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.

Private sector engagement and contributions to immunisation service delivery and coverage in Sudan.

For more than two decades, the private sector in the Sudan (henceforth, Sudan), including non-governmental organisations and for-profit providers, has played a key role in delivering immunisation services, especially in the conflict-affected Darfur region and the most populated Khartoum state. The agreements that the providers enter into with state governments necessitate that they are licenced; follow the national immunisation policy and reporting and supervision requirements; use the vaccines supplied by government; and offer vaccinations free-of-charge. These private providers are well integrated into the states' immunisation programmes as they take part in the Ministry of Health immunisation trainings and district review meetings and they are incorporated into annual district immunisation microplans. The purpose of this article is to describe the private sector contributions to equitable access to immunisation services and coverage, as well as key challenges, lessons learned and future considerations. Fifty-five per cent of private health facilities in Sudan (411 out of 752) provide immunisation services, with 75% (307 out of 411) based in Khartoum state and the Darfur region. In 2017, private providers administered around 16% of all third doses of pentavalent (diphtheria, pertussis, tetanus, hepatitis B and Haemophilus influenzae type b) vaccines to children. Private health providers of immunisation services have especially been critical in filling the gaps in government services in hard-to-reach or conflict-affected areas and among marginalised populations, and thus in reducing inequities in access. Through its experience in engaging the private sector, Sudan has learned the importance of regulating and licencing private facilities and incorporating them into the immunisation programme's decision-making, planning, regular evaluation and supervision system to ensure their compliance with immunisation guidelines and the overall quality of services. In moving forward, strategic engagement with the private sector will become more prominent as Sudan transitions out of donors' financial assistance with its projected income growth.

Breaking the inertia in coverage: Mainstreaming under-utilized immunization strategies in the Middle East and North Africa region.

Vaccination coverage rates have stagnated in the past several years in many middle-income countries (MICs), especially in the UNICEF Middle East and North Africa region, with political and economic turmoil as contributing factors. This paper reviews country experiences with three under-utilized strategies aimed at increasing vaccination coverage and reducing disparities between socio-economic and geographic groups in MICs. These strategies include: (1) identifying and accounting for displaced, mobile and neglected populations; (2) assessing and addressing missed opportunities for vaccination, including by expanding immunization into the second year of life and beyond; and (3) engaging effectively with the private/nongovernmental health providers in the coordination, provision and reporting of immunization services. The examples focus primarily on quality data collection, analysis, use and reporting aspects of the strategies. While data are limited, there is evidence from MICs that each of these strategies can have a positive impact on vaccination coverage, especially among marginalized populations.

The impact and cost-effectiveness of controlling cholera through the use of oral cholera vaccines in urban Bangladesh: A disease modeling and economic analysis.

BACKGROUND: Cholera remains an important public health problem in major cities in Bangladesh, especially in slum areas. In response to growing interest among local policymakers to control this disease, this study estimated the impact and cost-effectiveness of preventive cholera vaccination over a ten-year period in a high-risk slum population in Dhaka to inform decisions about the use of oral cholera vaccines as a key tool in reducing cholera risk in such populations. METHODOLOGY/PRINCIPAL FINDINGS: Assuming use of a two-dose killed whole-cell oral cholera vaccine to be produced locally, the number of cholera cases and deaths averted was estimated for three target group options (1-4 year olds, 1-14 year olds, and all persons 1+), using cholera incidence data from Dhaka, estimates of vaccination coverage rates from the literature, and a dynamic model of cholera transmission based on data from Matlab, which incorporates herd effects. Local estimates of vaccination costs minus savings in treatment costs, were used to obtain incremental cost-effectiveness ratios for one- and ten-dose vial sizes. Vaccinating 1-14 year olds every three years, combined with annual routine vaccination of children, would be the most cost-effective strategy, reducing incidence in this population by 45% (assuming 10% annual migration), and costing was $823 (2015 USD) for single dose vials and $591 (2015 USD) for ten-dose vials per disability-adjusted life year (DALY) averted. Vaccinating all ages one year and above would reduce incidence by >90%, but would be 50% less cost-effective ($894-1,234/DALY averted). Limiting vaccination to 1-4 year olds would be the least cost-effective strategy (preventing only 7% of cases and costing $1,276-$1,731/DALY averted), due to the limited herd effects of vaccinating this small population and the lower vaccine efficacy in this age group. CONCLUSIONS/SIGNIFICANCE: Providing cholera vaccine to slum populations in Dhaka through periodic vaccination campaigns would significantly reduce cholera incidence and inequities, and be especially cost-effective if all 1-14 year olds are targeted.

The use of typhoid vaccines in Asia: the DOMI experience.

BACKGROUND: Two currently licensed typhoid vaccines have been evaluated in Asia, yet few Asian countries have considered including typhoid vaccines in their vaccination programs. The Diseases of the Most Impoverished (DOMI) Program was initiated to provide evidence to decide on the introduction of typhoid vaccines in Asian countries. METHODS: The centerpiece of the program is a multidisciplinary demonstration project with Vi vaccine in 5 Asian countries. The project includes epidemiologic, economic, sociobehavioral, and policy studies. RESULTS: Policy makers want evidence on which to base their vaccine-related decisions. The DOMI Program has provided updated information on the typhoid fever burden at several Asian sites. Cost-of-illness studies found high costs to governments and individuals. Sociobehavioral studies indicated a positive attitude toward typhoid vaccines. The results of the demonstration projects indicate that mass-immunization campaigns are feasible and acceptable. CONCLUSIONS: The DOMI Program has begun to provide momentum for the evidence-based, rational introduction of typhoid vaccines into the public health programs of several Asian countries.

The importance of engaging policy-makers at the outset to guide research on and introduction of vaccines: the use of policy-maker surveys.

Face-to-face surveys of policy-makers and other influential leaders are a useful tool to identify, at an early stage, (a) major issues regarding the introduction of a new vaccine, (b) persons and groups in a country who play a major decision-making or influential role in the introduction of vaccines, (c) potential obstacles to the introduction of vaccines, and (d) data-needs of policy-makers to overcome these obstacles. By surveying the opinions and beliefs of those who will make or influence decisions on whether to introduce a new vaccine, these studies can help ensure that research activities respond to the needs of policy-makers in countries endemic for the target diseases. These surveys can also inform vaccine-introduction strategies by identifying financially and politically feasible means of distributing, targeting, and financing the vaccines. This paper describes the methodology used in conducting such surveys and discusses methodological issues. It also presents lessons learnt from two policy-maker surveys carried out in several Asian countries in regard to new-generation vaccines against cholera, typhoid fever, and shigellosis; and future vaccines against dengue fever/dengue haemorrhagic fever.

Will dengue vaccines be used in the public sector and if so, how? Findings from an 8-country survey of policymakers and opinion leaders.

BACKGROUND: A face-to-face survey of 158 policymakers and other influential professionals was conducted in eight dengue-endemic countries in Asia (India, Sri Lanka, Thailand, Vietnam) and Latin America (Brazil, Colombia, Mexico, Nicaragua) to provide an indication of the potential demand for dengue vaccination in endemic countries, and to anticipate their research and other requirements in order to make decisions about the introduction of dengue vaccines. The study took place in anticipation of the licensure of the first dengue vaccine in the next several years. METHODS/PRINCIPAL FINDINGS: Semi-structured interviews were conducted on an individual or small group basis with government health officials, research scientists, medical association officers, vaccine producers, local-level health authorities, and others considered to have a role in influencing decisions about dengue control and vaccines. Most informants across countries considered dengue a priority disease and expressed interest in the public sector use of dengue vaccines, with a major driver being the political pressure from the public and the medical community to control the disease. There was interest in a vaccine that protects children as young as possible and that can fit into existing childhood immunization schedules. Dengue vaccination in most countries surveyed will likely be targeted to high-risk areas and begin with routine immunization of infants and young children, followed by catch-up campaigns for older age groups, as funding permits. Key data requirements for decision-making were additional local dengue surveillance data, vaccine cost-effectiveness estimates, post-marketing safety surveillance data and, in some countries vaccine safety and immunogenicity data in the local population. CONCLUSIONS/SIGNIFICANCE: The lookout for the public sector use of dengue vaccines in the eight countries appears quite favorable. Major determinants of whether and when countries will introduce dengue vaccines include whether WHO recommends the vaccines, their price, the availability of external financing for lower income countries, and whether they can be incorporated into countries' routine immunization schedules.

Informing decision makers: experience and process of 15 National Immunization Technical Advisory Groups.

This supplement of Vaccine contains detailed descriptions of the experiences and processes of 15 well-established National Immunization Technical Advisory Committees from all regions of the world. All of these committees provide information to national governments that is used to make evidence-based decisions regarding vaccine and immunization policy. Nevertheless, many differences between committees exist including their legal basis, size and scope of committee membership, scope of work, role of the Ministry of Health on the committee, existence of conflict of interest policies, and ultimate role in the decision-making process. Individual country authors identified numerous areas for improvement and these are summarized here.

Typhoid vaccination: the Asian experience.

The WHO has recently issued updated recommendations for the programmatic use of new-generation typhoid vaccines in high-risk areas of countries where typhoid fever is still endemic. Countries have subsequently been instructed to discuss how these recommendations can be implemented and to develop plans for targeted typhoid vaccination. These plans can be informed by the experiences with typhoid vaccination that several Asian countries have had. This article reviews past and current typhoid vaccination programs that have taken place in Thailand (using the old whole-cell vaccine) and in China, Vietnam and India (using the new-generation injectable Vi polysaccharide vaccine). This review also describes recent typhoid Vi vaccine demonstration projects that were conducted in five Asian countries.

Regional group purchasing of vaccines: review of the Pan American Health Organization EPI revolving fund and the Gulf Cooperation Council group purchasing program.

This paper reviews the key design features, accomplishments of and lessons learned from two regional group procurement mechanisms dealing with vaccines that have been in operation for more than 25 years. The Pan American Health Organization (PAHO) EPI Revolving Fund purchases vaccines and immunization supplies on behalf of more than 35 countries in the Latin American and Caribbean region. Based on a 'central contracting' model, the program handles most aspects of procurement-from tendering to contracting with and paying producers--using a common fund to pay producers before being reimbursed by countries once goods are received in-country. The Gulf Cooperation Council (GCC) Group Purchasing Program among seven Persian Gulf States issues joint tenders for vaccines, as well as drugs and other medical goods. Through this 'group contracting' program, countries are responsible for contracting with and paying producers on their own, once the group has selected winning bids. Both programs have experienced substantial growth in the past two decades and are considered to have contributed to or accelerated achievements of immunization programs in both regions, including the introduction of new vaccines. The paper identifies several features of both programs--both those designed to attract country participation and those designed to ensure the programs' financial viability--which help explain their success and longevity.

Policymakers' views regarding the introduction of new-generation vaccines against typhoid fever, shigellosis and cholera in Asia.

Face-to-face interviews and meetings with more than 160 policymakers and other influential professionals in seven large Asian countries (Bangladesh, China, India, Indonesia, Pakistan, Thailand and Vietnam) were conducted to survey opinions regarding the need for, and potential uses of new-generation vaccines against cholera, typhoid fever and shigellosis. Despite several barriers to their uptake--notably uncertainty of the burden of enteric diseases; preference for water, sanitation and other environmental improvements over vaccination for disease control; and high prices of the current vaccines relative to basic EPI vaccines, and their moderate protection levels--considerable interest was found in the targeted use of Vi typhoid vaccine in most countries, followed by (future) Shigella and oral cholera vaccines. The introduction of these vaccines in Asia could be greatly facilitated by country-specific evidence of disease burden, local or regional vaccine production, field studies demonstrating their safety and efficacy in local populations, evidence of potential economic savings from vaccination, and effective dissemination of research results to all those who make or influence immunization policy.

Policymakers' views on dengue fever/dengue haemorrhagic fever and the need for dengue vaccines in four southeast Asian countries.

A survey of policymakers and other influential professionals in four southeast Asian countries (Cambodia, Indonesia, Philippines and Vietnam) was conducted to determine policymakers' views on the public health importance of dengue fever and dengue haemorrhagic fever (DHF), the need for a vaccine and the determinants influencing its potential introduction. The survey, which involved face-to-face interviews with policymakers, health programme managers, researchers, opinion leaders and other key informants, revealed an almost uniformly high level of concern about dengue fever/DHF and a high perceived need for a dengue vaccine. Several characteristics of the disease contribute to this high sense of priority, including its geographic spread, occurrence in outbreaks, the recurrent risk of infection each dengue season, its severity and the difficulty in diagnosis and management, its urban predominance, its burden on hospitals, and its economic toll on governments and families. Research felt to be key to future decision-making regarding dengue vaccine introduction include: disease surveillance studies, in-country vaccine trials or pilot projects, and studies on the economic burden of dengue and the cost-effectiveness of dengue vaccines. The results suggest favourable conditions for public and private sector markets for dengue vaccines and the need for creative financing strategies to ensure their accessibility to poor children in dengue-endemic countries.