Abstract
The only currently available drug that effectively removes malaria hypnozoites from the human host is primaquine. The use of 8-aminoquinolines is hampered by haemolytic side effects in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. Recently a number of qualitative and a quantitative rapid diagnostic test (RDT) format have been developed that provide an alternative to the current standard G6PD activity assays. The WHO has recently recommended routine testing of G6PD status prior to primaquine radical cure whenever possible. A workshop was held in the Philippines in early 2015 to discuss key challenges and knowledge gaps that hinder the introduction of routine G6PD testing. Two point-of-care (PoC) test formats for the measurement of G6PD activity are currently available: qualitative tests comparable to malaria RDT as well as biosensors that provide a quantitative reading. Qualitative G6PD PoC tests provide a binomial test result, are easy to use and some products are comparable in price to the widely used fluorescent spot test. Qualitative test results can accurately classify hemizygous males, heterozygous females, but may misclassify females with intermediate G6PD activity. Biosensors provide a more complex quantitative readout and are better suited to identify heterozygous females. While associated with higher costs per sample tested biosensors have the potential for broader use in other scenarios where knowledge of G6PD activity is relevant as well. The introduction of routine G6PD testing is associated with additional costs on top of routine treatment that will vary by setting and will need to be assessed prior to test introduction. Reliable G6PD PoC tests have the potential to play an essential role in future malaria elimination programmes, however require an improved understanding on how to best integrate routine G6PD testing into different health settings.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0896-8) contains supplementary material, which is available to authorized users.
Highlights
Plasmodium vivax has long been considered a benign form of malaria, but this paradigm is changing
Glucose-6-phosphate dehydrogenase (G6PD) is an essential enzyme in the pentose phosphate pathway which is the sole source of energy for red blood cells (RBCs) and the only mechanism to maintain the cells redox potential [11]
The biosensor has a quantitative readout of glucose-6-phosphate dehydrogenase (G6PD) activity and provides a number of advantages over a qualitative rapid diagnostic test (RDT), including the possibility to design malaria treatment schemes based on the test readout, the ability to use readouts for drugs outside of 8-aminoquinolines and improved identification of heterozygous females with intermediate G6PD activity
Summary
Plasmodium vivax has long been considered a benign form of malaria, but this paradigm is changing. For several decades the research agenda for radical cure has been neglected and the demand for reliable, easy-touse G6PD tests has not been a priority. Based on the experience in G6PD deficient African American soldiers, radical cure with primaquine was long considered safe; the potential risks in more severe variants of G6PD deficiency can be considerable. Since 2012 a series of workshops have been held by the Asia Pacific Malaria Elimination Network (APMEN) to discuss G6PD testing in the context of vivax malaria treatment in the Asia Pacific. The first workshop of this series was held in Incheon, South Korea in May 2012, where the research agenda for G6PD deficiency and the radical cure of P. vivax was reviewed, an update of available tests presented, and a target product profile for a point-of-care test for G6PD deficiency proposed [7]. The discussion was timely in the context of the most recent recommendations emerging from the 2014 WHO expert review group on G6PD deficiency [10], the resulting guidance from the March 2015 WHO Malaria Policy Advisory Committee and the recently published malaria treatment guidelines by the WHO [8]
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