Abstract
BackgroundExtensive studies investigating the role of host genetic factors during malaria associate glucose-6-phosphate dehydrogenase deficiency with relative protection. G6PD deficiency had been reported to associate with anti-malarial drug induced with haemolytic anaemia.MethodsA total of 301 Gabonese, Ghanaian, and Kenyan children aged 6–120 months with severe malaria recruited in a multicentre trial on artesunate were included in this sub-study. G6PD normal (type B), heterozygous (type A+) and deficient (type A−) genotypes were determined by direct sequencing of the common African mutations G202A and A376G. Furthermore, multivariate analyses were executed to associate possible contributions of G6PD deficiency with baseline haemoglobin levels, parasitaemia and with severe malarial anaemia.ResultsTwo hundred and seventy-eight children (132 females and 146 males) were successfully genotyped for G6PD variants. The overall prevalence of G6PD deficiency was 13 % [36/278; 3 % (4/132) female homozygous and 22 % (32/146) male hemizygous], 14 % (40/278) children were female heterozygous while 73 % (202/278) were G6PD normal [67 % (88/132) females and 78 % (114/146) males] individuals. Multivariate regression revealed a significant association of moderately and severely deficient G6PD genotypes with haemoglobin levels according to the baseline data (p < 0.0001; G6PD heterozygous: p < 0.0001; G6PD deficient: p = 0.009), but not with severe malarial anaemia (p = 0.66). No association of G6PD genotypes with baseline parasitaemia.ConclusionsIn this study, moderately (type A+) and severely (type A−) G6PD deficiency showed significant association with lower haemoglobin concentrations at baseline in African children with severe malaria without leading to severe malarial anaemia. In addition, there was no association of G6PD variant types with parasite densities on admission.
Highlights
Extensive studies investigating the role of host genetic factors during malaria associate glucose6-phosphate dehydrogenase deficiency with relative protection
Patients According to the Severe Malaria in African Children” (SMAC) definition of severe malaria which perfectly reflects the policies of most African hospitals [21, 22], the frequency of severe malaria syndromes at presentation were substantially different across the three study sites (Table 1)
The majority of children fulfilled one or more criteria of the World Health Organization (WHO) definition of severe malaria [23, 24], which include severe anaemia, hyperlactataemia (≥5 mmol/L), hyperparasitaemia (>250,000 parasites/μL), hypoglycaemia, and haemoglobinuria
Summary
Extensive studies investigating the role of host genetic factors during malaria associate glucose6-phosphate dehydrogenase deficiency with relative protection. G6PD deficiency is a common, X-linked hereditary enzyme deficiency affecting approximately 400 million people worldwide [9], mainly in malaria-endemic regions [10]. Among the 186 mutations identified until 2012 in the G6PD gene [11], the variants 376A (G6PD type B), 376G (G6PD deficiency type A+ and 202A (severe G6PD deficiency type A−) are the most common ones. The deficiency types A+ (moderately deficient) and A− (severely deficient) constitute up to 90 % of reported G6PD variants [8, 12, 13]. Other mutations such as A542T, G680T or T968C have been identified in parts of Africa and been suggested to contribute to G6PD deficiency. Any attempts to control malaria need to take into account tertian malaria, which, occurring rarely only in many parts of Africa, contributes to the world-wide malaria burden
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