Countries grapple with global shortage of oral cholera vaccine

In February, the World Health Organization reported that its stock of oral cholera vaccines, or OCV, was empty. It was replenished by South Korean biopharmaceutical company EuBiologics but stocks ran low again in October, and that month the health agency was unable to entirely fulfill requests from countries experiencing outbreaks, including Bangladesh, Sudan, Niger, Ethiopia, and Myanmar. Health professionals are worried that unless manufacturing is ramped up, shortages will continue amid growing demand, putting more people at risk of the deadly waterborne virus. “A potential stock-out of the WHO’s OCV is indeed a grave concern, particularly for the vulnerable populations in cholera endemic regions,” said Dr. Firdausi Qadri, senior scientist at the International Centre for Diarrhoeal Disease Research, Bangladesh, or icddr,b. Cholera spreads via the consumption of contaminated water causing severe diarrhea and dehydration. It can be easily treated with antibiotics and fluids, but without action, it can kill within hours. The number of cases has been climbing in recent years. In 2023, more than 4,000 people died of the disease, 71% more than in 2022, and 2024 is set to see a further increase as the death toll had already exceeded 4,000 as of Oct. 27. The number of reported cases climbed by 13% from 2022 to 2023, triggering greater demand for OCV. To meet this, vaccine production jumped by 30% from 2023 to 2024, and production reached a record high in November, but still hasn’t been enough to meet the current demand. According to WHO, the target is to have 5 million OCV doses at all times — yet the average was less than 600,000 doses in October. There is only one supplier, EuBiologics, approved by WHO to replenish its global stockpile of OCV despite other manufacturers producing the vaccine. WHO’s International Coordinating Group for Vaccine Provision, or ICG, then allocates it to countries based on need. Since 2013, Gavi, The Vaccine Alliance has funded the doses, transport, and vaccination activities. WHO estimates that over 1 billion people in 43 countries are currently at risk of cholera, but the disconnect between demand and supply means the ICG has to be strategic in its allocation and has had to halt preventative vaccine campaigns. The Global Task Force on Cholera Control had estimated that 250 million doses of OCV would be needed between 2022 and 2026 period to support its road map to achieving a 90% reduction in deaths and cholera elimination in up to 20 countries by 2030. However, as demand grows, a WHO spokesperson told Devex via email that it may have to revise its figures “including in countries not previously listed as endemic.” As of December, the stockpile had been replenished but the WHO remains wary of another potential shortage. Despite record production that month, “the global OCV stockpile has only one million doses as of 7 November 2024,” a WHO spokesperson wrote via email. “This is far below the target of five million doses needed for emergency stockpile at all times for effective outbreak response,” The climbing rates The increase in cholera has been attributed to growing numbers of conflicts around the world as well as to climate change. As conflict breaks out, displacement increases, and in such contexts where access to clean water, sanitation, and hygiene is limited that diseases such as cholera thrive. Furthermore, climate change is drying up water sources, causing sea levels to rise and contaminating previously reliable water sources, and forcing people to drink more while floods, droughts, and storms damage infrastructure, drive up displacement, and again lead to more contaminated water. Bangladesh has one of the worst global rates of cholera alongside countries such as Malawi, Haiti, Zambia, and the Democratic Republic of Congo. Bangladesh is home to the world’s largest refugee camp in Cox’s Bazar and is susceptible to floods, heat waves, and droughts — creating the perfect storm of conditions for cholera to thrive. The icddr,b, located in the capital of Bangladesh, saw record cases of cholera this year. Its typical daily admission rate is around 500, but exceeded 1,300 in April and May, according to Dr. Shoeb Bin Islam, clinical lead at the hospital and research center. Staff had to funnel gurneys into hallways and the parking lot in order to make room for the sick. The surge, said Islam, correlates to the pre-monsoon and post-monsoon season. At this time, temperatures rise and people drink more water, but in a country where clean water is hard to find, waterborne diseases such as cholera run rampant. Almost half of the population doesn’t have access to clean water and yearly cholera cases in Bangladesh number over 100,000. On a Thursday morning in November, the beds of the short-stay ward of the icddr,b hospital are mostly occupied by toddlers, their parents trying to soothe their wails or usher them into rest. Without adequate access to OCV, more people, including children, are likely to contract cholera. Not only do these shortages mean higher mortality rates, said Qadri, but they undermine years of progress in cholera prevention and control, leaving “millions at risk of preventable illness and mortality.” Bangladesh, for example, has had to halt its preventative cholera campaign throughout 2024. The solution The main solution to the problem is to support more manufacturers in producing the vaccine, said Qadri, as part of a coordinated global response to secure adequate funding, and maintain a reliable supply. Several, such as Bharat Biotech International Limited in India, Biovac in South Africa, and Vabiotech in Vietnam are working on it with the support of the International Vaccine Institute. Bangladesh has also commercially registered an OCV that it developed through technology transfer from the IVI, but the issue, as with many of these initiatives, is that Bangladesh’s National Regulatory Authority is not WHO-prequalified, which means the new dose can’t be given at scale. Such a process takes time. In April, Eubiologics did, however, receive WHO prequalification status for a simplified formulation of the OCV that could help meet global demand. But the consensus is that more manufacturers are needed — and soon. “Because a vaccine market dependent on outbreak demand is not sustainable -- given the wide variations in supply needed year-to-year – preventive vaccination programs are also critical to create predictable demand over time to incentivize long-term investments by manufacturers,” a Gavi spokesperson said in an email. “In the meantime, we have to continue to use vaccines sparingly and strategically,” said the WHO spokesperson. “But this is not sustainable long-term and will not fully stop cholera.”