Impact of proactive and reactive vaccination strategies for health-care workers against MERS-CoV: a mathematical modelling study.

Background: Several vaccine candidates are in development against MERS-CoV, which remains a major public health concern. In anticipation of available MERS-CoV vaccines, we examine strategies for their optimal deployment among health-care workers.

Methods: Using data from the 2013-14 Saudi Arabia epidemic, we use a counterfactual analysis on inferred transmission trees (who-infected-whom analysis) to assess the potential impact of vaccination campaigns targeting health-care workers, as quantified by the proportion of cases or deaths averted. We investigate the conditions under which proactive campaigns (ie vaccinating in anticipation of the next outbreak) would outperform reactive campaigns (ie vaccinating in response to an unfolding outbreak), considering vaccine efficacy, duration of vaccine protection, effectiveness of animal reservoir control measures, wait (time between vaccination and next outbreak, for proactive campaigns), reaction time (for reactive campaigns), and spatial level (hospital, regional, or national, for reactive campaigns). We also examine the relative efficiency (cases averted per thousand doses) of different strategies.

Findings: The spatial scale of reactive campaigns is crucial. Proactive campaigns outperform campaigns that vaccinate health-care workers in response to outbreaks at their hospital, unless vaccine efficacy has waned significantly. However, reactive campaigns at the regional or national levels consistently outperform proactive campaigns, regardless of vaccine efficacy. When considering the number of cases averted per vaccine dose administered, the rank order is reversed: hospital-level reactive campaigns are most efficient, followed by regional-level reactive campaigns, with national-level and proactive campaigns being least efficient. If the number of cases required to trigger reactive vaccination increases, the performance of hospital-level campaigns is greatly reduced; the impact of regional-level campaigns is variable, but that of national-level campaigns is preserved unless triggers have high thresholds.

Interpretation: Substantial reduction of MERS-CoV morbidity and mortality is possible when vaccinating only health-care workers, underlining the need for countries at risk of outbreaks to stockpile vaccines when available.

Funding: UK Medical Research Council, UK National Institute for Health Research, UK Research and Innovation, UK Academy of Medical Sciences, The Novo Nordisk Foundation, The Schmidt Foundation, and Investissement d'Avenir France.