Impact of oral cholera vaccine outbreak response immunization in sub-Saharan Africa, 2010–2020: a modeling analysis
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Background
Oral cholera vaccine (OCV) is a critical tool for controlling cholera outbreaks. However, the effectiveness and efficiency of reactive OCV campaigns depend strongly on implementation timing and targeting strategy.
Methods
Using data from 1,192 cholera outbreaks (2010–2020) in sub-Saharan Africa, we conducted stochastic simulations of single-dose OCV outbreak response immunization (ORI) strategies varying by timing, coverage, triggering criteria, and outbreak selection. Outcomes included impact (cases, deaths, and DALYs averted), efficiency (impact per 1,000 OCV doses), and cost-effectiveness (cost per unit of impact).
Findings
Week-1 ORIs with 75% vaccine coverage averted a median of 70% of cases (129 cases, IQR 41–375) whereas week-9 ORIs—comparable to historical response times—averted only ∼8% (16 cases; IQR 0–112). Effectiveness declined exponentially by 23.6% per week (IQR 10.7–77.4), halving every 2.6 weeks. Efficiency fell from 0.69 to 0.09 cases averted per 1,000 doses, and cost-effectiveness worsened from US$4,662 to US$13,043 per case averted. When ORIs were triggered after case accumulation, effectiveness decreased by 6.4% (IQR 2.5–4.2) for every 10 additional cases, halving every ∼104 cases. Prioritizing large or high-attack-rate outbreaks (top 10%) improved efficiency 14–27-fold and reduced cost per DALY averted by 95%–99%. Even with delays, week-9 ORIs deployed across multiple outbreaks, achieved a median 0.44 (IQR: 0.28–0.44) cases averted per 1,000 doses, which increasing further with targeted deployment.
Interpretation
Rapid deployment of OCV, with priority to large and high-attack-rate outbreaks, is essential to maximize the impact, efficiency, and cost-effectiveness of cholera response in Africa. Even delayed reactive vaccination can meaningfully reduce cholera burden.
Key messages
We analyzed 1,192 cholera outbreaks across sub-Saharan Africa (2010–2020) to estimate the impact, efficiency, and cost effectiveness of single-dose oral cholera vaccine (OCV) outbreak response immunization (ORIs).
ORI implemented in week 1 of outbreak averted a median 129 cases (IQR 41–375) averted, corresponding to 70% (IQR 49.8–82.5) reduction; impact declined sharply with delay, halving each median 2.6 (IQR 0.5–6.1) weeks.
Prioritizing large, prolonged, and high-attack-rate outbreaks markedly improved impact, efficiency, and cost-effectiveness, with up to 99% reduction in cost per DALY averted among the top 10% of outbreaks by attack rate.
In simulations reflecting historical OCV stockpile use, even delayed week-9 ORIs averted 0·44 (IQR 0·28–0·44) cases per 1,000 doses, increasing further with targeted deployment.
Rapid and targeted deployment of reactive OCV is essential to maximize the impact of limited global OCV supply and to reduce cholera burden in Africa.
Research in context
Evidence before this study
We searched PubMed on March 15, 2024, without language or date restrictions, using the search terms (("Cholera"[Mesh] OR "Vibrio cholerae"[Mesh])) AND "Cholera Vaccines"[Mesh] AND ((model*[Title/Abstract]) OR (math*[Title/Abstract])) AND (vaccine*[Title/Abstract]). The search yielded 164 articles, of which 17 studies met the inclusion criteria, focusing on mathematical models assessing the impact of oral cholera vaccines (OCVs) under different scenarios. Most studies simulated outbreaks in single geographic settings—such as Bangladesh 1–4 , Chad 5 , Haiti 6–8 , South Sudan, 9 or Zimbabwe 10 — or not anchored in a specific setting. 11 A few analyses considered outbreaks across multiple countries. 12–16 These studies varied widely in campaign design (reactive mass campaigns, proactive campaigns, “hotspot” or area-targeted campaigns), outbreak scale, and modeling assumptions, including delays in vaccine delivery and onset of protection. While some models assumed protection immediately following vaccination 13,14,17,18 , others considered a lag between vaccination and protection. 5,7,12,19 Most previous work focused on large, well-documented outbreaks (e.g., Zimbabwe with 98,591 cases or Haiti with 119,902 cases) 14,19 and did not represent the outbreaks that may be typically found in sub-Saharan Africa. These gaps highlight the need for models that capture heterogeneity of outbreaks to improve the generalizability of vaccine impact assessments.
Added value of this study
To our knowledge, this is the first study to model the impact, efficiency, and cost- effectiveness of OCV outbreak response immunizations (ORIs) across a large and diverse set of outbreaks from multiple temporal and geographic contexts in sub-Saharan Africa. Using data from 1,192 outbreaks from 2010 to 2020—spanning wide variation in size, duration, and attack rate—we developed a comprehensive framework to evaluate how vaccination timing, coverage, and targeting influence outcomes. Unlike previous studies focused on isolated large outbreaks, our model quantifies the distribution of vaccine impact across heterogeneous epidemics, providing a generalizable basis for reactive vaccination planning and optimization of global OCV stockpile use.
Implications of the available evidence
Our findings underscore the critical importance of rapid and targeted vaccine deployment. ORI impact declined by half approximately every 2·6 weeks of implementation delay, yet substantial benefits persisted even with late campaigns, particularly in large and high–attack-rate outbreaks. When aggregated across outbreaks, week-9 ORIs, comparable to historical response times, still averted 0·44 [IQR: 0·28–0·44] cases per 1,000 OCV doses, rising to 2·2 [IQR: 1·9–2·2] with week-1 campaigns targeting the top 70% of outbreaks by attack rate. Prioritizing large, sustained outbreaks increased cost-effectiveness of week-9 ORI by up to 85-fold. These results provide a quantitative basis for optimizing reactive vaccination strategies under constrained OCV supply to maximize health impact across Africa.
