Fifty Years of Global Immunization at CDC, 1966-2015

Monday, 9th of January 2017

Fifty Years of Global Immunization at CDC, 1966-2015

Eric E. Mast, MD, MPH, Stephen L. Cochi, MD, MPH, Olen M. Kew, PhD, K. Lisa Cairns, MD, MPH, Peter B. Bloland, DVM, MPVM, Rebecca Martin, PhD

First Published December 19, 2016 research-article

Best viewed at http://journals.sagepub.com/doi/full/10.1177/0033354916681490

On November 23, 1965, President Lyndon Johnson announced plans for a 5-year smallpox eradication and measles control program in West Africa that enabled the Centers for Disease Control and Prevention (CDC) to establish a Smallpox Eradication Program in January 1966. Since then, CDC´s global immunization endeavors have encompassed global smallpox eradication, the establishment and growth of the Expanded Program on Immunization (EPI) to strengthen national immunization programs, global efforts to eradicate polio and eliminate measles and rubella, and vaccine introduction into national immunization schedules beyond the original 6 EPI vaccines. CDC has provided scientific leadership, evidence-based guidance, and programmatic strategies to build public health infrastructure around the world, needed to achieve and measure the impact of these global immunization initiatives. This article marks the 50th anniversary of CDC´s global immunization leadership, highlights key historical events, and provides an overview of CDC´s future directions.

Before 1955, smallpox and diphtheria-tetanus-pertussis vaccines were the only routinely recommended childhood vaccines in the United States. The roots of global immunization at CDC began after clinical trials for the Salk inactivated polio vaccine (IPV) in 1954. After investigators announced on April 12, 1955, that Salk IPV was safe and effective, large-scale vaccination campaigns were implemented across the United States, and IPV was set to join diphtheria-tetanus-pertussis and smallpox vaccines in the childhood vaccination schedule. However, improperly prepared IPV by Cutter Pharmaceuticals used for the vaccination campaigns led to 200 cases of paralysis and 10 deaths.¹

Referred to as the “Cutter incident,” this tragedy set the stage for CDC´s leadership in global immunization, highlighting both the importance of population-based surveillance and CDC´s ability to rapidly analyze data to inform the response to public health emergencies. CDC´s response to the Cutter incident was a major factor leading to the transfer of responsibility for collection and reporting of communicable disease data in 1960 from the National Office of Vital Statistics to CDC.² CDC´s use of vaccine-preventable disease (VPD) surveillance data to inform program and policy decisions developed during the Cutter incident has been a foundation of CDC´s mission and subsequent VPD control initiatives.³

In 1961, incoming CDC Epidemic Intelligence Service Officer Donald Millar was assigned by Epidemic Intelligence Service founder Alexander Langmuir to “keep an eye on smallpox around the world and see if you can make sense of the trends.”⁴ This directive led to the formation of a smallpox surveillance unit that grew into the Smallpox Eradication Program. (Global eradication is defined as the worldwide absence of a disease agent in nature as a result of deliberate control efforts that may be discontinued when the agent is judged no longer to present a significant risk of infection.) During the early 1960s, CDC established itself as an organization with the practical capability to implement immunization work in field conditions by supporting US Agency for International Development–funded measles vaccination campaigns in West Africa⁵ and by conducting evaluations of jet injectors (medical devices used for vaccination that use a high-pressure narrow stream of fluid to penetrate the skin instead of a hypodermic needle), which demonstrated that intradermal administration of smallpox vaccine was practical and effective^6-8(Figure 1).

Figure 1. Fifty years of global immunization progress at the Centers for Disease Control and Prevention (CDC), 1966-2016.

Smallpox Eradication, 1966-1977

Concern that smallpox could be imported into the United States, as well as a broader interest in solving health challenges facing humanity, catalyzed the US government´s commitment to global smallpox eradication, culminating on November 23, 1965, with a White House press release announcing plans for a 5-year smallpox eradication and measles control program in West Africa.⁴

Shortly afterward, CDC developed the Smallpox Eradication Program in the office of CDC Director David Sencer, demonstrating a commitment to smallpox eradication and enabling the use of agency resources.⁴ CDC began staff deployments to countries in West Africa in January 1967; >300 staff members participated in the initiative. One year later, the 25 millionth smallpox vaccination was administered⁹; by May 1970, smallpox was eliminated from West Africa.¹⁰

The critical role that assignees from CDC to international agencies could play was recognized soon after the CDC Smallpox Eradication Program was established. CDC´s first global immunization assignee to the World Health Organization (WHO), D. A. Henderson, led the Intensified Global Smallpox Eradication Program from 1967 to 1976.⁴ Building on lessons learned from the success in West Africa, CDC also provided expertise to WHO to support national smallpox eradication programs in Latin America, Asia, and East Africa.^4,11

CDC developed a model with WHO to track surveillance and immunization data to guide the program, including joint CDC-WHO reports tracking ongoing surveillance and programmatic progress that were published in CDC´s Morbidity and Mortality Weekly Report and the WHO Weekly Epidemiological Record.^12-14 CDC provided technical consultation and laboratory expertise for the independent international commissions that certified countries and regions as free of smallpox and for the Global Commission convened by WHO, which made certification conclusions and recommendations for global eradication to the World Health Assembly¹⁵ (please see photo).

Photo. Ali Maow Maalin, the last person in the world to have naturally occurring smallpox. Merca, Somalia. Photo credit: J. Wickett, Centers for Disease Control and Prevention/World Health Organization, 1977.

Establishing and Building the EPI, 1977-1987

The Global Smallpox Eradication Program´s success in providing access to immunization services laid the foundation for establishing the EPI within WHO in 1974.^16,17 Although vaccines against diphtheria, tetanus, pertussis, measles, polio, and tuberculosis existed at this time, these vaccines reached only a small proportion of the population in low-income countries. From 1977 to 1993, CDC assigned Rafe Henderson and, subsequently, Robert Kim Farley to WHO to lead the program. At CDC headquarters in Atlanta, drawing on staff members with smallpox eradication program experience, CDC provided technical assistance to implement immunization and other child health interventions from 1982 to 1993 through the US Agency for International Development–funded Africa Child Survival Initiative Combating Childhood Communicable Diseases.¹⁸

EPI incorporated key lessons learned from CDC´s work on smallpox eradication, including establishing measurable disease control and programmatic objectives and a commitment to high-quality program management practices related to resource planning and allocation. In addition, the program incorporated CDC´s experience with collecting and analyzing vaccination delivery data to monitor and manage immunization program performance and VPD surveillance data to measure impact.

Former CDC employees played a role in establishing and implementing global collaboration needed for EPI to succeed. In 1984, former CDC Director Bill Foege collaborated with colleagues to found the Task Force for Child Survival, which provided the secretariat for a consortium of global health organizations, including WHO, UNICEF, Rockefeller Foundation, World Bank, and the United Nations Development Program. A goal of the consortium was to work with the EPI to achieve the 1978 Universal Childhood Immunization target of 80% global vaccine coverage by 1990. The success of the Task Force for Child Survival in facilitating global coordination of the consortium led to an expansion of its mandate in 1991 to include other issues that improve children´s quality of life.¹⁹

CDC´s support to build regional immunization program infrastructure began in the 1980s. In 1985, when the Pan American Health Organization regional director announced a goal to eliminate polio in the WHO Region of the Americas by 1990 as a pillar for health system strengthening in the region,²⁰ CDC began a program to strengthen public health laboratories. This program established acute flaccid paralysis surveillance to detect and track poliovirus.²¹ In 1985, CDC also provided leadership and support to the Pan American Health Organization to establish a regional immunization technical advisory group to develop evidence-based strategies for polio eradication for countries in the WHO Region of the Americas.²² This technical advisory group was eventually extended to include policy and practice development and review for all VPDs.

Expansion of CDC´s Role in Global Immunization, 1988 to Present

Polio Eradication

In 1988, WHO´s World Health Assembly endorsed a resolution to eradicate polio, citing the success of smallpox eradication.²³ Shortly thereafter, the Global Polio Eradication Initiative was established, with WHO, UNICEF, Rotary International, and CDC as founding partners.²⁴ The Bill and Melinda Gates Foundation later joined the Global Polio Eradication Initiative as a core partner. Based on the WHO-CDC collaboration model established with smallpox eradication, regular reports tracking polio eradication surveillance and programmatic progress have been published in Morbidity and Mortality Weekly Report and WHO Weekly Epidemiological Record since 1989.^25,26 This reporting and publication collaboration subsequently evolved to encompass the full breadth of global immunization goals and strategies. In 1990, CDC and WHO established the Global Polio Laboratory and Surveillance Network based on experience in implementing acute flaccid paralysis surveillance in the Region of the Americas.^27,28 Also in 1990, the US Congress directed CDC to lead US technical engagement for polio eradication; funding to CDC for polio eradication began in 1991, enabling CDC to create an organizational structure to implement polio eradication activities.

In the 1990s, CDC staff members deployed to collaborate with multiple countries to conduct trainings, assess surveillance systems, develop national plans of action, assist in planning and implementing national immunization days, investigate outbreaks, and conduct research in support of polio eradication. In 1999, CDC and WHO created the Global Polio Eradication Initiative Stop Transmission of Polio Program based on experience from the 1970s Global Smallpox Eradication Program. This program deployed international public health field staff members to assist national immunization programs with polio outbreak investigation, surveillance, and planning vaccination activities.²⁹ The Stop Transmission of Polio workforce capacity development objectives were expanded in 2002 to support implementation of measles mortality reduction strategies, disease surveillance, and data management, in 2003 to support strengthening of vaccination service delivery, and in 2011 to support management of immunization programs in various countries.

Rapid early progress was made with polio-free certification in the Americas (1994), Western Pacific (2000), and European (2002) WHO regions (Figure 2), and wild poliovirus type 2 was last detected in 1999.^30-34 However, from 2003 to 2014, resurgent transmission in Nigeria and India led to 191 new importations and 3763 reported paralytic polio cases in 43 previously polio-free countries.^35,36

Figure 2. Global progress toward polio eradication, 1988-2015. Major milestones in the progress toward polio eradication: In 1988, the World Health Assembly published a resolution to eradicate polio; in 1991, the last case of polio in the Americas Region was documented; in 1997, the last case of polio in the Western Pacific region; in 1998, the last case of polio in the Europe Region; in 1999, the last case of type 2 poliovirus in the world; and in 2011, the last case of polio in the South-East Asia Region. Sources: World Health Assembly,²³ Centers for Disease Control and Prevention.^30,34

In December 2011, CDC Director Thomas Frieden placed polio eradication activities in CDC´s Emergency Operations Center to draw on agency resources.³⁷ CDC subsequently helped establish emergency operations at national and subnational levels in the last remaining polio-endemic countries of Nigeria, Pakistan, and Afghanistan (India was removed from the list of endemic countries in February 2012).³⁸ In 2014, the national polio eradication Emergency Operations Center was used to effectively respond to an Ebola outbreak in Nigeria.³⁹ Wild poliovirus type 3 was last detected in 2012,⁴⁰ and polio-free certification in the Southeast Asia Region was announced in 2014.⁴¹ As of December 2016, Afghanistan, Nigeria, and Pakistan were the last 3 countries with endemic wild poliovirus type 1 transmission.

Measles and Other Global Immunization Activities

The US government began funding CDC for measles and other global immunization activities in 1999, which has enabled CDC to expand support to other VPD elimination (defined as the absence of a disease or infection caused by an agent in a defined geographic area as the result of deliberate control efforts that must be continued in perpetuity to prevent reemergence of disease) and control initiatives (control is defined as reduction of disease morbidity and mortality to a locally acceptable level).

In 2001, the American Red Cross, UNICEF, United Nations Foundation, WHO, and CDC cofounded the Measles Initiative.⁴² The Measles Initiative initially focused on implementing measles mortality reduction strategies, which led to an estimated 79% decrease in measles deaths, from 651 600 in 2000 to 134 200 in 2015. After achieving the elimination of endemic measles in the Region of the Americas in 2002, measles elimination goals were established in all WHO regions (Figure 3).⁴³

Figure 3. Global progress toward measles mortality reduction, 2000-2015: 20.3 million deaths were averted by measles vaccination. Sources: Patel et al,⁴³ Liu et al,⁷³ unpublished data from the Centers for Disease Control and Prevention.

In 2012, the Measles Initiative developed an updated strategic plan. It also became the Measles & Rubella Initiative when it expanded to include rubella, capitalizing on the use of a combined measles-rubella vaccine and integrated measles and rubella surveillance.⁴⁴ Rubella elimination was announced in the WHO Region of the Americas in April 2015. Elimination targets were also established in the WHO European and Western Pacific regions.⁴⁵

In 2000, CDC began to support introduction of new vaccines into the EPI schedule with the availability of funding from Gavi for hepatitis B vaccine in low-income countries, and beginning in 2005, CDC led the Hib Initiative to accelerate introduction of Haemophilus influenzae type b (Hib) vaccine. CDC subsequently provided scientific and technical expertise to accelerate introduction of pneumococcal, rotavirus, human papillomavirus, rubella, and IPV vaccines and measure the impact of these vaccines on disease burden.^46-50

In 2005, CDC began work with WHO´s Western Pacific Region to adopt a regional control goal of <1% chronic hepatitis B virus infection prevalence among children from an estimated prevalence of >8%. The Western Pacific Region achieved an interim milestone to reduce regional chronic hepatitis B virus infection prevalence to <2% among children by 2012.⁵¹ Regional hepatitis B control goals were also set in the WHO Africa, Eastern Mediterranean, and European regions.

Since 2010, CDC has collaborated with Meningitis Vaccine Project partners to introduce wide-age-range meningococcal group A conjugate vaccine campaigns, reaching >217 million people in 15 African meningitis-belt countries.^52,53 CDC helped establish meningitis surveillance, which demonstrated that the supplementary immunization activities used were highly effective in eliminating meningococcal meningitis.^54,55 New vaccines are also being developed: during the 2014-2015 Ebola outbreak in West Africa, CDC supported the development of Ebola vaccines,⁵⁶and CDC has supported the development of malaria and dengue vaccines.^57,58

In addition to targeted VPD initiatives, CDC has worked to strengthen public health infrastructure for immunization programs at global, regional, and country levels. The model of integrated epidemiologic and laboratory surveillance developed for influenza in the 1950s, smallpox in the 1960s, and polio in the 1980s has been used to establish global and regional surveillance and laboratory networks for other viral VPDs, including human papillomavirus infection, influenza, Japanese encephalitis, measles and rubella, rotavirus diarrhea, and yellow fever, and for invasive bacterial VPDs, including Hib, meningococcus, and pneumococcus.^59-64 CDC laboratories serve as global special-reference laboratories supporting these networks. CDC has also formed teams to focus on workforce capacity development; immunization information systems; access to and use of vaccines; and demand, policy, and communication.

CDC works to strengthen immunization policy bodies, which play important roles in reviewing technical, operational, and programmatic evidence and developing immunization goals, policies, and guidelines. WHO used the model of CDC´s Advisory Committee on Immunization Practices⁶⁵to establish in 1997 the Strategic Advisory Group of Experts on Immunization to develop and review immunization policy. The immunization technical advisory group established for the Region of the Americas in the 1980s was used as a model for regional immunization technical advisory groups in all WHO regions. In addition, CDC has provided technical support for development, strengthening, and evaluation of national immunization technical advisory groups around the world.⁶⁶

The Past as a Guide to the Future

Beginning with smallpox eradication, CDC has maintained a dual mission for its global immunization efforts. CDC´s efforts to control, eliminate, and eradicate VPDs and strengthen worldwide immunization programs protect Americans at home and the millions working and traveling abroad from VPDs that have been eliminated or occur infrequently in the United States but persist elsewhere in the world. In addition, CDC´s global immunization efforts help to fulfill the US government´s broader commitment to improve global health. Vaccines are among the most cost-effective ways to improve health, and healthy people improve the economic well-being of communities and nations, cascading into myriad benefits necessary for a stable society.^67,68

CDC´s engagement in global immunization is built on a foundation of public health leadership and immunization expertise that draws on its US-based program leadership and experience.⁶⁹ The agency´s core strengths to implement public health policies and programs include having expertise in infectious disease epidemiology, surveillance, and laboratory science; implementing and evaluating evidence-based VPD prevention strategies and practices; providing quality-assured public health laboratory systems; and building public health institutional and workforce capacity.⁷⁰

A major focus of CDC´s global immunization work has been to apply the principles of integrated epidemiologic and laboratory disease surveillance to immunization program management to achieve and measure the health impact of vaccination goals and strategies. During the smallpox eradication program, surveillance was initially used to identify insufficient vaccination coverage achieved through mass vaccination campaigns. Subsequently, when the number of cases was substantially reduced by vaccination campaigns, surveillance and containment were used to eliminate residual foci of smallpox virus transmission.^10,71 Acute flaccid paralysis surveillance and subsequent testing of stool specimens for polioviruses have been essential to track progress toward polio eradication.⁷²

Based on a model developed to track measles mortality through measles surveillance data, measles vaccination coverage, and age- and country-specific case-fatality ratios, measles vaccination prevented an estimated 20.3 million deaths globally from 2000 to 2015,⁴³ accounting for >10% of the overall reduction in all-cause child mortality during this period.⁷³ Measles and rubella surveillance is also an essential component of measles and rubella elimination strategies.⁴³ Additionally, disease surveillance has been crucial to measure the impact of meningococcal vaccination campaigns in Africa⁵⁵ and the impact of introduction of hepatitis B, Hib, pneumococcal, and rotavirus vaccines into national immunization programs.^51,74

In 2016, CDC began implementing a new 5-year Strategic Framework for Global Immunization, which is built on 5 interconnected goals.⁷⁵ The overarching goal is to increase the health impact of vaccines on improving disease outcomes. Three goals focus on building the capacity needed for sustainable country-owned immunization programs, including vaccination service delivery to achieve high and equitable coverage; integrated epidemiologic and laboratory-based VPD surveillance with the capability to detect and respond to VPD outbreaks; and availability of high-quality immunization information to monitor, evaluate, and improve immunization programs (Figure 4). The foundational goal focuses on increasing the evidence base for immunization policy and practices by conducting and promoting research, together with fostering innovation and evaluating programs.

Figure 4. Goals in Centers for Disease Control and Prevention´s Strategic Framework for Global Immunization, 2016-2020. Source: Centers for Disease Control and Prevention.⁷⁵ Abbreviation: VPD, vaccine-preventable disease.

The priorities in the strategic framework are aligned with the 2010 National Vaccine Plan of the US Department of Health and Human Services,⁷⁶ the 2014 Global Health Security Agenda,⁷⁷ and the Global Vaccine Action Plan, 2011-2020.⁷⁸ The strategic framework also is designed to advance the United Nations 2030 Sustainable Development Goals.⁷⁹

The highest priority during the next 5 years will be to achieve polio eradication by continuing to advance peak program performance and by devising and adopting new methods to address programmatic challenges to interrupt the last chains of poliovirus transmission. The next 5 years are also crucial to build on and leverage the successful achievement of polio eradication to advance additional health targets. Key targets for CDC will include achieving a world free of measles and rubella, ending VPD deaths among children <5 years, and reducing chronic disease and cancer deaths from VPDs (ie, cirrhosis and liver cancer caused by hepatitis B virus infection, cervical cancer caused by human papillomavirus).

CDC also is increasing its focus on helping countries develop the capacity to prevent, detect, and respond to VPD outbreaks as part of the Global Health Security Agenda.⁷⁷ These public health capacities also serve a critical function in protecting Americans and people around the world during public health emergencies. In addition, CDC is supporting the development and introduction of new vaccines to protect against leading causes of morbidity and mortality and emerging infectious disease threats, such as those from the Ebola and Zika viruses.

CDC is engaged in planning for the transition of polio eradication assets and knowledge, which will ensure that country immunization program capacity supported by the Global Polio Eradication Initiative is repurposed to support other immunization priorities while sustaining essential polio functions still needed in a post–polio eradication world.⁸⁰ These capabilities include effective communication networks, community engagement to mobilize community support for vaccination, state-of-the-art laboratory networks, real-time disease detection and response, and unprecedented access allowing delivery of health services to chronically neglected communities.

CDC now has >1700 staff members assigned to >60 countries, enabling a strategy to achieve global health impact by providing technical assistance, mentoring, and emergency surge capacity to build national public health capacity.⁸¹ A key CDC focus for the future is to help countries achieve both the national and subnational vaccination coverage targets and the measles and rubella elimination targets, as committed to in the Global Vaccine Action Plan, 2011-2020, and endorsed by the World Health Assembly.⁷⁸

Partnerships that promote a harmonized approach to implementing immunization programs under country government leadership are crucial to achieve the full impact of vaccination. CDC strengthens capacity and coordination to implement national immunization programs through global, regional, and country-level immunization partnerships with ministries of health, multilateral organizations (ie, organizations with participation of multiple countries), nongovernment organizations, and US government agencies. CDC assignees to other organizations—including WHO, UNICEF, World Bank, Gavi, American Red Cross, and International Federation of Red Cross and Red Crescent Societies— have been important in coordinating global immunization initiatives.

Achieving smallpox eradication, developing the EPI and increasing global vaccination coverage from less than 20% in 1980 to nearly 80% by 1990, certifying polio eradication in 4 of 6 WHO regions, reducing measles deaths and eliminating endemic measles and rubella in the WHO Region of the Americas, and eliminating meningitis A in the Africa meningitis belt provide compelling demonstrations of what can be accomplished when there is unity of purpose and collaboration among partners.

Acknowledgements

We thank Luz Adriana Gaffga, Alison Amoroso, and Clarice Conley for assistance with editing the article and Jarrad Hogg for graphic design.

Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.

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