Feverish activity

The scourge of malaria continues to kill millions of people annually. Monash is playing a vital role in a renewed assault on the disease, writes DAVID BRUCE

Malaria is generally a preventable and treatable disease, yet every 30 seconds another child dies from it. That’s about 3000 children under five dying each day – and those who do not die from the infection can still become severely ill. About 500 million people contract the disease each year.

Monash University medical researchers are now part of a renewed global assault on this life-threatening parasite.

One team, in the Faculty of Medicine, Nursing and Health Sciences, is working on a range of projects to develop vaccines and to better understand how the parasite successfully lives inside the body, while researchers at Monash’s Victorian College of Pharmacy are developing new and more effective drugs for treating the disease.

Each year, malaria kills more than two million people, mostly in developing countries where control measures are difficult to enforce and medical facilities are poor. And due to the spread of drug resistance, many common malaria treatments are becoming less effective.

No vaccine exists to prevent the onset of the disease, although several trials are under way. Worldwide, most current research into new drugs and vaccines lacks the resources to discover, develop, register and commercialise new products.

In Australia and many other Western countries, the scourge of malaria had disappeared or been controlled by the middle of the last century. The chances of contracting the mosquito-borne disease in Australia today are remote, and the impact of malaria is now confined to travellers to tropical countries who can return with the disease.

But in the world’s developing nations in Africa and Asia, malaria has gone from strength to strength yet has only occasionally appeared as a priority on the agenda of the world’s pharmaceutical companies.

Instead, diseases prevalent in more affluent countries, such as heart disease, neurological diseases and cancer, have attracted the bulk of the research funds from governments and pharmaceutical companies.

As a notable exception to this trend, the Rockefeller Foundation in the United States began its Great Neglected Diseases program in the mid-1970s and devoted funds to research to defeat a range of ‘forgotten’ diseases including malaria. This encouraged researchers from other fields to start looking at the problem of malaria.

Then, more than 20 years later, the World Health Organisation, along with an array of other international agencies including the World Bank, the Bill and Melinda Gates Foundation and the Rockefeller Foundation, established the Roll Back Malaria Program. The program, with associated initiatives such as the Medicines for Malaria Venture, aimed to defeat the disease by developing effective prevention tools and treatments.

"One of the reasons that malaria vaccines and treatments have taken so long to be effective is that malaria has always been a fringe area," says Professor Ross Coppel, who leads the team working on potential new vaccines at Monash’s Department of Microbiology.

"We have had tiny amounts of money directed towards research compared to the numbers of affected people.

"But lately, there has been a resurgence of interest in malaria from major governments around the world and from charitable foundations. It is now understood that to get many countries to develop economically you first need to solve their health problems."

Research in Professor Coppel’s laboratory has focused on understanding the basic biology of the malaria parasite, Plasmodium falciparum, and its behaviour in the human body.

More specifically, the group has moved into the emerging field of bioinformatics to assist them in isolating the proteins within the malaria parasite that provoke an immune response and therefore have the greatest potential to be components of a malaria vaccine.

"The availability of the parasite’s DNA sequence has revolutionised our work over the past year," Professor Coppel says.

"Previously, our task had been to identify the genes. Now we know what all the genes are, but we have the job of sorting through the many thousands of them and working out which are the most useful to us. We use quite sophisticated data-mining techniques to recognise the behaviour patterns of vaccine molecules.

"Our work is already yielding results – we have identified several molecules which can be used in association with vaccine molecules from our earlier studies to give more effective protection. We have some very promising results in the laboratory and must now start the long and expensive process of developing these for use in humans."

An exciting offshoot of this research is the collaboration with other Monash colleagues on their work on oral vaccinations with transgenic plants.

Led by Professor Steve Wesselingh, the Monash team from the Infectious Diseases Unit based at Melbourne’s Alfred Hospital has successfully tested an edible vaccine for measles in animals. Although research is still in an early phase, the same technique is now being used by Professor Coppel’s group to develop an edible malaria vaccine.

Meanwhile, researchers at the Victorian College of Pharmacy are an integral part of the WHO Medicines for Malaria Venture. This partnership between the public and private sectors is driven by its goal of developing a new anti-malarial drug every five years.

The project director at Monash, Professor Bill Charman, says it was a unique opportunity for his research team to join international research and philanthropic agencies in the development of a new drug.

"We are now in the process of developing a whole new class of drugs for malaria. The work is building upon our past involvement with a whole range of different types of drugs for different diseases," Professor Charman says.

Monash is teaming up with the University of Nebraska and the Swiss Tropical Institute in one project that aims to discover a new drug compound for human trials within the next two years.

The University of Nebraska will be responsible for the medicinal chemistry in identifying a new class of compounds, the Swiss Tropical Institute will test the compounds, both in culture and in animals, and Monash will assess and improve the compound’s properties.

Professor Charman says the Victorian College of Pharmacy is internationally recognised as a leader in drug discovery, and the fact that malaria is not a major problem in Australia does not exclude the Monash scientists from playing a role finding new treatments.

"It is also important that an Australian research team has been acknowledged at an international level for its valuable intellectual property and research skills," he says.

For information on Monash microbiology research, visit www.med.monash. edu.au/microbiology/research/coppel/rsch_rlc.html or for more general information on malaria visit www.wehi.edu.au/MalDB-www/who.html or www.malaria.org

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