The ring vaccination trial: a novel cluster randomised controlled trial design to evaluate vaccine efficacy and effectiveness during outbreaks, with special reference to Ebola.

A World Health Organization expert meeting on Ebola vaccines proposed urgent safety and efficacy studies in response to the outbreak in West Africa. One approach to communicable disease control is ring vaccination of individuals at high risk of infection due to their social or geographical connection to a known case. This paper describes the protocol for a novel cluster randomised controlled trial design which uses ring vaccination.In the Ebola ça suffit ring vaccination trial, rings are randomised 1:1 to (a) immediate vaccination of eligible adults with single dose vaccination or (b) vaccination delayed by 21 days. Vaccine efficacy against disease is assessed in participants over equivalent periods from the day of randomisation. Secondary objectives include vaccine effectiveness at the level of the ring, and incidence of serious adverse events. Ring vaccination trials are adaptive, can be run until disease elimination, allow interim analysis, and can go dormant during inter-epidemic periods

Spatiotemporal dynamics of the Ebola epidemic in Guinea and implications for vaccination and disease elimination: a computational modeling analysis

BACKGROUND: Among the three countries most affected by the Ebola virus disease outbreak in 2014–2015, Guinea presents an unusual spatiotemporal epidemic pattern, with several waves and a long tail in the decay of the epidemic incidence. METHODS: Here, we develop a stochastic agent-based model at the level of a single household that integrates detailed data on Guinean demography, hospitals, Ebola treatment units, contact tracing, and safe burial interventions. The microsimulation-based model is used to assess the effect of each control strategy and the probability of elimination of the epidemic according to different intervention scenarios, including ring vaccination with the recombinant vesicular stomatitis virus-vectored vaccine. RESULTS: The numerical results indicate that the dynamics of the Ebola epidemic in Guinea can be quantitatively explained by the timeline of the implemented interventions. In particular, the early availability of Ebola treatment units and the associated isolation of cases and safe burials helped to limit the number of Ebola cases experienced by Guinea. We provide quantitative evidence of a strong negative correlation between the time series of cases and the number of traced contacts. This result is confirmed by the computational model that suggests that contact tracing effort is a key determinant in the control and elimination of the disease. In data-driven microsimulations, we find that tracing at least 5–10 contacts per case is crucial in preventing epidemic resurgence during the epidemic elimination phase. The computational model is used to provide an analysis of the ring vaccination trial highlighting its potential effect on disease elimination. CONCLUSIONS: We identify contact tracing as one of the key determinants of the epidemic’s behavior in Guinea, and we show that the early availability of Ebola treatment unit beds helped to limit the number of Ebola cases in Guinea. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-016-0678-3) contains supplementary material, which is available to authorized users