Introducing multiple vaccines in low- and lower-middle-income countries: issues, opportunities and challenges.

Low- and lower-middle-income countries are faced with a large and increasingly complicated portfolio of vaccines to introduce into their national immunization programmes. Countries must also incorporate their vaccine introduction plans into donor-required assessments and multi-year plans. An international workshop and series of key informant interviews were conducted to explore the interest, opportunities and challenges for the proactive planning of multiple vaccine introduction within a single planning cycle and the underlying processes for planning the introduction of new vaccines. The study found limited experience with this proactive planning process in low-income countries and used the experience of two lower-middle-income countries in simultaneously introducing rotavirus and pneumococcal vaccines to highlight the importance of integrating the planning processes for new vaccine introduction into broader immunization systems planning and financing. The study's findings suggest that this strategy for vaccine introduction may have promise for accelerating the pace of new vaccine introduction. However, we also show that realizing these benefits will require improved logistic and financial planning activities and continued actions to resolve uncertainties in the relationships between donors, technical agencies, and the national immunization programmes.

The future of immunisation policy, implementation, and financing.

Vaccines have already saved many lives and they have the potential to save many more as increasingly elaborate technologies deliver new and effective vaccines against both infectious diseases--for which there are currently no effective licensed vaccines--such as malaria, tuberculosis, and HIV and non-infectious diseases such as hypertension and diabetes. However, these new vaccines are likely to be more complex and expensive than those that have been used so effectively in the past, and they could have a multifaceted effect on the disease that they are designed to prevent, as has already been seen with pneumococcal conjugate vaccines. Deciding which new vaccines a country should invest in requires not only sound advice from international organisations such as WHO but also a well informed national immunisation advisory committee with access to appropriate data for local disease burden. Introduction of vaccines might need modification of immunisation schedules and delivery procedures. Novel methods are needed to finance the increasing number of new vaccines that have the potential to save lives in countries that are too poor to afford them. Here, we discuss some options.

A policy framework for accelerating adoption of new vaccines.

Rapid uptake of new vaccines can improve health and wealth and contribute to meeting Millennium Development Goals. In the past, however, the introduction and use of new vaccines has been characterized by delayed uptake in the countries where the need is greatest. Based on experience with accelerating the adoption of Hib, pneumococcal and rotavirus vaccines, we propose here a framework for new vaccine adoption that may be useful for future efforts. The framework organizes the major steps in the process into a continuum from evidence to policy, implementation and finally access. It highlights the important roles of different actors at various times in the process and may allow new vaccine initiatives to save time and improve their efficiency by anticipating key steps and actions.

Rotavirus vaccines: the role of researchers in moving evidence to action.

Evidence generated through years of research has built a solid scientific foundation on the safety and efficacy of rotavirus vaccines, and has served to raise awareness of global rotavirus disease burden and the potential impact of vaccination. In this commentary, we explore the role that researchers can play in closing key gaps of knowledge, demand, and financing to support decision-making on introduction of new vaccines in developing countries. With safe and efficacious rotavirus vaccines now on the verge of widespread adoption, researchers can be vital advocates for their uptake into routine immunization programs.

Global rotavirus surveillance: determining the need and measuring the impact of rotavirus vaccines.

Rotavirus remains the most common cause of severe childhood diarrhea worldwide and of diarrheal mortality in poor countries. In 2003, the GAVI Alliance launched the Rotavirus Vaccine Program and the Accelerated Development and Introduction Plan to close the gap of access to rotavirus vaccines in industrialized and developing countries by generating data on rotavirus disease burden, projected impact, and cost-effectiveness of vaccination and by conducting clinical trials of existing vaccines in impoverished settings. By the end of 2008, rotavirus vaccines were licensed in >100 countries, although only 17 countries have introduced routine rotavirus vaccination. Increased uptake of the vaccine by countries with the highest childhood mortality will depend in part on a solid evidence base of estimated burden and cost of rotavirus illness. Since 2001, regional surveillance networks worldwide have generated burden and strain data from 196 sites in 59 countries. Among children aged <5 years who are hospitalized for severe diarrhea in different regions of the world, a regional median of 39% (range by country, 20%-73%) test positive for rotavirus. Rotavirus vaccines are a cost-effective intervention and may be cost saving with a GAVI Alliance subsidy from the health care perspective. Punctual vaccination and high coverage of populations at highest risk of mortality will maximize the impact of vaccination. Surveillance platforms will allow measurement of the rapid impact of rotavirus vaccine introduction on the heavy burden of rotavirus on child health worldwide.

Rotavirus vaccination: cost-effectiveness and impact on child mortality in developing countries.

BACKGROUND: Rotavirus is the leading cause of severe gastroenteritis in children <5 years of age and is responsible for >500,000 deaths annually; approximately 85% of this burden is in low-income countries eligible for financial support from the GAVI Alliance. We projected the uptake, health impact, and cost-effectiveness of introducing rotavirus vaccination in GAVI-eligible countries to help policy makers in prioritizing resources to gain the greatest health improvements for their constituencies. METHODS: A demand forecast model was used to predict adoption of rotavirus vaccine in the poorest countries in the world. We then modeled health outcomes and direct costs of a hypothetical birth cohort in the target population for scenarios with and without a rotavirus vaccine with use of data on health outcomes of rotavirus infection, vaccine effectiveness, and immunization rates. RESULTS: Vaccination would prevent 2.4 million rotavirus deaths and >82 million disability-adjusted life-years (DALYs) in 64 of the 72 GAVI-eligible countries introducing vaccine from 2007 through 2025. The cost per DALY averted decreases over time, from a high of US$450 per DALY averted in the first year to a sustained low of $30 per DALY during 2017-2025, with a cumulative figure of $43 per DALY averted during 2008-2025. By applying the baseline scenario with an initial vaccine price of $7 per dose for a 2-dose vaccine, with a gradual decrease beginning in 2012 and stabilizing at $1.25 per dose by 2017, vaccination was very cost-effective in all GAVI-eligible countries with use of each country's gross domestic product per DALY averted as a threshold. CONCLUSIONS: Introduction of rotavirus vaccines into the world's poorest countries is very cost-effective and is projected to substantially reduce childhood mortality.

Development of priority vaccines for disease-endemic countries: risk and benefit.

Decisions regarding vaccine regulation and use made by institutions in industrialized countries can have an unintended impact on vaccines' availability in disease-endemic countries. However, regulatory and programmatic decision making by such countries, taking into consideration local risks and benefits, requires adequate resources, both human and financial. Such differing risk-benefit determinations between industrialized and disease-endemic countries will increase product divergence. We propose a single universal standard for risk assessment, based on maximizing net benefit, and an action plan to improve access to priority vaccines through a more robust determination of risk and benefit.