Webala, Brenda Akinyi2017-02-032017-02-032016-06http://ir-library.ku.ac.ke/handle/123456789/15328A Thesis Submitted in Partial Fulfillment of the Requirements for the Award of the Degree of Master of Science (Immunology) in the School of Pure and Applied Sciences of Kenyatta University. June 2016Malaria is a major public health problem worldwide with increasing cases and deaths in sub-Saharan Africa. Sickle cell disease conditions relate geographically with malaria endemic areas. Fetal hemoglobin (HbF) moderates the clinical severity of sickle cell disease (SCD) and also provides protection against malaria. Consequently, it provides survival advantage but the data is limited. Designing a study linking HbF with protection against malaria infection has been a challenge due to potential confounders on the exposure outcome. This study therefore investigated the prevalence and levels of HbF and the IgG responses to Plasmodium falciparum antigens in 100 SCD patients aged 5-30 years living in a malariaendemic area in Western Kenya. A cross-sectional study was conducted to determine the prevalence and levels of HbF and the IgG responses to a panel of eleven recombinant P. falciparum antigens in SCD patients. The levels of HbF and the IgG responses to each of the 11 antigens were determined using the alkali denaturation (Betke) method and the cytometric bead assay in a Luminexsuspension array technology respectively. The study reports a prevalence of up to 77 % of the SCD patients with high fetal hemoglobin (>10%) with a mean and range of 19.09% (1.44-56.25%) respectively. Generally the levels of HbF increased with age (r = 0.17, P < 0.05) indicating that fetal hemoglobin provides survival advantage in SCD, in males there was an increase in HbF with age (r=0.31; P<0.05) while in females it was not significant (r = 0.02; P>0.05). The IgG responses to the multiple P. falciparum antigens were differently expressed in the SCD patients, preerythrocytic antigens showed a statistical difference when the mean IgG levels were compared using unpaired T test between the seropositive SCD patients and non- SCD individuals with the later having high IgG levels (P<0.05). In contrast LSANRC had high IgG levels in SCD patients (P<0.05). The IgG responses to blood stage antigens on the other hand were not statistically different between the SCD patients and non- SCD individuals (P>0.05). The IgG responses to MSP-1-42-FVO were high both in the seropositive SCD and non-SCD individuals. However, when compared with the non-SCD individuals using unpaired T-test, the non- SCD individuals had significantly high levels of IgG responses to both the preerythrocytic and the blood stage antigens than the SCD patients (P<0.05). Using Spearmans’ rank correlation analysis, HbF positively correlated with the IgG responses to LSA-NRC (r= 0.26; P<0.05), other antigens showed no correlation. This implies that HbF can provide protection against malaria in SCD patients living in malaria endemic areas and thus increase their life expectancy. The findings also reinforce the previous findings that antibody cooperates with fetal hemoglobin to provide protection against malaria. Nonetheless, further rigorous study design approach should be used for investigations on the role of HbF on pathogenesis and chemotherapy of malaria in SCD patients.enThesis