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Fractional Dosing of Yellow Fever Vaccine to Extend Supply: A Modeling Study

Joseph T. Wu, Corey M. Peak, Gabriel M. Leung, View ORCID ProfileMarc Lipsitch
doi: https://doi.org/10.1101/053421
Joseph T. Wu
1WHO 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
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  • For correspondence: joewu@hku.hk mlipsitc@hsph.harvard.edu
Corey M. Peak
2Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston MA 02115 USA
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Gabriel M. Leung
1WHO 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
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Marc Lipsitch
2Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston MA 02115 USA
3Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston MA 02115 USA. +1-617-432-4559.
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  • For correspondence: joewu@hku.hk mlipsitc@hsph.harvard.edu
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Abstract

Background The ongoing yellow fever (YF) epidemic in Angola strains the global vaccine supply, prompting WHO to adopt dose sparing for its vaccination campaign in Kinshasa 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 elucidating the conditions under which dose fractionation would reduce transmission.

Methods We estimate the effective reproductive number for YF in Angola using disease natural history and case report data. With simple mathematical models of YF transmission, we calculate the infection attack rate (IAR, the proportion of population infected over the course of an epidemic) under varying levels of transmissibility and five-fold fractional-dose vaccine efficacy for two vaccination scenarios: (i) random vaccination in a hypothetical population that is completely susceptible; (ii) the Kinshasa vaccination campaign in July-August 2016 with different age cutoff for fractional-dose vaccines.

Findings 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 (i.e. a proportion VE of vaccinees receives complete and the remainder receive no protection), n-fold fractionation can dramatically reduce IAR as long as efficacy VE exceeds 1/n. This benefit threshold becomes more stringent if vaccine action is leaky (i.e. the susceptibility of each vaccinee is reduced by a factor that is equal to the vaccine efficacy VE). The age cutoff for fractional-dose vaccines chosen by the WHO for the Kinshasa vaccination campaign (namely, 2 years) provides the largest reduction in IAR if the efficacy of five-fold fractional-dose vaccines exceeds 20%.

Interpretation Dose fractionation is a very effective strategy for reducing infection attack rate that would be robust with a large margin for error in case fractional-dose VE is lower than expected.

Funding NIH-MIDAS, HMRF-Hong Kong

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted July 25, 2016.
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Fractional Dosing of Yellow Fever Vaccine to Extend Supply: A Modeling Study
Joseph T. Wu, Corey M. Peak, Gabriel M. Leung, Marc Lipsitch
bioRxiv 053421; doi: https://doi.org/10.1101/053421
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Fractional Dosing of Yellow Fever Vaccine to Extend Supply: A Modeling Study
Joseph T. Wu, Corey M. Peak, Gabriel M. Leung, Marc Lipsitch
bioRxiv 053421; doi: https://doi.org/10.1101/053421

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