Yellow fever (ORPHA:99829)
Yellow fever (YF), caused by YF virus, is a zoonotic disease characterized by fever and constitutional symptoms, with the potential to progress to severe and fatal viral hemorrhagic fever with shock and multi-organ system failure.
Epidemiology
YF is endemic to the tropics of the Americas and Africa, where collectively an estimated 5,000-200,000 clinical cases and 30,000 deaths occur annually, the vast majority in Africa.
Clinical description
Most infections are mild or asymptomatic. After an incubation period of 3-6 days, patients typically present with the abrupt onset of non-specific signs and symptoms including fever, malaise, headache, chest pain, and myalgia/arthralgia, followed rapidly by gastrointestinal (nausea, vomiting, diarrhea) symptoms. Most cases will then resolve. In a minority, after a quiescent period of a few days, more severe manifestations ensue, including jaundice, hepato-renal failure, hemorrhage, shock, and meningoencephalitis. Disease is usually mild in children. Clinical laboratory findings typically include elevated hepatic transaminases and proteinuria.
Etiology
Over 25 different viruses cause viral hemorrhagic fever. YF virus is a member of the virus family Flaviviridae, genus Flavivirus. The virus is maintained in a cycle between monkeys and forest canopy mosquitoes. Sporadic cases occur when humans are bitten by these mosquitoes (sylvatic YF). Larger outbreaks occur when humans bring the virus back to more settled environments, where the urban container-breeding mosquito Aedes aegypti can spread YF virus directly between humans (urban YF). Sanitation and mosquito control measures have virtually eliminated urban yellow fever in the Americas, but urban outbreaks continue to be noted in Africa, where 90% of all YF virus infections occur.
Diagnostic methods
Common diagnostic modalities include cell culture, serologic testing by enzyme linked immunosorbent assay (ELISA) or indirect fluorescent antibody (IFA), and reverse transcription polymerase chain reaction (RT-PCR). Because no commercial assays are presently available, these tests are typically performed only in a few specialized laboratories.
Differential diagnosis
YF is difficult to distinguish from a host of other febrile illnesses, at least early in the course of disease. Other viral hemorrhagic fevers, malaria, typhoid fever, leptospirosis, rickettsial infection (see these terms), viral hepatitis and meningococcemia need to be excluded.
Management and treatment
As there is presently no antiviral drug available for YF, treatment is supportive, following the guidelines for treatment of severe septicemia. Insecticide-treated bed nets and/or room screens should be used in open-air settings to prevent further transmission. The YF-17D live attenuated vaccine is highly efficacious, conferring long-term protection in over 95% of recipients within 10 days. YF-17D is indicated for persons over 9 months of age who are traveling to or living in YF endemic areas. Vaccination is contraindicated in children <4 months old and pregnant women and caution is advised in persons with egg allergy, the immunocompromised, children 4-9 months of age and elderly persons, especially if the risk is minimal, such as trips restricted to attending conferences in modern urban hotels with no rural exposure.
Prognosis
Case fatality rates in symptomatic cases are 20-50%. Shock, tachycardia, bleeding, oliguria, proteinuria and azotemia confer a poor prognosis. Although convalescence may be prolonged, survivors usually have no lasting sequelae.

                            Last update: 
                            December 2012


                            - Expert reviewer(s): 
                            Dr Daniel BAUSCH  -  Andrew BENNETT