Risk of hemolysis in Plasmodium vivax malaria patients receiving standard primaquine treatment in a population with high prevalence of G6PD deficiency

Infection. 2023 Feb;51(1):213-222. doi: 10.1007/s15010-022-01905-9. Epub 2022 Aug 17.

Abstract

Background: Primaquine is essential for the radical cure of Plasmodium vivax malaria, but it poses a potential danger of severe hemolysis in G6PD-deficient (G6PDd) patients. This study aimed to determine whether primaquine is safe in a population with high G6PD prevalence but lacking G6PD diagnosis capacity.

Methods: In Myanmar, 152 vivax patients were gender- and age-matched at 1:3 for G6PDd versus G6PD-normal (G6PDn). Their risk of acute hemolysis was followed for 28 days after treatment with the standard chloroquine and 14-day primaquine (0.25 mg/kg/day) regimen.

Results: Patients anemic and non-anemic at enrollment showed a rising and declining trend in the mean hemoglobin level, respectively. In males, the G6PDd group showed substantially larger magnitudes of hemoglobin reduction and lower hemoglobin nadir levels than the G6PDn group, but this trend was not evident in females. Almost 1/3 of the patients experienced clinically concerning declines in hemoglobin, with five requiring blood transfusion.

Conclusions: The standard 14-day primaquine regimen carries a significant risk of acute hemolytic anemia (AHA) in vivax patients without G6PD testing in a population with a high prevalence of G6PD deficiency and anemia. G6PD testing would avoid most of the clinically significant Hb reductions and AHA in male patients.

Keywords: Anemia; Gender; Glucose-6-phosphate dehydrogenase; Hemolysis; Parasitemia; Primaquine.

MeSH terms

  • Antimalarials* / adverse effects
  • Female
  • Glucosephosphate Dehydrogenase / therapeutic use
  • Glucosephosphate Dehydrogenase Deficiency* / complications
  • Glucosephosphate Dehydrogenase Deficiency* / diagnosis
  • Glucosephosphate Dehydrogenase Deficiency* / epidemiology
  • Hemoglobins
  • Hemolysis
  • Humans
  • Malaria, Vivax* / drug therapy
  • Malaria, Vivax* / epidemiology
  • Male
  • Plasmodium vivax
  • Prevalence
  • Primaquine / adverse effects

Substances

  • Primaquine
  • Antimalarials
  • Glucosephosphate Dehydrogenase
  • Hemoglobins