title: Fractional dosing of yellow fever vaccine to extend supply: a modelling study.
abstract: The ongoing yellow fever epidemic in Angola strains the global vaccine supply, prompting WHO to adopt dose sparing for its vaccination campaign in Kinshasa, Democratic Republic of the Congo, in July-August, 2016. Although a 5-fold fractional-dose vaccine is similar to standard-dose vaccine in safety and immunogenicity, efficacy is untested. There is an urgent need to ensure the robustness of fractional-dose vaccination by elucidation of the conditions under which dose fractionation would reduce transmission.
  
  
  
  We estimate the effective reproductive number for yellow fever in Angola using disease natural history and case report data. With simple mathematical models of yellow fever transmission, we calculate the infection attack rate (the proportion of population infected over the course of an epidemic) with various levels of transmissibility and 5-fold fractional-dose vaccine efficacy for two vaccination scenarios, ie, random vaccination in a hypothetical population that is completely susceptible, and the Kinshasa vaccination campaign in July-August, 2016, with different age cutoff for fractional-dose vaccines.
  
  
  
  We estimate the effective reproductive number early in the Angola outbreak was between 5·2 and 7·1. If vaccine action is all-or-nothing (ie, a proportion of vaccine recipients receive complete protection [VE] and the remainder receive no protection), n-fold fractionation can greatly reduce infection attack rate as long as VE exceeds 1/n. This benefit threshold becomes more stringent if vaccine action is leaky (ie, the susceptibility of each vaccine recipient is reduced by a factor that is equal to the vaccine efficacy). The age cutoff for fractional-dose vaccines chosen by WHO for the Kinshasa vaccination campaign (2 years) provides the largest reduction in infection attack rate if the efficacy of 5-fold fractional-dose vaccines exceeds 20%.
  
  
  
  Dose fractionation is an effective strategy for reduction of the infection attack rate that would be robust with a large margin for error in case fractional-dose VE is lower than expected.
  
  
  
  NIH-MIDAS, HMRF-Hong Kong.
authors.affiliation: WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. Electronic address: joewu@hku.hk.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Wu
authors.affiliation: Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, MA, USA.
authors.forename: Corey M
authors.initials: CM
authors.lastname: Peak
authors.affiliation: WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Leung
authors.affiliation: Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, MA, USA; Department of Immunology and Infectious Diseases, Harvard T H Chan School of Public Health, Boston, MA, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Lipsitch
mesh_terms: D000810:Angola / Q000453:epidemiology; D015023:Democratic Republic of the Congo / Q000453:epidemiology; D004196:Disease Outbreaks / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008962:Models, Theoretical; D014611:Vaccination / Q000379:methods; D015004:Yellow Fever / Q000188:drug therapy* / Q000453:epidemiology / Q000635:transmission; D022341:Yellow Fever Vaccine / Q000008:administration & dosage* / Q000600:supply & distribution*
chemical_list: D022341:Yellow Fever Vaccine