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Yellow fever

August 19, 2023

"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 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]

Yellow fever
Other namesYellow jack, yellow plague,[1] bronze john[2]
A TEM micrograph of yellow fever virus (234,000× magnification)
SpecialtyInfectious disease
SymptomsFever, chills, muscle pain, headache, yellow skin[3]
ComplicationsLiver failure, bleeding[3]
Usual onset3–6 days post exposure[3]
Duration3–4 days[3]
CausesYellow fever virus spread by mosquitoes[3]
Diagnostic methodBlood test[4]
PreventionYellow fever vaccine[3]
TreatmentSupportive care[3]
Frequency~130,000 severe cases in Africa alone (2013)[3][5]
Deaths~78,000 in Africa alone (2013)[3][5]

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 was the first human virus to be isolated.[10][18]

Signs and symptoms

Yellow fever begins after an incubation period of three to six days.[19] Most cases cause only a mild infection with fever, headache, chills, back pain, fatigue, loss of appetite, muscle pain, nausea, and vomiting.[20] In these cases, the infection lasts only three to six days.[21]

But in 15% of cases, people enter a second, toxic phase of the disease characterized by recurring fever, this time accompanied by jaundice due to liver damage, as well as abdominal pain.[22] Bleeding in the mouth, nose, the eyes, and the gastrointestinal tract cause vomit containing blood, hence one of the names in Spanish for yellow fever, vómito negro ("black vomit").[23] There may also be kidney failure, hiccups, and delirium.[24][25]

Among those who develop jaundice, the fatality rate is 20 to 50%, while the overall fatality rate is about 3 to 7.5%.[26] Severe cases may have a mortality greater than 50%.[27]

Surviving the infection provides lifelong immunity,[28] and normally results in no permanent organ damage.[29][30]

Complication

Yellow fever can lead to death for 20% to 50% of those who develop severe disease. Jaundice, fatigue, heart rhythm problems, seizures and internal bleeding may also appear as complications of yellow fever during recovery time.[31][32]

Cause

Yellow fever virus
 
Flavivirus structure and genome
Virus classification  
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Kitrinoviricota
Class: Flasuviricetes
Order: Amarillovirales
Family: Flaviviridae
Genus: Flavivirus
Species:
Yellow fever virus

Yellow fever is caused by Yellow fever virus (YFV), an enveloped RNA virus 40–50 nm in width, the type species and namesake of the family Flaviviridae.[10] It was the first illness shown to be transmissible by filtered human serum and transmitted by mosquitoes, by American doctor Walter Reed around 1900.[33] The positive-sense, single-stranded RNA is around 10,862 nucleotides long and has a single open reading frame encoding a polyprotein.[34] Host proteases cut this polyprotein into three structural (C, prM, E) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5); the enumeration corresponds to the arrangement of the protein coding genes in the genome.[35] Minimal YFV 3′UTR region is required for stalling of the host 5′-3′ exonuclease XRN1.[36] The UTR contains PKS3 pseudoknot structure, which serves as a molecular signal to stall the exonuclease and is the only viral requirement for subgenomic flavivirus RNA (sfRNA) production.[37] The sfRNAs are a result of incomplete degradation of the viral genome by the exonuclease and are important for viral pathogenicity.[38] Yellow fever belongs to the group of hemorrhagic fevers.[39]

The viruses infect, amongst others, monocytes, macrophages, Schwann cells, and dendritic cells. They attach to the cell surfaces via specific receptors and are taken up by an endosomal vesicle.[40] Inside the endosome, the decreased pH induces the fusion of the endosomal membrane with the virus envelope.[41] The capsid enters the cytosol, decays, and releases the genome.[42] Receptor binding, as well as membrane fusion, are catalyzed by the protein E, which changes its conformation at low pH, causing a rearrangement of the 90 homodimers to 60 homotrimers.[35][43]

After entering the host cell, the viral genome is replicated in the rough endoplasmic reticulum (ER) and in the so-called vesicle packets.[44] At first, an immature form of the virus particle is produced inside the ER, whose M-protein is not yet cleaved to its mature form, so is denoted as precursor M (prM) and forms a complex with protein E.[45] The immature particles are processed in the Golgi apparatus by the host protein furin, which cleaves prM to M.[46] This releases E from the complex, which can now take its place in the mature, infectious virion.[35]

Transmission

 
Aedes aegypti feeding
 
Adults of the yellow fever mosquito A. aegypti: The male is on the left, females are on the right. Only the female mosquito bites humans to transmit the disease.

Yellow fever virus is mainly transmitted through the bite of the yellow fever mosquito Aedes aegypti, but other mostly Aedes mosquitoes such as the tiger mosquito (Aedes albopictus) can also serve as a vector for this virus.[47] Like other arboviruses, which are transmitted by mosquitoes, yellow fever virus is taken up by a female mosquito when it ingests the blood of an infected human or another primate.[48] Viruses reach the stomach of the mosquito, and if the virus concentration is high enough, the virions can infect epithelial cells and replicate there. From there, they reach the haemocoel (the blood system of mosquitoes) and from there the salivary glands.[49] When the mosquito next sucks blood, it injects its saliva into the wound, and the virus reaches the bloodstream of the bitten person.[50] Transovarial transmissionial and transstadial transmission of yellow fever virus within A. aegypti, that is, the transmission from a female mosquito to its eggs and then larvae, are indicated.[51] This infection of vectors without a previous blood meal seems to play a role in single, sudden breakouts of the disease.[52]

Three epidemiologically different infectious cycles occur[16] in which the virus is transmitted from mosquitoes to humans or other primates.[53] In the "urban cycle", only the yellow fever mosquito A. aegypti is involved. It is well adapted to urban areas, and can also transmit other diseases, including Zika fever, dengue fever, and chikungunya.[54] The urban cycle is responsible for the major outbreaks of yellow fever that occur in Africa. Except for an outbreak in Bolivia in 1999, this urban cycle no longer exists in South America.[55]

Besides the urban cycle, both in Africa and South America, a sylvatic cycle (forest or jungle cycle) is present, where Aedes africanus (in Africa) or mosquitoes of the genus Haemagogus and Sabethes (in South America) serve as vectors.[56] In the jungle, the mosquitoes infect mainly nonhuman primates; the disease is mostly asymptomatic in African primates.[50] In South America, the sylvatic cycle is currently the only way humans can become infected, which explains the low incidence of yellow fever cases on the continent.[47] People who become infected in the jungle can carry the virus to urban areas, where A. aegypti acts as a vector. Because of this sylvatic cycle, yellow fever cannot be eradicated except by eradicating the mosquitoes that serve as vectors.[16]

In Africa, a third infectious cycle known as "savannah cycle" or intermediate cycle, occurs between the jungle and urban cycles.[57] Different mosquitoes of the genus Aedes are involved. In recent years, this has been the most common form of transmission of yellow fever in Africa.[58]

Concern exists about yellow fever spreading to southeast Asia, where its vector A. aegypti already occurs.[59]

Pathogenesis

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.[60][61]

Fatality may occur when cytokine storm, shock, and multiple organ failure follow.[26]

Diagnosis

Yellow fever is most frequently a clinical diagnosis, based on symptomatology and travel history. Mild cases of the disease can only be confirmed virologically.[48] 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.[48]

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.[62][63]

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.[64] 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.[65]

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.[66]

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.[67]

Prevention

Personal prevention of yellow fever includes vaccination and avoidance of mosquito bites in areas where yellow fever is endemic.[47] Institutional measures for prevention of yellow fever include vaccination programmes and measures to control mosquitoes. Programmes for distribution of mosquito nets for use in homes produce reductions in cases of both malaria and yellow fever. Use of EPA-registered insect repellent is recommended when outdoors. Exposure for even a short time is enough for a potential mosquito bite. Long-sleeved clothing, long pants, and socks are useful for prevention. The application of larvicides to water-storage containers can help eliminate potential mosquito breeding sites. EPA-registered insecticide spray decreases the transmission of yellow fever.[68]

  • Use insect repellent when outdoors such as those containing DEET, picaridin, ethyl butylacetylaminopropionate (IR3535), or oil of lemon eucalyptus on exposed skin.[69]
  • Mosquitoes may bite through thin clothing, so spraying clothes with repellent containing permethrin or another EPA-registered repellent gives extra protection.[70] Clothing treated with permethrin is commercially available. Mosquito repellents containing permethrin are not approved for application directly to the skin.[71]
  • The peak biting times for many mosquito species are dusk to dawn. However, A. aegypti, one of the mosquitoes that transmit yellow fever virus, feeds during the daytime.[72] Staying in accommodations with screened or air-conditioned rooms, particularly during peak biting times, also reduces the risk of mosquito bites.[72]

Vaccination

 
The cover of a certificate that confirms the holder has been vaccinated against yellow fever
 
Vaccination against yellow fever 10 days before entering this country/territory is required for travellers coming from...[73]
  All countries
  Risk countries (including airport transfers)[note 1]
  Risk countries (excluding airport transfers)[note 2]
  No requirement (risk country)[note 3]
  No requirement (non-risk country)
Main article: Yellow fever vaccine

Vaccination is recommended for those traveling to affected areas, because non-native people tend to develop more severe illness when infected. Protection begins by the 10th day after vaccine administration in 95% of people,[74] and had been reported to last for at least 10 years. The World Health Organization (WHO) now states that a single dose of vaccine is sufficient to confer lifelong immunity against yellow fever disease.[75] The attenuated live vaccine stem 17D was developed in 1937 by Max Theiler.[74] The WHO recommends routine vaccination for people living in affected areas between the 9th and 12th month after birth.[4]

Up to one in four people experience fever, aches, and local soreness and redness at the site of injection.[76] In rare cases (less than one in 200,000 to 300,000),[74] the vaccination can cause yellow fever vaccine-associated viscerotropic disease, which is fatal in 60% of cases. It is probably due to the genetic morphology of the immune system. Another possible side effect is an infection of the nervous system, which occurs in one in 200,000 to 300,000 cases, causing yellow fever vaccine-associated neurotropic disease, which can lead to meningoencephalitis and is fatal in less than 5%[74] of cases.[4][26]

The Yellow Fever Initiative, launched by the WHO in 2006, vaccinated more than 105 million people in 14 countries in West Africa.[77] No outbreaks were reported during 2015. The campaign was supported by the GAVI alliance and governmental organizations in Europe and Africa.[78] According to the WHO, mass vaccination cannot eliminate yellow fever because of the vast number of infected mosquitoes in urban areas of the target countries, but it will significantly reduce the number of people infected.[79]

Demand for yellow fever vaccine has continued to increase due to the growing number of countries implementing yellow fever vaccination as part of their routine immunization programmes.[80] Recent upsurges in yellow fever outbreaks in Angola (2015), the Democratic Republic of Congo (2016), Uganda (2016), and more recently in Nigeria and Brazil in 2017 have further increased demand, while straining global vaccine supply.[80][81] Therefore, to vaccinate susceptible populations in preventive mass immunization campaigns during outbreaks, fractional dosing of the vaccine is being considered as a dose-sparing strategy to maximize limited vaccine supplies.[80] Fractional dose yellow fever vaccination refers to administration of a reduced volume of vaccine dose, which has been reconstituted as per manufacturer recommendations.[80][82] The first practical use of fractional dose yellow fever vaccination was in response to a large yellow fever outbreak in the Democratic Republic of the Congo in mid-2016.[80] Available evidence shows that fractional dose yellow fever vaccination induces a level of immune response similar to that of the standard full dose.[83]

In March 2017, the WHO launched a vaccination campaign in Brazil with 3.5 million doses from an emergency stockpile.[84] In March 2017 the WHO recommended vaccination for travellers to certain parts of Brazil.[85] In March 2018, Brazil shifted its policy and announced it planned to vaccinate all 77.5 million currently unvaccinated citizens by April 2019.[86]

Compulsory vaccination

Some countries in Asia are considered to be potentially in danger of yellow fever epidemics, as both mosquitoes with the capability to transmit yellow fever as well as susceptible monkeys are present.[87] The disease does not yet occur in Asia. To prevent introduction of the virus, some countries demand previous vaccination of foreign visitors who have passed through yellow fever areas.[88] Vaccination has to be proved by a vaccination certificate, which is valid 10 days after the vaccination and lasts for 10 years. Although the WHO on 17 May 2013 advised that subsequent booster vaccinations are unnecessary, an older (than 10 years) certificate may not be acceptable at all border posts in all affected countries. A list of the countries that require yellow fever vaccination is published by the WHO.[73] If the vaccination cannot be given for some reason, dispensation may be possible. In this case, an exemption certificate issued by a WHO-approved vaccination center is required. Although 32 of 44 countries where yellow fever occurs endemically do have vaccination programmes, in many of these countries, less than 50% of their population is vaccinated.[4]

Vector control

 
Information campaign for prevention of dengue and yellow fever in Paraguay

Control of the yellow fever mosquito A. aegypti is of major importance, especially because the same mosquito can also transmit dengue fever and chikungunya disease.[89] A. aegypti breeds preferentially in water, for example, in installations by inhabitants of areas with precarious drinking water supplies, or in domestic refuse, especially tires, cans, and plastic bottles. These conditions are common in urban areas in developing countries.[90]

Two main strategies are employed to reduce A. aegypti populations.[91] One approach is to kill the developing larvae. Measures are taken to reduce the water accumulations in which the larvae develop. Larvicides are used, along with larvae-eating fish and copepods, which reduce the number of larvae.[92] For many years, copepods of the genus Mesocyclops have been used in Vietnam for preventing dengue fever.[93] This eradicated the mosquito vector in several areas. Similar efforts may prove effective against yellow fever. Pyriproxyfen is recommended as a chemical larvicide, mainly because it is safe for humans and effective in small doses.[4]

The second strategy is to reduce populations of the adult yellow fever mosquito. Lethal ovitraps can reduce Aedes populations, using lesser amounts of pesticide because it targets the pest directly.[94] Curtains and lids of water tanks can be sprayed with insecticides, but application inside houses is not recommended by the WHO.[95] Insecticide-treated mosquito nets are effective, just as they are against the Anopheles mosquito that carries malaria.[4]

Treatment

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.[96]

Epidemiology

Yellow fever is common in tropical and subtropical areas of South America and Africa.[97] Worldwide, about 600 million people live in endemic areas. The WHO estimates 200,000 cases of yellow fever worldwide each year.[98] About 15% of people infected with yellow fever progress to a severe form of the illness, and up to half of those will die, as there is no cure for yellow fever.[99]

Africa

 
Areas with risk of yellow fever in Africa (2017)

An estimated 90% of yellow fever infections occur on the African continent.[4] In 2016, a large outbreak originated in Angola and spread to neighboring countries before being contained by a massive vaccination campaign.[100] In March and April 2016, 11 imported cases of the Angola genotype in unvaccinated Chinese nationals were reported in China, the first appearance of the disease in Asia in recorded history.[101][102]

Phylogenetic analysis has identified seven genotypes of yellow fever viruses, and they are assumed to be differently adapted to humans and to the vector A. aegypti. Five genotypes (Angola, Central/East Africa, East Africa, West Africa I, and West Africa II) occur only in Africa. West Africa genotype I is found in Nigeria and the surrounding region.[103] West Africa genotype I appears to be especially infectious, as it is often associated with major outbreaks. The three genotypes found outside of Nigeria and Angola occur in areas where outbreaks are rare. Two outbreaks, in Kenya (1992–1993) and Sudan (2003 and 2005), involved the East African genotype, which had remained undetected in the previous 40 years.[104]

South America

 
Areas with risk of yellow fever in South America (2018)

In South America, two genotypes have been identified (South American genotypes I and II).[16] Based on phylogenetic analysis these two genotypes appear to have originated in West Africa[105] and were first introduced into Brazil.[106] The date of introduction of the predecessor African genotype which gave rise to the South American genotypes appears to be 1822 (95% confidence interval 1701 to 1911).[106] The historical record shows an outbreak of yellow fever occurred in Recife, Brazil, between 1685 and 1690. The disease seems to have disappeared, with the next outbreak occurring in 1849.[107] It was likely introduced with the trafficking of slaves through the slave trade from Africa. Genotype I has been divided into five subclades, A through E.[108]

In late 2016, a large outbreak began in Minas Gerais state of Brazil that was characterized as a sylvan or jungle epizootic.[109] It began as an outbreak in brown howler monkeys,[110] which serve as a sentinel species for yellow fever, that then spread to men working in the jungle. No cases had been transmitted between humans by the A. aegypti mosquito, which can sustain urban outbreaks that can spread rapidly. In April 2017, the sylvan outbreak continued moving toward the Brazilian coast, where most people were unvaccinated.[85] By the end of May the outbreak appeared to be declining after more than 3,000 suspected cases, 758 confirmed and 264 deaths confirmed to be yellow fever.[111] The Health Ministry launched a vaccination campaign and was concerned about spread during the Carnival season in February and March. The CDC issued a Level 2 alert (practice enhanced precautions.)[112]

A Bayesian analysis of genotypes I and II has shown that genotype I accounts for virtually all the current infections in Brazil, Colombia, Venezuela, and Trinidad and Tobago, while genotype II accounted for all cases in Peru.[113] Genotype I originated in the northern Brazilian region around 1908 (95% highest posterior density interval [HPD]: 1870–1936). Genotype II originated in Peru in 1920 (95% HPD: 1867–1958).[114] The estimated rate of mutation for both genotypes was about 5 × 10−4 substitutions/site/year, similar to that of other RNA viruses.[115]

Asia

The main vector (A. aegypti) also occurs in tropical and subtropical regions of Asia, the Pacific, and Australia, but yellow fever had never occurred there until jet travel introduced 11 cases from the 2016 Angola and DR Congo yellow fever outbreak in Africa. Proposed explanations include:[116]

  • That the strains of the mosquito in the east are less able to transmit yellow fever virus.[117]
  • That immunity is present in the populations because of other diseases caused by related viruses (for example, dengue).[118]
  • That the disease was never introduced because the shipping trade was insufficient.

But none is considered satisfactory.[119][120] Another proposal is the absence of a slave trade to Asia on the scale of that to the Americas.[121] The trans-Atlantic slave trade probably introduced yellow fever into the Western Hemisphere from Africa.[122]

History

Main article: History of yellow fever

Early history

The evolutionary origins of yellow fever most likely lie in Africa, with transmission of the disease from nonhuman primates to humans.[123][124] The virus is thought to have originated in East or Central Africa and spread from there to West Africa. As it was endemic in Africa, local populations had developed some immunity to it. When an outbreak of yellow fever would occur in an African community where colonists resided, most Europeans died, while the indigenous Africans usually developed nonlethal symptoms resembling influenza.[125] This phenomenon, in which certain populations develop immunity to yellow fever due to prolonged exposure in their childhood, is known as acquired immunity.[126] The virus, as well as the vector A. aegypti, were probably transferred to North and South America with the trafficking of slaves from Africa, part of the Columbian exchange following European exploration and colonization.[127] However, some researchers have argued that yellow fever might have existed in the Americas during the pre-Columbian period as mosquitoes of the genus Haemagogus, which is indigenous to the Americas, have been known to carry the disease.[128]

The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados.[129] An outbreak was recorded by Spanish colonists in 1648 in the Yucatán Peninsula, where the indigenous Mayan people called the illness xekik ("blood vomit"). In 1685, Brazil suffered its first epidemic in Recife. The first mention of the disease by the name "yellow fever" occurred in 1744.[130]

  • (John Mitchell) (1805) (Mitchell's account of the Yellow Fever in Virginia in 1741–2) 2017-02-23 at the Wayback Machine, The Philadelphia Medical Museum, 1 (1) : 1–20.
  • (John Mitchell) (1814) "Account of the Yellow fever which prevailed in Virginia in the years 1737, 1741, and 1742, in a letter to the late Cadwallader Colden, Esq. of New York, from the late John Mitchell, M.D.F.R.S. of Virginia," 2017-02-23 at the Wayback Machine American Medical and Philosophical Register, 4 : 181–215. The term "yellow fever" appears on p. 186. On p. 188, Mitchell mentions "... the distemper was what is generally called yellow fever in America". However, on pages 191–192, he states "... I shall consider the cause of the yellowness which is so remarkable in this distemper, as to have given it the name of the Yellow Fever."[citation needed]

However, Dr. Mitchell misdiagnosed the disease that he observed and treated, and the disease was probably Weil's disease or hepatitis.[131] McNeill argues that the environmental and ecological disruption caused by the introduction of sugar plantations created the conditions for mosquito and viral reproduction, and subsequent outbreaks of yellow fever.[132] Deforestation reduced populations of insectivorous birds and other creatures that fed on mosquitoes and their eggs.[133]

 
Sugar curing house, 1762: Sugar pots and jars on sugar plantations served as breeding place for larvae of A. aegypti, the vector of yellow fever.

In Colonial times and during the Napoleonic Wars, the West Indies were known as a particularly dangerous posting for soldiers due to yellow fever being endemic in the area.[134] The mortality rate in British garrisons in Jamaica was seven times that of garrisons in Canada, mostly because of yellow fever and other tropical diseases.[135] Both English and French forces posted there were seriously affected by the "yellow jack".[136] Wanting to regain control of the lucrative sugar trade in Saint-Domingue (Hispaniola), and with an eye on regaining France's New World empire, Napoleon sent an army under the command of his brother-in-law General Charles Leclerc to Saint-Domingue to seize control after a slave revolt.[137] The historian J. R. McNeill asserts that yellow fever accounted for about 35,000 to 45,000 casualties of these forces during the fighting.[138] Only one third of the French troops survived for withdrawal and return to France. Napoleon gave up on the island and his plans for North America, selling the Louisiana Purchase to the US in 1803. In 1804, Haiti proclaimed its independence as the second republic in the Western Hemisphere.[139] Considerable debate exists over whether the number of deaths caused by disease in the Haitian Revolution was exaggerated.[140]

Although yellow fever is most prevalent in tropical-like climates, the northern United States were not exempted from the fever. The first outbreak in English-speaking North America occurred in New York City in 1668.[141] English colonists in Philadelphia and the French in the Mississippi River Valley recorded major outbreaks in 1669, as well as additional yellow fever epidemics in Philadelphia, Baltimore, and New York City in the 18th and 19th centuries. The disease traveled along steamboat routes from New Orleans, causing some 100,000–150,000 deaths in total.[142] The yellow fever epidemic of 1793 in Philadelphia, which was then the capital of the United States, resulted in the deaths of several thousand people, more than 9% of the population.[143] One of these deaths was James Hutchinson, a physician helping to treat the population of the city. The national government fled the city to Trenton, New Jersey, including President George Washington.[144]

 
Headstones of people who died in the yellow fever epidemic of 1878 can be found in New Orleans' cemeteries

The southern city of New Orleans was plagued with major epidemics during the 19th century, most notably in 1833 and 1853.[145] A major epidemic occurred in both New Orleans and Shreveport, Louisiana in 1873. Its residents called the disease "yellow jack". Urban epidemics continued in the United States until 1905, with the last outbreak affecting New Orleans.[146][16][147]

At least 25 major outbreaks took place in the Americas during the 18th and 19th centuries, including particularly serious ones in Cartagena, Chile, in 1741; Cuba in 1762 and 1900; Santo Domingo in 1803; and Memphis, Tennessee, in 1878.[148]

In the early nineteenth century, the prevalence of yellow fever in the Caribbean "led to serious health problems" and alarmed the United States Navy as numerous deaths and sickness curtailed naval operations and destroyed morale.[149] One episode began in April 1822 when the frigate USS Macedonian left Boston and became part of Commodore James Biddle's West India Squadron. Unbeknownst to all, they were about to embark on a cruise to disaster and their assignment "would prove a cruise through hell".[150] Secretary of the Navy Smith Thompson had assigned the squadron to guard United States merchant shipping and suppress piracy.[151] During their time on deployment from 26 May to 3 August 1822, 76 of the Macedonian's officers and men died, including John Cadle, surgeon USN. Seventy-four of these deaths were attributed to yellow fever. Biddle reported that another 52 of his crew were on sick-list. In their report to the secretary of the Navy, Biddle and Surgeon's Mate Charles Chase stated the cause as "fever". As a consequence of this loss, Biddle noted that his squadron was forced to return to Norfolk Navy Yard early. Upon arrival, the Macedonian's crew were provided medical care and quarantined at Craney Island, Virginia.[152][153][154]

 
A page from Commodore James Biddle's list of the 76 dead (74 of yellow fever) aboard the USS Macedonian, dated 3 August 1822

In 1853, Cloutierville, Louisiana, had a late-summer outbreak of yellow fever that quickly killed 68 of the 91 inhabitants. A local doctor concluded that some unspecified infectious agent had arrived in a package from New Orleans.[155][156] In 1854, 650 residents of Savannah, Georgia, died from yellow fever.[157] In 1858, St. Matthew's German Evangelical Lutheran Church in Charleston, South Carolina, had 308 yellow fever deaths, reducing the congregation by half.[158] A ship carrying persons infected with the virus arrived in Hampton Roads in southeastern Virginia in June 1855.[159] The disease spread quickly through the community, eventually killing over 3,000 people, mostly residents of Norfolk and Portsmouth.[160] In 1873, Shreveport, Louisiana, lost 759 citizens in an 80-day period to a yellow fever epidemic, with over 400 additional victims eventually succumbing. The total death toll from August through November was approximately 1,200.[161][162]

In 1878, about 20,000 people died in a widespread epidemic in the Mississippi River Valley.[163] That year, Memphis had an unusually large amount of rain, which led to an increase in the mosquito population. The result was a huge epidemic of yellow fever.[164] The steamship John D. Porter took people fleeing Memphis northward in hopes of escaping the disease, but passengers were not allowed to disembark due to concerns of spreading yellow fever. The ship roamed the Mississippi River for the next two months before unloading her passengers.[165]

Major outbreaks have also occurred in southern Europe. Gibraltar lost many lives to outbreaks in 1804, 1814, and 1828.[166] Barcelona suffered the loss of several thousand citizens during an outbreak in 1821. The Duke de Richelieu deployed 30,000 French troops to the border between France and Spain in the Pyrenees Mountains, to establish a cordon sanitaire in order to prevent the epidemic from spreading from Spain into France.[167]

Causes and transmission

 
A painting depicting yellow fever in Buenos Aires, 1871
 
Carlos Finlay
 
Walter Reed

Ezekiel Stone Wiggins, known as the Ottawa Prophet, proposed that the cause of a yellow fever epidemic in Jacksonville, Florida, in 1888, was astrological.[168]

The planets were in the same line as the sun and earth and this produced, besides Cyclones, Earthquakes, etc., a denser atmosphere holding more carbon and creating microbes. Mars had an uncommonly dense atmosphere, but its inhabitants were probably protected from the fever by their newly discovered canals, which were perhaps made to absorb carbon and prevent the disease.[169]

In 1848, Josiah C. Nott suggested that yellow fever was spread by insects such as moths or mosquitoes, basing his ideas on the pattern of transmission of the disease.[170] Carlos Finlay, a Cuban doctor and scientist, proposed in 1881 that yellow fever might be transmitted by previously infected mosquitoes rather than by direct contact from person to person, as had long been believed.[171][172] Since the losses from yellow fever in the Spanish–American War in the 1890s were extremely high, Army doctors began research experiments with a team led by Walter Reed, and composed of doctors James Carroll, Aristides Agramonte, and Jesse William Lazear. They successfully proved Finlay's "mosquito hypothesis". Yellow fever was the first virus shown to be transmitted by mosquitoes. The physician William Gorgas applied these insights and eradicated yellow fever from Havana. He also campaigned against yellow fever during the construction of the Panama Canal. A previous effort of canal building by the French had failed in part due to mortality from the high incidence of yellow fever and malaria, which killed many workers.[16]

Although Reed has received much of the credit in United States history books for "beating" yellow fever, he had fully credited Finlay with the discovery of the yellow fever vector, and how it might be controlled. Reed often cited Finlay's papers in his own articles, and also credited him for the discovery in his personal correspondence.[173] The acceptance of Finlay's work was one of the most important and far-reaching effects of the U.S. Army Yellow Fever Commission of 1900.[174] Applying methods first suggested by Finlay, the United States government and Army eradicated yellow fever in Cuba and later in Panama, allowing completion of the Panama Canal. While Reed built on the research of Finlay, historian François Delaporte notes that yellow fever research was a contentious issue. Scientists, including Finlay and Reed, became successful by building on the work of less prominent scientists, without always giving them the credit they were due.[175] Reed's research was essential in the fight against yellow fever. He is also credited for using the first type of medical consent form during his experiments in Cuba, an attempt to ensure that participants knew they were taking a risk by being part of testing.[176]

Like Cuba and Panama, Brazil also led a highly successful sanitation campaign against mosquitoes and yellow fever. Beginning in 1903, the campaign led by Oswaldo Cruz, then director general of public health, resulted not only in eradicating the disease but also in reshaping the physical landscape of Brazilian cities such as Rio de Janeiro.[177] During rainy seasons, Rio de Janeiro had regularly suffered floods, as water from the bay surrounding the city overflowed into Rio's narrow streets. Coupled with the poor drainage systems found throughout Rio, this created swampy conditions in the city's neighborhoods. Pools of stagnant water stood year-long in city streets and proved to be a fertile ground for disease-carrying mosquitoes. Thus, under Cruz's direction, public health units known as "mosquito inspectors" fiercely worked to combat yellow fever throughout Rio by spraying, exterminating rats, improving drainage, and destroying unsanitary housing. Ultimately, the city's sanitation and renovation campaigns reshaped Rio de Janeiro's neighborhoods. Its poor residents were pushed from city centers to Rio's suburbs, or to towns found in the outskirts of the city. In later years, Rio's most impoverished inhabitants would come to reside in favelas.[178]

 
Max Theiler

During 1920–1923, the Rockefeller Foundation's International Health Board undertook an expensive and successful yellow fever eradication campaign in Mexico.[179] The IHB gained the respect of Mexico's federal government because of the success. The eradication of yellow fever strengthened the relationship between the US and Mexico, which had not been very good in the years prior. The eradication of yellow fever was also a major step toward better global health.[180]

In 1927, scientists isolated the yellow fever virus in West Africa.[181] Following this, two vaccines were developed in the 1930s. Max Theiler led the completion of the 17D yellow fever vaccine in 1937, for which he was subsequently awarded the Nobel Prize in Physiology or Medicine.[182] That vaccine, 17D, is still in use, although newer vaccines, based on vero cells, are in development (as of 2018).[4][183][184]

Current status

Using vector control and strict vaccination programs, the urban cycle of yellow fever was nearly eradicated from South America.[185] Since 1943, only a single urban outbreak in Santa Cruz de la Sierra, Bolivia, has occurred. Since the 1980s, however, the number of yellow fever cases has been increasing again, and A. aegypti has returned to the urban centers of South America. This is partly due to limitations on available insecticides, as well as habitat dislocations caused by climate change. It is also because the vector control program was abandoned. Although no new urban cycle has yet been established, scientists believe this could happen again at any point. An outbreak in Paraguay in 2008 was thought to be urban in nature, but this ultimately proved not to be the case.[4]

In Africa, virus eradication programs have mostly relied upon vaccination.[186] These programs have largely been unsuccessful because they were unable to break the sylvatic cycle involving wild primates. With few countries establishing regular vaccination programs, measures to fight yellow fever have been neglected, making the future spread of the virus more likely.[4]

Research

In the hamster model of yellow fever, early administration of the antiviral ribavirin is an effective treatment of many pathological features of the disease.[187] 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.[187] 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.[188] Infection was reduced in mosquitoes with the wMel strain of Wolbachia.[189]

Yellow fever has been researched by several countries as a potential biological weapon.[190]

Notes

  1. ^ Also required for travellers having transited (more than 12 hours) through a risk country's airport.
  2. ^ Not required for travellers having transited through a risk country's airport.
  3. ^ The WHO has designated (parts of) Argentina, Brazil and Peru as risk countries, but these countries do not require incoming travellers to vaccinate against yellow fever.

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Further reading

  • Crosby M (2006). The American Plague: The Untold Story of Yellow Fever, the Epidemic that Shaped Our History. New York: The Berkley Publishing Group. ISBN 978-0-425-21202-8.
  • Espinosa M (2009). Epidemic Invasions: Yellow Fever and the Limits of Cuban Independence, 1878–1930. Chicago: University of Chicago Press. ISBN 978-0-226-21811-3.
  • Gessner I (2016). Yellow Fever Years: An Epidemiology of Nineteenth-Century American Literature and Culture. Frankfurt/Main: Peter Lang. ISBN 978-3-631-67412-3.
  • Harcourt-Smith S (1974). "'Yellow Jack': Caribbean Fever". History Today. 23 (9): 618–624.
  • Murphy J (2003). An American Plague: The True and Terrifying Story of the Yellow Fever Epidemic of 1793. New York: Clarion Books. ISBN 978-0-395-77608-7.
  • Nuwer DS (2009). Plague Among the Magnolias: The 1878 Yellow Fever Epidemic in Mississippi. University of Alabama Press. ISBN 978-0-8173-1653-2.

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External links

 
Wikimedia Commons has media related to Yellow fever.
 
Wikivoyage has a travel guide for Yellow fever.
 
Look up yellow fever in Wiktionary, the free dictionary.
 
Wikipedia's health care articles can be viewed offline with the Medical Wikipedia app.
  • Yellow fever at Curlie
  • Finlay CJ (January 2012). "The Mosquito Hypothetically Considered as the Transmitting Agent of Yellow Fever". MEDICC Review. 14 (1): 56–59. doi:10.37757/MR2012V14.N1.10. PMID 34503309.
  • "U.S. Army Yellow Fever Commission." Claude Moore Health Sciences Library, University of Virginia
  • "Yellow fever virus". NCBI Taxonomy Browser. 11089.

August 19, 2023
yellow, fever, american, plague, yellow, plague, redirect, here, rock, band, american, plague, yellow, plague, rhos, medieval, wales, maelgwn, gwynedd, other, uses, disambiguation, viral, disease, typically, short, duration, most, cases, symptoms, include, fev. 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 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 Yellow feverOther namesYellow jack yellow plague 1 bronze john 2 A TEM micrograph of yellow fever virus 234 000 magnification SpecialtyInfectious diseaseSymptomsFever chills muscle pain headache yellow skin 3 ComplicationsLiver failure bleeding 3 Usual onset3 6 days post exposure 3 Duration3 4 days 3 CausesYellow fever virus spread by mosquitoes 3 Diagnostic methodBlood test 4 PreventionYellow fever vaccine 3 TreatmentSupportive care 3 Frequency 130 000 severe cases in Africa alone 2013 3 5 Deaths 78 000 in Africa alone 2013 3 5 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 was the first human virus to be isolated 10 18 Contents 1 Signs and symptoms 1 1 Complication 2 Cause 2 1 Transmission 3 Pathogenesis 4 Diagnosis 5 Prevention 5 1 Vaccination 5 1 1 Compulsory vaccination 5 2 Vector control 6 Treatment 7 Epidemiology 7 1 Africa 7 2 South America 7 3 Asia 8 History 8 1 Early history 8 2 Causes and transmission 8 3 Current status 9 Research 10 Notes 11 References 12 Further reading 13 External linksSigns and symptoms EditYellow fever begins after an incubation period of three to six days 19 Most cases cause only a mild infection with fever headache chills back pain fatigue loss of appetite muscle pain nausea and vomiting 20 In these cases the infection lasts only three to six days 21 But in 15 of cases people enter a second toxic phase of the disease characterized by recurring fever this time accompanied by jaundice due to liver damage as well as abdominal pain 22 Bleeding in the mouth nose the eyes and the gastrointestinal tract cause vomit containing blood hence one of the names in Spanish for yellow fever vomito negro black vomit 23 There may also be kidney failure hiccups and delirium 24 25 Among those who develop jaundice the fatality rate is 20 to 50 while the overall fatality rate is about 3 to 7 5 26 Severe cases may have a mortality greater than 50 27 Surviving the infection provides lifelong immunity 28 and normally results in no permanent organ damage 29 30 Complication Edit Yellow fever can lead to death for 20 to 50 of those who develop severe disease Jaundice fatigue heart rhythm problems seizures and internal bleeding may also appear as complications of yellow fever during recovery time 31 32 Cause EditYellow fever virus Flavivirus structure and genomeVirus classification unranked VirusRealm RiboviriaKingdom OrthornaviraePhylum KitrinoviricotaClass FlasuviricetesOrder AmarilloviralesFamily FlaviviridaeGenus FlavivirusSpecies Yellow fever virusYellow fever is caused by Yellow fever virus YFV an enveloped RNA virus 40 50 nm in width the type species and namesake of the family Flaviviridae 10 It was the first illness shown to be transmissible by filtered human serum and transmitted by mosquitoes by American doctor Walter Reed around 1900 33 The positive sense single stranded RNA is around 10 862 nucleotides long and has a single open reading frame encoding a polyprotein 34 Host proteases cut this polyprotein into three structural C prM E and seven nonstructural proteins NS1 NS2A NS2B NS3 NS4A NS4B NS5 the enumeration corresponds to the arrangement of the protein coding genes in the genome 35 Minimal YFV 3 UTR region is required for stalling of the host 5 3 exonuclease XRN1 36 The UTR contains PKS3 pseudoknot structure which serves as a molecular signal to stall the exonuclease and is the only viral requirement for subgenomic flavivirus RNA sfRNA production 37 The sfRNAs are a result of incomplete degradation of the viral genome by the exonuclease and are important for viral pathogenicity 38 Yellow fever belongs to the group of hemorrhagic fevers 39 The viruses infect amongst others monocytes macrophages Schwann cells and dendritic cells They attach to the cell surfaces via specific receptors and are taken up by an endosomal vesicle 40 Inside the endosome the decreased pH induces the fusion of the endosomal membrane with the virus envelope 41 The capsid enters the cytosol decays and releases the genome 42 Receptor binding as well as membrane fusion are catalyzed by the protein E which changes its conformation at low pH causing a rearrangement of the 90 homodimers to 60 homotrimers 35 43 After entering the host cell the viral genome is replicated in the rough endoplasmic reticulum ER and in the so called vesicle packets 44 At first an immature form of the virus particle is produced inside the ER whose M protein is not yet cleaved to its mature form so is denoted as precursor M prM and forms a complex with protein E 45 The immature particles are processed in the Golgi apparatus by the host protein furin which cleaves prM to M 46 This releases E from the complex which can now take its place in the mature infectious virion 35 Transmission Edit Aedes aegypti feeding Adults of the yellow fever mosquito A aegypti The male is on the left females are on the right Only the female mosquito bites humans to transmit the disease Yellow fever virus is mainly transmitted through the bite of the yellow fever mosquito Aedes aegypti but other mostly Aedes mosquitoes such as the tiger mosquito Aedes albopictus can also serve as a vector for this virus 47 Like other arboviruses which are transmitted by mosquitoes yellow fever virus is taken up by a female mosquito when it ingests the blood of an infected human or another primate 48 Viruses reach the stomach of the mosquito and if the virus concentration is high enough the virions can infect epithelial cells and replicate there From there they reach the haemocoel the blood system of mosquitoes and from there the salivary glands 49 When the mosquito next sucks blood it injects its saliva into the wound and the virus reaches the bloodstream of the bitten person 50 Transovarial transmissionial and transstadial transmission of yellow fever virus within A aegypti that is the transmission from a female mosquito to its eggs and then larvae are indicated 51 This infection of vectors without a previous blood meal seems to play a role in single sudden breakouts of the disease 52 Three epidemiologically different infectious cycles occur 16 in which the virus is transmitted from mosquitoes to humans or other primates 53 In the urban cycle only the yellow fever mosquito A aegypti is involved It is well adapted to urban areas and can also transmit other diseases including Zika fever dengue fever and chikungunya 54 The urban cycle is responsible for the major outbreaks of yellow fever that occur in Africa Except for an outbreak in Bolivia in 1999 this urban cycle no longer exists in South America 55 Besides the urban cycle both in Africa and South America a sylvatic cycle forest or jungle cycle is present where Aedes africanus in Africa or mosquitoes of the genus Haemagogus and Sabethes in South America serve as vectors 56 In the jungle the mosquitoes infect mainly nonhuman primates the disease is mostly asymptomatic in African primates 50 In South America the sylvatic cycle is currently the only way humans can become infected which explains the low incidence of yellow fever cases on the continent 47 People who become infected in the jungle can carry the virus to urban areas where A aegypti acts as a vector Because of this sylvatic cycle yellow fever cannot be eradicated except by eradicating the mosquitoes that serve as vectors 16 In Africa a third infectious cycle known as savannah cycle or intermediate cycle occurs between the jungle and urban cycles 57 Different mosquitoes of the genus Aedes are involved In recent years this has been the most common form of transmission of yellow fever in Africa 58 Concern exists about yellow fever spreading to southeast Asia where its vector A aegypti already occurs 59 Pathogenesis EditAfter 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 60 61 Fatality may occur when cytokine storm shock and multiple organ failure follow 26 Diagnosis EditYellow fever is most frequently a clinical diagnosis based on symptomatology and travel history Mild cases of the disease can only be confirmed virologically 48 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 48 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 62 63 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 64 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 65 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 66 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 67 Prevention EditPersonal prevention of yellow fever includes vaccination and avoidance of mosquito bites in areas where yellow fever is endemic 47 Institutional measures for prevention of yellow fever include vaccination programmes and measures to control mosquitoes Programmes for distribution of mosquito nets for use in homes produce reductions in cases of both malaria and yellow fever Use of EPA registered insect repellent is recommended when outdoors Exposure for even a short time is enough for a potential mosquito bite Long sleeved clothing long pants and socks are useful for prevention The application of larvicides to water storage containers can help eliminate potential mosquito breeding sites EPA registered insecticide spray decreases the transmission of yellow fever 68 Use insect repellent when outdoors such as those containing DEET picaridin ethyl butylacetylaminopropionate IR3535 or oil of lemon eucalyptus on exposed skin 69 Mosquitoes may bite through thin clothing so spraying clothes with repellent containing permethrin or another EPA registered repellent gives extra protection 70 Clothing treated with permethrin is commercially available Mosquito repellents containing permethrin are not approved for application directly to the skin 71 The peak biting times for many mosquito species are dusk to dawn However A aegypti one of the mosquitoes that transmit yellow fever virus feeds during the daytime 72 Staying in accommodations with screened or air conditioned rooms particularly during peak biting times also reduces the risk of mosquito bites 72 Vaccination Edit The cover of a certificate that confirms the holder has been vaccinated against yellow fever Vaccination against yellow fever 10 days before entering this country territory is required for travellers coming from 73 All countries Risk countries including airport transfers note 1 Risk countries excluding airport transfers note 2 No requirement risk country note 3 No requirement non risk country Main article Yellow fever vaccine Vaccination is recommended for those traveling to affected areas because non native people tend to develop more severe illness when infected Protection begins by the 10th day after vaccine administration in 95 of people 74 and had been reported to last for at least 10 years The World Health Organization WHO now states that a single dose of vaccine is sufficient to confer lifelong immunity against yellow fever disease 75 The attenuated live vaccine stem 17D was developed in 1937 by Max Theiler 74 The WHO recommends routine vaccination for people living in affected areas between the 9th and 12th month after birth 4 Up to one in four people experience fever aches and local soreness and redness at the site of injection 76 In rare cases less than one in 200 000 to 300 000 74 the vaccination can cause yellow fever vaccine associated viscerotropic disease which is fatal in 60 of cases It is probably due to the genetic morphology of the immune system Another possible side effect is an infection of the nervous system which occurs in one in 200 000 to 300 000 cases causing yellow fever vaccine associated neurotropic disease which can lead to meningoencephalitis and is fatal in less than 5 74 of cases 4 26 The Yellow Fever Initiative launched by the WHO in 2006 vaccinated more than 105 million people in 14 countries in West Africa 77 No outbreaks were reported during 2015 The campaign was supported by the GAVI alliance and governmental organizations in Europe and Africa 78 According to the WHO mass vaccination cannot eliminate yellow fever because of the vast number of infected mosquitoes in urban areas of the target countries but it will significantly reduce the number of people infected 79 Demand for yellow fever vaccine has continued to increase due to the growing number of countries implementing yellow fever vaccination as part of their routine immunization programmes 80 Recent upsurges in yellow fever outbreaks in Angola 2015 the Democratic Republic of Congo 2016 Uganda 2016 and more recently in Nigeria and Brazil in 2017 have further increased demand while straining global vaccine supply 80 81 Therefore to vaccinate susceptible populations in preventive mass immunization campaigns during outbreaks fractional dosing of the vaccine is being considered as a dose sparing strategy to maximize limited vaccine supplies 80 Fractional dose yellow fever vaccination refers to administration of a reduced volume of vaccine dose which has been reconstituted as per manufacturer recommendations 80 82 The first practical use of fractional dose yellow fever vaccination was in response to a large yellow fever outbreak in the Democratic Republic of the Congo in mid 2016 80 Available evidence shows that fractional dose yellow fever vaccination induces a level of immune response similar to that of the standard full dose 83 In March 2017 the WHO launched a vaccination campaign in Brazil with 3 5 million doses from an emergency stockpile 84 In March 2017 the WHO recommended vaccination for travellers to certain parts of Brazil 85 In March 2018 Brazil shifted its policy and announced it planned to vaccinate all 77 5 million currently unvaccinated citizens by April 2019 86 Compulsory vaccination Edit Some countries in Asia are considered to be potentially in danger of yellow fever epidemics as both mosquitoes with the capability to transmit yellow fever as well as susceptible monkeys are present 87 The disease does not yet occur in Asia To prevent introduction of the virus some countries demand previous vaccination of foreign visitors who have passed through yellow fever areas 88 Vaccination has to be proved by a vaccination certificate which is valid 10 days after the vaccination and lasts for 10 years Although the WHO on 17 May 2013 advised that subsequent booster vaccinations are unnecessary an older than 10 years certificate may not be acceptable at all border posts in all affected countries A list of the countries that require yellow fever vaccination is published by the WHO 73 If the vaccination cannot be given for some reason dispensation may be possible In this case an exemption certificate issued by a WHO approved vaccination center is required Although 32 of 44 countries where yellow fever occurs endemically do have vaccination programmes in many of these countries less than 50 of their population is vaccinated 4 Vector control Edit Information campaign for prevention of dengue and yellow fever in ParaguayControl of the yellow fever mosquito A aegypti is of major importance especially because the same mosquito can also transmit dengue fever and chikungunya disease 89 A aegypti breeds preferentially in water for example in installations by inhabitants of areas with precarious drinking water supplies or in domestic refuse especially tires cans and plastic bottles These conditions are common in urban areas in developing countries 90 Two main strategies are employed to reduce A aegypti populations 91 One approach is to kill the developing larvae Measures are taken to reduce the water accumulations in which the larvae develop Larvicides are used along with larvae eating fish and copepods which reduce the number of larvae 92 For many years copepods of the genus Mesocyclops have been used in Vietnam for preventing dengue fever 93 This eradicated the mosquito vector in several areas Similar efforts may prove effective against yellow fever Pyriproxyfen is recommended as a chemical larvicide mainly because it is safe for humans and effective in small doses 4 The second strategy is to reduce populations of the adult yellow fever mosquito Lethal ovitraps can reduce Aedes populations using lesser amounts of pesticide because it targets the pest directly 94 Curtains and lids of water tanks can be sprayed with insecticides but application inside houses is not recommended by the WHO 95 Insecticide treated mosquito nets are effective just as they are against the Anopheles mosquito that carries malaria 4 Treatment EditAs 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 96 Epidemiology EditYellow fever is common in tropical and subtropical areas of South America and Africa 97 Worldwide about 600 million people live in endemic areas The WHO estimates 200 000 cases of yellow fever worldwide each year 98 About 15 of people infected with yellow fever progress to a severe form of the illness and up to half of those will die as there is no cure for yellow fever 99 Africa Edit Areas with risk of yellow fever in Africa 2017 An estimated 90 of yellow fever infections occur on the African continent 4 In 2016 a large outbreak originated in Angola and spread to neighboring countries before being contained by a massive vaccination campaign 100 In March and April 2016 11 imported cases of the Angola genotype in unvaccinated Chinese nationals were reported in China the first appearance of the disease in Asia in recorded history 101 102 Phylogenetic analysis has identified seven genotypes of yellow fever viruses and they are assumed to be differently adapted to humans and to the vector A aegypti Five genotypes Angola Central East Africa East Africa West Africa I and West Africa II occur only in Africa West Africa genotype I is found in Nigeria and the surrounding region 103 West Africa genotype I appears to be especially infectious as it is often associated with major outbreaks The three genotypes found outside of Nigeria and Angola occur in areas where outbreaks are rare Two outbreaks in Kenya 1992 1993 and Sudan 2003 and 2005 involved the East African genotype which had remained undetected in the previous 40 years 104 South America Edit Areas with risk of yellow fever in South America 2018 In South America two genotypes have been identified South American genotypes I and II 16 Based on phylogenetic analysis these two genotypes appear to have originated in West Africa 105 and were first introduced into Brazil 106 The date of introduction of the predecessor African genotype which gave rise to the South American genotypes appears to be 1822 95 confidence interval 1701 to 1911 106 The historical record shows an outbreak of yellow fever occurred in Recife Brazil between 1685 and 1690 The disease seems to have disappeared with the next outbreak occurring in 1849 107 It was likely introduced with the trafficking of slaves through the slave trade from Africa Genotype I has been divided into five subclades A through E 108 In late 2016 a large outbreak began in Minas Gerais state of Brazil that was characterized as a sylvan or jungle epizootic 109 It began as an outbreak in brown howler monkeys 110 which serve as a sentinel species for yellow fever that then spread to men working in the jungle No cases had been transmitted between humans by the A aegypti mosquito which can sustain urban outbreaks that can spread rapidly In April 2017 the sylvan outbreak continued moving toward the Brazilian coast where most people were unvaccinated 85 By the end of May the outbreak appeared to be declining after more than 3 000 suspected cases 758 confirmed and 264 deaths confirmed to be yellow fever 111 The Health Ministry launched a vaccination campaign and was concerned about spread during the Carnival season in February and March The CDC issued a Level 2 alert practice enhanced precautions 112 A Bayesian analysis of genotypes I and II has shown that genotype I accounts for virtually all the current infections in Brazil Colombia Venezuela and Trinidad and Tobago while genotype II accounted for all cases in Peru 113 Genotype I originated in the northern Brazilian region around 1908 95 highest posterior density interval HPD 1870 1936 Genotype II originated in Peru in 1920 95 HPD 1867 1958 114 The estimated rate of mutation for both genotypes was about 5 10 4 substitutions site year similar to that of other RNA viruses 115 Asia Edit The main vector A aegypti also occurs in tropical and subtropical regions of Asia the Pacific and Australia but yellow fever had never occurred there until jet travel introduced 11 cases from the 2016 Angola and DR Congo yellow fever outbreak in Africa Proposed explanations include 116 That the strains of the mosquito in the east are less able to transmit yellow fever virus 117 That immunity is present in the populations because of other diseases caused by related viruses for example dengue 118 That the disease was never introduced because the shipping trade was insufficient But none is considered satisfactory 119 120 Another proposal is the absence of a slave trade to Asia on the scale of that to the Americas 121 The trans Atlantic slave trade probably introduced yellow fever into the Western Hemisphere from Africa 122 History EditMain article History of yellow fever Early history Edit The evolutionary origins of yellow fever most likely lie in Africa with transmission of the disease from nonhuman primates to humans 123 124 The virus is thought to have originated in East or Central Africa and spread from there to West Africa As it was endemic in Africa local populations had developed some immunity to it When an outbreak of yellow fever would occur in an African community where colonists resided most Europeans died while the indigenous Africans usually developed nonlethal symptoms resembling influenza 125 This phenomenon in which certain populations develop immunity to yellow fever due to prolonged exposure in their childhood is known as acquired immunity 126 The virus as well as the vector A aegypti were probably transferred to North and South America with the trafficking of slaves from Africa part of the Columbian exchange following European exploration and colonization 127 However some researchers have argued that yellow fever might have existed in the Americas during the pre Columbian period as mosquitoes of the genus Haemagogus which is indigenous to the Americas have been known to carry the disease 128 The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados 129 An outbreak was recorded by Spanish colonists in 1648 in the Yucatan Peninsula where the indigenous Mayan people called the illness xekik blood vomit In 1685 Brazil suffered its first epidemic in Recife The first mention of the disease by the name yellow fever occurred in 1744 130 John Mitchell 1805 Mitchell s account of the Yellow Fever in Virginia in 1741 2 Archived 2017 02 23 at the Wayback Machine The Philadelphia Medical Museum 1 1 1 20 John Mitchell 1814 Account of the Yellow fever which prevailed in Virginia in the years 1737 1741 and 1742 in a letter to the late Cadwallader Colden Esq of New York from the late John Mitchell M D F R S of Virginia Archived 2017 02 23 at the Wayback Machine American Medical and Philosophical Register 4 181 215 The term yellow fever appears on p 186 On p 188 Mitchell mentions the distemper was what is generally called yellow fever in America However on pages 191 192 he states I shall consider the cause of the yellowness which is so remarkable in this distemper as to have given it the name of the Yellow Fever citation needed However Dr Mitchell misdiagnosed the disease that he observed and treated and the disease was probably Weil s disease or hepatitis 131 McNeill argues that the environmental and ecological disruption caused by the introduction of sugar plantations created the conditions for mosquito and viral reproduction and subsequent outbreaks of yellow fever 132 Deforestation reduced populations of insectivorous birds and other creatures that fed on mosquitoes and their eggs 133 Sugar curing house 1762 Sugar pots and jars on sugar plantations served as breeding place for larvae of A aegypti the vector of yellow fever In Colonial times and during the Napoleonic Wars the West Indies were known as a particularly dangerous posting for soldiers due to yellow fever being endemic in the area 134 The mortality rate in British garrisons in Jamaica was seven times that of garrisons in Canada mostly because of yellow fever and other tropical diseases 135 Both English and French forces posted there were seriously affected by the yellow jack 136 Wanting to regain control of the lucrative sugar trade in Saint Domingue Hispaniola and with an eye on regaining France s New World empire Napoleon sent an army under the command of his brother in law General Charles Leclerc to Saint Domingue to seize control after a slave revolt 137 The historian J R McNeill asserts that yellow fever accounted for about 35 000 to 45 000 casualties of these forces during the fighting 138 Only one third of the French troops survived for withdrawal and return to France Napoleon gave up on the island and his plans for North America selling the Louisiana Purchase to the US in 1803 In 1804 Haiti proclaimed its independence as the second republic in the Western Hemisphere 139 Considerable debate exists over whether the number of deaths caused by disease in the Haitian Revolution was exaggerated 140 Although yellow fever is most prevalent in tropical like climates the northern United States were not exempted from the fever The first outbreak in English speaking North America occurred in New York City in 1668 141 English colonists in Philadelphia and the French in the Mississippi River Valley recorded major outbreaks in 1669 as well as additional yellow fever epidemics in Philadelphia Baltimore and New York City in the 18th and 19th centuries The disease traveled along steamboat routes from New Orleans causing some 100 000 150 000 deaths in total 142 The yellow fever epidemic of 1793 in Philadelphia which was then the capital of the United States resulted in the deaths of several thousand people more than 9 of the population 143 One of these deaths was James Hutchinson a physician helping to treat the population of the city The national government fled the city to Trenton New Jersey including President George Washington 144 Headstones of people who died in the yellow fever epidemic of 1878 can be found in New Orleans cemeteriesThe southern city of New Orleans was plagued with major epidemics during the 19th century most notably in 1833 and 1853 145 A major epidemic occurred in both New Orleans and Shreveport Louisiana in 1873 Its residents called the disease yellow jack Urban epidemics continued in the United States until 1905 with the last outbreak affecting New Orleans 146 16 147 At least 25 major outbreaks took place in the Americas during the 18th and 19th centuries including particularly serious ones in Cartagena Chile in 1741 Cuba in 1762 and 1900 Santo Domingo in 1803 and Memphis Tennessee in 1878 148 In the early nineteenth century the prevalence of yellow fever in the Caribbean led to serious health problems and alarmed the United States Navy as numerous deaths and sickness curtailed naval operations and destroyed morale 149 One episode began in April 1822 when the frigate USS Macedonian left Boston and became part of Commodore James Biddle s West India Squadron Unbeknownst to all they were about to embark on a cruise to disaster and their assignment would prove a cruise through hell 150 Secretary of the Navy Smith Thompson had assigned the squadron to guard United States merchant shipping and suppress piracy 151 During their time on deployment from 26 May to 3 August 1822 76 of the Macedonian s officers and men died including John Cadle surgeon USN Seventy four of these deaths were attributed to yellow fever Biddle reported that another 52 of his crew were on sick list In their report to the secretary of the Navy Biddle and Surgeon s Mate Charles Chase stated the cause as fever As a consequence of this loss Biddle noted that his squadron was forced to return to Norfolk Navy Yard early Upon arrival the Macedonian s crew were provided medical care and quarantined at Craney Island Virginia 152 153 154 A page from Commodore James Biddle s list of the 76 dead 74 of yellow fever aboard the USS Macedonian dated 3 August 1822In 1853 Cloutierville Louisiana had a late summer outbreak of yellow fever that quickly killed 68 of the 91 inhabitants A local doctor concluded that some unspecified infectious agent had arrived in a package from New Orleans 155 156 In 1854 650 residents of Savannah Georgia died from yellow fever 157 In 1858 St Matthew s German Evangelical Lutheran Church in Charleston South Carolina had 308 yellow fever deaths reducing the congregation by half 158 A ship carrying persons infected with the virus arrived in Hampton Roads in southeastern Virginia in June 1855 159 The disease spread quickly through the community eventually killing over 3 000 people mostly residents of Norfolk and Portsmouth 160 In 1873 Shreveport Louisiana lost 759 citizens in an 80 day period to a yellow fever epidemic with over 400 additional victims eventually succumbing The total death toll from August through November was approximately 1 200 161 162 In 1878 about 20 000 people died in a widespread epidemic in the Mississippi River Valley 163 That year Memphis had an unusually large amount of rain which led to an increase in the mosquito population The result was a huge epidemic of yellow fever 164 The steamship John D Porter took people fleeing Memphis northward in hopes of escaping the disease but passengers were not allowed to disembark due to concerns of spreading yellow fever The ship roamed the Mississippi River for the next two months before unloading her passengers 165 Major outbreaks have also occurred in southern Europe Gibraltar lost many lives to outbreaks in 1804 1814 and 1828 166 Barcelona suffered the loss of several thousand citizens during an outbreak in 1821 The Duke de Richelieu deployed 30 000 French troops to the border between France and Spain in the Pyrenees Mountains to establish a cordon sanitaire in order to prevent the epidemic from spreading from Spain into France 167 Causes and transmission Edit A painting depicting yellow fever in Buenos Aires 1871 Carlos Finlay Walter ReedEzekiel Stone Wiggins known as the Ottawa Prophet proposed that the cause of a yellow fever epidemic in Jacksonville Florida in 1888 was astrological 168 The planets were in the same line as the sun and earth and this produced besides Cyclones Earthquakes etc a denser atmosphere holding more carbon and creating microbes Mars had an uncommonly dense atmosphere but its inhabitants were probably protected from the fever by their newly discovered canals which were perhaps made to absorb carbon and prevent the disease 169 In 1848 Josiah C Nott suggested that yellow fever was spread by insects such as moths or mosquitoes basing his ideas on the pattern of transmission of the disease 170 Carlos Finlay a Cuban doctor and scientist proposed in 1881 that yellow fever might be transmitted by previously infected mosquitoes rather than by direct contact from person to person as had long been believed 171 172 Since the losses from yellow fever in the Spanish American War in the 1890s were extremely high Army doctors began research experiments with a team led by Walter Reed and composed of doctors James Carroll Aristides Agramonte and Jesse William Lazear They successfully proved Finlay s mosquito hypothesis Yellow fever was the first virus shown to be transmitted by mosquitoes The physician William Gorgas applied these insights and eradicated yellow fever from Havana He also campaigned against yellow fever during the construction of the Panama Canal A previous effort of canal building by the French had failed in part due to mortality from the high incidence of yellow fever and malaria which killed many workers 16 Although Reed has received much of the credit in United States history books for beating yellow fever he had fully credited Finlay with the discovery of the yellow fever vector and how it might be controlled Reed often cited Finlay s papers in his own articles and also credited him for the discovery in his personal correspondence 173 The acceptance of Finlay s work was one of the most important and far reaching effects of the U S Army Yellow Fever Commission of 1900 174 Applying methods first suggested by Finlay the United States government and Army eradicated yellow fever in Cuba and later in Panama allowing completion of the Panama Canal While Reed built on the research of Finlay historian Francois Delaporte notes that yellow fever research was a contentious issue Scientists including Finlay and Reed became successful by building on the work of less prominent scientists without always giving them the credit they were due 175 Reed s research was essential in the fight against yellow fever He is also credited for using the first type of medical consent form during his experiments in Cuba an attempt to ensure that participants knew they were taking a risk by being part of testing 176 Like Cuba and Panama Brazil also led a highly successful sanitation campaign against mosquitoes and yellow fever Beginning in 1903 the campaign led by Oswaldo Cruz then director general of public health resulted not only in eradicating the disease but also in reshaping the physical landscape of Brazilian cities such as Rio de Janeiro 177 During rainy seasons Rio de Janeiro had regularly suffered floods as water from the bay surrounding the city overflowed into Rio s narrow streets Coupled with the poor drainage systems found throughout Rio this created swampy conditions in the city s neighborhoods Pools of stagnant water stood year long in city streets and proved to be a fertile ground for disease carrying mosquitoes Thus under Cruz s direction public health units known as mosquito inspectors fiercely worked to combat yellow fever throughout Rio by spraying exterminating rats improving drainage and destroying unsanitary housing Ultimately the city s sanitation and renovation campaigns reshaped Rio de Janeiro s neighborhoods Its poor residents were pushed from city centers to Rio s suburbs or to towns found in the outskirts of the city In later years Rio s most impoverished inhabitants would come to reside in favelas 178 Max TheilerDuring 1920 1923 the Rockefeller Foundation s International Health Board undertook an expensive and successful yellow fever eradication campaign in Mexico 179 The IHB gained the respect of Mexico s federal government because of the success The eradication of yellow fever strengthened the relationship between the US and Mexico which had not been very good in the years prior The eradication of yellow fever was also a major step toward better global health 180 In 1927 scientists isolated the yellow fever virus in West Africa 181 Following this two vaccines were developed in the 1930s Max Theiler led the completion of the 17D yellow fever vaccine in 1937 for which he was subsequently awarded the Nobel Prize in Physiology or Medicine 182 That vaccine 17D is still in use although newer vaccines based on vero cells are in development as of 2018 4 183 184 Current status Edit Using vector control and strict vaccination programs the urban cycle of yellow fever was nearly eradicated from South America 185 Since 1943 only a single urban outbreak in Santa Cruz de la Sierra Bolivia has occurred Since the 1980s however the number of yellow fever cases has been increasing again and A aegypti has returned to the urban centers of South America This is partly due to limitations on available insecticides as well as habitat dislocations caused by climate change It is also because the vector control program was abandoned Although no new urban cycle has yet been established scientists believe this could happen again at any point An outbreak in Paraguay in 2008 was thought to be urban in nature but this ultimately proved not to be the case 4 In Africa virus eradication programs have mostly relied upon vaccination 186 These programs have largely been unsuccessful because they were unable to break the sylvatic cycle involving wild primates With few countries establishing regular vaccination programs measures to fight yellow fever have been neglected making the future spread of the virus more likely 4 Research EditIn the hamster model of yellow fever early administration of the antiviral ribavirin is an effective treatment of many pathological features of the disease 187 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 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21 11407 11417 doi 10 1128 JVI 01159 10 PMC 2953152 PMID 20719943 Silva PA Pereira CF Dalebout TJ Spaan WJ Bredenbeek PJ November 2010 An RNA pseudoknot is required for production of yellow fever virus subgenomic RNA by the host nuclease XRN1 Journal of Virology 84 21 11395 11406 doi 10 1128 jvi 01047 10 PMC 2953177 PMID 20739539 Hemorrhagic Fevers medlineplus gov Retrieved 2022 04 24 Vercammen E Staal J Beyaert R January 2008 Sensing of viral infection and activation of innate immunity by toll like receptor 3 Clinical Microbiology Reviews 21 1 13 25 doi 10 1128 CMR 00022 07 PMC 2223843 PMID 18202435 Zhang Xingwang Wu Wei July 2014 Receptor Mediated Endocytosis an overview ScienceDirect Topics Drug Discovery Today 19 7 898 904 doi 10 1016 j drudis 2014 03 001 PMID 24631680 Retrieved 2022 04 24 Mudhakir D Harashima H March 2009 Learning from the viral journey how to enter cells and how to overcome intracellular barriers to reach the nucleus The AAPS Journal 11 1 65 77 doi 10 1208 s12248 009 9080 9 PMC 2664881 PMID 19194803 Dhiman G Abraham R Griffin DE July 2019 Human Schwann cells are susceptible to infection with Zika and yellow fever viruses but not dengue virus Scientific Reports 9 1 9951 Bibcode 2019NatSR 9 9951D doi 10 1038 s41598 019 46389 0 PMC 6616448 PMID 31289325 Inoue T Tsai B January 2013 How viruses use the endoplasmic reticulum for entry replication and assembly Cold Spring Harbor Perspectives in Biology 5 1 a013250 doi 10 1101 cshperspect a013250 PMC 3579393 PMID 23284050 Veesler D Johnson JE 2012 Virus maturation Annual Review of Biophysics 41 473 496 doi 10 1146 annurev biophys 042910 155407 PMC 3607295 PMID 22404678 Op De Beeck A Molenkamp R Caron M Ben Younes A Bredenbeek P Dubuisson J January 2003 Role of the transmembrane domains of prM and E proteins in the formation of yellow fever virus envelope Journal of Virology 77 2 813 820 doi 10 1128 JVI 77 2 813 820 2003 PMC 140810 PMID 12502797 a b c Yellow fever www who int Retrieved 2022 04 24 a b c 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19039426 Talwani R Gilliam BL Howell C February 2011 Infectious diseases and the liver Clinics in Liver Disease 15 1 111 130 doi 10 1016 j cld 2010 09 002 PMC 3660095 PMID 21111996 Cleri DJ Ricketti AJ Porwancher RB Ramos Bonner LS Vernaleo JR June 2006 Viral hemorrhagic fevers current status of endemic disease and strategies for control Infectious Disease Clinics of North America 20 2 359 93 x doi 10 1016 j idc 2006 02 001 PMC 7135140 PMID 16762743 Prevention Yellow Fever CDC www cdc gov Archived from the original on 2016 10 26 Retrieved 2016 10 26 Lo WL Mok KL Yu Pui Ming SD September 2018 Which insect repellents should we choose Implications from results of local market survey and review of current guidelines Hong Kong Journal of Emergency Medicine 25 5 272 280 doi 10 1177 1024907918773630 ISSN 1024 9079 S2CID 115355721 Shmaefsky BR November 2009 Yellow Fever Infobase Publishing ISBN 978 1 60413 231 1 US EPA OCSPP 2013 07 15 Repellent Treated Clothing www epa gov Retrieved 2022 04 25 a b Frequently Asked Questions www cdc gov 2020 02 26 Retrieved 2022 04 25 a b Countries with risk of yellow fever transmission and countries requiring yellow fever vaccination May 2021 World Health Organization United Nations 26 May 2021 Retrieved 16 January 2022 a b c d Barrett AD Teuwen DE June 2009 Yellow fever vaccine how does it work and why do rare cases of serious adverse events take place Current Opinion in Immunology 21 3 308 313 doi 10 1016 j coi 2009 05 018 PMID 19520559 WHO Yellow fever vaccination booster not needed Archived 2013 06 09 at the Wayback Machine Who int 2013 05 17 Retrieved on 2014 05 12 Yellow Fever Vaccine Information Statement Archived 2013 09 21 at the Wayback Machine Centers for Disease Control and Prevention March 30 2011 Yellow fever World Health Organization Archived from the original on 18 April 2017 Retrieved 2 April 2017 Measles vaccination has saved an estimated 17 1 million lives since 2000 www who int Retrieved 2022 04 25 Twelve million West Africans get yellow fever vaccines BBC News 23 November 2009 Archived from the original on 8 September 2017 Retrieved 23 November 2009 a b c d e Fractional Dose Yellow Fever Vaccine as a Dose sparing Option for Outbreak Response WHO Secretariat Information Paper Department of Immunization Vaccines and Biologicals WHO reference number WHO YF SAGE 16 1 World Health Organization 20 July 2016 Retrieved 2 September 2018 WHO supports the immunization of 874 000 people against yellow fever in Nigeria News Release World Health Organization 16 October 2017 Retrieved 2 September 2018 World Health Organization October 2017 Human papillomavirus vaccines WHO position paper May 2017 Recommendations Vaccine 35 43 5753 5755 doi 10 1016 j vaccine 2017 05 069 PMID 28596091 Nnaji CA Shey MS Adetokunboh OO Wiysonge CS February 2020 Immunogenicity and safety of fractional dose yellow fever vaccination A systematic review and meta analysis Vaccine 38 6 1291 1301 doi 10 1016 j vaccine 2019 12 018 PMID 31859201 S2CID 209427280 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint multiple names authors list link WHO dispatched 3 5 million doses of yellow fever vaccine for outbreak response in Brazil World Health Organization Archived from the original on 1 April 2017 Retrieved 2 April 2017 a b Yellow fever Brazil Nature 150 3811 573 1942 Bibcode 1942Natur 150T 573 doi 10 1038 150573d0 Darlington S 20 March 2018 Fearing New Outbreaks Brazil Will Vaccinate Country Against Yellow Fever The New York Times Retrieved 21 March 2018 Kuno G November 2020 The Absence of Yellow Fever in Asia History Hypotheses Vector Dispersal Possibility of YF in Asia and Other Enigmas Viruses 12 12 1349 doi 10 3390 v12121349 PMC 7759908 PMID 33255615 Wasserman S Tambyah PA Lim PL July 2016 Yellow fever cases in Asia primed for an epidemic International Journal of Infectious Diseases 48 98 103 doi 10 1016 j ijid 2016 04 025 PMID 27156836 Vector borne diseases www who int 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al October 2010 Yellow fever virus maintenance in Trinidad and its dispersal throughout the Americas Journal of Virology 84 19 9967 9977 doi 10 1128 JVI 00588 10 PMC 2937779 PMID 20631128 Bhattacharya A 7 June 2013 A REVIEW ON VIRAL HEMORRHAGIC FEVER Lulu com ISBN 978 1 304 11397 9 de Souza RP Foster PG Sallum MA Coimbra TL Maeda AY Silveira VR et al January 2010 Detection of a new yellow fever virus lineage within the South American genotype I in Brazil Journal of Medical Virology 82 1 175 185 doi 10 1002 jmv 21606 PMID 19950229 S2CID 96746 YELLOW FEVER AMERICAS 01 PAHO WHO 2016 www promedmail org International Society for Infectious Diseases Archived from the original on 16 February 2017 Retrieved 16 February 2017 Yellow fever killing thousands of monkeys in Brazil www sciencedaily com Archived from the original on 24 March 2017 Retrieved 24 March 2017 ProMED mail post Yellow fever Americas 47 Brazil PAHO WHO www promedmail org International Society for Infectious Diseases Archived 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Kamgang B et al November 2020 Risk of yellow fever virus transmission in the Asia Pacific region Nature Communications 11 1 5801 Bibcode 2020NatCo 11 5801L doi 10 1038 s41467 020 19625 9 PMC 7669885 PMID 33199712 Yellow Fever Virus an overview ScienceDirect Topics www sciencedirect com Retrieved 2022 04 25 Dengue and severe dengue www who int Retrieved 2022 04 25 Vainio J Cutts F eds 1998 Yellow Fever WHO Division of Emerging and other Communicable Diseases Surveillance and Control Monath TP 1989 The absence of yellow fever in Asia hypotheses A cause for concern Virus Inf Exch Newslett 106 7 Cathey JT Marr JS May 2014 Yellow fever Asia and the East African slave trade Transactions of the Royal Society of Tropical Medicine and Hygiene 108 5 252 257 doi 10 1093 trstmh tru043 PMID 24743951 Bryant JE Holmes EC Barrett AD May 2007 Out of Africa a molecular perspective on the introduction of yellow fever virus into the Americas PLOS Pathogens 3 5 e75 doi 10 1371 journal ppat 0030075 PMC 1868956 PMID 17511518 Gould EA de Lamballerie X Zanotto PM Holmes EC 2003 Origins evolution coadaptations within the genus Flavivirus pp 277 314 doi 10 1016 S0065 3527 03 59008 X ISBN 978 0 12 039859 1 PMID 14696332 a href Template Cite book html title Template Cite book cite book a journal ignored help Bryant JE Holmes EC Barrett AD May 2007 Out of Africa a molecular perspective on the introduction of yellow fever virus into the Americas PLOS Pathogens 3 5 e75 doi 10 1371 journal ppat 0030075 PMC 1868956 PMID 17511518 Oldstone M 1998 Viruses Plagues and History New York Oxford University Press McNeill JR 2010 Mosquito Empires Ecology and war in the greater Caribbean 1620 1914 NY Cambridge University Press pp 44 45 Chippaux JP Chippaux A 2018 Yellow fever in Africa and the Americas a historical and epidemiological perspective The Journal of Venomous Animals and Toxins Including Tropical Diseases 24 20 doi 10 1186 s40409 018 0162 y PMC 6109282 PMID 30158957 Wilkninson Robert 1995 Yellow Fever Ecology Epidemiology and Role in the Collapse of the Classic Lowland Maya Civilization Medical Anthropology McNeill JR 1 April 2004 Yellow Jack and Geopolitics Environment Epidemics and the Struggles for Empire in the American Tropics 1650 1825 OAH Magazine of History 18 3 9 13 doi 10 1093 maghis 18 3 9 The earliest mention of yellow fever appears in a manuscript of 1744 by Dr John Mitchell of Virginia copies of the manuscript were sent to Mr Cadwallader Colden a physician in New York and to Dr Benjamin Rush of Philadelphia the manuscript was eventually printed in large part in 1805 and reprinted in 1814 See Dr John Mitchell s Account of the Yellow Fever in Virginia in 1741 42 Written in 1748 Annals of Medical History 6 1 91 92 January 1934 PMC 7943142 PMID 33944007 Jarcho S 1957 John Mitchell Benjamin Rush and yellow fever Bulletin of the History of Medicine 31 2 132 136 PMID 13426674 McNeill J 2010 Mosquito Empires Ecology and War in the Greater Caribbean 1620 1914 New York NY Cambridge University Press ISBN 978 0 511 67268 2 Burkett Cadena ND Vittor AY February 2018 Deforestation and vector borne disease Forest conversion favors important mosquito vectors of human pathogens Basic and Applied Ecology 26 101 110 doi 10 1016 j baae 2017 09 012 PMC 8290921 PMID 34290566 Buckley RN 1978 The Destruction of the British Army in the West Indies 1793 1815 A Medical History Journal of the Society for Army Historical Research 56 226 79 92 ISSN 0037 9700 JSTOR 44224266 PMID 11614813 McNeill JR 2002 Yellow fever and geopolitics environment epidemics and the struggles for empire in the American tropics 1650 1900 History Now 8 2 10 16 PMID 20690235 McNeill JR 2004 Yellow Jack and Geopolitics Environment Epidemics and the Struggles for Empire in the American Tropics 1640 1830 Review Fernand Braudel Center 27 4 343 364 ISSN 0147 9032 JSTOR 40241611 Marshall A 2020 11 18 What was the Haitian Revolution 1791 1804 Boot Camp amp Military Fitness Institute Retrieved 2022 04 25 McNeill JR 2010 Mosquito Empires Ecology and War in the Greater Caribbean 1620 1914 Cambridge University Press p 259 Haiti profile Timeline BBC News 2019 02 11 Retrieved 2022 04 25 Girard PR 2011 The Slaves Who Defeated Napoleon Toussaint Louverture and the Haitian War of Independence 1801 1804 University of Alabama Press pp 179 80 ISBN 978 0 8173 1732 4 Archived from the original on 2016 09 11 Kotar SL Gessler JE 2017 02 03 Yellow Fever A Worldwide History McFarland ISBN 978 1 4766 2628 4 Patterson KD April 1992 Yellow fever epidemics and mortality in the United States 1693 1905 Social Science amp Medicine 34 8 855 865 doi 10 1016 0277 9536 92 90255 O PMID 1604377 Miller JC 2005 The Wages of Blackness African American Workers and the Meanings of Race during Philadelphia s 1793 Yellow Fever Epidemic The Pennsylvania Magazine of History and Biography 129 2 163 194 Yellow Fever Attacks Philadelphia 1793 EyeWitness to History Archived from the original on 2007 06 07 Retrieved 2009 08 14 How Yellow Fever Turned New Orleans Into The City Of The Dead NPR org Retrieved 2022 04 25 Pierce J Writer J 2005 Yellow Jack How Yellow Fever ravaged America and Walter Reed Discovered Its Deadly Secrets Hoboken John Wiley amp Sons p 3 The Tennessee Encyclopedia of History and Culture Yellow Fever Epidemics Tennessee Historical Society Archived from the original on December 12 2013 Retrieved June 20 2013 John S Marr and John T Cathey The 1802 Saint Domingue yellow fever epidemic and the Louisiana Purchase Journal of Public Health Management and Practice 19 1 2013 77 82 online Archived 2016 02 04 at the Wayback Machine Langley Harold D A History of Medicine in the Early U S Navy Johns Hopkins Press Baltimore 1995 274 275 Sharp JG The Disastrous Voyage Yellow Fever aboard the USS Macedonian amp USS Peacock 1822 Archived from the original on 25 October 2019 Retrieved 15 August 2020 Annual Report of the Secretary of the Navy 1823 public2 nhhcaws local Retrieved 2022 04 25 permanent dead link James Biddle to Smith Thompson 3 August 1822 Captains Letters Nara M125 79 letter no 15 The Macedonian a list of the deaths Connecticut Herald 20 August 1822 p 2 Sharp Ibid The Transactions of the American Medical Association Volume IX TK and PG Collins 1856 page 704 Yellow Fever at the Village of Cloutierville La in the Years 1853 and 1854 by Samuel O Scruggs M D New Orleans Genesis June 1970 page 261 262 Cloutierville Yellow Fever Deaths 1853 Lockley T 2012 Like a clap of thunder in a clear sky differential mortality during Savannah s yellow fever epidemic of 1854 PDF Social History 37 2 166 186 doi 10 1080 03071022 2012 675657 S2CID 2571401 Retrieved 22 February 2018 St Matthew s Evangelical Lutheran Church 125 Years of Christian Service 1967 Mauer HB Mosquito control ends fatal plague of yellow fever etext lib virginia edu Archived from the original on 2012 12 12 Retrieved 2007 06 11 undated newspaper clipping Yellow Fever www usgwarchives net Retrieved 30 September 2019 Louisiana Office of Public Health Statistics page 6 PDF Tour Stop 1 Yellow Fever Victims Tour Oakland Cemetery Shreveport Louisiana Founded 1847 www oaklandcemeteryla org Archived from the original on 2018 09 28 Retrieved 2018 09 28 Crosby MC 2006 The American Plague New York Berkley Publishing Group p 75 Yellow Fever the plague of Memphis HistoricMemphis com Archived from the original on August 21 2014 Retrieved August 20 2014 Barnes E 2005 Diseases and Human Evolution Albuquerque University of New Mexico ISBN 978 0 8263 3065 9 Sawchuk LA Burke SD January 1998 Gibraltar s 1804 yellow fever scourge the search for scapegoats Journal of the History of Medicine and Allied Sciences 53 1 3 42 doi 10 1093 jhmas 53 1 3 PMID 9510598 James Taylor The age we live in a history of the nineteenth century Oxford University 1882 p 222 World Diseases Yellow Fever West Bend News 2020 06 30 Retrieved 2022 04 25 John W Cowart Yellow Jack in Jacksonville Yellow Fever visited Duval County Florida in 1888 Archived 2013 01 05 at the Wayback Machine Historical Text Archive Josiah C Nott 1848 Yellow Fever contrasted with Bilious Fever Reasons for believing it a disease sui generis Its mode of Propagation Remote Cause Probable insect or animalcular origin The New Orleans Medical and Surgical Journal 4 563 601 Carlos Juan Finlay presented August 14 1881 published 1882 El mosquito hipoteticamente considerado como agente de transmission de la fiebre amarilla Archived 2017 02 23 at the Wayback Machine The mosquito hypothetically considered as an agent in the transmission of yellow fever Anales de la Real Academia de Ciencias Medicas Fisicas y Naturales de la Habana 18 147 169 Available on line in English at Charles Finlay with Rudolph Matas translator 1881 The mosquito hypothetically considered as an agent in the transmission of yellow fever poison Archived 2017 02 23 at the Wayback Machine New Orleans Medical and Surgical Journal 9 601 616 Delta Omega org Archived 2012 05 09 at the Wayback Machine Chaves Carballo E October 2005 Carlos Finlay and yellow fever triumph over adversity Military Medicine 170 10 881 885 doi 10 7205 milmed 170 10 881 PMID 16435764 Pierce JR Writer J 2005 Yellow Jack How Yellow Fever Ravaged America and Walter Reed Discovered Its Deadly Secrets Wiley ISBN 978 0 471 47261 2 U S Army Yellow Fever Commission UVA Health Sciences Historical Collections Archived from the original on 2017 04 26 Retrieved 2017 08 01 Delaporte F 1991 The History of Yellow Fever An Essay on the Birth of Tropical Medicine Cambridge MIT Press pp 89 90 ISBN 9780262041126 Crosby MC 2006 The American Plague New York Berkley Publishing Group p 177 Wilson AL Courtenay O Kelly Hope LA Scott TW Takken W Torr SJ Lindsay SW January 2020 The importance of vector control for the control and elimination of vector borne diseases PLOS Neglected Tropical Diseases 14 1 e0007831 doi 10 1371 journal pntd 0007831 PMC 6964823 PMID 31945061 Teresa A Meade A History of Modern Latin America 1800 To The Present 1st ed Chichester Wiley Blackwell 2010 pp 148 149 Fosdick RB 1952 The Story of the Rockefeller Foundation New York Harper amp Brothers pp 58 79 Birn AE Solorzano A November 1999 Public health policy paradoxes science and politics in the Rockefeller Foundation s hookworm campaign in Mexico in the 1920s Social Science amp Medicine 49 9 1197 1213 doi 10 1016 s0277 9536 99 00160 4 PMID 10501641 Bigon L 2014 Transnational Networks of Administrating Disease and Urban Planning in West Africa The Inter Colonial Conference on Yellow Fever Dakar 1928 GeoJournal 79 1 103 111 doi 10 1007 s10708 013 9476 z S2CID 153603689 The Nobel Prize in Physiology or Medicine 1951 Nobel Foundation Retrieved 2017 11 30 National Institutes of Health July 27 2016 NIH launches early stage yellow fever vaccine trial Press release United States Department of Health and Human Services Retrieved July 14 2019 National Institute of Allergy and Infectious Diseases NIAID June 1 2018 A Phase I Trial to Evaluate the Safety Reactogenicity and Immunogenicity of MVA BN Yellow Fever Vaccine With and Without Montanide ISA 720 Adjuvant in 18 45 Year Old Healthy Volunteers NCT number NCT02743455 United States National Library of Medicine retrieved July 14 2019 Yellow fever www who int Retrieved 2022 04 25 Deressa W Kayembe P Neel AH Mafuta E Seme A Alonge O December 2020 Lessons learned from the polio eradication initiative in the Democratic Republic of Congo and Ethiopia analysis of implementation barriers and strategies BMC Public Health 20 Suppl 4 1807 doi 10 1186 s12889 020 09879 9 PMC 7747367 PMID 33339529 a b Sbrana E Xiao SY Guzman H Ye M Travassos da Rosa AP Tesh RB September 2004 Efficacy of post exposure treatment of yellow fever with ribavirin in a hamster model of the disease The American Journal of Tropical Medicine and Hygiene 71 3 306 312 doi 10 4269 ajtmh 2004 71 306 PMID 15381811 Huggins JW 1989 Prospects for treatment of viral hemorrhagic fevers with ribavirin a broad spectrum antiviral drug Reviews of Infectious Diseases 11 Suppl 4 S750 S761 doi 10 1093 clinids 11 Supplement 4 S750 PMID 2546248 van den Hurk AF Hall Mendelin S Pyke AT Frentiu FD McElroy K Day A et al 2012 Impact of Wolbachia on infection with chikungunya and yellow fever viruses in the mosquito vector Aedes aegypti PLOS Neglected Tropical Diseases 6 11 e1892 doi 10 1371 journal pntd 0001892 PMC 3486898 PMID 23133693 Endicott SL Hageman E 1998 The United States and Biological Warfare Secrets from the Early Cold War and Korea Indiana University Press ISBN 978 0 253 33472 5 Further reading EditCrosby M 2006 The American Plague The Untold Story of Yellow Fever the Epidemic that Shaped Our History New York The Berkley Publishing Group ISBN 978 0 425 21202 8 Espinosa M 2009 Epidemic Invasions Yellow Fever and the Limits of Cuban Independence 1878 1930 Chicago University of Chicago Press ISBN 978 0 226 21811 3 Gessner I 2016 Yellow Fever Years An Epidemiology of Nineteenth Century American Literature and Culture Frankfurt Main Peter Lang ISBN 978 3 631 67412 3 Harcourt Smith S 1974 Yellow Jack Caribbean Fever History Today 23 9 618 624 Murphy J 2003 An American Plague The True and Terrifying Story of the Yellow Fever Epidemic of 1793 New York Clarion Books ISBN 978 0 395 77608 7 Nuwer DS 2009 Plague Among the Magnolias The 1878 Yellow Fever Epidemic in Mississippi University of Alabama Press ISBN 978 0 8173 1653 2 stop spammingExternal links Edit Wikimedia Commons has media related to Yellow fever Wikivoyage has a travel guide for Yellow fever Look up yellow fever in Wiktionary the free dictionary Wikipedia s health care articles can be viewed offline with the Medical Wikipedia app Yellow fever at Curlie Finlay CJ January 2012 The Mosquito Hypothetically Considered as the Transmitting Agent of Yellow Fever MEDICC Review 14 1 56 59 doi 10 37757 MR2012V14 N1 10 PMID 34503309 U S Army Yellow Fever Commission Claude Moore Health Sciences Library University of Virginia Yellow fever virus NCBI Taxonomy Browser 11089 Portals Medicine Viruses Retrieved from https en wikipedia org w index php title Yellow fever amp oldid 1170822779, wikipedia, wiki, book, books, library,

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