Yellow fever
The yellow fever virus measures 40 to 50 nanometers in width. It belongs to the genus Orthoflavivirus and carries a single-stranded RNA genome of approximately 10,862 nucleotides. This genetic material encodes a polyprotein that host proteases cut into three structural proteins and seven nonstructural proteins. The viral particle enters human cells by attaching to specific receptors on the cell surface. A drop in pH inside an endosomal vesicle triggers the fusion of the viral envelope with the cell membrane. The capsid then releases its genetic code into the cytosol for replication. Inside the rough endoplasmic reticulum, immature virus particles form before maturing in the Golgi apparatus. These mature virions exit the cell to infect new targets like hepatocytes in the liver. The infection process leads to eosinophilic degradation of liver cells and the release of cytokines. Apoptotic masses known as Councilman bodies appear within the cytoplasm of these infected liver cells. When a cytokine storm follows, shock and multiple organ failure can occur.
A female mosquito named Aedes aegypti serves as the primary vector for spreading this disease across tropical regions. Only females bite humans to transmit the virus after ingesting blood from an infected person or primate. The virus reaches the mosquito's stomach and replicates within epithelial cells there. From the gut, it travels to the haemocoel and finally to the salivary glands. When the insect bites again, it injects saliva containing the virus directly into the bloodstream. Three distinct epidemiological cycles exist where transmission occurs between mosquitoes and hosts. The urban cycle involves only Aedes aegypti and is responsible for major outbreaks in Africa. This specific cycle no longer exists in South America except for one outbreak in Bolivia during 1999. A sylvatic cycle operates in forests where Haemagogus and Sabethes mosquitoes infect nonhuman primates. In South America, unvaccinated humans contract the disease through this jungle cycle before carrying it to cities. An intermediate savannah cycle occurs in Africa involving different Aedes species and has become the most common form of transmission recently. Transovarial transmission allows the virus to pass from a female mosquito to her eggs without a previous blood meal.
Symptoms typically appear three to six days after infection begins. Most cases result in mild fever, chills, loss of appetite, nausea, and muscle pain particularly in the back. These initial symptoms usually improve within five days. About 15% of infected individuals experience a second toxic phase shortly after recovering from the first stage. This severe phase brings recurring fever, abdominal pain, and liver damage causing yellow skin. Bleeding occurs in the mouth, nose, eyes, and gastrointestinal tract leading to vomit containing blood. One Spanish name for the disease translates to black vomit due to this symptom. Kidney failure, hiccups, and delirium may also develop during this critical period. The fatality rate reaches 20 to 50% among those who develop jaundice while overall mortality sits around 3 to 7.5%. Surviving the infection generally provides lifelong immunity with no permanent organ damage. Severe cases can see mortality rates exceeding 50% when complications arise.
The first definitive outbreak in the New World occurred on Barbados island in 1647. Spanish colonists recorded an epidemic in the Yucatán Peninsula in 1648 where Mayan people called it xekik meaning blood vomit. Brazil suffered its first major epidemic in Recife between 1685 and 1690. Dr. John Mitchell made the earliest recorded mention of yellow fever by that specific name in 1744. Colonial times saw the West Indies become a dangerous posting for soldiers due to endemic presence. British garrisons in Jamaica experienced mortality rates seven times higher than those in Canada largely because of this disease. Napoleon sent General Charles Leclerc to Saint-Domingue in 1802 but lost between 35,000 and 45,000 troops to yellow fever. This loss forced France to abandon plans for North America and sell Louisiana to the United States in 1803. The first outbreak in English-speaking North America hit New York City in 1668. Philadelphia faced thousands of deaths during an 1793 epidemic that caused over 9% of the city's population to perish. James Hutchinson was one physician who helped treat the population during that crisis. The federal government fled piecemeal to Trenton, New Jersey while President George Washington joined them briefly before returning. An 1878 Lower Mississippi Valley epidemic caused an estimated 20,000 fatalities across multiple cities.
Carlos Finlay proposed in 1881 that mosquitoes transmitted yellow fever rather than direct contact between people. U.S. Army doctors led by Walter Reed tested this hypothesis starting around 1900. The team included James Carroll, Aristides Agramonte, and Jesse William Lazear. They successfully proved Finlay's mosquito hypothesis after years of research. Yellow fever became the first virus shown to be transmissible by filtered human serum via mosquitoes. William Gorgas applied these insights to eradicate yellow fever from Havana. He also campaigned against the disease during the construction of the Panama Canal. Previous French efforts to build the canal had failed partly due to high mortality rates among workers. Reed credited Finlay with the discovery in his correspondence despite receiving much public credit himself. The acceptance of Finlay's work marked a turning point for global health initiatives. Applying methods suggested by Finlay allowed the United States government to eliminate yellow fever in Cuba and later Panama. This success enabled the completion of the Panama Canal project. Reed is also noted for using the first type of medical consent form during his experiments in Cuba.
Scientists isolated the yellow fever virus in West Africa in 1927. Two vaccines were subsequently developed during the 1930s following this isolation. Max Theiler completed the creation of the 17D vaccine in 1937. He received the Nobel Prize in Physiology or Medicine for this achievement. Protection begins by the 10th day after administration in 95% of people. The World Health Organization now states that a single dose confers lifelong immunity. Up to one in four people experience fever, aches, local soreness, and redness at the injection site. Rare cases occur where vaccination causes fatal yellow fever vaccine-associated viscerotropic disease affecting less than one in 200,000 recipients. Another possible side effect involves infection of the nervous system occurring in one in 200,000 to 300,000 cases. The Yellow Fever Initiative launched by the WHO in 2006 vaccinated more than 105 million people in 14 countries across West Africa. No outbreaks were reported during 2015 following that massive campaign. Fractional dosing strategies are being considered to maximize limited vaccine supplies during outbreaks.
About 90 percent of an estimated 200,000 annual cases occur on the African continent. In 2016, a large outbreak originated in Angola and spread to neighboring countries before containment efforts succeeded. Eleven imported cases appeared in China involving unvaccinated Chinese nationals from the Angola genotype. This marked the first appearance of the disease in Asia in recorded history. Phylogenetic analysis identified seven genotypes of yellow fever viruses adapted differently to humans and vectors. Five genotypes exist only in Africa while two appear in South America. A large outbreak began in Minas Gerais state of Brazil in late 2016 characterized as a sylvatic epizootic. Real-time phylogenetic investigations revealed the virus lineage came from the Amazon region around July 2016. More than 3,000 suspected cases resulted in 758 confirmed infections and 264 deaths by May 2017. The Health Ministry launched a vaccination campaign concerned about spread during Carnival season. Since the 1980s, the number of cases has been increasing due to fewer immune people and changing climate patterns. Vector control programs were abandoned allowing Aedes aegypti to return to urban centers in South America.
Continue Browsing
Common questions
What is the size and genetic structure of the yellow fever virus?
The yellow fever virus measures 40 to 50 nanometers in width and carries a single-stranded RNA genome of approximately 10,862 nucleotides. This genetic material encodes a polyprotein that host proteases cut into three structural proteins and seven nonstructural proteins.
How does the Aedes aegypti mosquito transmit the yellow fever virus to humans?
A female Aedes aegypti mosquito transmits the virus by biting humans after ingesting blood from an infected person or primate. The virus replicates within the mosquito's stomach epithelial cells before traveling to the salivary glands for injection into human bloodstream during subsequent bites.
When do symptoms typically appear after infection with the yellow fever virus?
Symptoms typically appear three to six days after infection begins. Most cases result in mild fever, chills, loss of appetite, nausea, and muscle pain particularly in the back which usually improve within five days.
Where did the first definitive outbreak of yellow fever occur in the New World?
The first definitive outbreak in the New World occurred on Barbados island in 1647. Spanish colonists recorded an epidemic in the Yucatán Peninsula in 1648 where Mayan people called it xekik meaning blood vomit.
Who developed the 17D vaccine for yellow fever and when was it completed?
Max Theiler completed the creation of the 17D vaccine in 1937. He received the Nobel Prize in Physiology or Medicine for this achievement and protection begins by the 10th day after administration in 95% of people.
How many annual cases of yellow fever occur globally and where are they concentrated?
About 90 percent of an estimated 200,000 annual cases occur on the African continent. In 2016 a large outbreak originated in Angola and spread to neighboring countries before containment efforts succeeded.