==== Front Braz J MicrobiolBraz. J. MicrobiolBrazilian Journal of Microbiology1517-83821678-4405Elsevier S1517-8382(18)30196-510.1016/j.bjm.2018.02.003Letter to the editorIs a dose of 17D vaccine in the current context of Yellow Fever enough? Estofolete Cassia Fernanda Nogueira Mauricio Lacerda mnogueira@famerp.br⁎Fundação Faculdade Regional de Medicina de São José do Rio Preto (FUNFARME), Faculdade de Medicina de São José do Rio Preto (FAMERP), Hospital de Base de São José do Rio Preto, Laboratório de Pesquisas em Virologia, São José do Rio Preto, SP, Brazil⁎ Corresponding author at: Faculdade de Medicina de São José do Rio Preto (FAMERP), Avenida Brigadeiro Faria Lima, 5416, Vila São Pedro, São José do Rio Preto CEP: 15090-000, SP, Brazil. mnogueira@famerp.br13 3 2018 Jul-Sep 2018 13 3 2018 49 3 683 684 © 2018 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda.2018Sociedade Brasileira de MicrobiologiaThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Editor: Marina Baquerizo ==== Body Dear Editor, The availability of the effective 17D vaccine as well as an eradication program of Aedes aegypti dramatically decreased the urban Yellow Fever (YF) incidence in Americas.1, 2 However, in the last decades, the YF transmission was reported outside endemic area (Amazon region), with extension of viral circulation toward to densely populated and highly Aedes-infested regions and low vaccination coverage.3, 4, 5 Since 1990s, Yellow Fever virus (YFV) have been extending its traditional endemic area toward to Southern and Southeastern regions in Brazil.4 From July 2017, to epidemiological week 2, 2018, 470 YF cases were suspected in Brazil, 35 confirmed, and 20 deaths, with 411 epizootic confirmed.6 Besides, the susceptibility and competence of Ae. aegypti and Aedes albopictus to YFV transmission had been demonstrated and they can become active vectors in YF reemergence7 in YFV-free regions. The vector may be found in more than 130 countries with around 4 billion people at risk of introduction and spread of infection,8 highlighting the concern for the future about the YFV outbreaks. Considering this epidemiological scenario, the area to vaccine coverage has been expanding, following the current recommendation of World Health Organization (WHO), which a single dose of 17D vaccine confers life-long protection against YF.9 This decision is polemic for a series of reasons. Firstly, vaccine failures have already been demonstrated.3, 10 Neutralizing antibodies levels may decrease significantly in adults and children eight and four years after primary vaccination, respectively,11, 12 and the immunogenicity in children is lower. Besides, following 17D vaccination, the T cell response is invoked, contributing to protection against wild-type YFV13 and increasing the immune response. Studies have been also showing that even lower doses than standard may produce neutralizing antibodies levels.14, 15 This strategy was already used in early epidemic in the Democratic Republic of Congo, as an option to stretch vaccine supplies,16 which 98% (95% CI, 96–99) of seroconversion. All these factors may suggest a benefit of a booster in endemic or epidemic circumstances. However, it is important to consider that the method to measure antibody levels had low stringency (PRNT 50 rather than PRNT 80), which may result in detection of unspecific antibody. Besides, there is not correlation between protection and antibody titers. In light of this information, the recommendation of a single dose of 17D vaccine might be not reasonable. We are suggesting the immediate vaccination to more than 90% of population (with fractional or full doses, respecting the contraindication), followed by vaccination campaign with full dose in the near future, and new studies about a single dose of 17D vaccine and response to fractional doses in different population and epidemiological context. Until then, due to vaccine failures already described, we believe at least two doses are recommended while as long as sufficient vaccines are available. ==== Refs References 1 Vasconcelos P.F. Single shot of 17D vaccine may not confer life-long protection against yellow fever Mem Inst Oswaldo Cruz 113 2 2018 135 137 29185596 2 Staples J.E. Monath T.P. Yellow fever: 100 years of discovery JAMA 300 8 2008 960 962 18728272 3 Monath T.P. Vasconcelos P.F. Yellow fever J Clin Virol 64 2015 160 173 25453327 4 Romano A.P. Costa Z.G. Ramos D.G. Yellow Fever outbreaks in unvaccinated populations, Brazil, 2008–2009 PLoS Negl Trop Dis 8 3 2014 e2740 24625634 5 Carvalho R.G. Lourenço-de-Oliveira R. Braga I.A. Updating the geographical distribution and frequency of Aedes albopictus in Brazil with remarks regarding its range in the Americas Mem Inst Oswaldo Cruz 109 6 2014 787 796 25317707 6 Brazil Monitoramento do Período Sazonal da Febre Amarela, Brasil – 2017/2018. Informe n. 9 2018 Ministério da Saúde Brasilia 11 7 Couto-Lima D. Madec Y. Bersot M.I. Potential risk of re-emergence of urban transmission of Yellow Fever virus in Brazil facilitated by competent Aedes populations Sci Rep 7 1 2017 4848 28687779 8 Vasconcelos P.F. Monath T.P. Yellow fever remains a potential threat to public health Vector Borne Zoonotic Dis 16 8 2016 566 567 27400066 9 Who Vaccines and vaccination against yellow fever: WHO Position Paper, June 2013 – recommendations Vaccine 33 1 2015 76 77 24852721 10 Belmusto-Worn V.E. Sanchez J.L. McCarthy K. Randomized, double-blind, phase III, pivotal field trial of the comparative immunogenicity, safety, and tolerability of two yellow fever 17D vaccines (Arilvax and YF-VAX) in healthy infants and children in Peru Am J Trop Med Hyg 72 2 2005 189 197 15741556 11 Campi-Azevedo A.C. Costa-Pereira C. Antonelli L.R. Booster dose after 10 years is recommended following 17DD-YF primary vaccination Hum Vaccin Immunother 12 2 2016 491 502 26360663 12 Cgfsoyfv Duration of post-vaccination immunity against yellow fever in adults Vaccine 32 39 2014 4977 4984 25090646 13 Hepburn M.J. Kortepeter M.G. Pittman P.R. Neutralizing antibody response to booster vaccination with the 17d yellow fever vaccine Vaccine 24 15 2006 2843 2849 16494976 14 Monath T. Gershman M. Staphles E. Barret A. Yellow fever vaccine Plotkin S. Orenstein W. Offit P. Vaccines 6th ed. 2012 Saunders Elsevier 870 896 15 Roukens A.H. Vossen A.C. Bredenbeek P.J. van Dissel J.T. Visser L.G. Intradermally administered yellow fever vaccine at reduced dose induces a protective immune response: a randomized controlled non-inferiority trial PLoS ONE 3 4 2008 e1993 18431480 16 Ahuka-Mundeke S. Casey R.M. Harris J.B. Immunogenicity of fractional-dose vaccine during a yellow fever outbreak – preliminary report N Engl J Med 2018