Malaria causes approximately 500 million clinical infections a year, and is a major cause of morbidity and mortality in the region. The Menzies malaria research program spans a broad range of research activity aimed at both prevention and treatment, from epidemiology through pathophysiology, molecular parasitology, clinical trials, evaluation of the impact and cost-effectiveness of public health interventions. We work on all five species of the Plasmodium parasite that cause human malaria, with a particular focus on the three that cause most disease and death in the Asia Pacific region: falciparum, vivax and knowlesi malaria. Our work focuses on better understanding Plasmodium parasites: the ways in which they become resistant to drugs, how they cause severe disease and death, and how our immune system protects against malaria. Through improved knowledge of these parasites, we are identifying better ways to prevent and treat malaria in different environments, facilitating policy change and monitoring the impact of such change in the health of communities.

Over the last ten years, Menzies has been working closely with Indonesian partners, policy makers, researchers and health care providers to define the burden of malaria and optimise treatment guidelines in the eastern province of Papua. Our studies have confirmed the high levels of drug resistant in P. vivax and its association with severe and fatal malaria.
Severe malaria: In 2005 Menzies researchers joined a multicentre trial demonstrating that intravenous artestunate was more effective than quinine (the current treatment advised by World Health Organisation) for severe malaria, reducing mortality by 34%. This trial has defined WHO global policy as well as national policy for the treatment of severe malaria in Indonesia and Australia.  Despite this major advance with antiparasitic therapy, mortality from severe malaria remains high. We are undertaking trials of adjunctive L-arginine to increase nitric oxide and improve microvascular function in severe malaria.
Clinical trials in patients with uncomplicated malaria have defined the best treatment for local strains of drug resistant malaria, advocating a uniform policy for all species of malaria. Studies are ongoing to monitor the impact and cost effectiveness of this approach to malaria control.

In Sabah, Eastern Malaysia, Menzies is collaborating with the Queen Elizabeth Hospital, working on the study of a new form of severe malaria caused by P. knowlesi.  Studies are ongoing to define the epidemiology, pathophsyiology and treatment of this parasite, and optimise its clinical management.

Laboratory studies in Darwin and at field sites focus on both the parasite and host immune and pathological responses. Parasite studies aim to understand the mechanisms of drug resistance and its genetic basis.  Novel ex vivo tests have been developed to assess the drug susceptibility of P. vivax field isolates, which will help monitoring for the emergence and spread of drug resistance and the efficacy of new antimalarial agents.  Studies of the human response to malaria focus on cellular immune responses mediating protection in malaria and pathological responses causing impaired microvascular and endothelial function.

The Menzies malaria program is committed to a translational research agenda, building capacity in endemic countries to tackle key research priorities.  Menzies coordinates the Vivax Working Group of the Asia Pacific Malaria Elimination Network (APMEN).  We are undertaking capacity building research activities on malaria, through a combination of workshops, small grants and technical assistance to eleven member countries of the network.  Menzies staff also play a key role in the WorldWide Antimalarial Resistance Network, working to facilitate quality assured methods for monitoring the global spread of antimalarial drug resistance.

2011 Highlights:

• Epidemiological studies have shown congenital malaria to be an important cause of morbidity in early infancy.  The use of DHA-piperaquine (an artemisinin combination therapy) has resulted in a significant reduction in vertical transmission of malaria following its introduction in 2006.
• Studies in Timika, Papua show that while P. vivax is a major cause of severe anemia, most coma associated with P. vivax is actually due to other causes
• Elevated concentrations of a natural inhibitor of the enzyme producing nitric oxide predicts risk of death in both severe falciparum malaria and severe sepsis
• The Global Health Team have pioneered a novel in vitro assay with several publications on the drug susceptibility of new agents against both P. falciparum and P. vivax.
• Antimalarial clinical trials in Indonesia and Thailand have revealed high relapse rates of P. vivax infection after P. falciparum.  These studies highlight that the greatest transmission potential after uncomplicated malaria is in fact P. vivax rather than P. falciuparum.
• Studies of severe knowlesi malaria at Queen Elizabeth Hospital in Sabah demonstrate a high mortality, but excellent efficacy of intravenous artesunate. Prospective studies continue
  First reports of P. knowlesi causing malaria in children

Staff: Ric Price, Nick Anstey, Nick Douglas, Jutta Marfurt, Sarah Auburn, Gabriela Minigo, Tonia Woodberry, Hao Wang, Jessica Loughland, Kim Piera, Grennady Wirjanata, Lorenz von Seidlein, Tsin Yeo, Kylie Mannion, Ella Curry
Students: Grennady Wirjanata; Bridget Barber; George John; Josh Hanson, Hugh Kingston, Franscisco Thio, Matthew Grigg
Collaborators: Eijkman Institute for Molecular Biology, Indonesia, Queen Elizabeth Hospital, Malaysia, Papuan Health and Community Development Foundation, Timika, Indonesia, District Health Authority, Papua, Indonesia, University Gadjah Mada, Indonesia; Mahidol-Oxford Research Unit, Bangkok, Thailand, Centre of Tropical Medicine, Oxford University, UK, London School of Hygiene and Tropical Medicine, Australian Army Malaria Institute, Queensland Institute of Medical Research, University of Utah, USA, University of Otago, NZ, Duke University, USA, HKMU, Tanzania