Adapting existing tools to control and eliminate protracted epidemics and pandemics

Abstract

Cholera is a disease of inequity that today kills the poorest and most vulnerable people in Africa, Asia, and the Hispaniola region (comprising of Haiti and the Dominican Republic).1WHOMulti-country outbreak of cholera, external situation report #11–12 February 2024.https://www.who.int/publications/m/item/multi-country-outbreak-of-cholera--external-situation-report--11--12-february-2024Date accessed: February 14, 2024Google Scholar Data on cholera are often incomplete and underreported. Hence, the global burden of cholera is largely unknown. However, a previous study that used data collected from 2008 to 2012 estimated cholera to annually infect 1 300 000–4 000 000 individuals and kill 21 000–143 000 people globally.2Ali M Nelson AR Lopez AL Sack DA Updated global burden of cholera in endemic countries.PLoS Negl Trop Dis. 2015; 9e0003832 Crossref Scopus (708) Google Scholar Since 1817, there has been seven major cholera pandemics. The ongoing seventh protracted pandemic originated in Indonesia in 1961. Cholera control involves a multi-sectoral approach, including water, sanitation, and hygiene (WASH) services, oral cholera vaccine administration and other interventions (leadership, coordination, surveillance, case management, and community engagement). In 2017, WHO launched a global roadmap to reduce cholera deaths and eliminate the disease from more than 20 affected countries.3Global Taskforce on Cholera ControlEnding cholera: a global roadmap to 2030.https://www.gtfcc.org/wp-content/uploads/2019/10/gtfcc-ending-cholera-a-global-roadmap-to-2030.pdfDate accessed: March 6, 2024Google Scholar However, large outbreaks in southern and eastern Africa and the Middle East between 2022 and 2023 suggest little progress has been made toward this goal. Despite the slow improvement in WASH services for impoverished communities and increased cholera risk, the global oral cholera vaccine supply remains inadequate.5Qadri F Ali M Lynch J et al.Efficacy of a single-dose regimen of inactivated whole-cell oral cholera vaccine: results from 2 years of follow-up of a randomised trial.Lancet Infect Dis. 2018; 18: 666-674Summary Full Text Full Text PDF PubMed Scopus (54) Google Scholar Yet it was hoped that oral cholera vaccine would be a tool that could be used to reduce cholera rates until WASH improvements could be implemented worldwide. However, because of the inadequate supply of oral cholera vaccines, the International Coordinating Group is distributing oral cholera vaccines as a single dose.4WHOCholera–global situation.https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON437Date accessed: November 19, 2023Google Scholar A single dose is effective at preventing cholera (disease or infection), but the duration of protection is likely to be shorter than the recommended two dose schedule.5Qadri F Ali M Lynch J et al.Efficacy of a single-dose regimen of inactivated whole-cell oral cholera vaccine: results from 2 years of follow-up of a randomised trial.Lancet Infect Dis. 2018; 18: 666-674Summary Full Text Full Text PDF PubMed Scopus (54) Google Scholar WHO first recommended oral cholera vaccine use in endemic and in cholera high-risk settings in 2010. In 2011, for the first time a relatively low cost oral cholera vaccine WHO prequalified vaccine, Shanchol entered the global vaccine market. In 2016, the total cost for each dose of Shanchol was US$2·86, including a $0·91 delivery cost among recipients in Bangladesh.6Sarker AR Khan AI Islam MT et al.Cost of oral cholera vaccine delivery in a mass immunization program for children in urban Bangladesh.Vaccine X. 2022; 12100247 Crossref Scopus (0) Google Scholar But after 14 years, the production capacity and availability of the oral cholera vaccine remains inadequate. In The Lancet Global Health, Katerina Song and colleagues7Song KR Chapagain RH Tamrakar D et al.Safety and immunogenicity of the Euvichol-S oral cholera vaccine for prevention of Vibrio cholerae O1 infection in Nepal: an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial.Lancet Glob Health. 2024; 12: e826-e837Google Scholar report the results of a phase 3 clinical trial done in Nepal, which investigated the safety and immunogenicity of Euvichol-S, an oral cholera vaccine that is manufactured using fewer constituents than Euvichol (an oral cholera vaccine with similar composition to Euvichol). Previously, a phase 1 clinical trial of Euvichol oral cholera vaccine was conducted in South Korea in 2012, with promising safety and immunogenicity results. Furthermore, a phase 3 trial in the Philippines found that Euvichol was safe, immunogenic, and non-inferior to Shanchol with regard to vibriocidal antibody responses to the Vibrio cholerae O1 serotype. In 2015, Euvichol was prequalified by WHO. In 2017, the newer form, Euvichol-Plus, formulated with no thiomersal, in plastic vials received WHO prequalification. In 2017 and 2018, Euvichol-Plus was deployed in Lusaka (Zambia) for cholera outbreak control and provided high protective vaccine efficacy with one dose or two doses (74–81%).8Sialubanje C Kapina M Chewe O et al.Effectiveness of two doses of Euvichol-plus oral cholera vaccine in response to the 2017/2018 outbreak: a matched case-control study in Lusaka, Zambia.BMJ Open. 2022; 12e066945 Crossref Scopus (6) Google Scholar Thereafter, a phase 3 clinical trial of Euvichol-Plus in India (an endemic setting) found the vaccine to be non-inferior to Shanchol in terms of immunogenicity and safety among the vaccine recipients. Although only Shanchol and Euvichol are available in the global oral cholera vaccine stockpile, Sanofi Pasteur ceased production of Shanchol in 2023. Ceasing Shanchol production has worsened the current shortage of oral cholera vaccine.4WHOCholera–global situation.https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON437Date accessed: November 19, 2023Google Scholar Euvichol-S, with simple and inactivated ingredients (and potentially cheaper costs) has the potential to address the current oral cholera vaccine shortage. The formulation of Euvichol-S, which comprises two formalin-inactivated components (V cholerae O1 Inaba El Tor strain [900 lipopolysaccharide ELISA unit (LEU)] and O1 Ogawa classical strain [600 LEU]) has less antigenic variation than currently available vaccines. The International Vaccine Institute and EU Biologics assessed the production cost of Euvichol-S oral cholera vaccine and found it was around 25% lower than for Euvichol and production capacity was increased by 38% compared with Euvichol. Absence of the V cholerae O139 component in Euvichol-S increases specific cross-reactive protection against V cholerae O1. To expedite the process of WHO prequalification, regulatory authorities in cholera-endemic or high-risk countries should collaborate with the WHO prequalification group to create a roadmap. This roadmap should streamline the vaccine production process and ensure efficient licensure through regular meetings with funders, the National Regulatory Authorities of the respective country, and external collaborators. Lessons learnt from the ongoing and previous epidemics indicate that a shift is needed in the global management of the oral cholera vaccine stockpile to ensure that countries affected by cholera have several options to access oral cholera vaccines without depending on the global oral cholera vaccine stockpile located in Geneva, Switzerland.9Bwire G Tumuhairwe I Kwagonza L et al.Rapid cholera outbreak control following catastrophic landslides and floods: a case study of Bududa district, Uganda.Afr Health Sci. 2023; 23: 203-215Crossref Scopus (1) Google Scholar There is a need for policy makers to organise and finance additional oral cholera vaccine stockpile arrangements in endemic countries. This policy shift should be accompanied by revised regulatory frameworks that facilitate rapid importation, pre-positioning, and deployment of oral cholera vaccine in cholera endemic countries for outbreak control and prevention. Regulatory authorities within the affected countries should improve documentation and establish robust Good Clinical Practice guidelines for vaccine prequalification. To ensure rapid deployment of oral cholera vaccines to where they are needed most and to promote an equitable and larger supply of oral cholera vaccines, initially, the priority should be to establish production facilities in each of the affected continents (ie, Africa and Asia). Thereafter, establishment of additional production facilities within Africa or Asia should depend on feasibility studies. For example, a vaccine hub established in South Africa in 2023, and a facility in Rwanda due for completion in 2024, could address vaccine inequalities in Africa and should be supported to produce Euvichol-S in addition to other essential vaccines.10Saied ARA Building Africa's first mRNA vaccine facility.Lancet. 2023; 402: 287-288Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar Finally, further studies are required to enhance oral cholera vaccine cost reduction and to sustain oral cholera vaccine supply to meet the demand. Studies should include those on the new generation inactivated oral cholera vaccines and their protective properties and antigen composition for determination of correlation of the protective efficacy of these vaccines in the population. We declare no competing interests. Safety and immunogenicity of the Euvichol-S oral cholera vaccine for prevention of Vibrio cholerae O1 infection in Nepal: an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trialA two-dose regimen of Euvichol-S vaccine was non-inferior to the active control vaccine, Shanchol, in terms of seroconversion rates 2 weeks after the second dose. The simplified formulation and production requirements of the Euvichol-S vaccine have the potential to increase the supply of oral cholera vaccine and reduce the gap between the current oral cholera vaccine supply and demand. Full-Text PDF Open Access