Test vaccine for dengue fever seen as promising

By Agence France-Presse
Friday, July 11, 2014 5:32 EDT
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Behind air-tight doors in a lab in a southern French city, scientists in protective coveralls wage war against a fingernail-sized danger. Lurking in net cages is their foe: the Asian tiger mosquito, capable of spreading dengue fever and other tropical diseases in temperate Europe. First spotted in Albania in 1979, the black-and-white striped invader has gained a foothold on Europe's Mediterranean rim and is advancing north and west, according to captors' reports. Colonies are established in 20 European countries, in moderate climes as far north as Germany, Belgium and the Netherlands. "The risk of disease is very low but it is growing," entomologist Jean-Baptiste Ferre told AFP at France's leading mosquito-control institute. "The more mosquitoes there are, the higher the risk." The Asian tiger mosquito -- Latin name Aedes albopictus -- can spread many kinds of viruses. They include dengue, which can result in a deadly haemorrhagic fever, as well as West Nile virus, St. Louis encephalitis and a painful disease of the joints called chikungunya. A. albopictus transmits the virus by taking blood from a sick person and handing on the pathogen the next time it takes a meal. The worry is that the insect will spread disease in Europe by biting infected people arriving from tropical countries where the viruses are endemic. In 2007, the tiger mosquito caused a home-grown outbreak in Italy of chikungunya, and in 2010, 10 locally-transmitted cases of dengue occurred in Croatia. That same year, two cases of each disease surfaced in southern France, prompting the alarm bells to ring loudly. From Montpellier, Ferre and his colleagues at the Entente Interdepartementale pour la Demoustication en Mediterranee (EID) monitor the spread with some 1,500 traps dotted around France, luring mosquitoes to lay their eggs. These provide insights into how A. albopictus is adapting to European life, with its varied habitats and cooler climate. Ferre points to maps that begin in 2004, when a tiny red dot represented the first settling of albopictus in France around Menton, near the Italian border. Year by year, the dot grows into red tentacles that probe north and west. The insect has a flight range of only about 200 metres (yards), so it hitch-hikes a ride in cars, trucks and traded goods. With climate change, "further expansion is probable," the journal Vector-Borne and Zoonotic Diseases warned this year. That assessment is supported by scientists at Britain's University of Liverpool who point to warming trends in the Balkans and northwestern Europe. Asian tiger mosquitoes are aggressive and robust, able to breed prolifically in their short, 10-day lives. Feeding during the day, they can bite several people in quick succession, and their offspring can hatch even after long periods without water. Worse, the insect is a stealthy urban dweller. It does not need large, open bodies of water to reproduce, for it can lay its eggs in small, water-holding receptacles such as flowerpots, toys and blocked gutters, and this makes it much harder to fight. Since May this year, surveillance in France has thrown up 267 suspected dengue and chikungunya cases among people who had arrived from abroad, said EID project coordinator Gregory Lambert. The institute sometimes launches pre-emptive strikes if this can prevent the mosquitoes from spreading disease locally. It orders out insecticide trucks that spray streets in a 200-metre (650-foot) radius around the area where a case is notified. The operations take place before dawn, while most people are still in bed. "The imperative is to kill the mosquitoes before they transmit the disease," said Lambert. The war is unrelenting. "It is impossible to kill them all," said Anna-Bella Failloux of France's Pasteur Institute, one of the world's top centres for infectious disease. "Even if there is no mosquito around you, you still have eggs somewhere, waiting for the next rain."
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A prototype vaccine for dengue that two years ago yielded lukewarm results has proved more effective after wider trials and is a potential arm against the disease, researchers said Friday.

Devised by the French pharmaceutical giant Sanofi Pasteur, the so-called CYD-TDV vaccine provided only 30 percent protection against the dangerous fever when first tested among children in Thailand.

Widened to trials in four other Asian countries, where disease conditions vary greatly, the vaccine’s protection has been shown to be significantly higher, at 56.5 percent overall, the scientists said.

The result falls short of the benchmark set by classic vaccines such as those for polio and measles, which can be more than 99 percent effective.

One reason for this is that CYD-TDV performed poorly against one of the four strains of dengue virus, the investigators reported in The Lancet.

These strains, or serotypes, circulate simultaneously, which means a vaccine should ideally protect against all of them.

Even so, the prototype was safe and well tolerated and its shield, if only partial, means it should be enlisted in the fight against dengue, they argued.

“Our results suggest that vaccination with CYD-TDV can reduce the incidence of symptomatic dengue infection by more than half and importantly reduced severe disease and hospitalisations,” said Maria Rosario Capeding from the Philippines’ Research Institute for Tropical Medicine.

“This candidate vaccine has the potential to have a significant impact on public health in view of the high disease burden in endemic countries.”

Dengue is a potentially fatal fever, caused by a virus transmitted by a mosquito when it takes its blood meal, and is especially dangerous for children.

The virus infects around 390 million people each year, of whom about 96 million fall sick, according to UN estimates.

It was once considered a disease of the tropics that was endemic in only nine countries.

But globalisation, climate change and jet travel are helping it to move into more temperate zones.

According to the World Health Organization (WHO) cases of dengue have risen 30 fold over the last 50 years, and more than half of the world’s population are at risk of the disease.

- Wider trials -

The CYD-TDV vaccine was tested as a so-called Phase IIb trial among just over 4,000 children in rural Thailand, the results of which were reported in September 2012.

The new figures are those of a Phase III trial — normally the final step in the process to test new drugs for safety and efficiency — carried out in Indonesia, Malaysia, the Philippines and Vietnam, as well as in Thailand.

More than 10,000 children aged two to 14 years were enrolled. They were randomly assigned to receive three injections of the vaccine or a placebo over 12 months, and were followed for up to two years.

During this period a total of 150 dengue cases occurred, a majority of them in the placebo group, demonstrating an overall effectiveness of 56.5 percent.

But the protection varied according to the serotype — more than 75 percent against virus types 3 and 4; 50 percent against type 1; but only 35 percent against type 2.

On the plus side, those who had received the vaccine were also far less likely to fall ill with a severe form of the disease, dengue haemorrhagic fever, which leads to half a million hospitalisations each year.

In a commentary, Annelies Wilder-Smith, a professor at Singapore’s Nanyang Technological University, said a vaccine that halved annual cases of dengue “would present a significant public health benefit” but was not a magic bullet.

“For the moment, the CYD-TDV vaccine is the best we have; however, with 56 percent efficacy it will never be a single solution,” Wilder-Smith said.

Other strategies, including better approaches to tackling mosquitoes that cause the problem, would also have to be part of the campaign, she said.

The children in the trial are being followed up for another four years to see whether the vaccine’s promise still holds up.

Agence France-Presse
Agence France-Presse
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