Containing Ebola at the Source with Ring Vaccination

Abstract

Interim results from the Guinea Ebola ring vaccination trial suggest high efficacy of the rVSV-ZEBOV vaccine. These findings open the door to the use of ring vaccination strategies in which the contacts and contacts of contacts of each index case are promptly vaccinated to contain future Ebola virus disease outbreaks. To provide a numerical estimate of the effectiveness of ring vaccination strategies we introduce a spatially explicit agent-based model to simulate Ebola outbreaks in the Pujehun district, Sierra Leone, structurally similar to previous modelling approaches. We find that ring vaccination can successfully contain an outbreak for values of the effective reproduction number up to 1.6. Through an extensive sensitivity analysis of parameters characterising the readiness and capacity of the health care system, we identify interventions that, alongside ring vaccination, could increase the likelihood of containment. In particular, shortening the time from symptoms onset to hospitalisation to 2-3 days on average through improved contact tracing procedures, adding a 2km spatial component to the vaccination ring, and decreasing human mobility by quarantining affected areas might contribute increase our ability to contain outbreaks with effective reproduction number up to 2.6. These results have implications for future control of Ebola and other emerging infectious disease threats.

Fig 1. Ring vaccination with baseline parameters.

A Probability (with 95%CI; exact binomial test) of an uncontained outbreak (more than 300 cases) after introducing one infected case into a fully susceptible population for a range of R_e values. The dashed line represents the theoretical value 1 − 1/R_e under a homogeneous mixing assumption. B Estimated epidemic prevention potential and 95%CI for a range of R_e values. The shaded grey area denotes the most plausible R_e values for the 2014–15 West African epidemic. C Mean number of vaccine doses and 95%CIs for containing an outbreak for a range of R_e values. D As C but for the number of rings defined. Each estimate is based on 1,000 simulated outbreaks.

Fig 2. Sensitivity analysis.

A Estimated epidemic prevention potential (points) and 95%CI (vertical lines) as a function of R_e and by varying the vaccine coverage. Baseline coverage: 65% [4]. The shaded grey area represents the range of most plausible values of R_e for the 2014–15 epidemic in West Africa. B As in A but by varying the eligible population. Symbols: C indicates contacts of index cases; CC indicates contacts of contacts; S indicates geographical rings (ring radius: 2 km). Baseline value: C&CC [4]. C As in A but by varying the parameter regulating human mobility. Spatial transmission is proportional to a power law kernel 1/(1 + d^b) where d is the geographical distance and b regulates the decrease of transmission with distance. Baseline value: b = 2.25, resulting in an average distance of 7.7 km [23]. Other scenarios assume different values of b, corresponding to an average distance ranging from 1.5 to 25 km. In these scenarios, probabilities of outbreaks in the absence of interventions were recomputed for each value of the parameter b. D As in A but by varying the time from symptoms onset to hospitalisation. Baseline value: 4 days [9]. Each estimate is based on 1,000 simulated outbreaks.

Fig 3

A Estimated epidemic prevention potential and 95%CI for a range of R_e values using three ring-defining strategies: contacts and contacts of contacts (C&CC) of index cases; C&CC with a spatial ring of radius 2km around index cases (C&CC+S); C&CC+S (2km) plus “improved health systems”, which includes reducing time to isolation of cases (2–3 days from onset to hospitalisation), increasing ring vaccination coverage to 90% of eligible individuals, and reducing public access to infected areas. The shaded grey area denotes the most plausible R_e values for the 2014–15 epidemic in West Africa. B As A but considering mass vaccination (coverage 25% and 50%) and a spatial ring (S) of 20km around index cases. Each estimate is based on 1,000 simulated outbreaks.