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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
Intermittent Preventive Treatment In Pregnancy With Sulphadoxine-pyrimethamine Plus Dihydroartemisinin-piperaquine To Reduce Adverse Pregnancy Outcomes And Prevent Malaria In Papua New Guinea: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$2,938,453.00
Summary
Millions of pregnancies are complicated by malaria worldwide. Monthly sulphadoxine-pyrimethamine (SP) treatments, the current treatment strategy, no longer protects from malaria but improves birth outcomes through non-malarial effects. Dihydroartemisinin-piperaquine clears malaria but babies are smaller compared to women who received SP. A clinical trial of their combination has potential to substantially improve health outcomes for women and babies in Papua New Guinea and beyond.
Identification Of The Plasmodium Falciparum Translocon That Exports Parasite Proteins Into Their Erythocytic Hosts.
Funder
National Health and Medical Research Council
Funding Amount
$409,027.00
Summary
Up to 10% of the world's population will suffer from malaria in any given year and for over a million this disease will be fatal. This devastating disease is caused by the parasite Plasmodium falciparum that infects and destroys our red blood cells. Infected red cells are greatly modified by the parasites so they can feed and avoid elimination by the human immune system. We wish to investigate the red blood cell modification process and assess it as a potential target for anti-malarial drugs.
Griseofulvin, A Novel Host-directed Antimalarial Drug
Funder
National Health and Medical Research Council
Funding Amount
$461,551.00
Summary
This grant is for a Phase II clinical trial to test an FDA & TGA approved drug for a new use as an antimalarial drug. The parasite uses an enzyme from the human RBC to help it replicate & early trials show this drug appears to disrupt the life cycle of the parasite. This Phase II clinical trial will test the drug on human subjects, & if successful, the drug will be a new and novel way in which to treat and prevent malarial infections in humans.
Translating New Therapeutics And Diagnostics For Major Pregnancy Complications
Funder
National Health and Medical Research Council
Funding Amount
$481,156.00
Summary
My research is focussed on tackling major complications of pregnancy that are a threat to the lives of both mother’s and babies. We are developing new drug treatments for ectopic pregnancy (a dangerous condition where the pregnancy implants in the Fallopian tube), and preeclampsia (a condition where toxins leak out of the placenta into mum's blood, and can seriously injure many of mum's major organs). We are also generating a blood test that may help women avoid the tragedy of a stillbirth.
Development Of Vinorelbine As A Tablet Based Therapy To Cure Ectopic Pregnancies
Funder
National Health and Medical Research Council
Funding Amount
$361,594.00
Summary
Ectopic pregnancies occur if the pregnancy implants in the Fallopian tube. They can be deadly and most are treated surgically. We will examine the exciting possibility that instead of surgery, ectopic pregnancies may be cured with a tablet taken just once. We will perform laboratory studies and a clinical trial, giving vinorelbine to women with ectopic pregnancies.
Centre For Research Excellence In Malaria Elimination
Funder
National Health and Medical Research Council
Funding Amount
$2,470,291.00
Summary
The CRE will work to accelerate progress towards malaria elimination in our region, through Surveillance, to develop better ways to monitor malaria transmission and discover who is infected, and to track movement of malaria parasites and spread of drug resistance. Diagnosis, to develop and test new, more sensitive ways of detecting malaria. Treatment, to fast track development of new antimalarials, and improve access to ensure all infected people get highly effective drugs.
Targeting The Anti-angiogenic Factors Of Preeclampsia: Soluble Endoglin And SFlt1
Funder
National Health and Medical Research Council
Funding Amount
$447,024.00
Summary
Preeclampsia is a severe disease of pregnancy - the placenta releases toxins in to mum's bloodstream that circulate her body and damage her organs. As there are no efficacious treatments, clinicians are forced to deliver babies irrespective of gestation. Although the two toxins of preeclampsia have been identified, little is known about their regulation. This project aims to elucidate the regulation of these toxins and design therapeutics that can prevent their release in the clinic.
Combination Methotrexate And Gefitinib To Cure Ectopic Pregnancies: Phase I-II Clinical Trials
Funder
National Health and Medical Research Council
Funding Amount
$235,875.00
Summary
Ectopic pregnancies are dangerous emergencies that can cause fatal bleeding. Most require surgery. We plan to test a novel medication-based treatment that could be used to cure most ectopics. If successful, it could revolutionise current management.
Soluble Endoglin In The Pathogenesis Of Preeclampsia: Investigation Of Mechanisms And The Development Of Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$572,733.00
Summary
Preeclampsia is a severe disease of pregnancy. As the pathogenesis is poorly understood, the only treatment is for clinicians to deliver babies irrespective of gestation. We have identified MMP-14 as the molecular scissors that release soluble endoglin from placenta, a toxin centrally responsible for severe preeclampsia. In this project we aim to further investigate the mechanisms governing soluble endoglin release and to begin developing a potential therapeutic for use in the clinic.