The Resurgence of Cholera, "The Forgotten Pandemic", Amid Vaccine Shortages
Newsletter Edition #254 [The Files In-Depth]
Hi,
In today’s edition we take a deep dive on the resurgence of Cholera - the number of cases worldwide surged in 2024 to more than 800,000 — an increase of more than 50 per cent compared to the year before.
We look at not only the multi-faceted causes of such events, but also the structural shortcomings in the response including vaccine shortages.
The challenges faced in addressing in Cholera are illustrative of the very goals of a proposed new Pandemic Agreement current under negotiation, highlighting the importance of not only investments for prevention of outbreaks, but also diversifying manufacturing capacities in different parts of the world to meet unpredictable demand.
We are grateful to Heather Rilkoff, a journalist and an epidemiologist who brings for our readers, this comprehensively reported story that fluently connects the dots. Rilkoff is also a fellow affiliated with the Journalism and Health Impact program at the Dalla Lana School of Public Health, University of Toronto, Canada.
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I. STORY OF THE WEEK
The Resurgence of Cholera, "The Forgotten Pandemic", Amid Vaccine Shortages
By Heather Rilkoff
Rilkoff is a journalist and epidemiologist, and a fellow in the Journalism and Health Impact program at the Dalla Lana School of Public Health. You can reach her at rilkoffh@mail.utoronto.ca.
Cholera has been called “the forgotten pandemic” with a massive impact on global health, although it has often been overshadowed by other infectious diseases. Its forgotten status has now put it in an unprecedented territory: rapidly rising case numbers and deaths, and a global vaccine manufacturing industry that does not have the ability to scale up as needed.
The number of cholera cases worldwide surged in 2024 to more than 800,000 — an increase of more than 50 per cent from one year prior. The demand for cholera vaccines has skyrocketed, pushing an ongoing shortage of cholera vaccines to drastic levels.
“It needs to be taken with more urgency,” says Firdausi Qadri, infectious disease specialist and Senior Scientist of the International Centre for Diarrhoeal Disease Research in Dhaka, Bangladesh in a phone interview.
A Vaccine Shortage Amid a Surge of Cases
Cholera cases and deaths have increased each year since 2021. The reasons for the increase are multifaceted, and many factors are likely to blame. Climate emergencies like natural disasters and flooding, water shortages, overburdened or inaccessible healthcare systems, conflict, displacement and increased urbanization are all contributors. Afghanistan, Yemen, Sudan and the Democratic Republic of Congo — all areas struggling with conflict, mass displacement, climate emergencies and multiple other disease outbreaks — are among the highest afflicted of the 33 countries reporting cholera cases in 2024.
A significant number of people who lose their lives to cholera, die without ever receiving medical care for the condition. In 2023, four countries reported that over 40 per cent of deaths were “community deaths” — meaning they occurred outside of healthcare facilities.
Cholera is also likely to be substantially under-reported, with researchers estimating that anywhere from 1.3 million to 4 million cases and 21,000 to 143,000 deaths occur each year.
The best prevention strategy is a combined approach: water, sanitation and hygiene (WASH), along with vaccines, disease surveillance, community engagement and prompt treatment of those infected. But in areas where the population faces conflict, displacement or other complexities, WASH improvements can be difficult to implement. In these cases, vaccines take on more importance. While vaccines are not a standalone solution to cholera, they play a critical role in slowing outbreaks by reducing the number of people at risk.
“In terms of outbreak control, where the risk of disease is very high… it’s an excellent tool,” Andrew Azman, an associate scientist in the Department of Epidemiology at Johns Hopkins University in Baltimore, Maryland, United States, said in a phone interview.
But vaccines are not a sustainable solution, he adds. “It can give you some years of protection, but it’s not actually stopping the underlying causes of disease.”
Rise in Cholera Cases Outpacing Vaccine Supply
The World Health Organization (WHO) reported that requests for the oral cholera vaccine surged in recent years, with 82 million doses requested by 15 countries from January 2023 to March 2024 — nearly double the 46 million doses produced during this period. As a result, the global stockpile of cholera vaccines was depleted from January until early March of 2024, and again in October 2024, leaving country requests for vaccination unfulfilled.
The demand is so high that no doses have been available for preventative campaigns, which aim to vaccinate at-risk populations before cholera outbreaks occur, since January 2022.
Countries that could benefit greatly from prevention campaigns are also experiencing sustained outbreaks, Daniela Garone, an international medical coordinator with the Médecins Sans Frontières, member of the International Coordinating Group on Vaccine Provision (ICG), said in a phone interview. “It’s a chicken-or-egg situation — you can prevent or you can treat,” she said.
With vaccines in short supply, the ICG, which approves and allocates the vaccine to countries based on need, has recommended reducing the number of cholera vaccine doses provided from two doses to one dose in order to provide access to more countries over the last two years.
Garone explained that the recommendation for a one-dose strategy was necessary in order to provide access to more countries in need. But the one-dose regimen may reduce the time a person is immune to cholera following immunization, leaving them vulnerable to reinfection.
Another major drawback of the one dose strategy is that it does not work well in children under five years old. “You need at least two doses to protect them,” Qadri at ICDDR said.
A WHO spokesperson told Geneva Health Files in an email that the one-dose strategy is a temporary measure and the organization aims to transition back to the recommended two-dose regimen “as soon as sufficient vaccine supplies become available.”
With cholera concentrated in parts of the world that cannot afford to pay high prices for a vaccine, no market incentive exists for wealthy nations to buy the vaccine at the higher prices that could subsidize vaccines for lower-income countries, similar to what happens with vaccines for diseases such as influenza and rotavirus.
Instead, cholera vaccine manufacturers operate on a high-volume, low-profit model. They sell large quantities of cholera vaccines at low cost to UNICEF, which procures them using funding from Gavi - The Vaccine Alliance, an international organization that supports vaccine access in low-income countries.
This system can make it difficult for companies to recoup costs to manufacture vaccines unless companies have support during the early stages of the development process, said Julia Lynch, cholera program director at the non-profit organization International Vaccine Institute (IVI) in Seoul, South Korea. She explained that the IVI provides licensing agreements at a low cost to companies to help ensure that they can stay in business. “That's part of lowering the threshold for companies to get engaged in a market that's not going to be very profitable,” she says.
Erratic Demand for Vaccines
Over the last few years, the rising number of cholera outbreaks created unpredictability in the vaccine market and increased the need for vaccines, exacerbating the current shortage. “The demand is not stable — it’s erratic,” Garone at MSF said. “Therefore how much vaccine you might need in one year might change from one year to the next.”
The unpredictable nature of cholera outbreaks makes it difficult for manufacturers to match production with demand. Companies typically look 10 to 15 years ahead when making business decisions, says Lynch at IVI. “They’re not just looking at [the market] for the next few years. They’re changing their facilities. They’re putting in new equipment.”
Countries must submit multi-year national cholera prevention plans that describe how many people are at high risk of cholera and would benefit from preventative cholera vaccine campaigns. These plans are used by Gavi to generate estimates for future planning. Because of the recent shortage of vaccines, countries that submitted plans have not been able to start preventative vaccination campaigns.
A WHO spokesperson said the WHO had “significant concerns” for the impact of the cholera vaccine shortage on national cholera prevention plans, as countries may de-emphasize or even remove vaccine-based prevention due to unpredictable vaccine availability.
This may further stall progress in stabilizing the demand for vaccines and reducing cholera cases and deaths.
Expanding the Stockpile
Gavi’s current estimates suggest that approximately 85 million doses will be needed each year to support prevention and outbreak response. But these estimates are not based on a high-demand scenario for prevention and outbreak response, where 220 million doses annually will be needed.
In March 2024, the WHO approved a simplified version of the oral cholera vaccine produced by the South Korean manufacturer EuBiologics, which enabled the vaccine to be produced more quickly. That year, EuBiologics increased its production from 30 million to 40 million doses and in December 2024, the emergency stockpile of cholera vaccines had been replenished, according to the WHO.
EuBiologics has received funding from UNICEF to produce 72 million doses in 2025 and has a production capacity of 80 million. But this ramped-up production is still not enough. A recent WHO situation report said that “increased production has yet to meet growing global demand, as demand continues to exceed supply, which continues to hinder efforts to control cholera outbreaks and respond rapidly to the disease’s spread.”
Three new manufacturers are slated to start producing cholera vaccines over the next six years. Bharat Biotech, based in India, has stated that there is a global deficit of about 40 million doses and that it plans to bridge this gap with its vaccine, Hillchol. It is predicted that Bharat Biotech will start producing cholera vaccines for the global stockpile in 2025 or 2026.
Biological E, also based in India, and Biovac, a South African company, have both received technology transfer from the IVI to produce cholera vaccines. Biological E will likely enter the market in the next few years, while Biovac plans to enter the market at the end of 2028 with a goal of producing 30,000 vaccines annually a few years later.
Rachel Park, director of international business at EuBiologics in Seoul, South Korea, said that the uncertainty over future demand places manufacturers in a difficult position. “We don’t know when they’re going to resume preventative campaigns, and when they’re going to return to a two-dose regimen.”
Bangladesh alone will need about 100 million doses of the vaccine over the next four or five years to carry out preventative campaigns under its National Cholera Plans, according to Qadri.
Bangladesh has a locally manufactured vaccine, Cholvax, which is not available to international organizations. Its national regulatory body is currently working to obtain ML3 status from the WHO for vaccines and biologicals–- a critical step in the process to being able to produce the vaccine for international sale to the global stockpile. But the process is slow. “In COVID times, we saw so many things happen. We learned from that. We could make things simpler if we wanted,” she said. “Why should [the cholera vaccine] take so long, if the world needs it so much?”
Qadri believes that Bangladesh could produce 10 million vaccines once prequalification status to sell internationally is obtained and potentially 20 million or more in the next years following. But she noted that manufacturers cannot yet start working to expand production without a guarantee that Gavi will purchase their products.
The production of vaccines, and efforts to improve WASH are complex problems that require strategic, coordinated efforts to solve, she added. “I think this should be taken up as a special agenda [by the WHO],” Qadri said.
Potential solutions
Gavi launched the African Vaccine Manufacturing Accelerator (AVMA) in 2024 to encourage the growth of manufacturing in Africa, particularly for diseases that are of strategic importance to the continent. Cholera is listed as one of its top priority diseases. This is an important opportunity for Biovac, which is poised to become the first African company to produce the cholera vaccine end-to-end.
Morena Makhoana, CEO of Biovac in Cape Town, South Africa, expressed confidence that as part of the AVMA, organizations purchasing cholera vaccines will take geographic diversity into consideration, so that at least a portion of the purchasing space for cholera vaccines will go to an African manufacturer. This makes him less worried that the market will be overcrowded once Biovac begins producing vaccinations for the global stockpile in a few years’ time. “There has to be space for an African manufacturer,” he said in a phone interview to Geneva Health Files.
Countries need to obtain WHO prequalification status in order to receive incentive payments from AVMA, which ensures vaccines meet global safety, quality and efficiency standards for international procurement and distribution.
Heather Sherwin, Director of Impact Investments at Elma Philanthropies, which supports vaccine access and equity in Africa, said that getting this far in the process can be difficult for local manufacturers. A new manufacturer must prove that its vaccine performs as well as existing ones through a bioequivalence study before applying for approvals from a company’s regulatory authority and for WHO prequalification. Manufacturers need strong financial backing in order to survive this long approval process.
For Sherwin, having a structure in place to coordinate grant funding and ensure that manufacturers can make it past these early stages is critical to ensuring more manufacturers can produce the vaccine.
“Without the proper funding in place, a manufacturer simply doesn’t have the funds to keep themselves going, or the price of their product becomes so high they will be outcompeted in the market,” she said.
More Resources Needed
Some global health agencies have called for an expansion of the global stockpile, arguing that there is currently no buffer that would allow for unexpected increases in outbreak and prevention needs. But this would require increased and sustainable resourcing for cholera response.
A spokesperson for the WHO said in an email that they considered expanding the stockpile a “feasible, though complex solution,” with several barriers — including financial constraints, logistical hurdles and manufacturing limitations — that must be addressed.
At this moment, there is great uncertainty over funding for global health initiatives like vaccines. The United States has been a major supporter of Gavi, pledging US $300 million in 2024. But the Trump administration’s halt to foreign development assistance programs is expected to have a major effect on Gavi, which is currently seeking to raise US $9 billion over the next five years. The United Kingdom may also cut back its funding to GAVI as part of a reduction of the UK aid budget. These changes come after years of declining funding for WASH programs: a recent UN report showed a 15 per cent decline in water sector funding from 2015 to 2021.
These funding cuts are an additional burden on countries facing cholera outbreaks. Experts working on the global cholera response say it doesn’t have to be this way: cholera is preventable and highly treatable, provided resources are in place. Garone, of Médecins Sans Frontières, put it simply: “No one should die of cholera in 2025.”
II. PODCAST CORNER
On Neglected Tropical Diseases by Global Health Matters Podcast
Ability in Disability from Noma
This two-part episode shines a light on the lived experiences of two remarkable individuals affected by NTDs. We explore firsthand how disability influences and affects their lives. In part 1, host Garry Aslanyan speaks with Mulikat Okanlawon, a survivor of noma in Nigeria and President of the Elysium Noma Survivors Association. Thanks to the tireless advocacy of Mulikat and other survivors, noma was officially recognized as an NTD by the World Health Organization in 2023. Claire Jeantet, an award-winning documentary filmmaker, speaks about collaborating with Mulikat over the past eight years to bring her story and the stories of other noma survivors to policymakers, academics and the public.
Listen to the episode
Garry Aslanyan is the host and moderator of the Global Health Matters podcast. You can contact him at: aslanyang@who.int
From Disability to Advocacy for Leprosy
We explore firsthand how disability influences and affects their lives. In part 2, host Garry Aslanyan speaks with Dan Izzett, a former civil engineering technician and pastor who has turned his retirement into a powerful mission advocating for people living with leprosy. Peter Waddup, the CEO of the Leprosy Mission in Great Britain, provides a thoughtful reflection on Dan's message and its practical implications for the global health community.
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This podcast promotion is sponsored by the Global Health Matters podcast.
If you wish to promote relevant information for readers of Geneva Health Files, for a modest fee, get in touch with us at patnaik.reporting@gmail.com.
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