Dengue

Dengue is a mosquito-borne viral disease that  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, a Ribonucleic Acid (RNA) virus of the kind that causes yellow fever, Zika infection and chikungunya. Four different dengue viral serotypes (DENV 1- 4) infect humans.

Dengue viruses are primarily transmitted to humans by Aedes mosquitoes, particularly Aedes aegypti through the bites of infected female mosquitoes.

Infected symptomatic or asymptomatic humans are the main carriers and multipliers of the virus, serving as a source of the virus for uninfected mosquitoes. In rare case, dengue can also be transmitted through blood transfusions or organ transplants.

Consequences

Like malaria, dengue causes a spectrum of clinical effects from mild to life-threatening. According to WHO, dengue is classified in dengue fever and Dengue Haemorrhagic Fever (DHF) or Dengue Schok Syndrome (DSS) depending on the clinical symptoms. Dengue fever, the mild form causes   flu-like symptoms including high fever usually accompanied by at least two of the following signs: headaches, pain behind eyes, nausea, vomiting, swollen glands, joint, bone or muscle pains. Dengue fever affects infants, young children and adults. It is unpleasant but causes rarely death.

Patients with certain 'warning signs' (including severe abdominal pain, persistent vomiting, bleeding gums, vomiting blood, rapid breathing, fatigue, restlessness) are at risk of progressing from mild to severe dengue known as DHF. This form causes severe internal/external bleeding, serious dysfunction of organs such as the liver or brain, and - most seriously - circulatory failure. DHF can evolve to a ‘dengue shock syndrome' that tends to affect children in Asia but all ages in the Americas.  It can kill within hours of the onset of symptoms.

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. Approximately 50% of the world's population are now at risk in over 100 countries.

Dengue is a major public health problem worldwide. Each year there are about 58.4 million symptomatic dengue infections resulting in approximately 10 000 deaths. In 2013, dengue was responsible for 1.14 million Disability Adjusted Life Years (DALYS) (Stanaway and al. 2016).

Treatment

There is no specific treatment for dengue fever. The treatment is supportive and based on WHO guidelines and regions specific authorities.

For severe dengue (DHF/DSS), the treatment is fluid replacement therapy to maintain the patient’s body fluid volume.

Vaccines

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.

In 2015 the 1st dengue vaccine Dengvaxia® (CYD-TDV) was licensed in 9–45 years individuals living in endemic areas. The vaccine has since been approved by Regulatory Authorities in several endemic countries. But the vaccine is associated with increased risk of severe dengue in those who experience their first natural dengue infection.

Several others dengue vaccines are under different phase of development.

Three strategies are used for the prevention and the control of dengue vector transmission including environmental management, biological control and physical control

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

References

World Health Organisation (WHO). Facts sheets Dengue and severe dengue. http://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue, accessed on 20 September 2018

CDC. Dengue.  https://www.cdc.gov/dengue/epidemiology/index.html. Accessed on 20 September 2018.

Senanayake AMK 2015. Dengue fever, BMJ, 351, 1-10

K.S. Vannice et al. Status of vaccine research and development of vaccines for dengue. Vaccine 34 (2016) 2934–293

Rather IA and al. 2017. Prevention and Control Strategies to Counter Dengue Virus Infection. Frontiers in Cellular and Infection Microbiology 336, July, Volume 7