Yellow fever

Yellow fever

Yellow fever

Yellow fever is a non-contagious infectious disease caused by an arbovirus (arthropod-borne virus) belonging to the Flaviviridae family. The disease is endemic only in the tropical forests of the African continent and Latin America, with the possibility of determining urban cycles.

The vectors of the sylvatic form in Brazil are Haemagogus or Sabethes mosquitoes that live and feed on the treetops. Urban YF is associated with the participation of the vector Aedes aegypti, present in several Brazilian cities.

Yellow fever

Reservoir and Source:

In urban areas: humans and mosquitoes (Aedes aegypti);

In areas of rainforest: monkeys and mosquitoes; and in savannah areas: humans, monkeys and mosquitoes


Yellow fever virus is transmitted to humans through the bite of an infected mosquito, mainly the Aedes and Haemogogus species

There are three transmission patterns of YF:

1. Sylvatic/jungle – where the animal reservoir (non-human primates in forests or jungle) infect tree-dwelling species of mosquitoes (e.g. Haemogogus spp. in the Americas and Aedes spp. in Africa), which in turn bite and cause YF infection in humans who have close contact with the forest habitat;

2. Intermediate – where Aedes spp. mosquitoes moving between forest and human settlements are implicated, with humans serving as hosts in the transmission cycle. This cycle is unique to Africa and is observed in small towns or rural villages, sometimes called the emergence zone; or

3. Urban – where Aedes aegypti acts as a primary vector, facilitating rapid human-to-human transmission without reliance on a wildlife reservoir.

An e enzootic area a for yellow fever is understood as a geographical location with confirmed circulation of the virus that causes the jungle cycle of the disease and ecological conditions for maintaining transmission (the presence of competent vectors and susceptible vertebrates capable of maintaining the chain of transmission). When an area does not exhibit these conditions, it is considered none enzootic area.


The urban cycle is characterized by circulation of the virus among susceptible humans. The virus is transmitted through the bite of the Aedes aegypti mosquito, a domestic vector. The urban cycle begins when someone who has contracted the infection in the jungle moves to an urban center with high Ae. aegypti density during the phase in which the virus is circulating in his or her blood (viremia), and once there, is bitten by this vector, which in turn transmits the virus to another susceptible individual, thus establishing the chain of transmission of yellow fever in the urban environment.

In Africa, urban transmission occurs with large outbreaks and high mortality, particularly among children. In the Americas, transmission is mostly confined to those who live or work in tropical rainforests (sylvatic YF). Local occurrence of diseases caused by other Aedes-borne viruses (e.g., dengue, Zika, Japanese encephalitis, Chikungunya) indicate the potential for YF, due to their transmission by the same mosquito vector.

Clinical manifestation

The clinical manifestations of infection with the yellow fever virus vary considerably, ranging from asymptomatic forms to mild cases with nonspecific symptoms, to classic hemorrhagic fever, associated with high case-fatality.

The incubation period is from three to six days after a bite from an infected mosquito. The classic form of yellow fever is a severe systemic disease with a high case-fatality rate, characterized by fever, prostration, compromised liver, kidney, and cardiac function, hemorrhagic manifestations, and shock. The progression of the disease can include three clinically distinct stages: infection, remission, and intoxication.

The infection stage, which corresponds to the onset of symptoms and includes the viremia phase, begins abruptly with high fever (>39 °C), chills, headache, nausea, dizziness, malaise, and muscle pain, especially in the lower back. On physical examination, the patient is febrile, prostrate, with red conjunctiva and flushing. Bradycardia accompanied by fever (Faget’s sign) is sometimes observed. The main alterations revealed by the respective laboratory tests during this stage are leukopenia with relative neutropenia, elevated transaminase levels, and albuminuria.

The infection stage lasts roughly three to six days and is immediately followed by the remission stage. This can last anywhere from two to forty-eight hours, during which time the symptoms abate and the patient’s general condition improves. In mild forms of the disease, the patient enters the recovery phase, which takes two to four weeks. Yellow fever cases are generally very difficult to diagnose when the disease has not progressed to the intoxication stage.

In some 15% to 25% of cases, the symptoms recur in a more serious form and the intoxication stage begins, marked by jaundice, epigastric pain, hemorrhagic manifestations—mainly epistaxis, gingival hemorrhage, hematemesis (black vomit), melena, and oliguresis—followed by anuria, which is indicative of renal failure. Transaminase levels become very elevated. The fatality rate in cases that progress to the intoxication stage is about 50%. In the terminal phase, the patient exhibits hypotension, psychomotor agitation, stupor, and coma. Death generally occurs seven to ten days after the onset of symptoms.

Differential diagnosis

The clinical symptoms of yellow fever can also be seen in other febrile diseases that progress with jaundice, hemorrhagic manifestations, or both. In the Region of the Americas, the principal diseases that should be considered in the differential diagnosis of yellow fever are:

• Leptospirosis;

• Severe malaria;

• Viral hepatitis, especially the fulminating form of hepatitis B and D;

• Dengue hemorrhagic fever;

• Bolivian, Argentine, and Venezuelan hemorrhagic fevers.

Laboratory Diagnosis

Laboratory diagnosis is made by isolation of virus from blood (early in the illness) or molecular detection of yellow fever virus by polymerase chain reaction (PCR).  Yellow fever virus RNA has been detected in the blood as well as the urine and semen of infected humans.

Serologic diagnosis is made by a fourfold or greater rise in neutralizing antibody titre between acute and convalescent serum or by demonstrating specific IgM in early sera, in the absence of yellow fever vaccination in the previous two months.

Management of Cases: Management is supportive.  

Treatment: There is no specific treatment.

Yellow fever vaccine

Prevention is based on the use of attenuated live virus vaccine from strain 17D, developed in 1937 by Max Theiler, a virologist who received the Nobel Prize in Medicine in 1951. The vaccine is considered safe and highly effective (immunogenicity between 90% and 98% after day 10). Since 2013, the WHO has reviewed the need to repeat additional doses every 10 years.

Currently, only a single dose is indicated throughout life. In immunocompromised populations such as people living with HIV/ AIDS, women vaccinated while pregnant and children under 5 years of age, there may be changes in the recommendations in the near future. However, the main contraindication is related to the use of immunosuppressive drugs at the time of vaccination or weeks before receiving the vaccine



1.  Public Health Agency of Canada.  Case Definitions for Communicable Diseases under National Surveillance.  Canada Communicable Disease Report CCDR 2009; 35S2: 1-123.

2.  Heymann David L.  Yellow Fever.  In: Control of Communicable Diseases Manual 20th ed, American Public Health Association, Washington, 2014; 683-689.

3.  Thoma SJ, Endy TP, Rothman AL and Barrett AD.  Flaviviruses (Dengue, Yellow Fever, Japanese Encephalitis, West Nile Encephalitis, St. Louis Encephalitis, TickBorne Encephalitis, Kyasanur Forest Disease, Alkurma Hemorrhagic Fever, Zika) In:  Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases 8th ed. Elsevier, Philadelphia, 2015.

4.  Hamer DH, Angela K, Caumes E et al.  Fatal Yellow Fever in Travelers to Brazil, 2018.  MMWR 2018; 67(11): 340-341.

5. World Health Organization.  Emergencies preparedness, response.  Yellow fever— Nigeria.  Disease outbreak news 9 January 2019  

6. World Health Organization.  Emergencies preparedness, response.  Yellow fever— Brazil.  Disease outbreak news 18 April 2019

7. World Health Organization.  Yellow Fever Key Facts.  Available at:   


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