Abstract
Safe treatment of Plasmodium vivax requires diagnosis of both the infection and status of erythrocytic glucose-6-phosphate dehydrogenase (G6PD) activity because hypnozoitocidal therapy against relapse requires primaquine, which causes a mild to severe acute hemolytic anemia in G6PD deficient patients. Many national malaria control programs recommend primaquine therapy without G6PD screening but with monitoring due to a broad lack of G6PD deficiency screening capacity. The degree of risk in doing so hinges upon the level of residual G6PD activity among the variants present in any given area. We conducted studies on Sumba Island in eastern Indonesia in order to assess the potential threat posed by primaquine therapy without G6PD screening. We sampled 2,033 residents of three separate districts in western Sumba for quantitative G6PD activity and 104 (5.1%) were phenotypically deficient (<4.6U/gHb; median normal 10U/gHb). The villages were in two distinct ecosystems, coastal and inland. A positive correlation occurred between the prevalence of malaria and G6PD deficiency: 5.9% coastal versus inland 0.2% for malaria (P<0.001), and 6.7% and 3.1% for G6PD deficiency (P<0.001) at coastal and inland sites, respectively. The dominant genotypes of G6PD deficiency were Vanua Lava, Viangchan, and Chatham, accounting for 98.5% of the 70 samples genotyped. Subjects expressing the dominant genotypes all had less than 10% of normal enzyme activities and were thus considered severe variants. Blind administration of anti-relapse primaquine therapy at Sumba would likely impose risk of serious harm.
Highlights
glucose-6-phosphate dehydrogenase (G6PD) deficiency affects over 400 million people worldwide
The majority of people suffering acute malaria caused by Plasmodium vivax cannot safely receive primaquine therapy to prevent multiple recurrent attacks called relapses
The severity of acute hemolytic anemia (AHA) appears to be directly correlated with the extent to which G6PD activity is impaired, and such is the basis of the classification of the many known Glucose-6-phosphate dehydrogenase deficiency (G6PDd) variants put forth by the World Health Organization [10]
Summary
The majority of people suffering acute malaria caused by Plasmodium vivax cannot safely receive primaquine therapy to prevent multiple recurrent attacks called relapses. This extraordinary gap likely explains most of the heavy burdens of morbidity and mortality imposed by this long neglected species of parasite. Misunderstood as relatively harmless over past decades, recent work affirms an often pernicious and sometime fatal course with a diagnosis of P. vivax malaria [1][2][3][4][5] This realization awakened concern regarding the long neglect of therapy against relapse due to the problem of primaquine toxicity in patients with an inborn deficiency of glucose-6-phosphate dehydrogenase (G6PD). The severity of AHA appears to be directly correlated with the extent to which G6PD activity is impaired, and such is the basis of the classification of the many known G6PDd variants put forth by the World Health Organization [10]
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