the reasons for the shortage of vaccines

Cholera threatens nearly a billion people worldwide, according to the World Health Organization (WHO). In the Middle East with Syria and, potentially, southern Turkey, where living conditions deteriorated sharply after the violent earthquakes in February, in Haiti, in Asia and on the African continent, Malawi in the lead. South Africa, precisely, declared, Thursday, February 23, the death of a 24-year-old man, a first for the second economy of the continent which had, for fifteen years, experienced no death linked to the bacterium. Vibrio cholerae, considered a disease of poverty. Since the beginning of the month, five cases of vibrio contamination have been recorded.

The head of the UN agency, Tedros Adhanom Ghebreyesus, reaffirmed his concern earlier this month over cholera vaccine supply capacities which he described as “very limited”. Currently, 23 countries in the world are facing an epidemic, but around twenty neighboring countries could in turn be affected. In 2022, 31 of them were hit by cholera outbreaks and the number of victims had exceeded that accumulated over the previous five years. On the African continent, by far the most affected, between March 2022, the start of the cholera crisis, and the end of January, 106,000 cases of contamination and nearly 3,000 deaths were declared. Figures that we know are underestimated, for lack, for some countries, of effective monitoring and data collection systems.

Faced with this skyrocketing, the International Vaccine Supply Coordination Group (ICG) took the decision on October 19, 2022 to modify the cholera vaccination schedule from two to a single dose, despite the lower protection that this entails. An emergency measure, announced as temporary, taken to allow a greater number of people to be immunized.

Competition between diseases

The majority of the production of anti-cholera serum is now purchased by GAVI, the Vaccine Alliance, which finances in particular the emergency stock which must be permanently made up of 5 million doses to deal with the crises that arise. However, “en average, only 2.5 million doses are produced each month and all vaccines are allocated almost immediately “, deplores Phillippe Barboza, WHO team leader for cholera and epidemic diarrheal diseases. Indeed, the data published online by UNICEF indicate that just over 2 million vaccines are currently available.

” Since the beginning of this year, large shipments have been sent to Kenya, northwest Syria, Democratic Republic of Congo and Mozambique, which explains the current level of stocks, but we are awaiting the delivery of 1 .5 million doses next week with more planned for the coming weeks,” explains a spokesperson for GAVI, emphasizing that she never had “to say no to a country asking for an emergency delivery”.

Since 1^er January 2022, according to WHO data, just over 30 million cholera vaccines were able to be distributed worldwide, while nearly 63 million had been requested by countries and 40 million allocated by the ICG, which manages the distribution to the States.

The current shortage has been caused by the strong resurgence of cholera since 2021, the result of the conjunction of different factors, from natural disasters linked to climate change – floods but also increased droughts – to the Covid pandemic which put the systems of health under tension and has finished weakening the most vulnerable, also causing competition with the other infectious diseases for which funds and human resources have been greatly reduced for almost three years. The situation at the start of 2023 is thus very far from that imagined by GAVI in its last roadmap on cholera vaccine supply, produced in 2018 and soon to be updated.

The institution then projected an annual production exceeding 80 million doses in 2023, in particular thanks to a diversification of the producers of the oral vaccine, which were only two at the time. But today global production is only based on a single laboratory, the South Korean EuBiologics, the Indian subsidiary of Sanofi, Shanta Biotechnics, having abandoned its production at the end of 2022. According to Philippe Barboza, the director general of the WHO would have himself writes to the French laboratory to ask him to “reconsider this decision which has a negative impact on the availability of the vaccine”.

” When we want we can “

The cholera vaccine was only validated by the WHO as a front-line tool for epidemic response in 2017, so it is a relatively young market and considered unattractive. Indeed, this vaccination is mainly “reactive”that is to say deployed in response to an epidemic and not in prevention. “The consequence of this is that demand is very fluctuating: 60 million doses would have been needed in 2022, but much less in previous years, so it is very difficult for an industrialist to manage”, explains Alain Alsalhani, pharmacist in charge of the cell for access to essential medicines of the NGO Médecins sans frontières (MSF). In addition, vaccines are biological products that are more complex to produce than tablets, which reduces the number of countries with the capacity to manufacture them.

” One can wonder if the development of new sources of vaccine against cholera is a real priority for donors, asks the pharmacist, however. The example of Covid, for which a vaccine was developed and manufactured globally to reach 12 billion doses just two years after the discovery of the disease, shows that when you want you can. »

At the end of 2022, the South African laboratory Biovacs announced that it wanted to embark on the development and production of an oral vaccine against cholera in collaboration with the International Vaccine Institute (IVI). The laboratory could produce the first batches intended for clinical trials, necessary to obtain health authorizations and prequalification by the WHO, in 2024. “We welcome this announcement, but it will be a few years before doses hit the market”comments Philipe Barboza, who also mentions a request for prequalification from Eubiologics for ” a new vaccine with the possibility of increased production “. Another laboratory, Indian, would also be in the running. Encouraging news but which will not resolve the situation in the short term.

Preventive approach

The total availability of doses for 2023 being estimated by the WHO at 36 million, as in 2022, it is more than ever necessary to act upstream in order to limit epidemic outbreaks. This notably involves preventive vaccination campaigns. In addition to improving the protection of the populations most at risk, this preventive approach could also create a stable dose demand that is easy to anticipate.

“The more preventive campaigns are planned, the more we can work with suppliers to increase vaccine production,” insists GAVI. This paradigm shift in the response to cholera materialized last year in 13 countries particularly affected by the disease and will be deployed in other areas in the coming weeks. It remains to be seen whether a demand for doses that is more stable and easier to anticipate will be able to reassure manufacturers and investors, without whom the fight against cholera could become increasingly problematic.