Dengue is a mosquito-borne infection that in recent decades has become a major international public health concern. Dengue is caused by four distinct, closely related, enveloped RNA viruses which are members of the flavivirus group. The dengue viruses, are the most widespread arthropod-borne viruses (arboviruses). They also are the only known arboviruses that have fully adapted to the human host and lost the need of an animal host for maintenance. During the 20th century, the distribution and density of Aedes aegypti expanded dramatically in tropical areas, beginning in large cities then spreading to the countryside. This was followed by global circulation of the four dengue virus serotypes facilitated by international air travel.
Dengue fever is a febrile illness that affects infants, young children and adults. Symptoms range from a mild fever, to incapacitating high fever, with severe headache, pain behind the eyes, muscle and joint pain, and rash. More severe forms of the disease are dengue haemorrhagic fever (DHF) which is a potentially lethal complication with fever, abdominal pain, vomiting and bleeding which affects mainly children and dengue shock syndrome (DSS) where a very low blood pressure can cause organ dysfunction. Recovery from infection by one provides lifelong immunity against that virus but confers only partial and transient protection against subsequent infection by the other three viruses. There is good evidence that sequential infection increases the risk of developing (DHF) through immune-enhancement when infected by a second serotype. Dengue is endemic in more than 100 countries in Africa, the Americas, the Eastern Mediterranean, South-east Asia and the Western Pacific. South-east Asia and the Western Pacific are the most seriously affected. DHF affects most Asian countries and has become a leading cause of hospitalization and death among children in the region. It is estimated that from 50-100 million cases of dengue fever, 500,000 cases of DHF/DSS and more than 20,000 deaths occur each year.
These vaccines include:
- a live attenuated tetravalent dengue virus vaccine (a preparation of live attenuated dengue-1, dengue-2, dengue-3 and dengue-4 viruses);
- a live attenuated tetravalent dengue–yellow fever virus chimeric vaccine (a preparation of combined live attenuated chimeric viruses, based on the live attenuated yellow fever virus vaccine and each expressing dengue-1, dengue-2, dengue-3 or dengue-4 virus envelopes);
- a live attenuated tetravalent dengue–dengue 4 virus chimeric vaccine (a preparation of live attenuated chimeric viruses, based on the live attenuated dengue-4 vector and each expressing dengue-1, dengue-2, dengue-3 or dengue-4 virus envelopes); and
- a live attenuated tetravalent dengue-dengue 2 virus chimeric vaccine (a preparation of live attenuated chimeric viruses, based on the live attenuated dengue-2 vector and each expressing dengue-1, dengue-2, dengue-3 or dengue-4 virus envelopes).
Apart from these live candidate vaccines, non-replicating dengue vaccines such as subunit vaccine or DNA vaccines are under development.
Dengue vaccine standardization
Guidelines for candidate live attenuated tetravalent dengue virus vaccines were adopted by ECBS 2004.
Guidelines on the quality, safety and efficacy of dengue tetravalent vaccines (live, attenuated). Annex 2, Technical Report Series No. 979
No WHO reference materials for dengue vaccines are currently available.
WHO Working Group on Technical Specifications for Manufacture and Evaluation of Dengue Vaccines, Geneva, Switzerland, 11-12 May 2009
Meeting of the WHO Task Force on Clinical Trials of Dengue Vaccines, Bangkok, Thailand, October 2004
Report of the Steering Committee on Dengue and other Flaviviruses Vaccines, WHO, Geneva, April 2004
Report of the Steering Committee on Dengue and other Flaviviruses vaccines, WHO, Geneva, 2-3 April 2003
- Minutes of the Informal consultation on Antibody Protection against Dengue Infection, April 2003
- Meeting of the WHO Task Force on Clinical Trials of Dengue Vaccines, Atlanta, 11 November 2006
- WHO dengue fact sheet
- WHO dengue topic page
- Special Programme for Research and Training in tropical diseases
- Epidemic and endemic alert and response
- International travel and health