Prevalence of glucose-6-phosphate dehydrogenase deficiency and its association with plasmodium falciparum infection among children in iganga district.

Abstract

BACKGROUND/ RATIONALE: Glucose-6-phosphate (G6PD) is an enzyme that is present in the cytoplasm of all body cells with a role in the generation of reduced glutathione. This is necessary for the reduction of oxidant stress in cells. Worldwide, 400 million people have a deficiency of this enzyme. This deficiency is associated with varying levels of hemolysis. Ths striking geographic correlation of G6PD deficiency distribution with the historical endemicity patterns of malaria had led to suggestions that the two might be linked. Indeed some epidemiological studies have concluded that G6PD deficiency confers some resistance to malaria, although this is not a universal finding in these studies. Determining the frequency of G6PD deficiency and its impact on malaria incidence and severity can be of value for malaria control programs. OBJECTIVES: To determine the prevalence of G6pd deficiency among children and determine its relationship with the prevalence of P. falciparum infection in Iganga district. METHODS: This was a cross sectional study with an analytical component, done as a sub-study of an ongoing cohort project on malaria in Iganga district. It was conducted within the boundaries of the Iganga/Mayuge DSS. Two hundred forty five children were recruited from the community by a two stage sampling. A questionnaire was administered and blood samples taken to test for G6PD status and for presence of malaria parasites. G6PD status was assessed for by using PCR-RFLP method to determine for the G202A mutation in theG6PD gene. A thicker smear was done to determine presence of plasmodium trophozoites and if possible determine the parasite density. RESULTS: A total of 245 children between the ages of 6 months and 9 years (mean age 4.4 years) were recruited into the study. Of these 114(46.5%) were males. Overall for the x-linked G6PD A-mutation, 195 (79.59%) were wild type, 31(12.65%) were heterozygous and 19(7.76%) were homozygous or homozygous. Among the males 16(14%) were hemizygous. For malaria prevalence, 100 (40.8%) had asymptomatic p.falciparum infection. There was a lower prevalence of asymptomatic p.falciparum infection among the heterozygous G6PD-A-females compared to the wild type of 29% versus 42.6% although this was not statistically significant p=0.11. There was lower parasite densities among the heterozygous G6PD A-females compared to the wild type (2505 vs 941 parasites /ul;p=0.024). CONCLUSIONS AND RECOMMENDATIONS: This study has shown that the prevalence of the G6PD A-mutation is 20.41% in this part of Uganda. This is within the range 15-32% that has been seen in other parts of sub Saharan Africa. It has also shown that up to 40% of otherwise healthy children harbour malaria parasites. This study has shown that P.falciparum parasite densities are lower among G6PD A-heterozygous females and that G6PD A-heterozygous females have lower prevalence of P.Facliparum infection, although this did not reach statistical significance. These findings are consistent a similar study done in the Gambia. Given that various other genetic polymorphisms like HB SS, a-thalasemia, blood groups, TNF a, Nitic oxide synthetase, ICAM-1, and RANTES genotypes have been associated with malaria. It is likely that the interaction between malaria and these polymorphisms is complex thus a clear impact for one of them might not easily discernable from a single cross sectional study. A large longitudinal study to assess the role and interaction of each of these is necessary. Given this high prevalence of the G6PD A-mutation, screening for this mutation is warranted in the work up of patients with acute haemolytic anaemia in this population.