G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests

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.

G6PD deficiency in Latin America: systematic review on prevalence and variants

“…A rapid and accurate diagnosis of G6PDd under field conditions before starting PQ treatment is currently a major challenge (malERA 2011, Domingo et al 2013). A prerequisite to introducing G6PD testing is the availability of high-quality G6PDd tests with product profiles that are compatible with end-use cases.…”

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

“…It has been suggested that the gold standard for the diagnosis of the G6PD status is estimating the G6PD enzyme activity, which is the most direct, accessible, and reliable assessment method [17]. The fluorescent spot test used in this study was inexpensive and easy to perform, but only moderately reliable for detection of G6PD deficiency in heterozygous women.…”

“…A large number of countries have achieved elimination (i.e., the absence of transmission in the country) [15] or have been advancing towards malaria elimination [16]. Radical cure of asymptomatic infection and chronic infection by both Plasmodium falciparum and Plasmodium vivax is the main strategy in reducing transmission of malaria parasites and attaining malaria elimination [17]. A large burden of P. vivax, which is more difficult to eliminate than P. falciparum,poses a significant barrier to malaria elimination [18].…”

Malaria diagnosis for malaria elimination

“…Aspects of malaria diagnosis beyond the focus of this review include monitoring antimalarial drug resistance markers and developing products to assess glucose-6-phosphate dehydrogenase deficiency (G6PDd) to improve safety of primaquine (and ultimately tafenoquine) treatment of P. vivax and P. ovale hypnozoites. The Worldwide Antimalarial Resistance Network (http://www.wwarn.org) and recent publications by Domingo et al [6] and Satyagraha et al [7] on testing for G6PDd provide excellent material on these topics. by reduction of annual parasite incidence (API) (Control areas: API !5 cases/1000 population; Preelimination: API < 5/1000; Elimination: API < 1/ 1000; Prevention of Reintroduction: zero locally acquired cases; WHO Certification after three years of sustained zero local transmission [10 && ,13 && ]).…”