Sulfadoxine/pyrimethamine intermittent presumptive treatment relationship with newborn, maternal plasmodium falciparum infection and immunity

Abstract

Malaria in endemic areas affects mainly pregnant women and children below five years. Infants below six months are generally protected from severe infection because of anti-parasite antibodies transferred from mother and presence of fetal haemoglobin. The adults are protected by the time dependent exposure to parasites leading to production of antibodies. To prevent the adverse effects of pregnancy malaria, in 1998 WHO adopted a strategy for prevention which includes effective case management, use of insecticide treated nets and intermittent presumptive treatment (IPTp). Roll Back Malaria Partnership recommends use of self-reported data where data on directly observed therapy is not available to determine IPTp coverage yet self-reported data has been found to be prone to bias. The main aim of the study was to determine the effect of using IPTp on proportions of antibodies to selected P. falciparum blood stage antigens transferred from mother to baby. In addition to determine the validity of self-reported IPTp use during pregnancy. Methods In a cross sectional study 290 mothers were recruited at delivery after informed written and oral consent. Data on demographic and obstetric history was collected using interviewer administered questionnaire. Participants were asked if they took IPTp during pregnancy and drug given and when it was administered. Blood from the mother was drawn aseptically within four hours prior to delivery and after delivery venous cord blood was drawn. This was used to make thick blood smears and serum kept at -70oC till the analysis for sulfadoxine and antibody levels. Presence or absence of sulfadoxine in maternal blood at delivery was compared to self-reported IPTp use. To determine the congenital exposure and antibody transfer maternal and ii cord sera were tested for IgG and IgM antibodies against Glutamine Rich Protein (GLURP), Merozoite Surface Protein (MSP3), Merozoite Surface Protein 3a (MSP3a) and Histidine Rich Protein (HRPII). Then determined how the proportion of antibody transferred and congenital immune priming was affected by use of IPTp by the mother during pregnancy. Results and Conclusion There was only slight agreement between self-reported IPTp use during pregnancy and finding sulfadoxine in blood at delivery with kappa statistics of 0.03. The more educated and older mothers were more likely to report IPTp use during pregnancy. The sero-prevalance of GLURP in the mothers was 72.8%, HRPII 92%, MSP3 71% and 83.8% for MSP3a. Using IPTp during pregnancy did not affect the levels or seropositivity of the tested antibodies in the mothers and babies. The proportions of antibodies transferred were not affected by IPTp use; however mothers with high antibody levels transferred less compared to their counterparts. The prevalence of congenital malaria in the study population was 2.4%. The percentage of newborns with evidence of malaria immune priming was between three and 33% depending on the different representative antigen (GLURP, HRPII MSP3 and MSP3a). Using IPTp during pregnancy was found to be protective of congenital malaria and immune priming. Data presented in this thesis describes the effect of IPTp use during pregnancy on maternal and neonatal infection and immunity to P. falciparum blood stage infection. In addition, validation of self-reported IPTp use during pregnancy is described. It opens new possible research areas to determine how immune priming may affect the immunity in infants.