A Review of the Current Status of G6PD Deficiency Testing to Guide Radical Cure Treatment for Vivax Malaria

Abstract

Plasmodium vivax malaria continues to cause a significant burden of disease in the Asia-Pacific, the Horn of Africa, and the Americas. In addition to schizontocidal treatment, the 8-aminoquinoline drugs are crucial for the complete removal of the parasite from the human host (radical cure). While well tolerated in most recipients, 8-aminoquinolines can cause severe haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. G6PD deficiency is one of the most common enzymopathies worldwide; therefore, the WHO recommends routine testing to guide 8-aminoquinoline based treatment for vivax malaria whenever possible. In practice, this is not yet implemented in most malaria endemic countries. This review provides an update of the characteristics of the most used G6PD diagnostics. We describe the current state of policy and implementation of routine point-of-care G6PD testing in malaria endemic countries and highlight key knowledge gaps that hinder broader implementation. Identified challenges include optimal training of health facility staff on point-of-care diagnostics, quality control of novel G6PD diagnostics, and culturally appropriate information and communication with affected communities around G6PD deficiency and implications for treatment.

Primaquine dose and the risk of haemolysis in patients with uncomplicated Plasmodium vivax malaria: a systematic review and individual patient data meta-analysis

“…The point-of-care test has now been implemented in eight countries at a subnational or national level (Bangladesh, Brazil, Cambodia, Laos, Myanmar, Solomon Islands, Thailand, and Viet Nam). 45 Some barriers to its implementation in remote and low-resourced locations remain, including a need for training and a high cost for the devices and test strips. 46 …”

Primaquine radical cure in patients with Plasmodium falciparum malaria in areas co-endemic for P falciparum and Plasmodium vivax (PRIMA): a multicentre, open-label, superiority randomised controlled trial

“… 28 A novel quantitative G6PD testing option (STANDARD G6PD, SD Biosensor) is now available to screen patients at the point of care and identify individuals with intermediate and severe enzyme deficiency 24 and is being rolled out in several vivax-endemic countries. 30 This roll-out allows the wider scale use of tafenoquine and enables the use of higher and more effective doses of primaquine, including broadening the indication for radical cure to those at risk of relapse.…”

Case Series of Primaquine-Induced Haemolytic Events in Controlled Trials with G6PD Screening

“…Firstly, no G6PD field test can be assumed to have 100% sensitivity (and therefore flawless negative predictive value) even under ideal laboratory operating conditions [ 19 , 20 , 21 , 22 ]. However, currently available point-of-care G6PD tests represent evolving technologies, and improved sensitivity and specificity may yet be achieved [ 23 ]. Secondly, a number of operational factors may compromise diagnostic accuracy when deployed in field conditions.…”