Abstract
Background8-Aminoquinolines such as primaquine clear mature Plasmodium falciparum gametocytes that are responsible for transmission from human to mosquitoes and bring radical cure in Plasmodium vivax by clearing dormant liver stages. Deployment of primaquine is thus of relevance for malaria elimination efforts but challenged by the widespread prevalence of glucose-6-phosphate dehydrogenase deficiency (G6PDd) in endemic countries since primaquine in G6PDd individuals may lead to acute haemolysis. In this study, the prevalence of G6PDd was investigated in different settings in Ethiopia using phenotyping and genotyping approaches.MethodsCommunity and school based cross-sectional surveys were conducted from October to December 2016 in four administrative regions (Gambela, Benishangul Gumuz, Oromia, and Amhara) in Ethiopia. Finger prick blood samples were collected for G6PD enzyme activity using the CareStart™ G6PD screening test and genotyping of 36 selected single nucleotide polymorphisms (SNPs) located in the G6PD gene and its flanking regions.ResultsOverall, the prevalence of phenotypic G6PDd was 1.4% (22/1609). For the first time in the Ethiopian population, the African variant (A−) was detected in 3.5% (7/199) of the limited set of genotyped samples, which were all phenotypically normal. Interestingly, all of these individuals had a variation at the rs2515904 locus. Strong geographical variation was observed for both phenotypic and genotypic G6PDd; three-quarters of the phenotypically G6PDd individuals were detected in Gambela.ConclusionA very low prevalence of G6PDd was detected in the present study populations. The presence of the A− variant alongside other G6PD mutants and the patchy distribution of G6PDd indicate that larger studies specifically designed to unravel the distribution of G6PDd at small geographical scale may be needed to tailor malaria elimination efforts in Ethiopia to the local context.
Highlights
The substantial reduction in the global burden of malaria in the last 15 years prompted a renewed interest in malaria elimination [1]
Current antimalarial drugs primarily target the blood stage asexual parasites that are uniquely associated with the signs and symptoms of the disease; with incomplete activity against mature Plasmodium falciparum gametocytes that are responsible for human-tomosquito transmission [3] and the dormant liver stages in Plasmodium vivax that are responsible for multiple relapses weeks or months after the primary infections have resolved [4]
Compared to the Mediterranean and South East Asian variants, the African variant is generally considered to result in a milder degree of deficiency and less severe haemolysis [20]; incidents of life-threatening haemolysis have been reported for G6PD A− [26]
Summary
The substantial reduction in the global burden of malaria in the last 15 years prompted a renewed interest in malaria elimination [1]. Current antimalarial drugs primarily target the blood stage asexual parasites that are uniquely associated with the signs and symptoms of the disease; with incomplete activity against mature Plasmodium falciparum gametocytes (sexual stages) that are responsible for human-tomosquito transmission [3] and the dormant liver stages (hypnozoites) in Plasmodium vivax that are responsible for multiple relapses weeks or months after the primary infections have resolved [4] Transmission reduction for both P. vivax and P. falciparum [5] and radical cure in P. vivax [6] are integral parts of the effort to eliminate malaria. Compared to the Mediterranean (rs5030868) and South East Asian variants, the African variant is generally considered to result in a milder degree of deficiency and less severe haemolysis [20]; incidents of life-threatening haemolysis have been reported for G6PD A− [26]
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