Abstract
The diagnosis and management of glucose-6-phosphate dehydrogenase (G6PD) deficiency is a crucial aspect in the current phases of malaria control and elimination, which will require the wider use of 8-aminoquinolines for both reducing Plasmodium falciparum transmission and achieving the radical cure of Plasmodium vivax. 8-aminoquinolines, such as primaquine, can induce severe haemolysis in G6PD-deficient individuals, potentially creating significant morbidity and undermining confidence in 8-aminoquinoline prescription. On the other hand, erring on the side of safety and excluding large numbers of people with unconfirmed G6PD deficiency from treatment with 8-aminoquinolines will diminish the impact of these drugs. Estimating the remaining G6PD enzyme activity is the most direct, accessible, and reliable assessment of the phenotype and remains the gold standard for the diagnosis of patients who could be harmed by the administration of primaquine. Genotyping seems an unambiguous technique, but its use is limited by cost and the large range of recognized G6PD genotypes. A number of enzyme activity assays diagnose G6PD deficiency, but they require a cold chain, specialized equipment, and laboratory skills. These assays are impractical for care delivery where most patients with malaria live. Improvements to the diagnosis of G6PD deficiency are required for the broader and safer use of 8-aminoquinolines to kill hypnozoites, while lower doses of primaquine may be safely used to kill gametocytes without testing. The discussions and conclusions of a workshop conducted in Incheon, Korea in May 2012 to review key knowledge gaps in G6PD deficiency are reported here.
Highlights
The 8-aminoquinolines, a class of drugs discovered almost 80 years ago, remains unique among anti-malarial drugs in having activity against the sexual stages of P. falciparum and dormant stages of Plasmodium vivax
Despite being an intrinsic part of most national and international malaria treatment guidelines, the use of primaquine in the treatment of P. vivax as well as P. falciparum is often deferred by attending physicians and healthcare providers
A World Health Organization (WHO) expert committee came to the conclusion that primaquine can be safely used as a single dose (0.25 mg base/kg) even in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency [1]
Summary
The 8-aminoquinolines, a class of drugs discovered almost 80 years ago, remains unique among anti-malarial drugs in having activity against the sexual stages (gametocytes) of P. falciparum and dormant stages of Plasmodium vivax (hypnozoites). Upgrades of the CareStartW G6PD deficiency screening test are in development including a version which allows quantitative estimate of G6PD activity using a reader These biochemical approaches offer a functional analysis of G6PD deficiency, but are often difficult to interpret, especially for mosaic female heterozygotes, who may haemolyse following treatment with 8-aminoquinolines. The broader benefits of G6PD testing The broader benefits of a reliable point-of-care test are likely to be considerable, but benefits to individuals and to society need to be weighed against the potential costs and risks of the overall objective Such an analysis should consider the alternatives to the introduction of testing, including the status quo (in most cases no primaquine and no testing), as well as the introduction of different primaquine treatment regimens without prior G6PD testing.
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