Dengue

Dengue has spread rapidly across the planet in the past 50 years, driven by urbanisation and population growth.  Hopes for a vaccine are high but natural immunity to the four different viral serotypes is complex and poorly understood.  Infection with one of these serotypes provides immunity to only that serotype for life, so persons living in a dengue-endemic area can have more than one dengue infection during their lifetime.  The lack of an animal model for the disease is also a barrier to the development of an effective vaccine.

Cause

The agent of dengue is a flavivirus, an Ribonucleic Acid (RNA) virus of the kind that causes yellow fever.  Four different dengue viral serotypes infect humans.

Dengue viruses are transmitted in the saliva of an infected biting Aedes mosquito, most commonly Aedes aegypti.

Consequences

Like malaria, dengue causes a spectrum of clinical effects from mild to life-threatening. Dengue fever is a severe flu-like illness which presents as a 'fever-arthralgia-rash’ syndrome, sometimes with mild internal/external bleeding.  It is unpleasant but not life-threatening.

Patients with certain 'warning signs' are at risk of progressing from mild to severe dengue. The severe form of Dengue infection known as Dengue Haemorrhagic Fever (World Health Organization now recommends that dengue be classified as ‘dengue fever’ for the mild forms and ‘severe dengue’ for the more severe forms of the disease)causes severe internal/external bleeding, serious dysfunction of organs such as the liver or brain, and - most seriously - circulatory failure.  Such 'dengue shock syndrome' tends to affect children in Asia but all ages in the Americas.  It can kill within hours of the onset of symptoms.

An important feature of dengue for vaccine developers is that although recovery from infection confers lifelong immunity to the same viral serotype, of much concern is that infection may also sensitise patients to severe disease in a subsequent infection with a different serotype.  Thus any dengue vaccine must confer protection against all serotypes.

Global burden

Dengue is a disease of poverty in urban and semi-urban regions of the tropics and sub-tropics.  These areas harbour favoured Aedes 'container' breeding sites close to overcrowded populations living in sub-standard housing.

Dengue is the most rapidly spreading mosquito-borne viral disease in the world, with dramatic expansion since the 1950s driven by urbanisation and population growth.  Up to 40% of the world's population (2.5 billion people) are now at risk in over 100 countries.

Each year there are an estimated 50 million dengue infections, some 500,000 hospital cases and 15,000-20,000 deaths.  Most recorded cases are in Asia, the Western Pacific and the Americas.  Hospital costs alone run to an estimated US$ 440 million a year.

Dengue, including epidemics of severe disease, is a major public health problem and a significant economic and social burden in many countries.  In 2004, Dengue was responsible for 663,000 Disability Adjusted Life Years and 18,000 deaths ranking as the 10th highest cause of mortality from Negledted Tropical Diseases (G-Finder 2008). 

Vaccines

No medication or vaccines are available for treatment or prevention of Dengue.  Recommendation for travellers to disease infected areas is the use of insect repellents to prevent mosquito bites on exposed skin.  Vector control, including elimination of mosquito breeding sites, has not halted the rise of the disease.  A vaccine against dengue is needed and could be cost-effective to deploy.

A dengue vaccine might appear an easy goal: the virus is simple and a vaccine for yellow fever is already available.  A dengue vaccine would mimic natural immunity and elicit protective antibodies to neutralise the virus.

However, any vaccine needs to induce simultaneous protection against all four dengue viral serotypes, or risk sensitising people to severe disease.  Other challenges are the poor understanding of how natural immunity works and the lack of a good animal model.

Information on Dengue has been selected from Guidelines for diagnosis, treatment, prevention and control -- New edition. Geneva: WHO/TDR, 2009.