As multilateral negotiations on pandemic prevention, preparedness, and response continue in Geneva, one pandemic continues to linger globally, largely unnoticed by the global community. We are currently living through the seventh cholera pandemic, which is considered to have started in South Asia in 1961 and subsequently spread to Africa and the Americas.
Cholera, caused by the bacterium Vibrio cholerae, is an intestinal infection that causes severe diarrhea and dehydration and is usually spread through contaminated food and water. Cholera affects some of the world’s poorest and most marginalized communities in Africa, the Americas, and Asia, who do not have access to safe water and basic sanitation. Today, Afghanistan, Mozambique, Pakistan, Zambia, and Zimbabwe have the highest burden of cholera, and an estimated 143,000 people die from this disease globally. In a world with increasing inequalities, armed conflicts, and humanitarian crises — which exacerbate the disruption of water and sanitation systems and result in the displacement of populations — an estimated 1.1 billion people are at risk of contracting this deadly disease.
The Current Global Supply of Cholera Vaccines
Since the mid-1800s, there have been massive gains in the fight against cholera — including an increased understanding of its epidemiology and mode of transmission, the establishment of improved sanitation facilities (especially in higher-income countries), and the development of cholera vaccines. Currently, three oral cholera vaccines (OCV) which have been pre-qualified by the World Health Organization (WHO), are available for use: Dukoral, Shanchol, and Euvichol. The WHO has deemed these three vaccines to meet acceptable quality, safety, and efficacy standards, and international procurement agencies can procure them for global use. Indeed, Shanchol and Euvichol are part of the Global OCV Stockpile and have been used to target and respond to cholera outbreaks swiftly. An estimated 20 million doses of these vaccines have been used worldwide for multiple mass vaccination campaigns. For example, long-term mass vaccination campaigns in South Sudan, where cholera is endemic, have helped the country halt the disease’s transmission in recent years. In addition to improving water, sanitation, and hygiene practices, vaccines are a critical tool in the fight against cholera.
“In 2022, people should not die of cholera,” said Phillipe Barboza, the WHO’s team lead for cholera and epidemic diarrheal diseases. Yet, people continue to die of cholera to this day. Even though the current cholera pandemic started 63 years ago, containment efforts have been unsuccessful. In 2023 alone, the WHO estimated a cumulative total of 787,813 cholera cases and 5,586 deaths across 31 countries.
Although the demand for vaccines has increased with the greater frequency of cholera outbreaks, the WHO and others have raised the alarm about shortages of cholera vaccines in the Global OCV Stockpile. Between January 2023 and January 2024, 14 countries requested 76 million doses of cholera vaccines from the Global OCV Stockpile. Alarmingly, only 38 million doses were available in the stockpile. UNICEF also estimates that the demand for cholera vaccines in 2024 will range from 90–100 million doses, highlighting the stark difference between vaccine demand and availability. Concerningly, at the end of 2023, Shantha Biotechnics, a subsidiary of Sanofi, ceased the production and supply of Shanchol, citing small volumes of the vaccine produced. This decision leaves only the manufacturer of Euvichol as the sole contributor of OCVs to the global stockpile.
Shortfalls in R&D Funding for Cholera
This lack of investment in the development and production of drugs and vaccines is a recurring problem for “neglected” diseases, such as cholera. Because cholera predominately affects people living in lower-income countries, drug and vaccine manufacturers consider developing medical products to treat and prevent these diseases to be unprofitable due to small profit margins. Since there is no viable, limited, or uncertain commercial market for “neglected diseases,” there are glaring gaps in research and development (R&D) for these diseases. G-Finder estimated that while R&D investments for HIV/AIDS totaled $23.7 billion between 2007–2022, investments for cholera over the same period were $564 million. In 2022 alone, only $37 million was dedicated to cholera, with funding mainly from the public ($25 million) and philanthropic ($11 million) sources, while contributions from industry were approximately $200,000.
Although countries have attempted to provide viable commercial incentives to encourage manufacturers to invest in R&D for cholera, these efforts are not enough. For example, to spur R&D, the U.S. Food and Drug Administration (FDA) has included cholera as a disease that would qualify for certain incentives, such as awarding priority review vouchers to pharmaceutical companies for the successful development of drugs or vaccines for neglected diseases. However, as of 2020, the FDA has approved only one vaccine for cholera (Vaxchora) through the priority review voucher program since the program first began in 2007.
Strengthening Vaccine Innovation and Production to Meet the Global Demand
With Shanchol’s production being discontinued, we have lost an essential vaccine from our toolbox. As such, greater investments in drug and vaccine R&D for cholera are vital. Strategies to mobilize funding for cholera should employ a multi-stakeholder approach, engaging with governments (especially from low- and middle-income countries), the private sector, and philanthropic stakeholders. We urgently need more viable “pull” mechanisms, such as advance market commitments where donors commit funding to guarantee the prices of vaccines once vaccine manufacturers have developed them. A pooled procurement mechanism, wherein financial and other resources of multiple purchasing authorities are combined, can serve as a vital strategy to guarantee markets and create predictable demands for vaccines and drugs against cholera. For example, the African Union recently agreed to establish a pooled procurement mechanism where African countries can pool finances to buy drugs and vaccines for different diseases, creating a potential $50 billion market for medical products.
We also need “push” mechanisms, including direct funding and grants to manufacturers for translational research and clinical trial infrastructure to incentivize vaccine R&D for cholera. Additionally, high-level political engagement can and should direct attention toward the dismal R&D funding landscape of diarrheal diseases, including cholera. Political forums, like the G7 and G20, can play a crucial role in developing cross-national and multisectoral platforms and alliances that can direct much-needed investments into developing life-saving health products for these neglected diseases. Regular convenings of such multi-stakeholder consortia and alliances can maintain commitment towards investing in cholera R&D, assess gaps in the R&D pipeline, and provide information on key financing gaps and estimated markets for medical products.
In addition to being concerned about the pandemics of tomorrow, we must address the pandemics of today — especially those that impact the most vulnerable and disadvantaged populations. As we enter a world of compounding threats due to climate change, global conflicts, rising inequalities, and frequent outbreaks and pandemics, we must leverage rapid advancements in science and technology to develop novel vaccines for existing and emerging infectious disease threats.
In 2018, the 71st World Health Assembly significantly accelerated the momentum for developing cholera vaccines with the adoption of a resolution on “Cholera Control and Prevention,” which highlighted the need “to support, including through international cooperation, research for better prevention and control, including research for improved vaccines and better rapid diagnostics and treatment.” However, six years later, much work remains to be done. If we are to achieve the goal of reducing cholera deaths by 90% by 2030, we must end the continual neglect of cholera and invest in cholera vaccine research, development, and production.
