Yellow fever
Yellow fever is a viral disease of typically short duration.[3] In most cases, symptoms include fever, chills, loss of appetite, nausea, muscle pains—particularly in the back—and headaches.[3] Symptoms typically improve within five days.[3] In about 15% of people, within a day of improving the fever comes back, abdominal pain occurs, and liver damage begins causing yellow skin.[3][6] If this occurs, the risk of bleeding and kidney problems is increased.[3][7]
"American Plague" and "Yellow plague" redirect here. For the rock band, see The American Plague. For the Yellow Plague of Rhos in medieval Wales, see Maelgwn Gwynedd. For other uses, see Yellow fever (disambiguation).Yellow fever
The disease is caused by the yellow fever virus and is spread by the bite of an infected mosquito.[3][8] It infects humans, other primates,[9] and several types of mosquitoes.[3] In cities, it is spread primarily by Aedes aegypti, a type of mosquito found throughout the tropics and subtropics.[3] The virus is an RNA virus of the genus Flavivirus.[10][11] The disease may be difficult to tell apart from other illnesses, especially in the early stages.[3] To confirm a suspected case, blood-sample testing with a polymerase chain reaction is required.[4]
A safe and effective vaccine against yellow fever exists, and some countries require vaccinations for travelers.[3] Other efforts to prevent infection include reducing the population of the transmitting mosquitoes.[3] In areas where yellow fever is common, early diagnosis of cases and immunization of large parts of the population are important to prevent outbreaks.[3] Once a person is infected, management is symptomatic; no specific measures are effective against the virus.[3] Death occurs in up to half of those who get severe disease.[3][12]
In 2013, yellow fever was estimated to have caused 130,000 severe infections and 78,000 deaths in Africa.[3][5] Approximately 90 percent of an estimated 200,000 cases of yellow fever per year occur in Africa.[13] Nearly a billion people live in an area of the world where the disease is common.[3] It is common in tropical areas of the continents of South America and Africa,[14] but not in Asia.[3][15] Since the 1980s, the number of cases of yellow fever has been increasing.[3][16] This is believed to be due to fewer people being immune, more people living in cities, people moving frequently, and changing climate increasing the habitat for mosquitoes.[3]
The disease originated in Africa and spread to the Americas starting in the 17th century with the European trafficking of enslaved Africans from sub-Saharan Africa.[1][17] Since the 17th century, several major outbreaks of the disease have occurred in the Americas, Africa, and Europe.[1] In the 18th and 19th centuries, yellow fever was considered one of the most dangerous infectious diseases; numerous epidemics swept through major cities of the US and in other parts of the world.[1]
In 1927, yellow fever virus became the first human virus to be isolated.[10][18]
Pathogenesis[edit]
After transmission from a mosquito, the viruses replicate in the lymph nodes and infect dendritic cells in particular. From there, they reach the liver and infect hepatocytes (probably indirectly via Kupffer cells), which leads to eosinophilic degradation of these cells and to the release of cytokines. Apoptotic masses known as Councilman bodies appear in the cytoplasm of hepatocytes.[59][60]
Fatality may occur when cytokine storm, shock, and multiple organ failure follow.[26]
Diagnosis[edit]
Yellow fever is most frequently a clinical diagnosis, based on symptomatology and travel history. Mild cases of the disease can only be confirmed virologically.[47] Since mild cases of yellow fever can also contribute significantly to regional outbreaks, every suspected case of yellow fever (involving symptoms of fever, pain, nausea, and vomiting 6–10 days after leaving the affected area) is treated seriously.[47]
If yellow fever is suspected, the virus cannot be confirmed until 6–10 days following the illness. A direct confirmation can be obtained by reverse transcription polymerase chain reaction, where the genome of the virus is amplified.[4] Another direct approach is the isolation of the virus and its growth in cell culture using blood plasma; this can take 1–4 weeks.[61][13]
Serologically, an enzyme-linked immunosorbent assay during the acute phase of the disease using specific IgM against yellow fever or an increase in specific IgG titer (compared to an earlier sample) can confirm yellow fever.[62] Together with clinical symptoms, the detection of IgM or a four-fold increase in IgG titer is considered sufficient indication for yellow fever. As these tests can cross-react with other flaviviruses, such as dengue virus, these indirect methods cannot conclusively prove yellow fever infection.[63]
Liver biopsy can verify inflammation and necrosis of hepatocytes and detect viral antigens. Because of the bleeding tendency of yellow fever patients, a biopsy is only advisable post mortem to confirm the cause of death.[64]
In a differential diagnosis, infections with yellow fever must be distinguished from other feverish illnesses such as malaria. Other viral hemorrhagic fevers, such as Ebola virus, Lassa virus, Marburg virus, and Junin virus, must be excluded as the cause.[65]
Treatment[edit]
As with other Flavivirus infections, no cure is known for yellow fever. Hospitalization is advisable and intensive care may be necessary because of rapid deterioration in some cases. Certain acute treatment methods lack efficacy: passive immunization after the emergence of symptoms is probably without effect; ribavirin and other antiviral drugs, as well as treatment with interferons, are ineffective in yellow fever patients.[26] Symptomatic treatment includes rehydration and pain relief with drugs such as paracetamol (acetaminophen). However, aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are often avoided because of an increased risk of gastrointestinal bleeding due to their anticoagulant effects.[94]
Research[edit]
In the hamster model of yellow fever, early administration of the antiviral ribavirin is an effective treatment of many pathological features of the disease.[186] Ribavirin treatment during the first five days after virus infection improved survival rates, reduced tissue damage in the liver and spleen, prevented hepatocellular steatosis, and normalised levels of alanine aminotransferase, a liver damage marker. The mechanism of action of ribavirin in reducing liver pathology in yellow fever virus infection may be similar to its activity in treatment of hepatitis C, a related virus.[186] Because ribavirin had failed to improve survival in a virulent rhesus model of yellow fever infection, it had been previously discounted as a possible therapy.[187] Infection was reduced in mosquitoes with the wMel strain of Wolbachia.[188]
Yellow fever has been researched by several countries as a potential biological weapon.[189]