Potential for Controlling Cholera Using a Ring Vaccination Strategy

Re-analysis of Data from a Cluster-Randomized Clinical Trial

Citation: Ali M, Debes AK, Luquero FJ, Kim DR, Park JY, Digilio L, et al. (2016) Potential for Controlling Cholera Using a Ring Vaccination Strategy: Re-analysis of Data from a Cluster-Randomized Clinical Trial. PLoS Med 13(9): e1002120. doi:10.1371/journal.pmed.1002120
Published: September 13, 2016

Abstract
Introduction: Vaccinating a buffer of individuals around a case (ring vaccination) has the potential to target those who are at highest risk of infection, reducing the number of doses needed to control a disease. We explored the potential vaccine effectiveness (VE) of oral cholera vaccines (OCVs) for such a strategy.
Methods and Findings: This analysis uses existing data from a cluster-randomized clinical trial in which OCV or placebo was given to 71,900 participants in Kolkata, India, from 27 July to 10 September 2006. Cholera surveillance was then conducted on 144,106 individuals living in the study area, including trial participants, for 5 y following vaccination. First, we explored the risk of cholera among contacts of cholera patients, and, second, we measured VE among individuals living within 25 m of cholera cases between 8 and 28 d after onset of the index case. For the first analysis, individuals living around each index case identified during the 5-y period were assembled using a ring to define cohorts of individuals exposed to cholera index cases. An index control without cholera was randomly selected for each index case from the same population, matched by age group, and individuals living around each index control were assembled using a ring to define cohorts not exposed to cholera cases. Cholera attack rates among the exposed and non-exposed cohorts were compared using different distances from the index case/control to define the rings and different time frames to define the period at risk. For the VE analysis, the exposed cohorts were further stratified according to the level of vaccine coverage into high and low coverage strata. Overall VE was assessed by comparing the attack rates between high and low vaccine coverage strata irrespective of individuals’ vaccination status, and indirect VE was assessed by comparing the attack rates among unvaccinated members between high and low vaccine coverage strata.
Cholera risk among the cohort exposed to cholera cases was 5–11 times higher than that among the cohort not exposed to cholera cases. The risk gradually diminished with an increase in distance and time. The overall and indirect VE measured between 8 and 28 d after exposure to a cholera index case during the first 2 y was 91% (95% CI 62%–98%) and 93% (95% CI 44%–99%), respectively. VE persisted for 5 y after vaccination and was similar whether the index case was a young child (<5 y) or was older. Of note, this study was a reanalysis of a cholera vaccine trial that used two doses; thus, a limitation of the study relates to the assumption that a single dose, if administered quickly, will induce a similar level of total and indirect protection over the short term as did two doses.
Conclusions: These findings suggest that high-level protection can be achieved if individuals living close to cholera cases are living in a high coverage ring. Since this was an observational study including participants who had received two doses of vaccine (or placebo) in the clinical trial, further studies are needed to determine whether a ring vaccination strategy, in which vaccine is given quickly to those living close to a case, is feasible and effective.
Trial registration: ClinicalTrials.gov NCT00289224

Author Summary

Why Was This Study Done?

• Cholera remains a major health problem in many Asian and African countries and Haiti, and the current oral cholera vaccines approved by the World Health Organization are in limited supply.

• People are at higher risk of contracting cholera when they live near a cholera case, suggesting that a potential strategy to reduce infection rates would be to quickly vaccinate a buffer (ring) population around identified cases.

• There is a need to understand the magnitude of the increased risk for people living near a cholera case and how one might target oral cholera vaccines to those at highest risk to maximize the benefit from vaccination.

What Did the Researchers Do and Find?

• To explore the potential vaccine effectiveness of oral cholera vaccines in a ring vaccination strategy, we analyzed existing data from a previously conducted cluster-randomized clinical trial in which oral cholera vaccine or placebo was given to 71,900 individuals in Kolkata, India, from July through September 2006.

• Out of 144,106 individuals living in the study area, including trial participants, 672 cases of cholera (index cases) were detected between 1 October 2006 and 25 September 2011 and were matched with 672 randomly selected age-matched controls who did not have cholera.

• Individuals living within a certain distance of each index case and index control were used to define clusters of individuals exposed and not exposed to a cholera case. The overall and indirect protective effectiveness of the vaccine were estimated by comparing rates of cholera when a high proportion versus a low proportion of the people in these clusters around index cases had received vaccine.

• Cholera risk was significantly increased for people living within 25 to 50 m of the cases compared to people living within 25 to 50 m of controls without cholera; this risk persisted for a month but decreased over space and time during the month.

• When we compared clusters with high vaccine coverage with those with low coverage, the vaccine had an overall and indirect effectiveness greater than 90% for two years; the effectiveness persisted for five years but waned somewhat after the first two years.

What Do These Findings Mean?

• Cholera risk is increased for neighbors of cholera patients, but this risk is significantly decreased when a high proportion of neighbors have received vaccine.

• If vaccine supply is limited, a strategy of immunizing neighbors around a case (“ring vaccination”) may be beneficial for controlling cholera if such vaccination can be carried out rapidly.

• Future studies are needed to evaluate the feasibility and effectiveness of a ring vaccination strategy in which vaccine is provided to family and neighbors immediately after cases are detected.

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