Immunoglobulin g subclass responses to plasmodium Falciparum antigens during a period of low to absent Malaria transmission in the highlands of western Kenya

Abstract

Malaria control strategies have significantly reduced malaria transmission in many parts of Africa, including Kenya, yet the extent to which interruption of malaria transmission might affect immune correlates to malaria in areas of low and unstable malaria transmission is unknown which was the focus of this study. This thesis research was part of a prospective longitudinal cohort study undertaken in Nandi district, a highland area in'-.western Kenya with a low and unstable malaria transmission. This area experienced a 13 months interruption of malaria transmission from April 2007 to May 2008, following high-level coverage (>70% of households) with indoor residual insecticide spraying, distribution of insecticide treated bed nets and introduction of artemisinin combination therapy in 2007. A cohort of 1000 participants being followed was stratified into 4 age groups « 4 years, 4 ~ age< 8 years, 8 ~ age<17 years, and 17 ~ years) and 50 participants were selected from each age group for the cross sectional study where IgG subclass antibody frequencies and levels to II Plasmodium falciparum antigens were assessed by cytometric bead assay or enzyme linked immunosorbent assay (ELISA) at two time points over the 13 months of interrupted malaria transmission. Data was analyzed using McNemar Chi-square test and Wilcoxon matched-pair rank test. Results showed that the frequencies of IgGl antibodies against AMA-I, MSP-119, EBA-175, MSP-3, GLURP-RO and LSA-1 decreased significantly pre and post intervention from 2007 to 2008 with a P=0.0151. IgGI sero prevalence to MSP-142 antigen remained stable pre to post intervention with 49.1% and 49% prevalence, respectively, and P=0.07963. IgGI sero prevalence to TRAP, CSP and schizont extract increased pre to post intervention though not statistically significant. AMA-1 and MSP-142 antigens had the highest prevalence of IgGl antibodies pre and post intervention (58.5% to 49.5% and 49.1% to 49%, respectively). IgG,2 sero prevalence decreased against MSP-142,AMA-1, MSP-3, GLURPR-O, GLURPR-2, LSA-NRC, TRAP and schizont extract and increased for EBA-175 and CSP while it remained stable for MSP-119. IgG3 sero prevalence decreased pre to post intervention forMSP-142,MSP-119, EBA-175, MSP-3, GLURPR-O, GLURPR-2, LSA-NRC, TRAP and schizont extract. AMA-l and CSP sero prevalence increased pre to post intervention. IgG4 sero prevalence decreased for MSP-142,AMA-I, MSP-119, EBA-175, MSP-3, GLURPR-O, GLURPR-2, LSA-NRC, TRAP, while schizont extract remained stable and CSP increased significantly pre to post intervention. Across most of the malaria antigens tested, IgG subclass antibody frequencies and levels increased with age. IgG 1 antibodies to all antigens were acquired earliest in life compared to the rest of the IgG subclass antibodies. In 2007 and 2008, an average of >70% of individuals of~17 years were IgGI positive responders to blood stage malaria antigens compared to <50% for the pre-erythrocytic malaria antigens. These results show that successful malaria interruption may lead to substantial reductions in IgG subclass antibody levels and responses to Plasmodium falciparum in areas of unstable low transmission.