Vaccines are in short supply amid global cholera surge | Science

On 2 October, Haiti announced that cholera had returned to the country. Memories from the previous epidemic, which killed close to 10,000 Haitians between 2010 and 2019, are still raw; now, with violent gangs fighting for control over the country and the health system in disarray, things could again get very bad.

A few days later, Lebanon reported its first cholera cases since 1993, in a Syrian refugee and a health care worker in the north of the country. More cases quickly followed, and health organizations fear the Lebanese health system, hard-hit by a yearslong financial crisis, could buckle under the new burden. Two weeks later, Kenya, where millions of people have fled the worst drought in decades, reported its first cholera cases as well.

The outbreaks are part of what the World Health Organization (WHO) calls an “unprecedented” surge in cholera cases, driven in part by climate change and fallout from the COVID-19 pandemic. Thirty countries have reported outbreaks this year, up from fewer than 20 on average the past 5 years. “There is a trend of more countries affected, in more regions, with a longer duration of outbreaks,” says Daniela Garone, the international medical coordinator at Doctors Without Borders (MSF). A global cholera vaccine stockpile is falling short, forcing health organizations to ration doses—and rethink their control strategy.

Cholera, spread through water or food contaminated with the bacterium Vibrio cholerae, can cause severe diarrhea and kills an estimated 20,000 to 140,000 people each year. A lack of clean drinking water, poverty, natural disasters, and armed conflicts—such as the gang violence in Haiti—have traditionally fueled outbreaks.

Just a few years ago, the prospects for reducing the burden seemed to brighten. A new, cheap vaccine, made from inactivated bacteria lacking part of their toxin, was approved in 2015; millions of doses were added to an international stockpile for emergency use. In 2017, WHO and numerous international partners launched an ambitious new control strategy that relied on vaccination, improving sanitation, and widening access to clean drinking water and treatment. It was meant to cut cholera deaths by 90% and eliminate the disease in 20 countries by 2030.

Extreme weather fueled by global warming is part of the reason cases are instead trending up, says Philippe Barboza, who heads WHO’s Cholera and Epidemic Diarrheal Diseases section. Droughts in West Africa and the Horn of Africa, massive flooding in Southeast Asia, and cyclones in southern Africa have displaced people and destroyed water and sanitation infrastructure. COVID-19’s toll on the health care system made matters worse. The cholera case fatality rate in Africa was almost 3% in 2021, Barboza says, about three times higher than over the previous 5 years. “Every time we have investigated why the [death rate] was so high, the reason was the same: delayed access to health care,” he says.

The 36 million vaccine doses expected to be shipped from the stockpile this year won’t be enough. Full protection requires two doses given 2 weeks apart, so the supply covers just 18 million people—“not a lot when you think of [affected] countries like Bangladesh, Pakistan, Ethiopia, Nigeria,” Barboza says. Last month, the International Coordinating Group that runs the stockpile—made up of WHO, MSF, UNICEF, and the International Federation of the Red Cross and Red Crescent Societies—announced it would stop administering second doses to stretch supplies. A one-dose strategy has been used successfully before, says Charlie Weller, an immunologist at the Wellcome Trust, but it’s unclear how long protection will last. (Even the full two-dose regimen only protects for 3 years.)

David Sack, an infectious disease expert at Johns Hopkins University’s Bloomberg School of Public Health, says he is “puzzled” by the decision to abandon the second dose instead of postponing it. A clinical trial in Cameroon that Sack and colleagues published this month suggests giving the second dose after 1 year instead of 2 weeks actually increases the immune response. But unless the outbreaks slow down in the coming months, the vaccine supply won’t allow even a delayed second dose. Besides, current WHO guidelines don’t allow an interval of more than 6 months, says Garone, although that could change. “We have asked to fast-track the revision of the evidence on this,” she says.

Meanwhile, Shantha Biotechnics in India, which manufactures 10% of the global cholera vaccine supply, plans to stop production by the end of 2023. WHO Director-General Tedros Adhanom Ghebreyesus has urged Shantha and its parent company, Sanofi, to reconsider its decision, which would leave only one manufacturer, South Korea’s EuBiologics. The International Vaccine Institute (IVI), a nonprofit based in South Korea that helped develop the cheap oral vaccine, is working with EuBiologics to increase its production capacity to some 80 million to 
90 million doses annually, says Julia Lynch, who directs IVI’s cholera program. It’s also helping a South African company named Biovac set up a facility to produce the shots, in a project funded by the Wellcome Trust and the Bill & Melinda Gates Foundation.

But both efforts will take several years. For the foreseeable future, countries that have put together multiyear plans to control cholera and have requested vaccines from the stockpile are likely to get fewer doses than requested, or get them much later, Lynch says. That could lead other countries to not even bother with such plans, she adds. “I really worry about losing the momentum that has been gained.”

Barboza emphasizes that vaccines are only one way to address the crisis. Cholera is easy to treat with oral rehydration solution, as long as it’s administered quickly. That makes access to basic health care crucial. “You don’t need a respirator, an intensive care unit, and God knows what,” Barboza says. Meanwhile, countries should keep working to improve access to clean water and sanitation, he says: “We might have lost a fight, but we have not lost the war.”

On 2 October, Haiti announced that cholera had returned to the country. Memories from the previous epidemic, which killed close to 10,000 Haitians between 2010 and 2019, are still raw; now, with violent gangs fighting for control over the country and the health system in disarray, things could again get very bad.

A few days later, Lebanon reported its first cholera cases since 1993, in a Syrian refugee and a health care worker in the north of the country. More cases quickly followed, and health organizations fear the Lebanese health system, hard-hit by a yearslong financial crisis, could buckle under the new burden. Two weeks later, Kenya, where millions of people have fled the worst drought in decades, reported its first cholera cases as well.

The outbreaks are part of what the World Health Organization (WHO) calls an “unprecedented” surge in cholera cases, driven in part by climate change and fallout from the COVID-19 pandemic. Thirty countries have reported outbreaks this year, up from fewer than 20 on average the past 5 years. “There is a trend of more countries affected, in more regions, with a longer duration of outbreaks,” says Daniela Garone, the international medical coordinator at Doctors Without Borders (MSF). A global cholera vaccine stockpile is falling short, forcing health organizations to ration doses—and rethink their control strategy.

Cholera, spread through water or food contaminated with the bacterium Vibrio cholerae, can cause severe diarrhea and kills an estimated 20,000 to 140,000 people each year. A lack of clean drinking water, poverty, natural disasters, and armed conflicts—such as the gang violence in Haiti—have traditionally fueled outbreaks.

Just a few years ago, the prospects for reducing the burden seemed to brighten. A new, cheap vaccine, made from inactivated bacteria lacking part of their toxin, was approved in 2015; millions of doses were added to an international stockpile for emergency use. In 2017, WHO and numerous international partners launched an ambitious new control strategy that relied on vaccination, improving sanitation, and widening access to clean drinking water and treatment. It was meant to cut cholera deaths by 90% and eliminate the disease in 20 countries by 2030.

Extreme weather fueled by global warming is part of the reason cases are instead trending up, says Philippe Barboza, who heads WHO’s Cholera and Epidemic Diarrheal Diseases section. Droughts in West Africa and the Horn of Africa, massive flooding in Southeast Asia, and cyclones in southern Africa have displaced people and destroyed water and sanitation infrastructure. COVID-19’s toll on the health care system made matters worse. The cholera case fatality rate in Africa was almost 3% in 2021, Barboza says, about three times higher than over the previous 5 years. “Every time we have investigated why the [death rate] was so high, the reason was the same: delayed access to health care,” he says.

The 36 million vaccine doses expected to be shipped from the stockpile this year won’t be enough. Full protection requires two doses given 2 weeks apart, so the supply covers just 18 million people—“not a lot when you think of [affected] countries like Bangladesh, Pakistan, Ethiopia, Nigeria,” Barboza says. Last month, the International Coordinating Group that runs the stockpile—made up of WHO, MSF, UNICEF, and the International Federation of the Red Cross and Red Crescent Societies—announced it would stop administering second doses to stretch supplies. A one-dose strategy has been used successfully before, says Charlie Weller, an immunologist at the Wellcome Trust, but it’s unclear how long protection will last. (Even the full two-dose regimen only protects for 3 years.)

David Sack, an infectious disease expert at Johns Hopkins University’s Bloomberg School of Public Health, says he is “puzzled” by the decision to abandon the second dose instead of postponing it. A clinical trial in Cameroon that Sack and colleagues published this month suggests giving the second dose after 1 year instead of 2 weeks actually increases the immune response. But unless the outbreaks slow down in the coming months, the vaccine supply won’t allow even a delayed second dose. Besides, current WHO guidelines don’t allow an interval of more than 6 months, says Garone, although that could change. “We have asked to fast-track the revision of the evidence on this,” she says.

Meanwhile, Shantha Biotechnics in India, which manufactures 10% of the global cholera vaccine supply, plans to stop production by the end of 2023. WHO Director-General Tedros Adhanom Ghebreyesus has urged Shantha and its parent company, Sanofi, to reconsider its decision, which would leave only one manufacturer, South Korea’s EuBiologics. The International Vaccine Institute (IVI), a nonprofit based in South Korea that helped develop the cheap oral vaccine, is working with EuBiologics to increase its production capacity to some 80 million to 
90 million doses annually, says Julia Lynch, who directs IVI’s cholera program. It’s also helping a South African company named Biovac set up a facility to produce the shots, in a project funded by the Wellcome Trust and the Bill & Melinda Gates Foundation.

But both efforts will take several years. For the foreseeable future, countries that have put together multiyear plans to control cholera and have requested vaccines from the stockpile are likely to get fewer doses than requested, or get them much later, Lynch says. That could lead other countries to not even bother with such plans, she adds. “I really worry about losing the momentum that has been gained.”

Barboza emphasizes that vaccines are only one way to address the crisis. Cholera is easy to treat with oral rehydration solution, as long as it’s administered quickly. That makes access to basic health care crucial. “You don’t need a respirator, an intensive care unit, and God knows what,” Barboza says. Meanwhile, countries should keep working to improve access to clean water and sanitation, he says: “We might have lost a fight, but we have not lost the war.”