Cross Cutting - Pathogenesis and Immunity
Project Coordinator: Stephen Rogerson (Australia)
Principal Collaborators: Rose Leke (Cameroon) and Diane Taylor (USA; histopathology workshop; ultrasound); Jaume Ordi and Clara Menendez (Spain; Histopathology QC); Steve Meshnick (USA; drug resistance network).
This activity has four components, each designed to augment our understanding of the impact of malaria in pregnancy on maternal health, and the impact of our interventions on the burden of disease.
We are undertaking laboratory studies of maternal immunity to understand how malaria prevention affects the development of immunity to malaria in pregnancy. We will measure antibody responses that are specific for malaria in pregnancy, and examine the relationship between antibody levels and protection from complications of malaria in pregnancy.
We are using molecular diagnostics to investigate the impact of drug resistance on the success of our drug treatments, and to study the importance of malaria species other than P. falciparum in pregnancy. Drug resistance studies will enable us to (1) determine the effect of pre-existing mutations in the parasite on drug efficacy and (2) determine if our interventions select for drug-resistance in P. falciparum.Molecular detection of other species will be used to help determine the importance of P.vivax and P.malariae infections in pregnancy.
In several countries, we are examining the impact of malaria treatments on malaria in the placenta using placental histology. A training workshop held in Cameroon in 2009 is supported by ongoing quality control activities (based in Barcelona). This will allow comparison of the rates of placental malaria across different sites and drug treatments, providing important secondary endpoints for clinical trials.
We are building partnerships with other leading groups studying malaria interventions, drug resistance and immunity, such as the Pregnancy Malaria Initiative, the World Antimalarial Resistance Network, and the MalariaGEN consortium.
Finally, in Cameroon and Papua New Guinea we are using ultrasound examinations to date pregnancies, and to examine the impact of malaria on fetal growth in utero. These studies will determine whether malaria causes changes to the placenta which impairs foetal growth.