A multi-country retrospective analysis of the impact of reactive OCV campaigns

The potential impact of reactive vaccination campaigns is affected by the timing of vaccination campaigns relative as well as the coverage achieved. As the epidemic progresses, the proportion of people in the initial at-risk population who remain susceptible, and so who will benefit from vaccination, will decrease, as well as spatial expansion with potential spread to new areas and/or at-risk subpopulations. As a result, long delays may necessitate changes in the planned campaign (e.g. in the targeted population) to remain impactful with respect to controlling the outbreak.

The project will retrospectively analyze existing data of multi-country cholera incidence data and OCV reactive campaigns at subnational level in the following countries: Democratic Republic of the Congo, Ethiopia, Niger, Nigeria, Malawi, Mozambique, Somalia, and Zambia. The overall aim of the study is to generate evidence for efficient planning and implementation of reactive OCV campaigns by quantifying their short- and long-term impact on cholera transmission and persistence.

Objective 1A. Characterize timeline of historic reactive OCV campaigns relative to epidemic dynamics and campaign coverage.

Objective 1B. Impact of reactive OCV campaigns on population-level cholera transmission. We will implement statistical models to compare cholera incidence and transmission rates before and after reactive OCV campaigns. We will quantify the transmission rate by estimating the time-varying reproduction number (Rt), which represents the average number of secondary cases caused by an infected individual at a given time t.

Objective 1C. Use mechanistic modelling to generate counterfactual scenarios for alternative campaign timing and coverage. We will develop a population-level compartmental mathematical model of cholera transmission. We will calibrate the model using surveillance data from each country, estimating model parameters using Markov Chain Monte Carlo (MCMC) methods

Objective 2: Quantify the mid-to-long-term population-level impact of reactive OCV campaigns on cholera incidence and persistence. We will compare subnational cholera incidence and persistence before and after OCV campaigns. Pre-campaign baseline values for each metric will be calculated from one or multiple (where available) years of data before the OCV campaign at the subnational area where the campaign was targeted. Post-campaign values will be disaggregated by the time since the end of the last campaign and/or the most recent cholera outbreak. Statistical models will be used to assess the immediate impact of OCV campaigns on these metrics (during the first year post-campaign), and to assess how and where these metrics evolve in the mid-to-long-term since vaccination and/or cholera outbreak. 

Objective 3: Evaluate methods for estimating individual-level protection of OCV vaccination against infection and severe outcomes using routinely-collected surveillance data. We will compare existing methods (mathematical modelling and a test-negative study design) to estimate the individual-level protection of OCV vaccination against clinical cholera using surveillance data.

The study will use historic data on suspected and/or lab-confirmed cholera cases that are routinely reported via national surveillance programs and geographically aggregated. In addition, data on reactive OCV campaigns since 2013 is available from WHO and the GTFCC. We will compile a database of subnational reactive OCV campaigns based on the information available in these campaign reports, as well as additional sources provided by countries and partners. The database will include a number of key dates (receipt of request, decision, shipping, delivery, start and duration of campaign), plus the number of doses requested, decision status, and, for approved requests, the number of doses shipped, the campaign target location, and administrative coverage.

A multi-country retrospective analysis of reactive OCV campaigns will provide critical evidence for informing guidelines for OCV campaign planning, allocation and implementation, such as those set out by GTFCC and ICG and advise collaborating countries National Cholera Control Plans. Our study will also contribute evidence to two of the key research questions highlighted in the GTFCCs research agenda: the impact of targeted OCV strategies on transmission, morbidity and mortality; and the impact of timing of OCV use on outbreak control.