Introduction of Vaccines Into National Programs

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Introduction

The decision for a national government to adopt a population-based health intervention such as vaccines is a complex process involving political, economic, operational/logistics, and governance issues. There are as many variations of decisions as there are the number of countries and vaccines. Three important issues predominate: the financing and costs of the vaccine intervention, existing infrastructures on which to add a vaccine component, and the perceived disease burden including the potential benefits of mitigation. These and other factors are discussed in detail.

While variolation to protect against smallpox had been practiced in China, parts of Africa, and populations now considered as “developing countries” for hundreds of years, it was not until the completion of global smallpox eradication and the formation of the Pan American Health Organization (PAHO) and World Health Organization (WHO) Expanded Program for Immunization (EPI) that governments, with the aid of UNICEF, began to develop national immunization programs. The EPI introduced a limited number of vaccines against TB, diphtheria, tetanus, pertussis, polio, and measles since 1974 to protect infants and children. With the advent of additional antigens and combined vaccine products with the possibility to protect against numerous diseases, governments have been provided with opportunities to protect individuals or societies through adoption of new vaccines into existing national vaccine programs.

The decision to introduce a new vaccine into any national or subnational program is based on multiple factors related to political- biomedical-, public-health-, regulatory-, financial-, logistical-, and community-acceptance concerns ( Table 24.1 ). All of these factors can be quantified and accounted in various different dimensions to help define the usefulness of a vaccine to either an individual vaccine recipient, local community, or national government. Once the value of prevention from a vaccine is appreciated, it may be supported through the public and/or private market for the whole or targeted subpopulations. While the EPI has supported the addition of yellow fever vaccines for at-risk populations and vaccines for pregnant women to protect against neonatal tetanus, additional vaccines were not added to routine schedules until the 1990s. Vaccines had been developed for global markets including those against hepatitis B, rotavirus, Haemophilus influenzae type B and Streptococcal pneumonia infections for inclusion into infant and childhood routine vaccine schedules but had limited uptake. More recently, additional vaccines have been developed for various subpopulations within a country (human papilloma virus, HPV) or for certain geographic regions of the world at higher risk (Japanese encephalitis, Plasmodium falciparum malaria ).

The economics of vaccine development and innovative financing is covered elsewhere in the text. The chapter focuses on the political, epidemiologic, operational, and economic factors that are considered to help decisions to introduce a vaccine into a national program. Additionally, global efforts to help support local decision making processes are covered.

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Political considerations

Political decision makers may base the value of a vaccine based on their perception of the impact of a specific disease on their society and the political expediency from a vaccine versus other intervention(s) or doing nothing. A politician and community’s perception of disease may be affected by severity, communicability, the degree of acuteness or chronic nature and societal/economic disruption. In general, there is greater political support for interventions against severe diseases with relatively high communicability/incidence occurring in outbreaks compared to those that are perceived as indolent, mild, and chronic in nature. While the social and public health needs may be similar with diseases occurring in outbreaks or not, the immediacy of epidemics frequently demand a rapid political response due to its visibility. A recent example of this is the rapid development and deployment of pandemic influenza vaccine and the response to develop vaccines against the Ebola virus.

While a vaccine intervention, may be an effective tool, there may be other interventions that may also contribute to disease-burden reduction. Alternative interventions may act synergistically with vaccines or offer another option competing for public funds. An example of this may include municipal water supplies versus multiple vaccines against bacterial enteric agents. Vaccines are generally supported politically as they have popular characteristics: they prevent communicable diseases, can be equitably distributed, frequently benefit children, and have historically been low cost. Vaccines have additional positive externalities of offering direct and indirect protection to those unvaccinated. These are all positive attributes that a well-informed community would logically support. Political considerations, though, depend on accountability of national governments to their populations, which are highly variable over time.

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Natural history and epidemiologic considerations

Unlike therapeutic interventions, vaccines are provided to healthy populations to reduce risk of infection and disease. Policy makers should understand the natural history of disease, individual and collective risk based on the characteristics of the infectious organism, including mode and speed of transmissibility, and characteristics of susceptibility in the population. Infections and resulting disease incidence and prevalence may differ among various populations based on age, gender, comorbidities and therefore can potentially identify more specific target groups and strategies for a vaccination to offer direct or indirect protection to those most susceptible.

Additionally, characteristics of the vaccine must be considered, including the age-specific immunogenicity, the duration of protection and resulting effectiveness with various doses and dosages. The ideal vaccine would offer lifelong immunity with the least number of doses, no side effects, and can be administered in early infancy. Unfortunately, no such vaccine exists given the biological characteristics of vaccines and immune mechanisms during infancy. Knowledge of the natural history, transmissibility, and vaccine characteristics can be used to optimize the incorporation of a vaccine into an existing schedule, either as a coadministered or combined product. Many vaccines are designed to be incorporated as best as possible into existing infant schedules to minimize the burden of extra visits.

While many vaccines may be administered to the entire population, there may be high-risk groups that are more susceptible to infection and/or its consequences that could lead to a more targeted vaccination when resources are limited. Specialized populations may be based on gender, age, socioeconomic status, comorbidities, pregnancy, or engaged in higher risk activities. Differential risk for infection can define strategies to prioritize the direct or indirect insurance afforded by vaccines. For example, while influenza may infect everyone equally, pregnant women and the elderly are more susceptible to severe disease; however, the latter may not respond as well to vaccine. The complexities of heterogeneous response to infection and vaccination has led to vigorous debate to define the best way to protect various segments of the population, especially when potentially targeting populations outside of routine infant schedules. Sometimes the greatest impact may be achieved through the vaccination of those best able to respond to indirectly protect others in the population.

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Regulatory considerations

Vaccines are subjected to evaluation through national regulatory bodies for their licensure and use in a country. The demand for transparency has led to the registration of vaccine clinical trials to heighten awareness of positive and potentially negative results. While vaccines may be licensed and evaluated for safety and efficacy by a regulatory agency in a high-income country, epidemiologic conditions may be sufficiently different in populations in certain low-resource countries.

In addition, any new vaccine that would be introduced should not only have demonstrated safety and efficacy, they should also not reduce the effectiveness when used in combination or coadministered with other products. As national regulatory agencies have variable capabilities, the WHO frequently aids to assure that vaccines are qualified for purchase through partnerships with UNICEF procurement processes and regulatory authorities meeting approval standards to offer another level of accountability beyond what an individual nation could provide.

While demand to license vaccines may be highest in the case of epidemics like Ebola, deployment requires clinical safety and efficacy data. While Ebola vaccine candidates were shown to be effective in animals prior to the large 2014–2015 West Africa outbreak, only one had been tested for immunogenicity and safety in humans.