Malarial antibodies to Plasmodium falciparum during pregnancy in times of decreasing malaria prevalence

© 2015 Dr. Andrew Chin Chye TeoMalaria remains entrenched in tropical and sub-tropical countries with the highest burden in sub-Saharan Africa. Plasmodium falciparum infection during pregnancy, commonly termed as malaria in pregnancy (MiP), contributes a significant health risk to both pregnant women and their infants. Malaria exposure during pregnancy results in the development of pregnancy-associated antimalarial antibody, which is thought to protect against MiP and its severe consequences. Malaria preventive therapies such as intermittent preventive therapy during pregnancy (IPTp) with antimalarials and insecticide treated bed nets are protective against MiP, but the interventions may lead to reduced malaria exposure, and thus may affect the development of protective malarial antibodies. The present study investigated the impact of decreasing parasite prevalence on acquisition and maintenance of malarial antibodies in pregnant women from Malawi and Papua New Guinea (PNG). Secondary analyses evaluated whether pregnancy-associated malarial immunity is protective against the consequences of MiP. To address the research questions, enzyme-linked immunosorbent assays and flow cytometry based assays were performed on plasma samples from pregnant women residing in Malawi and PNG, to measure malarial antibodies to a range of P. falciparum antigens including recombinant proteins and whole parasites. In the context of decreasing parasite prevalence during pregnancy in Malawi and PNG, plasma samples collected at various time points (Malawi, from 1999-2006; PNG, from 2005-2012) were tested. Total antibody levels to recombinant merozoite antigens and to schizont extracts declined over time in both sample sets. Similarly, total antibody levels to variant surface antigens (VSA) of endothelial-binding infected erythrocytes (IEs) declined. However, total antibody to VSA of placental-binding IEs declined in PNG setting but not in Malawi, possibly due to differences in transmission setting. On the other hand, opsonising antibody to both whole merozoites (only tested in PNG) and whole IEs did not differ over time. Malaria prevention therapies for pregnant women may affect the acquisition of pregnancy-associated malaria antibody, and this was found in studies conducted in sub-Saharan Africa. Whether this observation will be seen in the Asia Pacific region is unclear. A subset of plasma samples from pregnant PNG women recruited for a clinical trial study was used. They were enrolled and randomised to receive either multiple courses of sulphadoxine-pyrimethamine (SP) with azithromycin or a single course of SP with chloroquine. Antibody levels to recombinant merozoite antigens, schizont extract and opsonising antibody to IEs at term were comparable between both interventions, suggesting minimal impact of malarial antibody development in both groups. Antibodies measured to recombinant antigens but not opsonising antibody to IEs declined over a course of pregnancy in both groups. Critically, multiple courses of antimalarials did not affect development of malarial antibodies after adjusting for confounders. SP-resistant parasites are prevalent in Malawi, and since resistance threatens the effectiveness of IPTp-SP, alternatives are needed. Plasma samples from a subset of Malawian women involved in a clinical trial were used. Women were recruited and randomly allocated to receive either IPTp-SP or intermittent screening and treatment with dihydroartemisinin-piperaquine. Plasma samples were collected at enrolment and at delivery and tested for malarial antibodies. At delivery, total antibody levels to recombinant antigens and IEs, and opsonising antibodies to IEs were comparable between both groups. Malarial antibodies to recombinant antigens, but not to VSA of IEs declined between enrolment and delivery in both groups. After adjusting for confounders, there were no significant differences in levels of malarial antibody between the two interventions. Pregnancy-associated malarial antibodies at enrolment from women enrolled to receive IPTp-SP were assayed and analysed to determine if they were predictive of good outcomes at delivery, on the presumption that SP was a sub-optimal drug. Pregnancy-associated malarial antibodies at enrolment were not protective of pregnancy and malaria clinical outcomes, instead, they were positively associated with malaria exposure during pregnancy. A subset of plasma collected at delivery from these women was tested for pregnancy-associated malarial antibody. This sub-study revealed that opsonising antibodies to placental-binding IEs were protective against placental malaria and maternal anaemia at delivery. Overall, this research provided several important pieces of new data: 1) the impact of falling parasite prevalence on anti-P. falciparum serological indicators differs in different settings; 2) different malaria interventions in both Malawi and PNG did not affect the development of malarial antibodies, however, over the course of pregnancy, antibodies to individual antigens were more likely to decline, and antibody levels may decline in the absence of boosters; 3) malarial antibodies targeting whole parasites were more stable over pregnancy than antibodies to recombinant antigens; 4) and opsonising antibody to placental-binding IEs may be a good correlate of protection from MiP