Prevalence and distribution of G6PD deficiency: implication for the use of primaquine in malaria treatment in Ethiopia

Abstract

Background G6PD enzyme deficiency is a common enzymatic X-linked disorder. Deficiency of the G6PD enzyme can cause free radical-mediated oxidative damage to red blood cells, leading to premature haemolysis. Treatment of Plasmodium vivax malaria with primaquine poses a potential risk of mild to severe acute haemolytic anaemia in G6PD deficient people. In this study, the prevalence and distribution of G6PD mutations were investigated across broad areas of Ethiopia, and tested the association between G6PD genotype and phenotype with the goal to provide additional information relevant to the use of primaquine in malaria treatment. Methods This study examined G6PD mutations in exons 3–11 for 344 febrile patient samples collected from seven sites across Ethiopia. In addition, the G6PD enzyme level of 400 febrile patient samples from Southwestern Ethiopia was determined by the CareStart™ biosensor. The association between G6PD phenotype and genotype was examined by Fisher exact test on a subset of 184 samples. Results Mutations were observed at three positions of the G6PD gene. The most common G6PD mutation across all sites was A376G, which was detected in 21 of 344 (6.1%) febrile patients. Thirteen of them were homozygous and eight were heterozygous for this mutation. The G267+119C/T mutation was found in 4 (1.2%) individuals in South Ethiopia, but absent in other sites. The G1116A mutation was also found in 4 (1.2%) individuals from East and South Ethiopia. For the 400 samples in the south, 17 (4.25%) were shown to be G6PD-deficient. G6PD enzyme level was not significantly different by age or gender. Among a subset of 202 febrile patients who were diagnosed with malaria, 11 (5.45%) were G6PD-deficient. These 11 infected samples were diagnosed with Plasmodium vivax by microscopy. Parasitaemia was not significantly different between the G6PD-deficient and G6PD-normal infections. Conclusions The prevalence of G6PD deficiency is modest among febrile patients in Ethiopia. G6PD deficiency testing is thus recommended before administrating primaquine for radical cure of P. vivax infected patients. The present study did not indicate a significant association between G6PD gene mutations and enzyme levels.

Spatial and genetic clustering of Plasmodium falciparum and Plasmodium vivax infections in a low-transmission area of Ethiopia

“…Control strategies against P. vivax need to target hypnozoites using radical cure, as the majority of infections detected are attributable to relapsing episodes rather than active infections 57 . Justified by the very low prevalence of glucose-6-phosphate dehydrogenase deficiency [58][59][60][61][62][63][64] . Ethiopia is currently implementing a 14-day dose primaquine for radical cure in P. vivax [65][66][67] .…”

Glucose-6-phosphate Dehydrogenase Deficiency: A Review

“…7,[14][15] This gene has 13 exons and 12 introns, spans 18.5 Kilobases, and has a GC rich promoter region that encodes a product of 1545 bp. 2,16,17 It has a high rate of heterogeneity, and over 300 variants have been found. Only 217 precise mutations, however, are currently known.…”

“…14 S188F (Mediterranean mutation) in the Arab population, C131G and G487A in Bangladesh, and A376G in North America, Africa, Yemen and Saudi Arabia are the commonest mutations discovered in G6PD-deficient patients. 2,[19][20][21] These variants can be either polymorphisms, with milder clinical signs, or sporadic variants. The frequency of variant polymorphs is higher than sporadic variants, 50% to 1% respectively.…”

“…Four-hundred million people across the globe are estimated to be affected, with the highest prevalence being in those of African, Asian and Mediterranean descent. 1,2 G6PD is an enzyme in the pentose phosphate pathway (PPP) that catalyzes the first step. 3 PPP plays a role in reductive biosynthesis, cell proliferation and processing of antioxidants.…”

Study of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency and Genotype Polymorphism of G6PD B and G6PD (A+/A-) in Patients Treated for Plasmodium vivax Malaria in a Tertiary Care Hospital in North East India

“…This deficiency offers selective protection against P. falciparum [6]. Trends of G6PD deficiency in Plasmodium vivax (P. vivax) endemic areas have been less revealing, with a weak association between the two being reported from around the world [7][8][9].…”