Ethiopia National Cholera Elimination Plan 2022-2028: Experiences, Challenges, and the Way Forward.

Cholera remains a significant public health concern in Ethiopia. More than 15.9 million Ethiopians, constituting 15% of the total population, live in areas with a history of recurrent cholera outbreaks. The last 9 years of national cholera surveillance data show the country has been experiencing cholera outbreaks every year. The current cholera outbreak, starting in August 2022, has affected the entire country, with 841 reported cases and a 3.13% case fatality rate (CFR) in 2022, and >30 000 cases with nearly a 1.4% CFR in 2023. In line with "Ending Cholera-A Global Roadmap to 2030," the government of Ethiopia is committed to eliminate cholera in the country and has prepared its "National Cholera Elimination Plan (NCP): 2022-2028" with aims to achieve zero local transmission in cholera hotspot areas by 2028 and 90% fatality reduction from the recent (2020-2022) average of 1.8% CFR. The plan is multisectoral, has a clear coordination platform, contains all interventions with in-depth situational analysis, is concordant with existing plans and strategies, and is cascaded at the regional level and implemented with existing government and public structures. Nationwide, total 118 cholera hotspot woredas (districts) were identified, and a comprehensive situation analysis of the existing cholera outbreak response capacity was assessed. This multisectoral and multiyear NCP has forecasted around US$404 million budget estimates with >90% allocated to improving the country's water, sanitation, and hygiene (US$222 million; 55% of total NCP budget) and case management (US$149 million; 37%). The cholera vaccination strategy included in the NCP exhibited a 5-year oral cholera vaccine (OCV) introduction plan with 2 doses (30 604 889 doses) and single dose (3 031 266 doses) in selected cholera hotspot areas. However, its implementation is challenged due to a lack of financial support, inability to get the requested vaccine for targeted hotspot woredas (due to the current shortage of doses in the OCV global stockpile), recurrent cholera outbreaks, and high humanitarian needs in the country. It is recommended to have a sustainable financial mechanism to support implementation, follow the requested vaccine doses, and reorganize the planned coordination platform to foster the implementation.

Mathematical Modeling of Endemic Cholera Transmission.

Mathematical modeling can be used to project the impact of mass vaccination on cholera transmission. Here, we discuss 2 examples for which indirect protection from mass vaccination needs to be considered. In the first, we show that nonvaccinees can be protected by mass vaccination campaigns. This additional benefit of indirect protection improves the cost-effectiveness of mass vaccination. In the second, we model the use of mass vaccination to eliminate cholera. In this case, a high population level of immunity, including contributions from infection and vaccination, is required to reach the "herd immunity" threshold needed to stop transmission and achieve elimination.

Use of Vibrio cholerae vaccine in an outbreak in Guinea.

BACKGROUND: The use of vaccines to prevent and control cholera is currently under debate. Shanchol is one of the two oral cholera vaccines prequalified by the World Health Organization; however, its effectiveness under field conditions and the protection it confers in the first months after administration remain unknown. The main objective of this study was to estimate the short-term effectiveness of two doses of Shanchol used as a part of the integrated response to a cholera outbreak in Africa. METHODS: We conducted a matched case-control study in Guinea between May 20 and October 19, 2012. Suspected cholera cases were confirmed by means of a rapid test, and controls were selected among neighbors of the same age and sex as the case patients. The odds of vaccination were compared between case patients and controls in bivariate and adjusted conditional logistic-regression models. Vaccine effectiveness was calculated as (1-odds ratio)×100. RESULTS: Between June 8 and October 19, 2012, we enrolled 40 case patients and 160 controls in the study for the primary analysis. After adjustment for potentially confounding variables, vaccination with two complete doses was associated with significant protection against cholera (effectiveness, 86.6%; 95% confidence interval, 56.7 to 95.8; P=0.001). CONCLUSIONS: In this study, Shanchol was effective when used in response to a cholera outbreak in Guinea. This study provides evidence supporting the addition of vaccination as part of the response to an outbreak. It also supports the ongoing efforts to establish a cholera vaccine stockpile for emergency use, which would enhance outbreak prevention and control strategies. (Funded by Médecins sans Frontières.).

Lessons learnt from 12 oral cholera vaccine campaigns in resource-poor settings.

Improving water and sanitation is the preferred choice for cholera control in the long-term. Nevertheless, vaccination is an available tool that has been shown to be a cost-effective option for cholera prevention in endemic countries or during outbreaks. In 2011 the first low-cost oral cholera vaccine for international use was given prequalification by the World Health Organization (WHO). To increase and prioritize use of the vaccine, WHO created a global stockpile in 2013 from which countries may request oral cholera vaccine for reactive campaigns. WHO has issued specific guidelines for applying for the vaccine, which was previously in short supply (despite prequalification for a second oral vaccine in 2015). The addition of a third WHO-prequalified oral cholera vaccine in 2016 is expected to increase the global stockpile considerably and alleviate supply issues. However, prioritization and best use of the vaccine (e.g. how, when and where to use) will remain challenges. We describe 12 past oral cholera vaccine campaigns, conducted in settings with varying burdens of cholera. These case studies illustrate three key challenges faced in the use of the oral cholera vaccines: regulatory hurdles, cold chain logistics and vaccine coverage and uptake. To pave the way for the introduction of current and future oral cholera vaccines, we discuss operational challenges and make recommendations for future research with respect to each of these challenges.

Améliorer l'accès à l'eau et à l'assainissement est le meilleur moyen de lutter contre le choléra à long terme. Néanmoins, la vaccination s'avère être un outil accessible et rentable pour la prévention du choléra dans les pays où cette maladie est endémique ou pendant des épidémies. En 2011, l'Organisation mondiale de la Santé (OMS) a présélectionné le premier vaccin anticholérique oral à faible coût destiné à un usage international. Afin de favoriser et de hiérarchiser l'usage de ce vaccin, l'OMS a créé en 2013 une réserve mondiale auprès de laquelle les pays peuvent demander des vaccins anticholériques oraux et mettre en œuvre des campagnes réactives. L'OMS a publié des directives spécifiques pour demander ce vaccin, qui n'était auparavant disponible qu'en quantité limitée (malgré la présélection d'un second vaccin oral en 2015). L'ajout, en 2016, d'un troisième vaccin anticholérique oral présélectionné par l'OMS devrait permettre d'augmenter sensiblement les réserves mondiales et d'atténuer les problèmes d'approvisionnement. Il restera cependant à traiter les questions de la hiérarchisation et du meilleur usage du vaccin (par ex., comment, à quel moment et à quel endroit l'utiliser). Nous décrivons ici 12 campagnes de vaccination orale contre le choléra qui ont été menées dans des régions diversement touchées par cette maladie. Ces études de cas illustrent trois grands défis qui se posent lors de l'utilisation de vaccins anticholériques oraux: les obstacles règlementaires, la logistique de la chaîne du froid et la couverture ainsi que le taux de vaccination. Afin de préparer l'introduction de vaccins anticholériques oraux, existants et futurs, nous examinons les difficultés opérationnelles et formulons des recommandations concernant de futurs travaux de recherche sur chacune de ces difficultés.

La mejora del agua y el saneamiento es la opción preferida para el control del cólera a largo plazo. Sin embargo, la vacunación es una herramienta disponible que ha demostrado ser una alternativa rentable para la prevención del cólera en países endémicos o durante brotes. En 2011, la Organización Mundial de la Salud (OMS) precalificó la primera vacuna anticolérica oral de bajo coste para uso internacional. Para aumentar y priorizar el uso de la vacuna, en 2013 la OMS creó una reserva global de la cual los países podían solicitar vacunas anticoléricas orales para campañas reactivas. La OMS ha publicado directrices específicas para la aplicación de la vacuna, cuyo suministro era escaso anteriormente (a pesar de la precalificación para una segunda vacuna oral en 2015). Está previsto que el hecho de añadir una tercera vacuna anticolérica oral precalificada por la OMS en 2016 aumente las reservas globales de forma considerable y reduzca los problemas de suministro. No obstante, la priorización y el buen uso de la vacuna (por ejemplo, cómo, cuándo y dónde utilizarla) seguirán siendo asuntos importantes. Se describen 12 campañas anteriores de vacunación oral contra el cólera, realizadas en entornos con distintos niveles de cólera. Estos estudios de casos ilustran los tres problemas principales que surgen al utilizar vacunas anticoléricas orales: obstáculos reglamentarios, logística de la gestión de la cadena de frío y cobertura y aceptación de la vacuna. Para allanar el terreno en la introducción de vacunas anticoléricas orales en el presente y en el futuro, se analizan las dificultades operativas y se presentan recomendaciones para futuras investigaciones con respecto a estos problemas.

Post-licensure deployment of oral cholera vaccines: a systematic review.

OBJECTIVE: To describe and analyse the characteristics of oral cholera vaccination campaigns; including location, target population, logistics, vaccine coverage and delivery costs. METHODS: We searched PubMed, the World Health Organization (WHO) website and the Cochrane database with no date or language restrictions. We contacted public health personnel, experts in the field and in ministries of health and did targeted web searches. FINDINGS: A total of 33 documents were included in the analysis. One country, Viet Nam, incorporates oral cholera vaccination into its public health programme and has administered approximately 10.9 million vaccine doses between 1997 and 2012. In addition, over 3 million doses of the two WHO pre-qualified oral cholera vaccines have been administered in more than 16 campaigns around the world between 1997 and 2014. These campaigns have either been pre-emptive or reactive and have taken place under diverse conditions, such as in refugee camps or natural disasters. Estimated two-dose coverage ranged from 46 to 88% of the target population. Approximate delivery cost per fully immunized person ranged from 0.11-3.99 United States dollars. CONCLUSION: Experience with oral cholera vaccination campaigns continues to increase. Public health officials may draw on this experience and conduct oral cholera vaccination campaigns more frequently.

Strategy, demand, management, and costs of an international cholera vaccine stockpile.

In this article, we review the feasibility of mass vaccination against cholera and estimate the global population at risk for epidemic cholera. We then examine the cost of establishing and managing a cholera vaccine stockpile and summarize published mathematical models of the estimated impact of reactive vaccination campaigns developed for the current Haitian outbreak and a recent outbreak in Zimbabwe. On the basis of these evaluations, we recommend a stockpile that starts at 2 million doses, with an estimated annual cost of $5.5-$13.9 million in 2013, and grows to 10 million doses per year by 2017, with an annual cost of $27-$51 million. We believe that the stockpile can enhance efforts to mitigate future cholera outbreaks by guaranteeing the availability of cholera vaccines and, through use of the stockpile, by revealing knowledge about the efficient use of cholera vaccines during and after crises.

The value of and challenges for cholera vaccines in Africa.

The 21st century saw a shift in the cholera burden from Asia to Africa. The risk factors for cholera outbreaks in Africa are incompletely understood, and the traditional emphasis on providing safe drinking water and improving sanitation and hygiene has proven remarkably insufficient to contain outbreaks. Current killed whole-cell oral cholera vaccines (OCVs) are safe and guarantee a high level of protection for several years. OCVs have been licensed for >20 years, but their potential for preventing and control cholera outbreaks in Africa has not been realized. Although each item in the long list of technical reasons why cholera vaccination campaigns have been deferred is plausible, we believe that the biggest barrier is that populations affected by cholera outbreaks are underprivileged and lack a strong political voice. The evaluation and use of OCVs as a tool for cholera control will require a new, more compassionate, less risk-averse generation of decision makers.

Social and cultural determinants of anticipated acceptance of an oral cholera vaccine prior to a mass vaccination campaign in Zanzibar.

Despite improvements in sanitation and water supply, cholera remains a serious public health burden. Vaccination is included among recommendations for cholera control. Cultural concepts of illness are likely to affect vaccine acceptance. This study examined social and cultural determinants of anticipated acceptance of an oral cholera vaccine (OCV) prior to a mass vaccination campaign in Zanzibar. Using a cultural epidemiological approach, 356 unaffected adult residents were studied with vignette-based semi-structured interviews. Anticipated acceptance was high for a free OCV (94%), but declined with increasing price. Logistic regression models examined social and cultural determinants of anticipated acceptance at low (USD 0.9), medium (USD 4.5) and high (USD 9) price. Models including somatic symptoms (low and high price), social impact (low and medium) and perceived causes (medium and high) explained anticipated OCV acceptance better than models containing only socio-demographic characteristics. Identifying thirst with cholera was positively associated with anticipated acceptance of the low-priced OCV, but acknowledging the value of home-based rehydration was negatively associated. Concern about spreading the infection to others was positively associated at low price among rural respondents. Confidence in the health system response to cholera outbreaks was negatively associated at medium price among peri-urban respondents. Identifying witchcraft as cause of cholera was negatively associated at medium and high price. Anticipated acceptance of free OCVs is nearly universal in cholera-endemic areas of Zanzibar; pre-intervention assessments of community demand for OCV should not only consider the social epidemiology, but also examine local socio-cultural features of cholera-like illness that explain vaccine acceptance.

Costing oral cholera vaccine delivery using a generic oral cholera vaccine delivery planning and costing tool (CholTool).

Cholera is both an endemic and epidemic disease in many low and middle-income countries (LMICs). Strategies for cholera control include improving water, sanitation, and hygiene; providing early and effective treatment; and deploying oral cholera vaccine (OCV). This last strategy is relatively new, and countries considering its introduction are interested in knowing the potential cost not only of the vaccine, but also the cost of introduction. This paper describes the costing of OCV introduction in LMICs using a publicly available Excel-based tool known as the CholTool. It includes estimates of delivery cost categories which cover not only the service delivery costs (e.g. vaccine procurement, handling, storage, and transport; vaccination administration, monitoring supervision, and field support), but also the programmatic costs associated with introducing a new vaccine (i.e. microplanning, communication and training materials development, sensitization/social mobilization, and personnel training) to ensure that a comprehensive estimate is provided with health payer perspective. CholTool takes the user through a structured sequence of interlinked modules containing input parameter cells (assumptions), decision cells (variable selections), and formulas (calculations) to produce customized cost estimates based on standardized methods. The tool provides both financial and economic cost estimates, to ensure that both costs are available for consideration. Four examples of applications of CholTool are presented in three countries- one in Ethiopia, two in Malawi and one in Nepal. The estimates of economic delivery cost per dose (including service delivery and programmatic costs) were (in USD 2016): $2.89 in Ethiopia, $3.04 in Malawi1, $3.35 in Malawi2 and $3.06 in Nepal. A cost projection conducted before the campaign using the tool and a retrospective costing using the tool in Nepal resulted in no significant difference between economic delivery costs per dose.

Willingness to pay for oral cholera vaccines in urban Bangladesh.

INTRODUCTION: Cholera is a highly infectious disease and remains a serious public health burden in Bangladesh. The objective of the study was to measure the private demand for oral cholera vaccines (OCV) in Bangladesh and to investigate the key determinants of this demand, reflected in the household's willingness to pay (WTP) for oral cholera vaccine. METHODS: A contingent valuation method was employed in an urban setting of Bangladesh during December 2015 to January 2016. All respondents (N = 1051) received a description of World Health Organization (WHO) prequalified OCV, Shanchol™. Interviews were conducted with either the head of households or their spouse or a major economic contributor of the households. Respondents were asked about how much at maximum they were willing to pay for OCV for their own and their household members' protection. Results are presented as the average and median of the reported maximum WTP of the respondents with standard deviations and 95% confidence interval. Natural log-linear regression model was employed to examine the factors influencing participants' WTP for OCV. RESULTS: About 99% of the respondents expressed WTP for OCV with a maximum mean and median WTP per vaccination (2 doses) of US$ 2.23 and US$ 1.92 respectively. On the household level with an average number of 4.62 members, the estimated mean WTP was US$ 10 (median: US$ 7.69) which represents the perceived demand for OCV of a household to vaccinate against cholera. CONCLUSIONS: The demand of vaccination further indicates that there is a potential scope for recovering a certain portion of the expenditure of immunization program by introducing direct user fees for future cholera vaccination in Bangladesh. Findings from this study will be useful for the policy-makers to make decision on cost-recovery in future oral cholera vaccination programs in Bangladesh and in similar countries.

Cost-effectiveness of new-generation oral cholera vaccines: a multisite analysis.

OBJECTIVES: We evaluated the cost-effectiveness of a low-cost cholera vaccine licensed and used in Vietnam, using recently collected data from four developing countries where cholera is endemic. Our analysis incorporated new findings on vaccine herd protective effects. METHODS: Using data from Matlab, Bangladesh, Kolkata, India, North Jakarta, Indonesia, and Beira, Mozambique, we calculated the net public cost per disability-adjusted life year avoided for three immunization strategies: 1) school-based vaccination of children 5 to 14 years of age; 2) school-based vaccination of school children plus use of the schools to vaccinate children aged 1 to 4 years; and 3) community-based vaccination of persons aged 1 year and older. RESULTS: We determined cost-effectiveness when vaccine herd protection was or was not considered, and compared this with commonly accepted cutoffs of gross domestic product (GDP) per person to classify interventions as cost-effective or very-cost effective. Without including herd protective effects, deployment of this vaccine would be cost-effective only in school-based programs in Kolkata and Beira. In contrast, after considering vaccine herd protection, all three programs were judged very cost-effective in Kolkata and Beira. Because these cost-effectiveness calculations include herd protection, the results are dependent on assumed vaccination coverage rates. CONCLUSIONS: Ignoring the indirect effects of cholera vaccination has led to underestimation of the cost-effectiveness of vaccination programs with oral cholera vaccines. Once these effects are included, use of the oral killed whole cell vaccine in programs to control endemic cholera meets the per capita GDP criterion in several developing country settings.

Effectiveness and economic analysis of the whole cell/recombinant B subunit (WC/rbs) inactivated oral cholera vaccine in the prevention of traveller's diarrhoea.

BACKGROUND: Nowadays there is a debate about the indication of the oral whole-cell/recombinant B-subunit cholera vaccine (WC/rBS) in traveller's diarrhoea. However, a cost-benefit analysis based on real data has not been published. METHODS: A cost-effectiveness and cost-benefit study of the oral cholera vaccine (WC/rBS), Dukoral for the prevention of traveller's diarrhoea (TD) was performed in subjects travelling to cholera risk areas. The effectiveness of WC/rBS vaccine in the prevention of TD was analyzed in 362 travellers attending two International Vaccination Centres in Spain between May and September 2005. RESULTS: The overall vaccine efficacy against TD was 42,6%. Direct healthcare-related costs as well as indirect costs (lost vacation days) subsequent to the disease were considered. Preventive vaccination against TD resulted in a mean saving of 79.26 euro per traveller. CONCLUSION: According to the cost-benefit analysis performed, the recommendation for WC/rBS vaccination in subjects travelling to zones at risk of TD is beneficial for the traveller, regardless of trip duration and visited continent.

Evaluating the costs of cholera illness and cost-effectiveness of a single dose oral vaccination campaign in Lusaka, Zambia.

INTRODUCTION: In 2016, for the very first time, the Ministry of Health in Zambia implemented a reactive outbreak response to control the spread of cholera and vaccinated at-risk populations with a single dose of Shancol-an oral cholera vaccine (OCV). This study aimed to assess the costs of cholera illness and determine the cost-effectiveness of the 2016 vaccination campaign. METHODOLOGY: From April to June 2017, we conducted a retrospective cost and cost-effectiveness analysis in three peri-urban areas of Lusaka. To estimate costs of illness from a household perspective, a systematic random sample of 189 in-patients confirmed with V. cholera were identified from Cholera Treatment Centre registers and interviewed for out-of-pocket costs. Vaccine delivery and health systems costs were extracted from financial records at the District Health Office and health facilities. The cost of cholera treatment was derived by multiplying the subsidized cost of drugs by the quantity administered to patients during hospitalisation. The cost-effectiveness analysis measured incremental cost-effectiveness ratio-cost per case averted, cost per life saved and cost per DALY averted-for a single dose OCV. RESULTS: The mean cost per administered vaccine was US$1.72. Treatment costs per hospitalized episode were US$14.49-US$18.03 for patients ≤15 years old and US$17.66-US$35.16 for older patients. Whereas households incurred costs on non-medical items such as communication, beverages, food and transport during illness, a large proportion of medical costs were borne by the health system. Assuming vaccine effectiveness of 88.9% and 63%, a life expectancy of 62 years and Gross Domestic Product (GDP) per capita of US$1,500, the costs per case averted were estimated US$369-US$532. Costs per life year saved ranged from US$18,515-US$27,976. The total cost per DALY averted was estimated between US$698-US$1,006 for patients ≤15 years old and US$666-US$1,000 for older patients. CONCLUSION: Our study determined that reactive vaccination campaign with a single dose of Shancol for cholera control in densely populated areas of Lusaka was cost-effective.

Feasibility, coverage and cost of oral cholera vaccination conducted by icddr,b using the existing national immunization service delivery mechanism in rural setting Keraniganj, Bangladesh.

Background: Cholera is a considerable health burden in developing country settings including Bangladesh. The oral cholera vaccine (OCV) is a preventative tool to control the disease. The objective of this study was to describe whether the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b), could provide the OCV to rural communities using existing government infrastructure. Methods: The study was conducted in rural sub-district Keraniganj, 20 km from the capital city Dhaka. All listed participants one year and above in age (excluding pregnant women) were offered two doses of OCV at a 14 day interval. Existing government facilities were used to deliver and also maintain the cold chain required for the vaccine. All events related to vaccination were recorded at the 17 vaccination sites to evaluate the coverage and feasibility of OCV program. Results: A total of 29,029 individuals received the 1st dose (90% of target) and 26,611 individuals received the 2nd dose (83% of target and 92% of 1st dose individuals) of OCV. The highest vaccination coverage was in younger children (1-9 years) and the lowest was amongst 18-29-year age group. Somewhat better coverage was seen amongst the female participants than males (92% vs. 88% for the 1st dose and 93% vs. 90% for the 2nd dose). The cost of vaccine cost was calculated as US$1.00 per dose plus freight, insurance, and transportation and the total vaccine delivery cost was US$70,957. Conclusion: This was a project undertaken using existing public health program resources to collect empirical evidence on the use of a mass OCV campaign in the rural setting. Mass vaccination with the OCV is feasible in the rural setting using existing governmental vaccine delivery systems in Bangladesh.

Implications and measurement of herd protection (indirect effects) for enteric vaccine development.

Diarrhea remains one of the top five causes of disease and death among young children in developing nations. Fortunately, scientists are making progress developing vaccines against enterotoxigenic E. coli (ETEC) and Shigella, two of the leading diarrhea pathogens. As vaccine developers start to consider field efficacy trials of these vaccines, they should be aware of the importance of evaluating not only vaccine direct effects on the immunized, but also the herd effects that vaccination can afford to the unimmunized in a community. In a workshop held at the conference titled "Vaccines against Shigella and ETEC (VASE)", we described to participants what herd effects are and we presented on methods used in cholera and rotavirus studies that could be useful for future ETEC and Shigella vaccine trials conducted in low and middle-income nations. We also presented evidence on the effects of vaccine herd effects for estimates of vaccine cost-effectiveness.