Prevalence of sickle cell and a-Thalassemania trait in children enrolled in a malaria vaccine clinical trial, in Kombewa, Western Kenya
Kifunde, Carolyne Musoriza
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Human genetic polymorphisms especially those affecting the red blood cell (RBC) haemoglobin occur in high frequencies in areas that are endemic for malaria. Of these, sickle cell and alpha thalassemia traits (a+ thal) are the most common erythroid polymorphisms that result from mutations and/or deletions in the globin gene. The high frequencies of these haemoglobinopathies in malaria endemic regions are attributable to the protective effect of the heterozygous forms against malaria. The homozygous individuals may, however, show clinical and haematological manifestations, some of which could be life threatening. Therefore, the presence of these traits in individuals participating in malaria intervention studies may confound interpretation of efficacy data, while homozygous individuals may have higher incidences of severe adverse effects. This study, sought to determine the prevalence of sickle cell and a+ thal traits in children aged between 12-48 months living in the malaria holoendemic area of Kombewa division in the Lake Victoria basin who were scheduled to receive an experimental malaria vaccine. To achieve this, blood samples were collected from 584 children who were being screened for eligibility in the vaccine trial. The samples were analyzed for abnormal hemoglobin by High Performance Liquid Chromatography (HPLC) method. DNA extracted from whole blood was used in PCR reaction to detect the presence of the common african a+ thal deletion (the - a3.7 deletions). Of the 584 subjects screened by HPLC, 462 (79.1 %) had normal Hb AA, 111 (19.0%) had the sickle cell trait (Hb AS) and 5 individuals (0.9 %) had the sickle cell disease (Hb SS). The individuals with sickle cell disease were not enrolled in the study. One individual (0.2%) had Hb AD. Five individuals had Hb Kenya, either with Hb AA (0.5 %) or in compound heterozygosity with Hb SS (0.3 %). Analysis of the - a3.7 genotypes showed remarkably high frequency of this deletion. Of the 584 subjects, 7 DNA samples did not amplify. Of those that amplified, 270 (46.8 %) had normal a-globin genotype ( aa/aa), 53.2 % had - a3.7 deletions in heterozygous (44.4 %) or homozygous (8.8 %) form. An investigation on the incidences of co-inheritance of a+ thal with other Hb variants was done. Hb AA was coinherited with: aa/aa 0.470 times, - a/aa 0.437 times and -a/-a 0.093 times while HbAS was co-inherited with: aa/aa 0.450 times, -a/aa 0.468 times and -a/a 0.081 times. None of these associations were significantly different from each other (Fishers exact test). Analysis of the effect of a-thal genotypes on the proportion of Hb S in AS subjects showed a statistically significant reduction in the proportion of Hb S in a+ thal homozygous individuals (-a/a) compared to individuals with all four a -globin genes (P < 0.01) The information obtained in this study will be used in the interpretation of malaria vaccine efficacy data when the study is eventually un-blinded.