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Concern over safety of yellow fever vaccine


Seven severe cases of illness - including 6 deaths - after yellow-fever vaccination are described in two articles and one research letter in this week's issue of THE LANCET. Although these reports call into question the safety of yellow-fever vaccination, the overall conclusion to be drawn is that vaccination programmes should be continued, with the need for new research to explain how some individuals can become sensitised to yellow-fever vaccine.

Yellow fever is an acute disease caused by a virus transmitted by mosquitoes, and is characterised by high fever, jaundice, kidney failure, and low blood pressure. The virus is common in tropical and subtropical Africa and South America, and vaccination programmes have increased over the past 20 years as the disease has spread to urban areas in these settings. Yellow-fever vaccine is regarded as one of the safest virus vaccines, with few side-effects or adverse events.

Pedro Vasconcelos and colleagues from WHO Collaborating Centre for Arbovirus Reference and Research, Brazil, report the occurrence of two fatal cases of haemorrhagic fever associated with yellow fever 17DD substrain vaccine in Brazil. The first case, a 5-year-old white girl, was characterised by sudden onset of fever accompanied by headache, malaise, and vomiting 3 days after receiving yellow fever and measles-mumps-rubella vaccines; she later died after a 5-day illness. The second patient - a 22-year-old Afro-Caribbean woman - developed a sore throat and fever, accompanied by headache, myalgia (muscle pain), nausea, and vomiting 4 days after yellow-fever vaccination. She then developed symptoms including jaundice and renal failure, and died after 6 days of illness. Tissue damage in both patients were typical of wild-type yellow fever. The investigators conclude that although these serious complications of yellow-fever vaccination are extremely rare, the safety of yellow fever 17DD vaccine needs to be reviewed.

In the second report, Michael Martin and colleagues from the Centres for Disease Control, Atlanta, USA, describe the illness and death (in three cases) of four elderly patients shortly after they had been vaccinated against yellow fever. The clinical presentations were characterised by fever, myalgia, headache, and confusion, followed by severe multisystemic illnesses. The investigators suggest that there may be a possible causal relation between the illnesses and yellow-fever vaccination. However, they caution that because yellow fever remains an important cause of illness and death in South America and Africa, vaccination should be maintained until the frequency of adverse events to vaccination is quantified.

Raymond Chan and colleagues from the South Western Area Pathology Service, Sydney, Australia, describe in a research letter a man vaccinated with the 17D204 strain of yellow fever virus, who later died of the disease. Genetic sequencing showed that the virus isolated from the patient was identical to the vaccine strain of the same batch, but differed from wild-type virus. Both viruses contained a mutation, although the association of this mutation with virulence is unknown. The investigators comment that severe, rapidly progressive and ultimately fatal disease can follow use of the 17D204 vaccine strain, and that there is need for renewed discussion as to the safety of the vaccine and the indications for its use.

In an accompanying Commentary (p 84), Philippe Marianneau and colleagues from Institut Pasteur, Lyons, France, conclude: "...the use of 17D vaccination remains highly advisable for people living in or travelling to endemic and epidemic zones. However, these three reports raise relevant questions about the mechanisms of attenuation of yellow-fever virus that should be urgently investigated."


* The first issue of a new monthly review journal, The Lancet Infectious Diseases, to be published on August 1, will contain a comprehensive review of yellow fever by Dr Thomas Monath, a co-author of the paper describing the Brazilian cases. Monath emphasises that, in the absence of preventive vaccination, yellow fever is a terrifying and untreatable disease that still causes 1000-fold more illness and death than the feared Ebola virus.

Contact: Dr Pedro Vasconcelos, WHO Collaborating Centre for Arbovirus Reference & Research, Instituto Evandro Chagas Belem, PA Brzil;; E)

Barbara Reynolds, Press Office, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA; T) +1 404 639 7286; F) +1 404 639 7394; E) or Dr MS Cetron, Medical Epidemiologist, Mailstop C-09, DBD/NICID/CDC, 1600 Clifton Road, Atlanta, GA 30333, USA; T) +1 404 639 3052; F) +1 404 639 3970; E)

Dr Raymond Chan, Department of Microbiology and Infectious Diseases, South Western Area Pathology Service, Liverpool BC 1871 Sydney, Australia; T) +61 2 9828 5124; F) +61 2 9828 5129; E)

Dr Vincent Deubel, Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, 69007 Lyon, France; T) +33 4 72 76 82 94;F) +33 4 72 71 04 48; E)

Dr Thomas P Monath, Acambis Inc, 38 Sidney Street, Cambridge, MA 02139, USA; T) +1 617 494 1339; F) +1 617 494 1741; E)

The article is available at

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