Yellow fever (YF) is an infection caused by a virus of the family Flaviviridae and it is transmitted by mosquitoes. There are two epidemiological forms of yellow fever:
• Urban YF frequently occurs in Africa as large outbreaks, is transmitted from infected to susceptible humans by Aedes aegypti, a mosquito species that breeds in the proximity of human habitation.
• Jungle YF is primarily an enzootic viral disease of non-human primates, with the mosquito vectors causing occasional cases or small outbreaks of YF among humans living in the forested savanna of Africa and in jungle areas of South America.
Following the bite of an infected mosquito, YF virus replicates and spreads to other areas of the body. Disease onset is typically abrupt and characterized by fever, chills, malaise, headache, back pain, nausea, and dizziness. In about 15% of cases the disease progresses to a more severe form with haemorrhagic manifestations. About 20-50% of patients with liver and kidney failure die, with case-fatality rates highest among children and the elderly. The virus present in the blood during the incubation period and early stages of illness can infect feeding A. aegypti, propagating the disease.
Yellow Fever Vaccines
The attenuated live YF 17D vaccine strain is derived from a wild-type YF virus (the Asibi strain) isolated in Ghana in 1927 and attenuated by serial passages in chicken embryo tissue culture. Two substrains of the 17D vaccine virus are currently used for vaccine production in embryonated chicken eggs, namely 17D-204 and 17DD. Some vaccines are also prepared from a distinct substrain of 17D-204 (17D-213). Sorbitol and gelatin are commonly used as stabilizers, and the vaccine preparation is lyophilized and kept under cold-chain conditions.
The YF vaccine is given as a single subcutaneous or intramuscular injection. Some countries require an International Certificate of Vaccination against yellow fever for incoming visitors. Vaccination for this purpose is done in nationally authorized sites using WHO prequalified YF vaccine.
Yellow Fever Vaccine Standardization
The WHO recommendations for the production and control of YF vaccines were first formulated in 1958 and revised in 1987 and 1995. An amendment was adopted by the Expert Committee for Biological Standardization in 2008 requiring the expression of potency of such vaccines in International Units. The most recent revision adopted by the Expert Committee on Biological Standardization in 2010 updates the manufacturing and quality control information and includes new sections addressing nonclinical and clinical evaluation of YF vaccines.
Recommendations to Assure the Quality, Safety and Efficacy of Live Attenuated Yellow Fever Vaccines. Replacement of Annex 2 of TRS 872, Annex 2 and Amendment to that annex in WHO TRS 964, Annex 5, Technical Report Series 878
A WHO reference material for Yellow Fever vaccine is available to qualified applicants:
WHO Working Group on Technical Specifications for Manufacture and Evaluation of Yellow Fever Vaccines, Geneva, Switzerland, 13-14 May 2009
WHO Informal Consultation of the minimum potency specification for Yellow Fever vaccines, NIBSC, Potters Bar, UK, 19-20 November 2007
IABS Scientific Workshop on Neurovirulence Tests for Live Virus Vaccines, WHO, Geneva, Switzerland, 31 January-1 February, 2005