Quantifying the contribution of Oral Cholera Vaccine to global health through tech-transfers and WHO stockpile deployment since its inception: a modeling study

IntroductionCholera has been a major public health concern in many parts of the world. The development of the low-cost Oral Cholera Vaccine (OCV) enabled creation of the OCV stockpile by the World Health Organization and Gavi, the Vaccine Alliance which have provided vaccine to cholera-affected countries since 2013. The current study aims to measure the impact of the OCV stockpile deployment on global health. MethodsDetailed OCV stockpile data were obtained and used to determine the size and timing of vaccination using a transmission model across all recipient countries over time. The model first estimated the impact of vaccination based on actual shipments. Considering several challenges including time lags until vaccination and the shortage of OCVs observed during the OCV stockpile implementations, multiple scenarios, so called what if scenarios were further investigated to provide guidance for the future decision-making processes on the OCV stockpile use. ResultsWith the actual OCV shipment scenario, vaccination prevented 8.1 million cases and 146,013 deaths which resulted in 6.7 million DALYs averted. If there were neither time lags nor the supply shortages, vaccination would avert 17.4 million cases, 321,730 deaths, and 15.1 million DALYs. The economic burden of cholera reduced by vaccination was estimated to be US$1.05 billion with the actual OCV shipment and US$2.33 billion without having any constraints. ConclusionOur models indicate that deployment of OCV from the stockpile may have had a significant positive impact on cholera-affected countries since its inception. Overcoming existing challenges resulting in delays in campaign implementation and shortage of vaccine will help maximize the impact of vaccination. KEY MESSAGESO_ST_ABSWhat is already known on this topicC_ST_ABSCholera outbreaks are currently ongoing in multiple countries, with the African and Eastern Mediterranean regions experiencing the most severe impacts. The Oral Cholera Vaccine (OCV) stockpile was established by World Health Organization (WHO) and Gavi since 2013 and has been widely used to control cholera outbreaks globally. Existing modeling studies assessed the potential impact of OCV and reported that OCV campaigns can contribute to effective cholera control in the near term. However, while the global OCV stockpile has been available since 2013 supporting more than 30 cholera-endemic countries, the studies mostly focused on a specific time period in selected geographical locations, missing the holistic impact of the global OCV stockpile. We further reviewed existing daily OCV stockpile shipment records thoroughly and identified that the program faced several challenges in meeting urgent demands due to administrative delays and OCV supply shortages. What this study addsWe evaluated the actual impact of deployed doses on cholera morbidity, mortality, and economic burden since the inception of the OCV stockpile in 2013. Our model further investigated what the impact of OCV would have been with no delays in implementation and no supply shortage by incorporating the detailed daily shipment data which included the number of OCV doses and dates for request, decision (approval), and delivery. The current analyses show that from 2013 to 2025, both reactive and preventive vaccination campaigns implemented through the global OCV stockpile averted more than 6.7 million DALYs, 146,013 deaths, and US$1.05 billion of the economic burden in 37 recipient countries. Our model demonstrates that vaccination impact would be further enhanced if there were no delays in the implementation of campaigns and if there were no shortage of OCV supplies. How this study might affect research, practice or policyTo our knowledge, no previous study has assessed the holistic contribution of the global OCV stockpile and investigated the optimal outcomes which may have been partially lost due to programmatic and logistical challenges. Since its inception, the impact of the OCV stockpile on global health has been substantial, and the additional benefits are expected if cholera vaccines can be deployed on time and if there is no supply constraint. In particular, the benefits induced by improving timing of vaccination does not necessarily come with additional costs associated with vaccine supplies which are known to be the major cost driver. In addition, because all stockpile recipient countries are currently required to implement a single-dose OCV campaign due to the shortage of OCVs, the continuous support for a two-dose vaccination campaign would bring much larger benefits than the single-dose vaccination scheme given a single-dose vaccination with the OCV is known to be much less efficacious among young children. Considering ongoing cholera outbreaks across multiple regions and other cholera vaccine candidates in development, our findings can be used not only to help provide guidance for the decision-making process on the future OCV stockpile deployment, but also to understand the optimal usage and potential impacts of multiple cholera vaccines which can be administered by different strategies in the future.