Frequency of glucose-6-phosphate dehydrogenase deficiency in malaria patients from six African countries enrolled in two randomized anti-malarial clinical trials
Open Access
- 17 August 2011
- journal article
- research article
- Published by Springer Nature in Malaria Journal
- Vol. 10 (1) , 241
- https://doi.org/10.1186/1475-2875-10-241
Abstract
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is common in populations living in malaria endemic areas. G6PD genotype and phenotype were determined for malaria patients enrolled in the chlorproguanil-dapsone-artesunate (CDA) phase III clinical trial programme. Study participants, aged > 1 year, with microscopically confirmed uncomplicated Plasmodium falciparum malaria, and haemoglobin ≥ 70 g/L or haematocrit ≥ 25%, were recruited into two clinical trials conducted in six African countries (Burkina Faso, Ghana, Kenya, Nigeria, Tanzania, Mali). G6PD genotype of the three most common African forms, G6PD*B, G6PD*A (A376G), and G6PD*A- (G202A, A542T, G680T and T968C), were determined and used for frequency estimation. G6PD phenotype was assessed qualitatively using the NADPH fluorescence test. Exploratory analyses investigated the effect of G6PD status on baseline haemoglobin concentration, temperature, asexual parasitaemia and anti-malarial efficacy after treatment with CDA 2/2.5/4 mg/kg or chlorproguanil-dapsone 2/2.5 mg/kg (both given once daily for three days) or six-dose artemether-lumefantrine. Of 2264 malaria patients enrolled, 2045 had G6PD genotype available and comprised the primary analysis population (1018 males, 1027 females). G6PD deficiency prevalence was 9.0% (184/2045; 7.2% [N = 147] male hemizygous plus 1.8% [N = 37] female homozygous), 13.3% (273/2045) of patients were heterozygous females, 77.7% (1588/2045) were G6PD normal. All deficient G6PD*A- genotypes were A376G/G202A. G6PD phenotype was available for 64.5% (1319/2045) of patients: 10.2% (134/1319) were G6PD deficient, 9.6% (127/1319) intermediate, and 80.2% (1058/1319) normal. Phenotype test specificity in detecting hemizygous males was 70.7% (70/99) and 48.0% (12/25) for homozygous females. Logistic regression found no significant effect of G6PD genotype on adjusted mean baseline haemoglobin (p = 0.154), adjusted mean baseline temperature (p = 0.9617), or adjusted log mean baseline parasitaemia (p = 0.365). There was no effect of G6PD genotype (p = 0.490) or phenotype (p = 0.391) on the rate of malaria recrudescence, or reinfection (p = 0.134 and p = 0.354, respectively). G6PD deficiency is common in African patients with malaria and until a reliable and simple G6PD test is available, the use of 8-aminoquinolines will remain problematic. G6PD status did not impact baseline haemoglobin, parasitaemia or temperature or the outcomes of anti-malarial therapy. Clinicaltrials.gov: NCT00344006 and NCT00371735.Keywords
This publication has 29 references indexed in Scilit:
- Plasmodium falciparum clearance with artemisinin-based combination therapy (ACT) in patients with glucose-6-phosphate dehydrogenase deficiency in MaliMalaria Journal, 2010
- Chlorproguanil–Dapsone–Artesunate versus Chlorproguanil–Dapsone: A Randomized, Double-Blind, Phase III Trial in African Children, Adolescents, and Adults with Uncomplicated Plasmodium falciparum MalariaThe American Journal of Tropical Medicine and Hygiene, 2009
- Impact of the Method of G6PD Deficiency Assessment on Genetic Association Studies of Malaria SusceptibilityPLOS ONE, 2009
- Chlorproguanil−Dapsone−Artesunate versus Artemether−Lumefantrine: A Randomized, Double-Blind Phase III Trial in African Children and Adolescents with Uncomplicated Plasmodium falciparum MalariaPLOS ONE, 2009
- Allelic heterogeneity of G6PD deficiency in West Africa and severe malaria susceptibilityEuropean Journal of Human Genetics, 2009
- Multiplicity of Plasmodium falciparum infection in asymptomatic children in Senegal: relation to transmission, age and erythrocyte variantsMalaria Journal, 2008
- X-Linked G6PD Deficiency Protects Hemizygous Males but Not Heterozygous Females against Severe MalariaPLoS Medicine, 2007
- Diagnosis of red cell G6PD deficiency in rural Burkina Faso. Comparison of a rapid fluorescent enzyme test on filter paper with polymerase chain reaction based genotypingBritish Journal of Haematology, 2005
- Red cell glucose‐6‐phosphate dehydrogenase status and pyruvate kinase activity in a Nigerian populationTropical Medicine & International Health, 2000
- Relationship between the Genes for Glucose-6-phosphate Dehydrogenase and for Haemoglobin in a Nigerian PopulationNature, 1968