New hope to treat deadly dengue virus

30 May 2008

After the initial devastation caused by Cyclone Nargis, the people of Burma face a second catastrophe - the threat of fatal diseases like cholera, malaria and dengue fever. So what are the prospects for their treatment today? Not good for dengue, but a breakthrough in a lab in Taiwan might offer hope for the future. Antenna investigates...

Contaminated water and a lack of medical supplies mean disease is a serious threat for the Burmese people.

image: iStockphoto/Leeuwtje

This research was published in the journal Nature on 29 May 2008.
A mosquito-spread menace, the deadly dengue virus hijacks the immune system and makes it attack the body it's supposed to protect.

There are no effective treatments to prevent or treat this poorly understood disease - but that could be about to change...

People bitten by dengue-carrying mosquitoes can develop leaky blood vessels, leading to severe bleeding from the gums, nose and internal organs.

image: Wikimedia Commons/US Department of Agriculture

Mice infected with dengue were given drugs that blocked the virus's progress. But will they work in humans too?

image: iStockphoto/Brandon Laufenberg

Investigating the disease in mice, scientists in Taiwan found that blocking the dengue virus from reaching a particular target on immune cells cut disease deaths by half. It's the first promising treatment for the illness.
The team have discovered that dengue targets a particular protein on immune cells - called CLEC5A. It's responsible for triggering the release of molecules called cytokines.
Cyto-what? Cytokines are released by immune cells when they encounter an infection - they signal other cells and antibodies to join in the fight.

The dengue virus has an unusually smooth surface compared to other viruses - a fact worth considering when planning how to fight the disease.

image: Purdue University Structural Virology

So what's the problem?

When hijacked by the dengue virus, immune cells trigger an abnormal and massive release of cytokines - a 'cytokine storm'. They flood the site of infection, attacking the body instead of the virus which causes fatal bleeding.
The Taiwanese team blocked the virus from triggering a storm using drugs called monoclonal antibodies, with interesting results...
'Blocking the virus prevented severe bleeding, but we were also excited to find that it didn't disrupt the body's normal immune response. So over 30% of the mice were able to clear the virus completely', says Dr Shie-Liang Hsieh, dengue fever expert.

Shie-Liang Hsieh, dengue fever expert, National Yang-Ming University, Taiwan.

image: Shie-Liang Hsieh

How soon could the breakthrough be put into action?
'If we move fast we might be able to start clinical trials to treat people within five years. And it's not only a breakthrough for dengue. The same treatment could help with other similar diseases such as the JEV virus which causes brain infections.' Shie-Liang Hsieh.

Map looks a bit strange? The country sizes have been distorted to show the number of dengue related deaths - you can see that many dengue deaths are in Southeast Asia.

image: SASI Group, University of Sheffield/Mark Newman, University of Michigan

Although this discovery comes too late for the Burmese cyclone victims, it's good news for future generations in dengue hot spots who could now have a fighting chance against a disease that kills over 20,000 people a year.
'Until now there has been little effective research into finding a drug to treat dengue. Previous efforts have focused on vaccine development which has proved very difficult, so work like this is to be encouraged.' Says Professor Jeremy Farrar, tropical disease expert.
'But it remains to be seen whether a treatment so effective in mice will be as effective in humans. Mice and humans respond to dengue very differently. So this is exciting research, but it may be many years before we see such a drug being used on patients.'

Professor Jeremy Farrar, tropical disease expert, Hospital for Tropical Diseases and Oxford University Clinical Research Unit, Vietnam.

image: Wellcome Trust UK

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