Special Report - Emerging Viruses

The challenge of dengue

The Aedes aegypti urban mosquito and dengue vector. ©Institut Pasteur Aedes aegypti urban mosquito and dengue vector
©Institut Pasteur
Dengue virus structure ©Jean-Louis Romette Dengue virus structure.
©Jean-Louis Romette

With 100 million cases and 25 000 deaths each year, dengue is the world’s commonest and fastest-spreading mosquito-transmitted disease. Its re-emergence in South America and South- East Asia is all the more worrying as resources for effectively combating it are sorely lacking. European research is working on all fronts.

Dengue is the least understood of all arboviral diseases (transmitted by invertebrate organisms or arthropods). Just one diagnostic test exists, but with a price tag that puts it out of reach of less developed countries. And even then this test cannot enable the distinction to be made between the typical, mild forms of the disease, with some 100 million cases a year, and the very dangerous dengue haemorrhagic fever that kills 25 000 people, mainly children, every year.

Why can the same virus provoke such different symptoms? It’s a mystery! Why are these atypical haemorrhagic fevers often fatal, even without the vascular lesions typical of Ebola infections? Another enigma… With no vaccine, pathological model or effective antiviral available to combat the virus, a major research effort was an urgent priority.

The second infection

One of the first tasks of the Denco and Denframe projects, linking EU laboratories with those in countries where the disease is prevalent, is to understand why certain infected patients develop haemorrhagic fever. “In the past thirty years the disease has spread to many countries not previously hit. Its forms have also become more diversified. We are looking for universal and easily identified clinical criteria that herald the advent of the dangerous types,” explains Denco coordinator Thomas Jänisch from Heidelberg University Hospital (DE).

Dengue is both a medical and a scientific challenge. “We know four families of the dengue virus, none of them specifically associated with its dangerous forms. This leads us to look for an explanation on the patient’s side. One hypothesis we are testing is that a second infection is a lot more dangerous than the first,” says Denframe coordinator Nathalie Pardigon from the Institut Pasteur in Paris. Teams have already put together a test group of several hundred people with well-defined medical records in Vietnam, Cambodia and soon in Brazil. “It is not uncommon for someone to have been infected by dengue without noticing it,” she continues. “With systematic blood sampling, we know each person’s history of infection and can therefore closely monitor the effects of any second infection.” This work will also help to standardise and improve diagnostic tests and hopefully make them more affordable.

Aedes, the urban mosquito

The second battlefront in the struggle against the disease involves its vector, the Aedes aegypti mosquito. The spectacular re-emergence of dengue in Latin America can be explained by the disorganised state of anti-mosquito programmes due to population growth, urbanisation and impoverishment. “Unlike the malaria vector, Aedes aegypti lives in cities and bites during the day. This requires us to invent new combat strategies,” explains Axel Kroeger from WHO, one of the partners in Denco. One study carried out by the programme in 36 districts of Veracruz in Venezuela and Trujillo in Mexico showed that insecticide-impregnated curtains have a long-term effect in reducing mosquito bites and consequently virus infections.

The final strategy in the fight against the disease involves drugs. Denframe is testing the effectiveness against dengue of thousands of compounds from the existing pharmacopoeia and of algae or animal extracts in cell cultures. “Brute force” is how Nathalie Pardigon describes this approach, given the number of compounds tested. But hardly excessive against a disease to which the WHO tells us 2.5 billion people are potentially exposed.

Mikhail Stein


To find out more

  • Denco – 8 partners – 8 countries (BE - CH - DE - PH - TH - UK - VE - VN)
  • Denframe – 12 partners – 10 countries (BE - BR - DE - CN - ES - IL - MX - UK - VN)
  • www.denframe.org