Oral cholera vaccination delivery cost in low- and middle-income countries: An analysis based on systematic review

Cholera is transmitted through the fecal-oral route, and humans are the natural host. It is caused by the ingestion of O1 and less commonly O139 serogroups of the Vibrio cholerae bacterium and characterized by severe, potentially life-threatening diarrhea [1]. The disease inflicts a significant health burden on many low-and-middle-income countries (LMICs) in settings where food and water are contaminated with human feces. Infrastructure disruption resulting from natural disasters, civil unrest, and war often precipitates cholera outbreaks, particularly in settings where there is endemic cholera risk. Cholera outbreak risk is further increased when infrastructure disruption is superimposed on the poor sanitation and unsafe drinking water found in parts of Africa, Asia, and South and Central America [2]. While improving water and sanitation infrastructure would greatly enhance the control of cholera in the long-term, the use of preventive vaccines has shown promise in the interim [3–5].

The struggle to develop a safe and effective cholera vaccine that can prevent and control the disease has a long history. Injectable whole-cell cholera vaccines were developed as early as the 19th century and extensively used in the 20th century in the Indian subcontinent and later abandoned due to their limited efficacy and systemic adverse events [6,7]. Subsequently, a new generation of live-attenuated or killed oral cholera vaccines were developed, licensed, and deployed. A killed whole-cell cholera vaccine with recombinant B subunit of cholera toxin (Dukoral) was licensed in 1991 (two-dose regimen for >2 years of age) [6] and used by travelers visiting cholera-endemic regions. This vaccine received World Health Organization (WHO) prequalification in 2001 and has a price of $5 per dose on the public market. Meanwhile, Vietnam developed and deployed a locally manufactured OCV, ORC-Vax [8]. The vaccine was licensed in 1997 in Vietnam and was modified to mORC-Vax in 2009 after improving the production process. Currently, the price of this vaccine is US$1.25 per dose on Vietnam’s public market. At the same time, international efforts were made to reformulate ORC-Vax into a less expensive modified killed whole-cell OCV, which was first licensed in India in 2009 (Shanchol, two-dose regimen for >1 year of age), and later WHO-prequalified in 2011. Currently, the price of this vaccine is $1.85 per dose on the public market worldwide. A WHO OCV stockpile was then created in 2013 to make the vaccine available and affordable in emergency settings [9,10]. These two WHO-prequalified OCVs, Dukoral and Shanchol have been deployed in mass vaccination campaigns across many endemic regions either pre-emptively or reactively; notably in Haiti, Comoros, Indonesia, Uganda, Mozambique, Tanzania, India, Bangladesh, Guinea, South Sudan, Malawi, Thailand, Ethiopia and Nepal.