Vaccine 23 (2005) 3908–3914 Yellow fever vaccination: How much is enough? Eduardo Massad a,b,∗ , Francisco Antonio Bezerra Coutinho a , Marcelo Nascimento Burattini a , Luis Fernandez Lopez a , Cl´ audio Jos´ e Struchiner c a School of Medicine, The University of S˜ ao Paulo and LIM 01/HCFMUSP, Av. Dr. Arnaldo, 455, S˜ ao Paulo CEP 01246-903, SP, Brazil b London School of Hygiene and Tropical Medicine, London University, UK c Program of Scientific Computation, Funda¸ c˜ ao Oswaldo Cruz-FIOCRUZ, Rio de Janeiro, Brazil Received 10 November 2004; accepted 9 March 2005 Available online 2 April 2005 Abstract In recent years, a growing number of serious adverse events (including deaths) associated with the yellow fever (YF) vaccine has been reported. If YF vaccination were incorporated in routine programs, administered to children, the risk of deaths from this vaccine would be minimized provided that mortality of children vaccinated below 1 year were negligible. However, in affected areas the vaccine is administered to all age groups. This poses a dilemma to public health authorities – what proportion of a population subject to low risk of YF outbreaks should be vaccinated in order to minimize the total number of serious adverse events (including deaths) due both to natural infection and vaccination? In other words, how much vaccination is safe? Our results suggest that, depending on the age-specific rates of developing vaccine-induced serious adverse events and the risk of yellow fever outbreaks, the optimum proportion to vaccinate may be lower than the proportion that would prevent an epidemics or even be zero. We also show that the vaccine should not be applied to individuals older than 60 years of age because the risk of serious adverse events (including deaths) is higher for that age class. Our work is instrumental to the discussion on the optimum strategy to vaccinate affected populations against yellow fever. Therefore, the aim of this work is to estimate the optimum proportion to vaccinate against YF taking into account the risks of serious adverse events associated with both the vaccine and natural infection. © 2005 Elsevier Ltd. All rights reserved. Keywords: Yellow fever; Vaccination; Adverse events 1. Introduction Yellow fever (YF) was one of the most feared lethal dis- eases before the development of an elective vaccine [1]. Even today, according to WHO, some few hundred to a few thousand new cases are reported every year, although up to 200,000 new cases are estimated to occur based on serosurveys from tropical regions of Africa. The main reser- voirs for the yellow fever virus are some species of mon- keys, and transmission occurs through the bites of infected mosquitoes. In the sylvatic cycle of South America the main vectors are mosquitoes from the genera Haemagogus and Sa- ∗ Corresponding author. Tel.: +55 11 30817717; fax: +55 11 30667382. E-mail address: edmassad@usp.br (E. Massad). bethes, whilst the urban cycle and the African sylvatic cycle involve mosquitoes of the genus Aedes, in particular Aedes aegypti. The bridge between the sylvatic and the urban cycles depends on humans that go to the sylvatic areas for leisure or work, eventually returning to the urban areas carrying the YF virus. The disease can be prevented by a live attenuated vaccine prepared from the 17D strain of YF virus, that induces se- roconversion in more than 95% of recipients and provides immunity for 30 years or longer [2]. Scattered YF vaccina- tion occurs in some places of South America and in Africa, but coverage rates are low in both continents. In addition, the vaccine is not efficiently used in YF endemic countries for primary prevention, instead being used as an emergency re- sponse tool to control epidemics after they have been reported 0264-410X/$ – see front matter © 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2005.03.002