Review of key knowledge gaps in glucose-6-phosphate dehydrogenase deficiency detection with regard to the safe clinical deployment of 8-aminoquinoline treatment regimens: a workshop report

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.

Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in southeast Iran: implications for malaria elimination

“…Primaquine administered to malaria patients with severe G6PD deficiency can cause lifethreatening complications such as acute intravascular hemolysis and acute renal failure, which in turn may undermine confidence in this anti-malarial drug [38]. On the other hand, patients with unconfirmed and/or undiagnosed G6PD deficiency who do not receive primaquine for treatment of malaria are highly likely to reduce the impact of this drug [39]. It is imperative to understand the situation clearly, as the country has been aiming to eliminate malaria, and even one case of treatment failure/loss due to unknown G6PD deficiency status is of high importance from an epidemiological point of view.…”

Performance of the CareStart Glucose-6-Phosphate Dehydrogenase (G6PD) Rapid Diagnostic Test in Gressier, Haiti

“…4 Concerns for G6PD-deficient individuals developing DIH after treatment with PQ have also delayed the use of this antimalarial drug in many countries. 5 Because malaria transmission continues to occur in Haiti, with 32,000 cases confirmed in 2011, this new policy could represent a major population-level risk of DIH given the likely similarities between G6PD rates in modern Haitians and their ancestral West Africans. 6 The determination of G6PD deficiency in patients is particularly relevant to the treatment of malaria in Haiti because of the recent addition of single dose PQ to the national malaria treatment policy, despite an absence of data on G6PD deficiency prevalence rates.…”

Key Knowledge Gaps for Plasmodium vivax Control and Elimination

“…At present, the use of a quantitative screening tool that informs the relative degree of enzyme activity is the most direct, accessible, and reliable approach, and remains the gold standard for G6PD-deficiency assessment 63. Qualitative tests are also available but only inform whether the person has a certain high level of G6PD in his or her cells.…”