Scientists bring their ground-breaking fight against dengue to Southeast Asia.

Sophal Heng lies limply in her hospital bed, the IV drip in her arm slowly re-energising her drained body. She complains of crippling joint and muscle pains and a debilitating headache.

Her impoverished parents sit beside her, hoping they didn't leave it too late to bring her to the hospital; dengue fever has to date killed three times more people in Cambodia this year compared to 2010.

One of almost 10,000 people to have been afflicted with the disease in the country so far this year, Sophal's story, unfortunately, is not an unusual one.

The mosquito-borne viral disease occurs in more than 100 countries worldwide and puts up to 40% of the world's population at risk of infection.

With no known vaccine or cure, this can result in 50 to 100 million cases and upwards of 40,000 deaths per year. Its most significant epidemics take place in Southeast Asia, as well as the Americas and the Western Pacific.

"Dengue is the most important vector-borne viral disease in the world," says Jason Rasgon of John Hopkins' Bloomberg School of Public Health.

The day-biting mosquito that transmits dengue is common in urban and suburban areas in the world's tropical regions, particularly where overcrowding happens.

"The ability of the Aedes aegypti mosquito to survive and multiply in this environment is enormous and should not be underestimated," says Dr Chang Moh Seng, the World Health Organisation's regional point man for the disease.

"Asia is the most severe hot spot for dengue fever when compared to other parts of the world," says Dr Pattamaporn Kittayapong, director of the Centre of Excellence for Vectors and Vector-Borne Diseases at Mahidol University, Thailand.

The disease, which affected 30,000 people in the first eight months of the year in Vietnam, has caused the most deaths and the third-highest number of infections among 28 common infectious diseases in the country, according to the Pasteur Institute in Ho Chi Minh City.

Meanwhile, Thailand spends about $8.2m to treat the 60,000 people who are affected by dengue fever each year, and a further $26m on mosquito control, according to figures from Mahidol University.

"Current approaches to control dengue focus on suppressing the mosquito populations that transmit the virus," says Rasgon. However, for decades, insecticide use has failed to stop the dengue problem.

In fact, in Cambodia, where dengue prevention efforts are hampered by a chronic lack of funding – the National Dengue Control Programme's annual budget is less than $500,000 – the number of people hospitalised with the disease has increased 25% this year compared with last year.

Major outbreaks typically strike Cambodia every three to five years; the last one occurred in 2007, when around 40,000 people were hospitalised, including more than 10,000 in one particularly bad week.

Over the last decade, investment in dengue research has increased, especially from donors in developed countries, as the disease is expanding from tropic al and sub-tropical countries to temperate zones, says Kittayapong.

In an attempt to ward off human disease, scientists from around the world have manipulated mosquito populations.

They have created transgenic mosquitoes resistant to malaria, for example, and have released 'genetically sterile' insects to help fight dengue, with limited success.

However, scientists from the Eliminate Dengue programme are experimenting with a ground,breaking approach that they hope will reduce dengue fever by "changing the mosquitoes rather than killing them".

In a unique programme, Eliminate Dengue, a team of international scientists from Australia, Brazil, Vietnam, Thailand and the US, aims to protect the mosquitoes themselves from dengue, thereby preventing them from transmitting the virus to humans.

By infecting the mosquito with a bacterial agent called Wolbachia pipientis, the team has found a way to stop the insect from spreading the dengue virus to people. The bacterium occurs naturally in up to 70% of all insect species, but not in the mosquito species that transmit dengue to humans.

"The Wolbachia infection in the mosquito reduces the ability of the dengue virus to grow in the mosquito," says Professor Scott O'Neill, head of the Eliminate Dengue programme and dean of the Faculty of Science at Monash University, Australia. "If the virus can't grow in the mosquito, then it can't get transmitted to people."

In January this year, the team conducted an open field trial in Australia, releasing more than 300,000 adult mosquitoes infected with the bacterium into wild Aedes aegypti populations over a period of nine to 10 weeks. Five weeks later, nearly all the wild mosquitoes tested had picked up the bacterium.

"That was a great day," says O'Neill. "These findings tell us that Wolbachia-based strategies are practical to implement and might hold the key to a new sustainable approach to dengue control, an approach that should be particularly suited to large cities of the developing world where conventional control with insecticides is largely ineffective and prohibitively expensive."

With no specific antiviral medicines available and a possible vaccine a few years away from being developed, the breakthrough could save a good proportion of the 593m at risk of dengue fever in Southeast Asia, or the two billion across the world.

The next stage of experiments will focus on measuring reductions in the disease in communities in Southeast Asia, where dengue fever is endemic (in Australia, it is sporadic). "In Southeast Asia, the dengue pressure is much greater and predictable," says O'Neill, "which makes for a better setting to measure efficacy of the approach."

Vietnam will become the new testing ground as early as 2012, with Thailand and Indonesia to follow soon after. "It will be the same basic experiment, but in Southeast Asia, the mosquito populations are not isolated," says Rasgon, "so I would expect the Wolbachia to spread widely outside of the release areas.

"If the [Southeast Asian] trials are successful, I expect that the Wolbachia will spread worldwide within a relatively short period of time – 10 years," adds Rasgon. "Additional implementation will not be necessary. That's the beauty and the worry about Wolbachia.

"If the system works the way it's supposed to, the spread of Wolbachia will be extremely difficult to stop. If you are the type to be fearful of such strategies, this is a concern. I'm not worried about it."

Eliminate Dengue is not the only team trying to find a way to reduce the prevalence of the disease. Earlier this year, France's Sanofi Pasteur began the world's first trial of a dengue fever vaccine in Thailand. The institute says early results seem promising and they hope to develop a vaccine in the coming years.

"Our aim is to prevent dengue, to give it [the vaccination] as part of the [national] immunisation programme… so that children are protected before large epidemics, which are now occurring regularly," Jean Long, head of Sanofi's dengue vaccine programme, told Reuters.

While it is not easy to create a vaccine for a virus that takes four different forms, Sanofi claims to be the first to reach the final stage of development trials and has said it will spend $480m building a site to produce some 100m doses a year.

"The human vaccine prevents the virus from growing in people. The Wolbachia approach prevents the virus from growing in the mosquito," says O'Neill. "The two strategies are complementary and should work well together for a combined solution that might be better than either strategy by itself."

Could this be the end of dengue fever? The cautious scientists were hesitant to say. But there is certainly hope that cases like Sophal's may become a thing of the past.