G6PD deficiency in Plasmodium falciparum and Plasmodium vivax malaria-infected Cambodian patients

Nimol Khim,Sovannaroth Siv,Sim Kheng,Christophe Benedet,Sinuon Muth,Saorin Kim,Nguon Chea,Soley Lek,Pety Tor,Pheaktra Chim,Benoit Witkowski,Rithea Leang,Socheat Duong,Alexandra Kerleguer,Didier Ménard,Lydie Canier,Char Meng Chuor,Walter Rj Taylor

doi:10.1186/1475-2875-12-171

Nimol Khim, Sovannaroth Siv + Show 16 more

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https://doi.org/10.1186/1475-2875-12-171

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Abstract

BackgroundGlucose-6-phosphate-dehydrogenase deficiency (G6PDd) rates are unknown in malaria-infected Cambodian patients. These data are key to a rational drug policy for malaria elimination of Plasmodium falciparum and Plasmodium vivax.MethodsFrom September 2010–2012, a two-year survey of G6PDd and haemoglobinopathies assessed by quantitative enzyme activity assay and haemoglobin electrophoresis, respectively, was conducted in malaria-infected patients presenting to 19 health centres throughout Cambodia.ResultsA total of 2,408 confirmed malaria patients of mean age 26.7 (range 2–81) years were recruited from mostly western Cambodia (n = 1,732, 71.9%); males outnumbered females by 3.9:1. Plasmodium falciparum was present in 1,443 (59.9%) and P. vivax in 965 (40.1%) patients. Mean G6PD activity was 11.6 (CI 95%: 11.4-11.8) U/g Hb, G6PDd was present in 13.9% of all patients (335/2,408) and severe G6PDd (including WHO Class I and II variants) was more common in western (158/1,732, 9.1%) versus eastern (21/414, 5.1%) Cambodia (P = 0.01). Of 997/2,408 (41.4%) had a haemoglobinopathy. Mean haemoglobin concentrations were inversely related to age: 8.1 g/dL < five years, 8.7 g/dL five to 14 years, and 10.4 g/dL >15 years (P <0.001).ConclusionsG6PDd prevalence, anaemia and haemoglobinopathies were common in malaria-infected patients. The deployment of primaquine in Cambodia should be preceded by primaquine safety studies paralleled with evaluations of easy to use tests to detect G6PDd.

Highlights

Glucose-6-phosphate-dehydrogenase deficiency (G6PDd) rates are unknown in malaria-infected Cambodian patients
Study population and site The study took place from 2010 to 2012 at 19 public health facilities from across Cambodia (Figure 1), which are involved in the National Network for Monitoring Anti-malarial Drug Resistance in Cambodia, collaboration between Control Programme (CNM) and Institut Pasteur du Cambodge (IPC)
Blood samples were divided into two aliquots for (i) complete blood count (CBC), quantitative determination of G6PD activity and haemoglobin electrophoresis, and, (ii) in vitro antimalarial drug sensitivity testing and detection of molecular markers related to anti-malarial drug resistance

Summary

Introduction

Glucose-6-phosphate-dehydrogenase deficiency (G6PDd) rates are unknown in malaria-infected Cambodian patients. These data are key to a rational drug policy for malaria elimination of Plasmodium falciparum and Plasmodium vivax. Half of the population, ~3,000,000, is estimated to be at risk of malaria [9] and public sector data from 2010 show an overall incidence of 4.07 cases/1,000 population (Cambodian National Malaria Control Programme, CNM Annual Reports 2000–2009), an historically low rate but one that is higher than neighbouring countries. Heterozygote females have mixed G6PD normal and deficient red cells and their total G6PD enzyme activity and susceptibility to haemolysis depends on the balance between the expression of the normal and abnormal X chromosomes [13]. Primaquine given to individuals with mild G6PDd (e g, African A-) tends to produce mild, self-limiting AHA [15,16,17,18] but greater AHA and longer times to haemoglobin recovery in severe G6PDd (e g, Asian or B- variants) [19,20,21,22]

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