What is the best method of prevention for the transmission of vaccine-preventable diseases?

Benefits of monitoring AEFIs

As vaccine-preventable infectious diseases continue to decline, people have become increasingly concerned about the risks associated with vaccines. Furthermore, technological advances and continuously increasing knowledge about vaccines have led to investigations focused on the safety of existing vaccines which have sometimes created a climate of concern. Allegations regarding vaccine-related adverse events that are not rapidly and effectively dealt with can undermine confidence in a vaccine and ultimately have dramatic consequences for immunization coverage and disease incidence.

Not only is public awareness of vaccine safety issues rising, there are increasing opportunities for AEFIs to occur due to various factors. For instance, an increasing number of vaccine doses is now given in campaigns than ever before (Table 4). Polio virus is targeted for eradication and measles elimination is being implemented in many parts of the world. As a result, vast numbers of doses of vaccine are being given over short time intervals. Thus, even if the AEFI rates stay the same, the actual number of cases is likely to be much higher than would be expected over the same time period, simply because so many doses have been administered.

Table 4. Possible effect of immunization campaigns on vaccine safety

Treatment

Chickenpox is a vaccine-preventable infectious disease. If a primary infection occurs during pregnancy, there is no known effective treatment to reduce the rate of vertical transmission. A recent review article described the safety and pregnancy outcomes in women who received varicella zoster immune globulin (VZIG) as prophylaxis after exposure to either VZV or herpes zoster. The incidence of varicella was 29% in a randomized control trial after VZIG and 7.3% in an open-label, expanded access program. This study further supports CDC recommendations to provide postexposure prophylaxis to nonimmune pregnant women exposed to VZV (Centers for Disease Control and Prevention, 2013; Swamy and Dotters-Katz, 2019). In the United States, VZIG is recommended for exposed newborns and prevent approximately 50% of symptomatic cases (Blumental and Lepage, 2019).

Vaccination to VZV is contraindicated during pregnancy, and women should avoid becoming pregnant within 28 days of vaccine, as the Zostavax vaccine contains a live-attenuated virus and could potentially affect the fetus.

In the rare cases of VZV meningoencephalitis, acyclovir has been used as treatment, including its use in one immunocompromised pregnant woman (Jayakrishnan et al., 2008).

Vaccines

Typically, vaccines are administered before exposure to an infectious agent and are otherwise not very useful after exposure has occurred. Historically, rabies is an exception, in comparison to most other vaccine-preventable infectious diseases, because immunization proceeds as a critical intervention not only before but also after exposure to virus. Over the past century, a variety of substrates, such as whole animal tissues, primary cell cultures, diploid cells, and continuous cell lines, have been used widely for virus propagation. Interestingly, all these systems remain in use today for human rabies vaccine production, which is probably not the case with other human viral vaccines that remain in widespread use. The field of rabies vaccinology has progressed enormously, especially during the latter part of the last century, with regard to authentication of cell substrates and virus strains, a better understanding of the risks of using animal origin materials, design of commercially viable serum-free medium, improvement in downstream processes, knowledge of problematic impurities, and strategies to mitigate these concerns.

Program for Appropriate Technology in Health

PATH6 originated in the 1970s and has expanded extensively in the last 30 years and considers itself “a catalyst for global health.” It focuses on a number of areas to improve public health, including advancing technologies, strengthening systems, and encouraging healthy behaviors, and works in over 70 countries. One of the foci of PATH is vaccine development with projects on technologies to improve the safety, effectiveness, and efficiency of vaccine delivery in countries that are disproportionately affected by vaccine-preventable infectious diseases.

Supporting the design, development, scale-up, production, commercialization, and distribution of technologies solely through the public sector is clearly beyond available resources and not economically viable within the countries that need the vaccines. Thus, public–private collaborations are indispensable for investment in suitable technologies to further vaccine development in developing countries. PATH has developed and refined many approaches for identifying and advancing vaccine-related technologies, and works collaboratively in partnerships with vaccine and technology companies, public and private sector partners, research institutes, universities, other nongovernmental organizations, research consortia, and international agencies to further vaccine development. All of the above are key to advancing candidate vaccines to usage in the community and improving public health. Projects have included maintaining the cold chain and issues that impact vaccine delivery and effectiveness at point of use, such as bench and field testing, technology transfer, scale-up, licensing, and market and product introduction for a number of vaccines, including Shigella, enterotoxigenic Escherichia coli, rotavirus, Japanese encephalitis, pneumococcal disease, seasonal and pandemic influenza, and cervical cancer.

Introduction

Active immunizations against diseases that cause substantial morbidity or potential mortality represent one of the greatest advances in medicine over the past century. Allergic patients should receive the same publicly recommended vaccines unless there is an allergy-specific risk that outweighs the risk of the infectious disease to be prevented.

Despite the dramatic benefits provided by immunization to vaccine-preventable infectious diseases, concerns regarding the potential for adverse reactions to immunizations have persisted since their introduction more than 200 years ago. Among potential adverse events following immunization (AEFI), concerns regarding vaccine allergy are commonly expressed by parents, patients, and immunizing physicians.

Allergic vaccine reactions to vaccines certainly occur, but severe allergic events are rare. For many routine vaccines the incidence is <1/100,000 doses.1 Patients with an antecedent allergic reaction to a vaccine or to a component contained in the vaccine are at heightened risk. Unfortunately, most allergic reactions occur in patients without known risk factors and cannot be predicted by currently available tools. Unfortunately, lack of knowledge about whether and how to immunize patients with concerns regarding possible allergic vaccine reactions can contribute to incomplete immunization coverage.

Aside worries regarding possible allergic reactions to the vaccine itself, considerable fear exists that routine childhood immunization may promote development of allergic sensitization and allergic disease. In one survey, apprehension that vaccines may increase the risk of developing allergy was identified as a major impediment to timely routine immunization.2

In this chapter we summarize current evidence with regard to allergic vaccine reactions and the impact of vaccines on the development of allergy. We also summarize expert recommendations with regard to immunization of children predisposed to allergy.

Health Risks of International Business Travelers

Historically the health risks of IBTs has been considered “low”; however, more recent studies suggest that the risks are similar to other international travelers.5 A study of business travelers from Canadian Oil and Gas showed 76% reported travel-related health problems.6 With changing travel patterns, travel risks have changed. In a recent study of travelers to Asia7 more than 60% of high-risk travelers listed a work-related reason for their trip. Further in a study of primarily corporate travelers, there were more hospitalizations for “low risk” travelers in total, although country risk level was a predictor.8 Noncommunicable disease risks (NCDs) are increased in business travelers in addition to acute illness. A World Bank study showed overall health plan costs were 70% higher for IBTs than for nontraveling counterparts and the risk increased with the frequency of travel. The study also showed increased risk for all 20 noncommunicable disease categories, particularly mental health.9 Extensive business travel has been correlated with higher body mass index (BMI), and increased cholesterol, hypertension, and mental stress in frequent business travelers. While the risks of most infectious gastrointestinal illnesses, malaria, and respiratory disease appear similar to other travelers, higher risks for influenza, sexually transmitted disease, hepatitis B, high alcohol consumption, and psychologic stress have been reported in IBTs. Sleep disorders and disruption of circadian rhythms are also more common in IBTs.10

Another significant issue for business travelers is underlying disease that creates risks during travel. For example, diabetes is rapidly increasing globally and thus creates increased risks particularly if the traveler is insulin dependent. Cardiovascular disease risks are important considerations for travel to remote areas. Immunoincompetence and pregnancy create increased risks too.

Hepatitis A Vaccine

Hepatitis A virus is a nonenveloped positive strand RNA virus, member of the Picornavirus family that is mainly transmitted through fecal-oral routes and exposure to contaminated food and water sources. It commonly causes a self-limited inflammatory response in the liver which is associated with nonspecific symptoms and signs including fatigue, nausea, vomiting, or low-grade fever, but in rare cases it may progress to fulminant hepatitis and liver failure.1 It affects about 1.5 million people worldwide per year, and it is one of the most common vaccine-preventable infectious diseases in travelers.2 Ideally individuals should plan to receive the hepatitis A vaccine at least 1 month in advance of travel. In practice, last-minute vaccination is given, and there is good evidence that hepatitis A vaccine is protective soon after it is given.3 The individual's immune response rises in response to acute encounters with hepatitis A virus during travel. This highly immunogenic vaccine is thought to provide lifelong protection once the primary course has been completed.4

There are two licensed Hepatitis A antigen vaccines available in the United States for individuals aged 12 months and above, HAVRIX (manufactured by GlaxoSmithKline) and VAQTA (manufactured by Merck & Co., Inc.). The schedule for HAVRIX is at 0 and 6–12 months and for VAQTA at 0 and 6–18 months. Vaccine is recommended for travelers to countries with intermediate-to-high prevalence for Hepatitis A.

Protective antibody levels are detected in 54%–62% of healthy adults at 14 days and >94% 1 month after vaccination.

A combined inactivated hepatitis A and hepatitis B vaccine (Twinrix, GlaxoSmithKline) is available for those aged 18 years and above to be given in a three-dose series at 0, 1, and 6 months or an accelerated schedule at 0, 7, and 21–30 days with a booster at 12 months.

Adverse effects: Pain at the injection site (56%–67%) and headache (14%–16%) are the most common vaccine side effects reported in adults.

Contraindications: Hepatitis A vaccine should not be administered to those with a history of severe allergic reaction such as anaphylaxis to any component of the vaccine.

Pregnancy: The risk to the fetus when the vaccine is given during pregnancy has not been determined; because the vaccine is inactivated, it is suspected to be low.5 If the risk of hepatitis A at destination is moderate to high, this outweighs the risk of giving hepatitis A vaccine.

Safety: The vaccine may be given to immunocompromised patient because it is inactivated.

Hepatitis A immunoglobulin: GamaSTAN S/D is available in the United States for temporary protection against hepatitis A infection, with recommended dosing of 0.1 mL/kg for up to 1 month of planned travel duration and 0.2 mL/kg for up to 2 months.6 It may be given in conjunction with the Hepatitis A vaccine for those traveling in less than 2 weeks, and it should be given at the same time at separate anatomic sites. It is rarely needed given the high immunogenicity of the Hepatitis A vaccine but is considered for use in older adult, immunocompromised persons, and those with chronic liver disease or other chronic medical conditions.7 Travelers may receive the Hepatitis A immunoglobulin alone if they are aged <12 months, are allergic to a component of the vaccine, or choose not to receive the vaccine.

For postexposure prophylaxis, immunoglobulin must be given within 2 weeks of exposure.6

US Health Targets

In 1979, the US Surgeon General’s Report Healthy People set a series of national health targets for a wide variety of public health issues. The program defined 226 objectives in 15 program areas within the three categories of prevention, protection, and promotion. These goals and objectives were formulated based on research and consultation by experts in different fields who participated in a conference by the US Public Health Service. Consensus is based on position papers, studies, and conferences involving the national governmental health agencies, the National Academy of Science Institute of Medicine, and professional organizations such as the American Academy of Pediatrics (AAP), the US Preventive Health Services Task Force, and the American College of Obstetrics and Gynecology (ACOG). Many private individuals and organizations contribute to this effort, including state and local health agencies, representatives of consumer and provider groups, academic centers, and voluntary health associations.

These targets are periodically assessed as performance indicators of the US health system and then updated. Progress made during the 1980s included major reductions in death rates for three of the leading causes of death: heart disease, stroke, and unintentional injuries. Infant mortality decreased, as did the incidence of vaccine-preventable infectious diseases.

The latest iteration, Healthy People 2020, identifies national health priorities. It strives to increase public awareness and understanding of the determinants of health, disease, disability, and opportunities for progress. It defines measurable objectives and goals for Federal, State, and local authorities in the areas of health promotion, health protection, preventive services, surveillance and data systems, and age-related and special population groups. The final reviews of Healthy People 2000 showed significant decreases in mortality from coronary heart disease and cancer. Healthy People 2020 renews this effort to establish national targets which are adopted by state level governments and strongly influence policy in health insurance systems.

The US has managed to achieve many of the targets set by the 1979 Surgeon General’s Healthy People report. At the same time, the average annual increases in health care expenditures in the United States slowed markedly from the 1986–90 period with average annual increases of 10.7 percent, falling to under 7 percent annually between 1995 and 2005. This is partly due to lower general inflation rates (<3%), but also cost-containment measures being adopted by government insurance (Medicare and Medicaid) programs, the health insurance industry, the growth of managed care, and rationalizing the hospital sector by downsizing and promoting lower-cost alternative forms of care.

National health insurance was delayed by congressional rejection of the Clinton health plan. President Barack Obama’s 2010 Affordable Care Act (ACA) provided millions of previously uninsured Americans health insurance within better regulated private insurance or in state-run Medicaid plans, but in 2017 is facing “repeal and replace” efforts by the President Trump administration and Republican Congress. A number of possibilities exist to extend health insurance coverage: state health insurance initiatives with federal waivers and cost-sharing; a federal single payer universal coverage plan based on the federal Medicare model or a federal-state Medicaid model.

Health Targets

Despite rapid increases in health care expenditures during the 1970s and 1980s, improved health promotion activities, and rapidly developing medical technology, the health status of the US population has improved less rapidly than that in other western countries. Infant mortality in the USA remains high in comparison to other OECD countries and ranked 34th among all countries in 2012 (estimated). Even the rate of infant mortality of the white population of the USA was higher than that of 16 countries that spent much less per person and a lesser percentage of gross national product (GNP) per capita on health care.

The 1979, the US Surgeon General’s Report Healthy People set forth a series of national health targets for a wide variety of public health issues. The program defined 226 objectives in 15 program areas within the three categories of prevention, protection, and promotion. These goals and objectives were formulated based on research and consultation by 167 experts in different fields who participated in a conference by the USPHS. Consensus was based on position papers, studies, and conferences involving the national governmental health authority, the National Academy of Sciences’ Institute of Medicine (IOM), and professional organizations, such as the American Academy of Pediatrics (AAP) and the American Congress of Obstetricians and Gynecologists (ACOG). Many private individuals and organizations contributed to this effort, including state and local health agencies, representatives of consumer and provider groups, academic centers, and voluntary health associations.

These targets (Table 13.5) are periodically assessed as performance indicators of the US health system and then updated. Progress made during the 1980s included major reductions in death rates for three of the leading causes of death: heart disease, stroke, and unintentional injuries. Infant mortality decreased, as did the incidence of vaccine-preventable infectious diseases.

TABLE 13.5. Healthy People 2020

Source: United States Department of Health and Human Services. Healthy People 2020 Framework. Available at: http://www.healthypeople.gov/2020/Consortium/HP2020Framework.pdf [Accessed 19 May 2013].

Healthy People 2000, published in 1992 by the Surgeon General, detailed 332 specific health targets, in six groups, for the year 2000, in the areas of health promotion, health protection, preventive services, surveillance and data systems, and age-related and special population groups (see Chapter 11). The final reviews of Healthy People 2000 showed significant decreases in mortality from coronary heart disease (CHD) and cancer. Healthy People 2020 is renewing this effort to establish national targets which are adopted by state-level governments and strongly influence policy in health insurance systems (Table 13.5). The 2010 “Obamacare” program will include over 30 million previously uninsured Americans in health insurance within better regulated private insurance or in state-run Medicaid plans (see Chapter 10).

In 2000, the DHHS released Healthy People 2010, with two main goals: to “increase the quality and years of healthy life” and to “eliminate health disparities”. These goals focus on 28 specific areas developed by over 350 national membership organizations and 250 state health, mental health, substance abuse, and environmental agencies. A midcourse review of Healthy People 2010 shows that 60 percent of the objectives are either being met or moving forward. The USA is moving towards the goal to “increase the quality and years of healthy life”, although there are still clear gender, race, and ethnic discrepancies. Reducing health disparities continues to be a challenge in the USA.

Many states have adopted these targets as their own measures of health status and performance. Annual publications by the USPHS, in cooperation with the NCHS, make available a wide set of data for updating health status and process measures relating to these national health goals. The value of working towards health targets is widely accepted. Healthy People 2020 has defined similar overarching goals (see Table 13.5).

Health promotion has received wide public, governmental, and professional support in the USA over the past decades. In part, this reflects a long tradition of education on health matters in the rural agricultural sector and school health education. Nutrition and antismoking consciousness has grown in part because of wide media attention to many important epidemiological studies.

Consumer advocacy has been a potent factor for change in the USA in the twenty-first century, and especially since the 1960s. It has contributed to strengthened governmental regulation in a wide area of public health-related fields (see Chapter 2). These include automobile safety features and emission control, environmental standards, Mothers Against Drunk Driving, nutritional labeling, vitamin and mineral fortification of basic foods, and legal action against cigarette manufacturers. Food fortification, pioneered in the USA, is not mandatory as in Canada, but is nevertheless nearly universal, and mandatory for those foods labeled “enriched” (see Chapter 8). This is accepted in the general population based on advocacy, informed public opinion, and an innovative, highly competitive food industry. Despite much public controversy, fluoridation of community water supplies covers 67 percent of the population, a higher coverage than in most industrialized countries.

Advocacy groups can also promote regression in public health measures, as with groups currently fighting against immunization on the grounds of disinformation and opposition to vital vaccination programs. Some opposed to abortion have greatly affected public policy and promote sometimes violent activities against proponents and providers of abortions. Groups opposed to hospital births have sparked a widespread home birthing movement, which may lead to dangerous complications. Research and wide media coverage of health issues encourage a high level of individual and community consciousness of health-related issues and a climate receptive to health promotion.

Surveillance and the European Centre for Disease Prevention and Control

The responsibility for surveillance of vaccine-preventable diseases lies with individual countries. Within the countries, some vaccine-preventable diseases are statutorily reportable (measles in the UK), some are collected nationally on a voluntary basis (pneumococcal infection in the UK), and others are kept under surveillance through sentinel systems (influenza in the UK).

To strengthen surveillance within the EU, a network for the epidemiological surveillance and control of com-municable diseases was established by Decision 2119/98/EC of the European Parliament and the Council of Europe and started work in 1999.8 This led to the creation of a number of surveillance networks funded by the Directorate General for Health and Consumer Affairs (DG SANCO), the European Commission, to coordinate national data into an EU-wide system.9 The networks funded for vaccine-preventable diseases included the European Laboratory Working Group for Diphtheria; the European Union Invasive Bacterial Infections Surveillance (EU IBIS), which includes Haemophilus influenzae and meningococcal infections; and the Surveillance Community Network for Vaccine Preventable Infectious Diseases (EUVAC NET), which has included measles and pertussis. Four countries taking part in a network for pneumococcal surveillance (Denmark, Italy, Finland, and the UK) work closely with EU IBIS.

In addition, a Basic Surveillance Network has been funded by DG SANCO to collect limited disease data, initially on 10 pilot diseases, but since 2004, on more than 40 diseases. The diseases include diphtheria, measles, mumps, pertussis, polio, rubella, hepatitis A and B, and Haemophilus influenzae type b, meningococcal and pneumococcal infections. The European Sero-Epidemiology Network was also established in 1996 through funding from DG SANCO to coordinate and harmonize the serologic surveillance of immunity to vaccine-preventable diseases in six countries (Denmark, England, France, Germany, Italy, and the Netherlands).10

The need for a more coordinated and integrated European surveillance and response capacity was evident, and in the spring of 2004, the European Parliament and Council passed a law creating the European Centre for Disease Prevention and Control (ECDC), to help strengthen Europe's defenses against infectious diseases, including vaccine-preventable diseases.11 The ECDC is intended to be a small agency, working in partnership with national health protection bodies across Europe to strengthen and develop continent-wide disease surveillance and early warning systems.12 By working with experts based in these national bodies, ECDC will pool Europe's health knowledge, so as to develop authoritative scientific opinions about the risks posed by new and emerging infectious diseases. ECDC became operational on 20 May 2005 and was officially inaugurated on 27 May. The ECDC offices are on the campus of the Karolinska Institute, Stockholm, Sweden.

ECDC, through the operation of the dedicated surveillance networks and the provision of technical and scientific expertise, supports the activities of the existing networks; however, a process has been defined that may lead to its taking over these responsibilities. For each disease, ECDC will either receive and analyze the surveillance data directly forwarded to it by national contact points, or it will conclude a contract with a third party to carry out this task on its behalf. In 2006, a 3-year process was begun by which each of the surveillance networks would be assessed.

The functions of ECDC include: 1) coordinating data collection, validation, analysis and dissemination at EU level, including on vaccination strategies; 2) supporting and assisting the European Commission and WHO by operating an early warning and response system (EWRS) and by ensuring with the Member States the capacity to respond in a coordinated manner; and 3) ensuring EWRS is efficiently linked with other EU alert systems (e.g., animal health, food and feed, and civil protection).

ECDC and WHO Regional Office for Europe have established a close working relationship, with WHO participation on ECDC management and technical advisory committees. ECDC is currently undertaking a review of diseases under epidemiological surveillance and the case definitions used. This should result in strengthened surveillance for vaccine-preventable diseases within the European Region through the availability of information on a broader range of diseases, using mutually agreed upon case definitions.

ECDC has assumed responsibility for publication of Eurosurveillance, and it has recently initiated publication of a bi-weekly newsletter on Vaccines and Immunization (V&I News).12 The aim of this publication is to provide regular news and brief highlights of activities and programs in the area of vaccine-preventable diseases in Europe.

The measurement of immunization coverage in the European Region has been problematic because of the wide range of techniques that have been employed in the individual countries. In Denmark, the Netherlands, and the UK, public health data are fully computerized and actively managed, thus coverage is calculated by comparing the number of children who have completed immunization by a specified age with the number of children of the same age residing in the particular community. In Austria, Belgium, France, Greece, and Spain, where private-sector providers give many immunizations, coverage is calculated by comparing the number of doses of vaccine imported or distributed with the estimated target population.13 In these countries, an allowance for wastage and inaccuracies in the target population make these coverage estimates unreliable. In non-EU countries, ‘administrative’ methods are usually used, whereby the number of doses reported to be given in each locality is compared with the estimated target population. Inaccuracies can occur in both the estimates of the numerators and denominators.

In most countries, coverage is measured at two years of age, but, in Germany, it has been measured at school entry at around five years of age. Because such different techniques for coverage estimation have been used, and the accuracy of the estimations may differ considerably, comparisons between countries’ coverage reports need to be made with caution.14 Nevertheless, some countries report very low coverage for certain vaccines.15