The global stockpile of the oral cholera vaccine is still worryingly depleted – even as outbreaks of the disease continue worldwide, and with predictions that these are unlikely to decrease any time soon.
Although the vaccine produced by the Indian firm Bharat Biotech is expected to become available in the second half of 2025, and one from South African firm Biovac by 2027, this will not provide the immediate relief needed by countries in crisis.
In 2022, the disease returned to Syria after an absence of 15 years and crossed the border into Lebanon, where it had not been detected since 1993. A huge outbreak took hold in Malawi after the country was hit by two tropical storms. Haiti had harboured hopes of eliminating cholera; instead, it experienced a resurgence of the disease.
In all, 472 697 cases of cholera and 2349 deaths were reported to WHO – and 2023 was even worse.
The Lancet reports that preliminary figures for last year place the number of cases of cholera or acute watery diarrhoea in the region of 708 000, with more than 4 300 deaths. Whether the upward trend will continue in 2024 remains to be seen.
The early indications are troubling: January saw 40 900 cases and 775 deaths in 17 countries.
One thing is certain: there will not be enough vaccines to meet the demand.
As The Lancet went to press, the global stockpile of the oral cholera vaccine had been entirely depleted. New doses are being produced at a rate of around 2.5m per month – all of them already allocated until at least mid-March.
“It is impossible to anticipate what is going to happen, but there is no reason to believe we will see fewer outbreaks of cholera this year,” said Philippe Barboza, team lead for Cholera and Epidemic Diarrhoeal Diseases at the WHO in Geneva.
“If we take the vaccine as the indicator, then we are in a worse position this year than we were last year, or the year before.”
Shantha Biotechnics, an Indian subsidiary of Sanofi, was responsible for around 15% of the oral cholera vaccine stockpile in 2023. It exited the market at the end of the year, leaving the stockpile completely reliant on a single manufacturer – the South Korean firm EuBiologics.
It has historically proven difficult to entice companies to produce the oral cholera vaccine, as demand is unpredictable and the price is low.
EuBiologics plans to make 35m doses of the currently used vaccine available this year. A further 15m or so doses could be released if, as expected, WHO prequalifies EuBiologics’ simplified oral cholera vaccine in April.
In that case, around 50m doses of vaccine will enter the global stockpile in 2024.
Unicef has suggested that demand for the year will be 90m to 100m doses. Any major new outbreak of cholera, for example, in the aftermath of an earthquake, flooding event, or conflict, could strain supplies even further.
The global stockpile of the oral cholera vaccine was established in 2013. At the time, 2m doses were available globally.
By 2023, production had expanded to 36m doses. The stockpile is overseen by the International Co-ordinating Group on Vaccine Provision (ICG), which is made up of the International Federation of the Red Cross and Red Crescent Societies, Médecins Sans Frontières, Unicef and WHO.
Gavi, the Vaccine Alliance, pays for both the oral cholera vaccine and the operational costs of distribution for all eligible countries, which in practice means virtually everywhere the disease is found.
Until recently, demand for the vaccine had been manageable. From 2016 to 2020, roughly half of the global supply remained available for preventive campaigns after emergency needs had been addressed.
Demand began to spike in 2021. Nearly 48m doses of the oral cholera vaccine were distributed in 2021 and 2022 alone, compared with a total of 38m doses for 2011-20.
Andrew Azman, associate scientist in the Department of Epidemiology at Johns Hopkins Centre for Humanitarian Health, USA, said: “During the Covid-19 pandemic, there was an apparent lull in cholera and control efforts were understandably deprioritised.”
“Many countries at risk of cholera emerged from the pandemic with a large pool of susceptible individuals, due to waning vaccine protection and fewer exposures to Vibrio cholerae.”
Three successive years of the La Niña weather event created conditions ripe for cholera across eastern and southern Africa.
In October, 2022, WHO Director-General Tedros Adhanom Ghebreyesus said cholera was “being turbocharged by climate change”. Conflict and population displacement are other important factors. Nine of the 30 countries to experience outbreaks in 2022 were subject to warfare or serious violence.
Aurélia Nguyen, chief programme officer at Gavi, said the destigmatisation of cholera might also have helped to drive demand for the vaccine, with countries being “more forthcoming these days” in reporting cholera.
Fortunately, the shortage looks likely to be temporary. If everything goes according to plan, EuBiologics should be able to produce 80m doses of vaccine in 2025.
“We have a very active pipeline,” said Nguyen. The vaccine produced by the Indian firm Bharat Biotech is also expected to become available in the second half of 2025, and one from South African firm Biovac is expected by 2027.
“Three manufacturers is the minimum you would want,” said Nguyen.
The Global Task Force on Cholera Control has set a target of reducing cases by 90% by 2030. Countries can apply to Gavi for support for preventive vaccination campaigns, but as things stand, there is not enough vaccine to go around.
The emergence of cholera invariably signals catastrophic systemic collapse. Several of the recent outbreaks have resulted in case fatality rates exceeding the 1% threshold at which deaths are considered to be unacceptably high.
“People are dying because they cannot get simple oral rehydration solution,” said Barboza. “If you have a cholera outbreak, you are ticking all the boxes for vulnerability, poverty, and lack of access to healthcare. It is 2024 and people are still dying because they are drinking unsafe water.”
He urged nation states and donors to commit to the same kind of improvements in water, sanitation, and hygiene that banished cholera from Europe and North America.
The Lancet article – The great cholera vaccine shortage (Open access)
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Desperate countries face world shortage of 50m cholera vaccines
WHO shifts to one-dose cholera jab as outbreaks increase, stocks dwindle
Malawi runs out of cholera vaccines as cases rise