[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] In areas where yellow fever is common, early diagnosis of cases and immunization of large parts of the population are important to prevent outbreaks.

[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.

[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.

Jaundice, fatigue, heart rhythm problems, seizures and internal bleeding may also appear as complications of yellow fever during recovery time.

[35] 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.

[41] 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.

[49] In South America, the sylvatic cycle is currently the only way unvaccinated humans can become infected, which explains the low incidence of yellow fever cases on the continent.

The World Health Organization (WHO) now states that a single dose of vaccine is sufficient to confer lifelong immunity against yellow fever disease.

[98] 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.

[99][100] 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.

Genotype I has been divided into five subclades, A through E.[106] In late 2016, a large outbreak began in Minas Gerais state of Brazil that was characterized as a sylvatic or jungle epizootic.

[107] Real-time phylogenetic investigations at the epicentre of the outbreak revealed that the outbreak was caused by the introduction of a virus lineage from the Amazon region into the southeast region around July 2016,[108] spreading rapidly across several neotropical monkey species, including brown howler monkeys,[109] which serve as a sentinel species for yellow fever.

[120] 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.

[123] An outbreak was recorded by Spanish colonists in 1648 in the Yucatán Peninsula, where the indigenous Mayan people called the illness xekik ("blood vomit").

[127] 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.

[129] 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.

[144] In the early 19th 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.

[145] One episode began in April 1822 when the frigate USS Macedonian left Boston and became part of Commodore James Biddle's West India Squadron.

[152] In 1858, St. Matthew's German Evangelical Lutheran Church in Charleston, South Carolina, had 308 yellow fever deaths, reducing the congregation by half.

[159] 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.

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

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.

[164]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.

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.

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.

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.

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.

[173] During 1920–1923, the Rockefeller Foundation's International Health Board undertook an expensive and successful yellow fever eradication campaign in Mexico.

With few countries establishing regular vaccination programs, measures to fight yellow fever have been neglected, making the future spread of the virus more likely.