Overview:
Dengue
Background
Dengue is a mosquito-borne viral infection that often causes a severe flu-like illness. Symptoms, if they occur, usually begin 4-7 days after a mosquito bite, and last up to 10 days. Severe cases (dengue hemorrhagic fever, DHF) can involve plasma leakage, severe organ damage, shock (dengue shock syndrome), and death. Dengue is transmitted mainly by Aedes aegypti and Aedes albopictus. Mosquitoes feed on the blood of an infected person and transmit the virus to a healthy person. Other routes of transmission (i.e., organ transplants, blood transfusion, and from mother to fetus) are known but not considered significant.[1]
Epidemiology .[2]
- Dengue is a tropical and sub tropical disease, found mainly in urban and semi-urban areas where conditions favor mosquito breeding.
- Dengue is endemic in more than 100 countries, particularly in South and Southeast Asia, the Western Pacific, and Latin America and the Caribbean. It may present with more intensity during the rainy season.
- WHO estimates that 2.5 billion people are at risk from dengue, with 50-100 million people infected annually; nearly 900,000 cases were reported in the Americas in 2007.
- Over the past 30 years, the incidence of dengue has grown dramatically, with some countries reporting a ten-fold rise in outbreaks.
- The number of countries reporting DHF has also increased from 9 in 1970 to more than 36 in recent years. An estimated 500,000 people with DHF require hospitalization each year, many of whom are children. Less than 1% to 20% die, depending on the context.
The intervention assessments below summarize evidence presented in the "Key Findings" table.
Prevention: What Works?
The only demonstrated way to prevent dengue virus transmission is to control the vector, i.e., mosquito adults and larvae. Thus, we report evidence for three categories of vector control: environmental and biological, chemical, and integrated.
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Environmental and biological
vector control strategies have evidence of 29-93% reduction in vector density (moderate and weak strength of evidence, respectively), as measured using standard indices. They lack evidence of reduction in mortality or disease.
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Chemical strategies (e.g., application of insecticides to larval habitats) prevent mosquito breeding for several weeks but must be re-applied periodically. Insecticides appear to reduce disease (52-71%), based on weak evidence, and have no clear evidence of reduction in vector density (19% increase to 95% reduction). During outbreaks, insecticides may be widely sprayed from portable or truck-mounted machines or aircraft. The mosquito-killing effect is transient and variable in effectiveness because aerosol droplets may not reach mosquitoes living indoors.
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Integrated vector management,
employing appropriate use of the above vector control strategies, appears to be the most efficacious approach. One review found a 67-88% reduction in vector density (moderate strength of evidence). A compilation of 6 studies found 66-100% reductions in dengue disease incidence (though weak evidence, due to lack of randomized trials). [3]
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Other (not in table).
Evidence is insufficient to assess whether community-based educational interventions lower vector or dengue incidence (not in the table).[4]
Treatment: What Works?
Management of severe clinical disease (DHF) focuses on non-specific fluid therapy[5]. Although we could find no formal reviews, this approach is thought to reduce case fatality from more than 20% to less than 1%[5],[6]. We review assessments of two therapeutic enhancements:
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Advanced fluid replacement has evidence, albeit weak, of lower mortality (42%, 3-65%) and less pleural effusion (60%, 10-80%). Intravenous immunoglobulin and Recombinant activated factor VII may lessen platelet and bleeding problems.[7]
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Corticosteroids may reduce mortality (32%, 11% increase to 58%, strong evidence). However, steroid use is not recommended, due to limited evidence and concern about adverse events (convulsions, pulmonary hemorrhage, and blood transmission).
Summary/Future Directions
Prevention. Integrated vector management has the strongest evidence of efficacy, better than individual environmental, chemical, biological, or behavioral strategies.
Treatment. Fluid therapy is the mainstay. Advanced fluids may enhance efficacy.
Future directions depend largely on potential technical advances, in at least three areas: Developing a vaccine is challenging, due in part to the presence of four related viruses that cause dengue. Several potential vaccines are in development, including Phase II trials and one Phase III trial.[8] Improved vector control methods (e.g., environmental techniques and delivery of insecticides) are under investigation. There is also research on the use of genetically modified mosquitoes to interrupt transmission. No antiviral treatment for dengue has proceeded beyond the laboratory stage, though important progress appears to be underway.[9]
Reference
1. Adapted from: CDC. Dengue homepage: Epidemiology. 2010. Available from: http://www.cdc.gov/dengue/epidemiology/index.html.
2. Adapted from: WHO. Media Centre: Dengue and haemorrhagic fever. Fact sheet No. 117, March 2009. Available from: http://www.who.int/mediacentre/factsheets/fs117/en/.
3. Erlanger, 2008. One study showed an increase in dengue; determined by the GHIR study team to be an unrepresentative outlier.
4. Heintze C, Valasco Garrido M, Kroeger A. What do community-based dengue control programmes achieve? A systematic review of published evaluations. Transaction of the Royal Society of Tropical Medicine and Hygiene. 2007; 101, 317-352.
5. WHO and Special Programme for Research and Training in Tropical Diseases. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control, 2009. Available from: http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf.
6. WHO. Dengue and dengue haemorrhagic fever. Fact sheet N°117, March 2009, Available from: http://www.who.int/mediacentre/factsheets/fs117/en/.
7. Alejandria MM. Dengue haemorrhagic fever or dengue shock syndrome in children. Clin Evid (Online). 2009 Jan 12; 2009. pii: 0917.
8. KFF. Sanofi Pasteur’s Dengue Fever Vaccine Enters Phase III Trial in Australia. Kaiser Daily Global Health Policy Report. 2010, Nov 4. Available from: http://globalhealth.kff.org/Daily-Reports/2010/November/04/GH-110410-Dengue-Malaria-Vaccine.aspx.
9. WHO. Opportunities in the development of anti-dengue drugs. Working paper for the Scientific Working Group on Dengue Research, convened by the Special Programme for Research and Training in Tropical Diseases, Geneva, 1-5 October 2006. Available from: http://www.tropika.net/review/061001-Dengue_Drugs/article.pdf; and NIH. New Understanding of Dengue Virus Points Way to Possible Therapies for Dengue Fever, 2009. Available from: http://www.niaid.nih.gov/news/newsreleases/2009/pages/dengue_virus.aspx.
-- Updated June 2011