The Role of Antibodies to Plasmodium falciparum Merozoite Antigens in the Resistance of Young Infants to Febrile Malaria and Their Place as a Biomarker in the Detection of Malaria Transmission Hotspots

Kangoye, Tiga David (2017). The Role of Antibodies to Plasmodium falciparum Merozoite Antigens in the Resistance of Young Infants to Febrile Malaria and Their Place as a Biomarker in the Detection of Malaria Transmission Hotspots. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000bf2c

Abstract

Over the last 15 years the malaria burden has globally declined, but not evenly across endemic areas. In areas with substantial decline, elimination became realistic. However, malaria elimination has to, in a cost-effective way, overcome problems such as increasing drug and insecticide resistance and the increasing heterogeneity in transmission as the transmission intensity declines. Vaccines are proven cost-effective tools in infectious disease control and substantial progress was made with the RTS, S vaccine. However, vaccine development is hampered by the lack of reliable immune correlates of protection.

We have analysed antibody responses in relation to the incidence of febrile malaria in young children, with the specific objective of investigating their contribution to the apparent resistance of young infants to febrile malaria. We have also analysed the dynamics of antibodies in relation to previously established protective thresholds.

We found that the antibody responses to 6 different falciparum antigens were not associated with protection against febrile malaria in young children and that their levels were consistently below the protective thresholds. Furthermore, we found that antibody titres were often actually associated with increasing risk of febrile malaria. A likely explanation is that the antibodies were markers of exposure and hence associated with higher risk.

We therefore analysed geo-spatial data on malaria risk to identify hotspots of clinical malaria and their association with hotspots of serological responses to malaria antigens.

We found that 1) antibody responses correlated well with asymptomatic parasitaemia detected by polymerase chain reaction, and 2) there was substantial overlapping between the hotspots detected using these markers.

Our data suggest that other mechanisms are responsible for the apparent resistance of infants to febrile malaria. Moreover, our data suggest that serology or polymerase chain reaction results may be used as markers for the detection of hotspots when the transmission declines to very low levels.