Dengue fever
Dengue fever, also known as breakbone fever, is a mosquito-borne tropical disease caused by the dengue virus. Symptoms include fever, headache, muscle and joint pains, and a characteristic skin rash that is similar to measles. In a small proportion of cases, the disease develops into the life-threatening dengue hemorrhagic fever, resulting in bleeding, low levels of blood platelets and blood plasma leakage, or into dengue shock syndrome, where dangerously low blood pressure occurs.
Dengue is transmitted by several species of mosquito within the genus Aedes, principally A. aegypti. The virus has five different types;[1] infection with one type usually gives lifelong immunity to that type, but only short-term immunity to the others. Subsequent infection with a different type increases the risk of severe complications. As there is no commercially available vaccine, prevention is sought by reducing the habitat and the number of mosquitoes and limiting exposure to bites.
Treatment of acute dengue is supportive, using either oral or intravenous rehydration for mild or moderate disease, and intravenous fluids and blood transfusion for more severe cases. The number of cases of dengue fever has increased dramatically since the 1960s, with between 50 and 528 million people infected yearly.[2][3] Early descriptions of the condition date from 1779, and its viral cause and transmission were understood by the early 20th century. Dengue has become a global problem since the Second World War and is endemic in more than 110 countries. Apart from eliminating the mosquitoes, work is ongoing on a dengue vaccine, as well as medication targeted directly at the virus.
cause
The mosquito Aedes aegypti feeding on a human host
Dengue virus is primarily transmitted by Aedes mosquitoes, particularly A. aegypti.[4] These mosquitoes usually live between the latitudes of 35° North and 35° South below an elevation of 1,000 metres (3,300 ft).[4] They typically bite during the day, particularly in the early morning and in the evening,[19][20] but they are able to bite and thus spread infection at any time of day all during the year.[21] Other Aedes species that transmit the disease include A. albopictus, A. polynesiensis and A. scutellaris.[4] Humans are the primary host of the virus,[4][14] but it also circulates in nonhuman primates.[22] An infection can be acquired via a single bite.[23] A female mosquito that takes a blood meal from a person infected with dengue fever, during the initial 2–10 day febrile period, becomes itself infected with the virus in the cells lining its gut.[24] About 8–10 days later, the virus spreads to other tissues including the mosquito's salivary glands and is subsequently released into its saliva. The virus seems to have no detrimental effect on the mosquito, which remains infected for life.[6] Aedes aegypti is particularly involved, as it prefers to lay its eggs in artificial water containers, to live in close proximity to humans, and to feed on people rather than other vertebrates.[6]
Dengue can also be transmitted via infected blood products and through organ donation.[25][26] In countries such as Singapore, where dengue is endemic, the risk is estimated to be between 1.6 and 6 per 10,000 transfusions.[27] Vertical transmission (from mother to child) during pregnancy or at birth has been reported.[28] Other person-to-person modes of transmission have also been reported, but are very unusual.[11] The genetic variation in dengue viruses is region specific, suggestive that establishment into new territories is relatively infrequent, despite dengue emerging in new regions in recent decades.[9]
protect
Research efforts to prevent and treat dengue include various means of vector control,[54] vaccine development, and antiviral drugs.[38]
With regards to vector control, a number of novel methods have been used to reduce mosquito numbers with some success including the placement of the guppy (Poecilia reticulata) or copepods in standing water to eat the mosquito larvae.[54] Attempts are ongoing to infect the mosquito population with bacteria of the Wolbachia genus, which makes the mosquitoes partially resistant to dengue virus.[9][55] There are also trials with genetically modified male A. aegypti that after release into the wild mate with females, and render their offspring unable to fly.[56]
There are ongoing programs working on a dengue vaccine to cover all four serotypes.[38] Now that there is a fifth serotype this will need to be factored in.[1] One of the concerns is that a vaccine could increase the risk of severe disease through antibody-dependent enhancement (ADE).[57] The ideal vaccine is safe, effective after one or two injections, covers all serotypes, does not contribute to ADE, is easily transported and stored, and is both affordable and cost-effective.[57] As of 2012, a number of vaccines were undergoing testing.[20][57] The most developed is based on a weakened combination of the yellow fever virus and each of the four dengue serotypes.[20][58] Two studies of a vaccine found it was 60% effective and prevented more than 80 to 90% of severe cases.[59][60] It is hoped that the first products will be commercially available by 2015.[38]
Apart from attempts to control the spread of the Aedes mosquito and work to develop a vaccine against dengue, there are ongoing efforts to develop antiviral drugs that would be used to treat attacks of dengue fever and prevent severe complications.[61][62] Discovery of the structure of the viral proteins may aid the development of effective drugs.[62] There are several plausible targets. The first approach is inhibition of the viral RNA-dependent RNA polymerase (coded by NS5), which copies the viral genetic material, with nucleoside analogs. Secondly, it may be possible to develop specific inhibitors of the viral protease (coded by NS3), which splices viral proteins.[63] Finally, it may be possible to develop entry inhibitors, which stop the virus entering cells, or inhibitors of the 5′ capping process, which is required for viral replication.[61]