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An unprecedented shortage of cholera vaccine has public health experts fearing that a recent surge of outbreaks across developing countries will only worsen, a situation they argue is as regrettable as it was avoidable.

At least 16 countries in Asia, Africa, and the Caribbean are dealing with cholera outbreaks. According to the latest report from the European Centre for Disease Prevention and Control, between Dec. 23 and Jan. 23, nearly 50,500 people contracted cholera and nearly 500 died. Those numbers will almost certainly rise amid the worst vaccine shortage since an oral vaccine was introduced in the 1990s.

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Experts describe the dearth of doses as an unforced error that reflects a lack of interest in a disease that is only deadly for the poorest of the poor. Out of three vaccines qualified for use by the World Health Organization, only one is still being made, and its supplies barely cover a fraction of the global need. Cases continue to grow as climate change worsens weather patterns that are linked with flooding and outbreaks. And without sufficient vaccine supplies, medical personnel on the ground are left with containment strategies that are hardly sufficient during a humanitarian crisis.

“Cholera is a neglected disease. And it is neglected for neglected populations that are poor and do not make a good market,” said Abdou Salam Gueye, the regional emergency director of the WHO African Region.

The global stockpile of cholera vaccine, which was established in 2013, is managed by the International Coordinating Group (ICG) on Vaccine Provision with the aim of supporting countries in need. That stockpile is supposed to have 5 million available doses ready to be delivered within a week. At the moment, it’s running dry, as only one of the vaccine makers, EuBiologics, is producing doses of its vaccine, Euvichol-Plus. As of 2022, Shantha Biotechnics, an Indian subsidiary of French pharmaceutical company Sanofi, stopped producing its cholera vaccine, Shanchol, which at the time constituted 15% of the global stockpile.

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Euvichol-Plus has been approved for people 1 and older and is supposed to be administered in two doses given at least two weeks apart. Yet last year, the ICG changed the administration protocol to one dose rather than two to stretch limited supplies further, even though that compromises the vaccine’s effectiveness.

“What we started to do is the second dose within six months. And then we needed to stop the second doses altogether,” said Daniela Garone, international medical coordinator at Médecins Sans Frontières and a member of the ICG. “But we don’t know how much protection we receive — it is more than a year, but we don’t know how long.”

A regular protocol would offer protection that starts 10 days after vaccination and is 90% effective against severe diarrhea and dehydration for the first three months, with protection lasting for up to three years. Vaccines are especially important in areas where outbreaks happen in rapid succession and where surges in cases can continue for a year or longer.

Thirty countries experienced cholera outbreaks in 2023, and 14 requested a total of 76 million doses from the ICG, which only had 38 million doses of Euvichol-Plus. This means that current production barely covered half the need for a one-dose protocol, and only a fourth of what would be needed for a two-dose protocol. And EuBiologics is already running at capacity in making its vaccine.

And ideally, said Garone, there would be extra vaccine to set up preventative programs to forestall outbreaks. That would require an estimated minimum 40 million additional doses for 2024.

At the moment, said Garone, 2.4 million doses are being made a week, and all the doses that will be produced in the coming months have already been allocated. Countries that have been approved by the ICG to receive vaccine doses now “will not receive it until the second or third week of March because the vaccine is not produced yet,” she said.

The reason behind this shortage is straightforward: At $1.50 a dose, cholera vaccines are unappealing to pharmaceutical companies, and demand is limited to poor countries or emergency situations such as wars or natural disasters. “The only way to maintain a healthy market is to have more than one manufacturer,” said Garona. “You need global investment because it’s not an attractive market.”

With no immediate solution in sight, health workers on the ground have stopped relying much on vaccines as a primary intervention. “Responding in many countries in Africa, we try to intervene without putting cholera vaccine in the center of our strategy,” said WHO’s Gueye.

Instead, he said, the first goal is to reduce mortality to under 1%. This helps build trust with the affected population, which can otherwise be hesitant to seek care, both because of high mortality rates in health care centers and because of the specific symptoms of cholera, which can quickly impede people’s ability to control vomiting and bowel movements. “Cholera [is] a disease that affects the dignity of people,” said Gueye.

Only once they’ve built trust with local communities do health workers take secondary steps to improve water and sanitation, Gueye said, although resources can be scarce.

“If it is very difficult to do the water and sanitation [intervention] and sometimes impossible to do the good clinical care, the vaccine remains the only possibility,” he said. “And unfortunately we don’t have those vaccines.”

In his experience, the one time African countries were able to access extra funding from the WHO to respond to cholera was in 2022, which helped bring an outbreak in Western Africa (Nigeria, Cameroon, and Niger) under control in record time. But recent requests for funding as cases rise have been unsuccessful. “We were able with less than $10 million to really do a good intervention,” he said. “But now we have nothing.”

Future outbreaks are only likely to intensify because of the effects of climate change, Gueye warns. In particular, in eastern and southern African nations such as Mozambique, Malawi, and Madagascar, flooding that can lead to cholera outbreaks used to be cyclical, but those cycles are now running into one another and prolonging outbreaks.

It’s a situation he said underscores how global crises affect the poorest nations. “In my opinion cholera is not a public health problem. It’s a development problem with public health consequences. If you support a country to have human development that is appropriate, the problem will disappear by itself,” he said.

This has become harder because, in many cases, economic growth in the Global South has fostered more economic inequality, with the poor sinking deeper into poverty even as countries become richer overall. The good news is that a little funding would go a long way, such as increased support for climate change remediation. For instance, cholera prevention and treatment programs should qualify to receive at least a small portion of the $13 billion United Nations Green Climate Fund, he said.

“You don’t need rocket science to know that cholera is a consequence of climate change,” Gueye said. “We asked last year for around $31 million; we got less than 4 million. And that $13 billion that is available for climate change — why is it not oriented toward the cholera funding gap?”

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