately 400 million people worldwide.Scaling up radical cure regimens will require testing for G6PD deficiency, at two levels: 1) the individual level to ensure safe case management, and 2) the population level to understand the risk in the local population to guide Plasmodium vivax treatment policy. Several technical and operational knowledge gaps must be addressed to expand access to G6PD deficiency testing and to ensure that a patient’s G6PD status is known before deciding to administer an 8-aminoquinoline-based drug.In this report from a stakeholder meeting held in Thailand on October 4 and 5, 2012, G6PD testing in support of radical cure is discussed in detail. The focus is on challenges to the development and evaluation of G6PD diagnostic tests, and on challenges related to the operational aspects of implementing G6PD testing in support of radical cure. The report also describes recommendations for evaluation of diagnostic tests for G6PD deficiency in support of radical cure.

Highlights

  • Background and contextglucose6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect, affecting more than 400 million people worldwide [5]

  • The protection conferred by G6PD deficiency may result in a reduced prevalence of G6PD deficiency among malarial patients as compared to the general population [9,10,11]

  • G6PD activity is typically determined by measuring G6PD activity in lysate from a whole blood specimen or a red blood cell preparation from a specimen

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Summary

Background and context

G6PD deficiency is the most common human enzyme defect, affecting more than 400 million people worldwide [5]. For the purpose of evaluating diagnostic tests for G6PD deficiency a standard approach for defining an absolute value for normal G6PD activity in a population is required. Published G6PD test evaluations use inconsistent definitions of normal G6PD activity and define test sensitivity and specificity based on different cut-off points or degrees of G6PD deficiency. The goal of operational research around G6PD deficiency testing and radical cure with 8-aminoquinolines should focus on how to ensure that G6PD status information is available at the point of case management for a patient presenting with P. vivax infection. This may involve linking drug availability to availability of a pointof-care G6PD test, to medical records, or a combination of the two. Cost-effectiveness studies should be designed to identify boundaries of these costs

Conclusions
13. World Health Organization
16. WHO Working Group
18. WHO Malaria Policy Advisory Committee and Secretariat
23. Frank JE
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