The ancient disease of cholera is making a comeback in 2024 – but the world’s supply of vaccines can’t keep up.

The global stockpile of cholera vaccines is empty. There are no doses in reserve. And while the vaccine manufacturer is churning out 700,000 doses a week, all those vials are going directly to active outbreaks.

“The demand is four times more than the supply,” said Daniela Garone, the international medical coordinator for Doctors Without Borders. “And we don’t have enough vaccines to use for the preventive programs.”

This couldn’t come at a worse time, experts say.

After a long period of global progress against cholera, the number of outbreaks has shot up since 2021. There are currently 17 countries reporting cases, and preliminary data from last year suggest there were over 700,000 cases of cholera and more than 4,000 deaths. Philippe Barboza, team lead of the cholera program at the World Health Organization, said the figures are likely a gross undercount and he’s witnessed an “exponential increase” in cases.

With cholera cases climbing, global health organizations saw the vaccine shortfall coming. In the past few years, they have tried several strategies to stretch the current vaccine supply and ramp up production of more doses. But the challenge, Garone said, is to break free from “a vicious cycle” where active outbreaks gobble up all the vaccines and there aren’t enough doses for prevention campaigns or to rebuild the reserves.

“Even though we’re still running into the headwind, some days we actually end up steps backwards, not steps forward,” said Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota. “Cholera really represents a perfect storm from a public health standpoint.”

Stretching the stockpile

In 2013, after watching a successful vaccination campaign help contain an active outbreak in Haiti, the World Health Organization teamed up with other public health groups to create a global cholera vaccine stockpile. Since outbreaks are unpredictable and cholera vaccines take a while to make, the plan was to ensure doses were available whenever they were needed.

For years, the stockpile grew, from roughly 2 million doses in 2013 to about 40 million a decade later.

The vials are stored in huge walk-in refrigerators in an unremarkable warehouse outside of Seoul, South Korea, near the factory where the vaccines are produced. But, lately, given the high demand, freshly made doses don’t linger in those refrigerators long.

“As soon as they’re on the shelf, they’re in a box and on an airplane going somewhere,” said Allyson Russell, the acting senior project manager for outbreaks and global health security at Gavi, the Vaccine Alliance. The international group helps fund and facilitate the stockpile.

Gavi, among others, has taken steps to address the vaccine shortage.

In October 2022, the international group managing the stockpile recommended giving just one dose of the vaccine – instead of the usual two doses. The protection doesn’t last quite as long, but “it basically allows you to vaccinate twice as many people,” said Russell.

At the same time, scientists set to work crafting a quicker, cheaper way to make the vaccine. Typically, the vaccine is made by growing five different strains of cholera bacteria, then killing them and finally mixing them together into the vaccine. But, it turns out, all five strains are not necessary, says Russell.

“There are two strains that are very critical. And so the simplified version we have seen in clinical trials to be just as efficacious as the five-strain version,” she said, adding that she hopes this new formulation will start being made in the coming months.

But those measures may not be enough to replenish the supply.

Rising demand but limited supply

There are a few big reasons why the stockpile has run dry.

First, the demand is greater than ever.

“We’ve never seen something like this,” said Livia Tampellini, the medical deputy for Doctors Without Borders’ emergency team, who recently returned from helping Zambia with its cholera outbreak. “We cannot support everybody. That is, for sure, impossible.”

There are all the usual culprits, including the lack of access to sewage systems and clean drinking water in certain parts of the Global South. Conflict and migration also give cholera the chance to spread. And climate change looms larger each year.

“Many of these very large outbreaks were triggered by a massive…climatic event [such as] a drought or cyclones,” said the WHO’s Barboza.

Those disasters can easily lead to drinking water being contaminated by human waste as sanitation systems are overwhelmed.

Another factor driving up demand has been a decrease in stigma over the past few years, says Russell of Gavi, the Vaccine Alliance.

“Countries are more willing to report that they have cholera cases, to declare cholera outbreaks,” she said, noting this has been seen both in how many cases they report and how many doses they request.

Between January 2023 and January 2024, 76 million vaccines were requested by 14 countries. That’s far more doses than available and more than have been requested in the past.

Vaccine supply has proved challenging, with only one company – EuBiologics in South Korea – making the global cholera vaccine.

The lack of additional manufacturers is “a good indicator of the lack of interest, investment, commitment to control cholera,” said Barboza.

There are companies in India and South Africa slated to start producing the vaccine in the coming years. However, he said, “this is taking time, especially for a vaccine which is cheap, which is only focused on the most poor part of the population in the poorest countries in the world. So, it does not attract big manufacturers.”

The vaccine typically sells for about $1.50 a dose, leaving thin profit margins for the vaccine maker. Another deterrent is the fact that the cholera vaccine is not part of a routine vaccination campaign and, thus, the demand is bumpy and depends on whether or not there are outbreaks.

Some public health experts are hoping for the resumption of preventive cholera vaccinations, which have been placed on hold given the depleted stockpile. They say it would not only help attract vaccine manufacturers, but it would be good for public health.

That’s what Ralph Ternier would like to see. He’s the chief medical officer for Zanmi Lasante in Haiti, a sister organization to Partners In Health. In 2022, Haiti was declared cholera-free, but that turned out to be premature. In 2023, the country experienced one of the world’s deadliest cholera outbreaks. Ternier worries that more cholera is on its way as Haiti heads into the rainy season struggling with political upheaval, gang violence and a lack of clean water.

He says vaccinating people now could help avoid an outbreak.

“When you vaccinate millions of people, you give yourself time, like three or five years of low cases of cholera,” he said.

That would lead to lives saved as well as time to build and repair drinking water and sewage systems, but for now, Ternier said, that’s just a dream.

“Honestly, based on the current situation, I’m not expecting to have vaccines,” he said.

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