dengue fever dengue fever dengue fever is a mosquito-borne tropical disease caused by the dengue virus. symptoms typically begin three to fourteen days after infection. these may include a high fever, headache, vomiting, muscle and joint pains, and a characteristic skin itching and skin rash. recovery generally takes two to seven days. in a small proportion of cases, the disease develops into a more severe 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 feverother namesdengue, breakbone feverthe typical rash seen in dengue feverpronunciation/ˈdɛŋɡi, -ɡeɪ/ specialtyinfectious diseasesymptomsfever, headache, muscle and joint pain, rashcomplicationsbleeding, low levels of blood platelets, dangerously low blood pressureusual onset3–14 days after exposureduration2–7 dayscausesdengue virus by aedes mosquitosdiagnostic methoddetecting antibodies to the virus or its rnadifferential diagnosismalaria, yellow fever, viral hepatitis, leptospirosispreventiondengue fever vaccine, decreasing mosquito exposuretreatmentsupportive care, intravenous fluids, blood transfusionsfrequency390 million per yeardeaths~40,000 (2017) dengue is spread by several species of female mosquitoes of the aedes genus, principally aedes aegypti. the virus has five serotypes; 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. a number of tests are available to confirm the diagnosis including detecting antibodies to the virus or its rna. two types of dengue vaccine have been approved and are commercially available. on 5 december 2022 the european medicines agency approved qdenga, a live tetravalent attenuated vaccine for adults, adolescents and kids from four years of age. the 2016 vaccine dengvaxia is only recommended in individuals who have been previously infected, or in populations with a high rate of prior infection by age nine. other methods of prevention include reducing mosquito habitat and limiting exposure to bites. this may be done by getting rid of or covering standing water and wearing clothing that covers much of the body. treatment of acute dengue is supportive and includes giving fluid either by mouth or intravenously for mild or moderate disease. for more severe cases, blood transfusion may be required. paracetamol (acetaminophen) is recommended instead of nonsteroidal anti-inflammatory drugs (nsaids) for fever reduction and pain relief in dengue due to an increased risk of bleeding from nsaid use. the earliest descriptions of an outbreak date from 1779. its viral cause and spread were understood by the early 20th century. dengue has become a global problem since the second world war and is common in more than 120 countries, mainly in southeast asia, south asia and south america. about 390 million people are infected per year, about half a million require hospital admission, and approximately 40,000 die. in 2019, a significant increase in the number of cases was seen. apart from eliminating the mosquitos, work is ongoing for medication targeted directly at the virus. it is classified as a neglected tropical disease. signs and symptoms schematic depiction of the symptoms of dengue feverclinical course of dengue fever typically, people infected with dengue virus are asymptomatic (80%) or have only mild symptoms such as an uncomplicated fever. others have more severe illness (5%), and in a small proportion it is life-threatening. the incubation period (time between exposure and onset of symptoms) ranges from 3 to 14 days, but most often it is 4 to 7 days. therefore, travelers returning from endemic areas are unlikely to have dengue fever if symptoms start more than 14 days after arriving home. children often experience symptoms similar to those of the common cold and gastroenteritis (vomiting and diarrhea) and have a greater risk of severe complications, though initial symptoms are generally mild but include high fever. clinical course the characteristic symptoms of dengue are sudden-onset fever, headache (typically located behind the eyes), muscle and joint pains, and a rash. an alternative name for dengue, "breakbone fever", comes from the associated muscle and joint pains. the course of infection is divided into three phases: febrile, critical, and recovery. the febrile phase involves high fever, potentially over 40 °c (104 °f), and is associated with generalized pain and a headache; this usually lasts two to seven days. nausea and vomiting may also occur. a rash occurs in 50–80% of those with symptoms in the first or second day of symptoms as flushed skin, or later in the course of illness (days 4–7), as a measles-like rash. a rash described as "islands of white in a sea of red" has also been observed. some petechiae (small red spots that do not disappear when the skin is pressed, which are caused by broken capillaries) can appear at this point, as may some mild bleeding from the mucous membranes of the mouth and nose. the fever itself is classically biphasic or saddleback in nature, breaking and then returning for one or two days. in some people, the disease proceeds to a critical phase as fever resolves. during this period, there is leakage of plasma from the blood vessels, typically lasting one to two days. this may result in fluid accumulation in the chest and abdominal cavity as well as depletion of fluid from the circulation and decreased blood supply to vital organs. there may also be organ dysfunction and severe bleeding, typically from the gastrointestinal tract. shock (dengue shock syndrome) and hemorrhage (dengue hemorrhagic fever) occur in less than 5% of all cases of dengue; however, those who have previously been infected with other serotypes of dengue virus ("secondary infection") are at an increased risk. this critical phase, while rare, occurs relatively more commonly in children and young adults. the recovery phase occurs next, with resorption of the leaked fluid into the bloodstream. this usually lasts two to three days. the improvement is often striking, and can be accompanied with severe itching and a slow heart rate. another rash may occur with either a maculopapular or a vasculitic appearance, which is followed by peeling of the skin. during this stage, a fluid overload state may occur; if it affects the brain, it may cause a reduced level of consciousness or seizures. a feeling of fatigue may last for weeks in adults. the rash of dengue fever in the acute stage of the infection blanches when pressed.the rash that commonly forms during the recovery from dengue fever with its classic islands of white in a sea of red associated problems dengue can occasionally affect several other body systems, either in isolation or along with the classic dengue symptoms. a decreased level of consciousness occurs in 0.5–6% of severe cases, which is attributable either to inflammation of the brain by the virus or indirectly as a result of impairment of vital organs, for example, the liver. other neurological disorders have been reported in the context of dengue, such as transverse myelitis and guillain–barré syndrome. infection of the heart and acute liver failure are among the rarer complications. a pregnant woman who develops dengue is at higher risk of miscarriage, low birth weight birth, and premature birth. cause virology main article: dengue virus a tem micrograph showing dengue virus virions (the cluster of dark dots near the center) dengue fever virus (denv) is an rna virus of the family flaviviridae; genus flavivirus. other members of the same genus include yellow fever virus, west nile virus, zika virus, st. louis encephalitis virus, japanese encephalitis virus, tick-borne encephalitis virus, kyasanur forest disease virus, and omsk hemorrhagic fever virus. most are transmitted by arthropods (mosquitos or ticks), and are therefore also referred to as arboviruses (arthropod-borne viruses). the dengue virus genome (genetic material) contains about 11,000 nucleotide bases, which code for the three different types of protein molecules (c, prm and e) that form the virus particle and seven other non-structural protein molecules (ns1, ns2a, ns2b, ns3, ns4a, ns4b, ns5) that are found in infected host cells only and are required for replication of the virus. there are five strains of the virus, called serotypes, of which the first four are referred to as denv-1, denv-2, denv-3 and denv-4. the fifth type was announced in 2013. the distinctions between the serotypes are based on their antigenicity. transmission the mosquito aedes aegypti feeding on a human host dengue virus is primarily transmitted by aedes mosquitos, particularly a. aegypti. these mosquitos usually live between the latitudes of 35° north and 35° south below an elevation of 1,000 metres (3,300 ft). they typically bite during the early morning and in the evening, but they may bite and thus spread infection at any time of day. other aedes species that transmit the disease include a. albopictus, a. polynesiensis and a. scutellaris. humans are the primary host of the virus, but it also circulates in nonhuman primates. an infection can be acquired via a single bite. a female mosquito that takes a blood meal from a person infected with dengue fever, during the initial 2- to 10-day febrile period, becomes itself infected with the virus in the cells lining its gut. 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. 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. dengue can also be transmitted via infected blood products and through organ donation. in countries such as singapore, where dengue is endemic, the risk is estimated to be between 1.6 and 6 per 10,000 transfusions. vertical transmission (from mother to child) during pregnancy or at birth has been reported. other person-to-person modes of transmission, including sexual transmission, have also been reported, but are very unusual. 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. predisposition severe disease is more common in babies and young children, and in contrast to many other infections, it is more common in children who are relatively well nourished. other risk factors for severe disease include female sex, high body mass index, and viral load. while each serotype can cause the full spectrum of disease, virus strain is a risk factor. infection with one serotype is thought to produce lifelong immunity to that type, but only short-term protection against the other three. the risk of severe disease from secondary infection increases if someone previously exposed to serotype denv-1 contracts serotype denv-2 or denv-3, or if someone previously exposed to denv-3 acquires denv-2. dengue can be life-threatening in people with chronic diseases such as diabetes and asthma. polymorphisms (normal variations) in particular genes have been linked with an increased risk of severe dengue complications. examples include the genes coding for the proteins tnfα, mannan-binding lectin, ctla4, tgfβ, dc-sign, plce1, and particular forms of human leukocyte antigen from gene variations of hla-b. a common genetic abnormality, especially in africans, known as glucose-6-phosphate dehydrogenase deficiency, appears to increase the risk. polymorphisms in the genes for the vitamin d receptor and fcγr seem to offer protection against severe disease in secondary dengue infection. mechanism when a mosquito carrying dengue virus bites a person, the virus enters the skin together with the mosquito's saliva. it binds to and enters white blood cells, and reproduces inside the cells while they move throughout the body. the white blood cells respond by producing several signaling proteins, such as cytokines and interferons, which are responsible for many of the symptoms, such as the fever, the flu-like symptoms, and the severe pains. in severe infection, the virus production inside the body is greatly increased, and many more organs (such as the liver and the bone marrow) can be affected. fluid from the bloodstream leaks through the wall of small blood vessels into body cavities due to capillary permeability. as a result, less blood circulates in the blood vessels, and the blood pressure becomes so low that it cannot supply sufficient blood to vital organs. furthermore, dysfunction of the bone marrow due to infection of the stromal cells leads to reduced numbers of platelets, which are necessary for effective blood clotting; this increases the risk of bleeding, the other major complication of dengue fever.