Antimalarial Drugs In Pregnancy: Preclinical And Clinical Studies Of Conventional And Novel Agents
Funder
National Health and Medical Research Council
Funding Amount
$470,115.00
Summary
Women in malaria-endemic areas such as coastal PNG are at high risk of malaria in pregnancy. To prevent the substantially increased malaria-associated morbidity and mortality in mother and child, and because even asymptomatic infections can be deleterious, there has been a move to giving antimalarial drugs regularly during pregnancy regardless of the mother's clinical or parasitological status. In poor tropical countries, such treatment usually comprises safe and inexpensive agents such as chlor ....Women in malaria-endemic areas such as coastal PNG are at high risk of malaria in pregnancy. To prevent the substantially increased malaria-associated morbidity and mortality in mother and child, and because even asymptomatic infections can be deleterious, there has been a move to giving antimalarial drugs regularly during pregnancy regardless of the mother's clinical or parasitological status. In poor tropical countries, such treatment usually comprises safe and inexpensive agents such as chloroquine and Fansidar. There are two main issues with this approach. First, the efficacy of such conventional agents is waning and this increases the risk of break-through malaria. Second, there are few data on how the drugs are handled in pregnancy on which to base recommendations for treatment. We plan to collect information on the disposition and effectiveness of chloroquine and Fansidar in women with malaria in pregnancy in PNG that should allow a critical appraisal of the usefulness of current regimens in PNG and in other tropical countries where parasite resistance to these agents is emerging. Artemisinin combination therapy (ACT) in the form of a novel artemisinin drug and a longer-acting partner has been suggested as the most promising alternative therapy for malaria in pregnancy if conventional drugs fail. We plan to assess the safety of a leading ACT formulation, namely dihydroartemisinin and the chloroquine-like drug piperaquine (DHA-PQ), in animals before extending our studies to women with malaria in PNG. These latter studies will allow an evaluation of the safety and efficacy of DHA-PQ as novel therapy for malaria in pregnancy in PNG and other tropical countries.Read moreRead less
The Immune Modulatory Function Of Chondroitin Sulphate A In Placental Malaria: Protecting The Fetus, Promoting The Parasite?
Funder
National Health and Medical Research Council
Funding Amount
$529,206.00
Summary
Pregnant women and their babies are susceptible to placental malaria infection. Malaria parasites infect the placenta by binding to chondroitin sulfate A (CSA). CSA levels increase in normal pregnancy. Studies suggest that CSA can suppress immune cell function. This study will look at the immune modulating function of CSA during pregnancy and placental malaria. CSA may act as camouflage, hiding the malaria parasite from immune cells. This may be a novel immune evasion pathway.
Malaria In Pregnancy: Exposure, Immunity And Complications
Funder
National Health and Medical Research Council
Funding Amount
$549,723.00
Summary
Increasing malaria control efforts may lead to lack of exposure needed to develop immunity. We will use plasma samples from Africa, PNG and Asia, and measures of immunity we have developed, to discover (1) which are the most important protective immune responses and (2) how are these affected by changing exposure or new drugs. Overall, we hope to identify markers of protective immunity that can be used to identify women at most risk of malaria in pregnancy and its complications
Functional Assays Of Immunity To Malaria In Pregnant Women
Funder
National Health and Medical Research Council
Funding Amount
$578,905.00
Summary
Pregnant women are highly susceptible to malaria due to the adhesion of infected erythrocytes to the placenta. Antibodies to these infected erythrocytes can block their placental adhesion and/or facilitate their clearance by immune cells, improving pregnancy outcomes. We aim at informing vaccine design by better understanding the placental adhesion mechanisms and identifying targets of protective immunity as well as antibody correlates of protection from placental malaria and its consequences.