Topics in Adult Immunization: Influenza and Beyond

Bruce G. Gellin, M.D., M.P.H., is executive director of the National Network for Immunization Information, a special educational initiative of several health-related organizations. Dr. Gellin is board-certified in infectious diseases and is a diplomate of the American Board of Internal Medicine. He is an associate professor at Vanderbilt University’s School of Medicine and School of Nursing as well as the Columbia University School of Public Health.

Q. How do vaccines work?

A. Vaccines protect against micro-organisms such as bacteria and viruses by stimulating a response from the immune system. These micro-organisms contain molecules called antigens that are specific to the microorganism and are recognized by the immune system as foreign. Vaccines introduce antigens into the body in a controlled way, stimulating an immune response that is designed to protect against disease if the micro-organism is encountered naturally.

Q. What types of vaccines are there?

A. Traditionally there were just two types of vaccines, inactivated vaccines and live vaccines, but heightened understanding of immunology coupled with advances in biotechnology have created new types of vaccines. Understanding more precisely which antigens are most important in developing a strong and protective immune response has also led to the development of a number of subunit vaccines that use only the desired antigens.

Most vaccines in use now are the inactivated type. Inactivated vaccines contain viruses or virus parts that have been treated or modified so that they cannot cause the diseases they protect us from. Influenza vaccines, for example, are made from inactivated virus and therefore cannot cause the flu. Inactivated vaccines cannot cause an infection. While this eliminates any chance that they can cause disease, because they do not infect cells, they often require components called adjuvants that enhance the immune response. In addition, as the immune response is not as robust, inactivated vaccines often require booster doses later to assure that the immune system remains prepared.

Live vaccines are made from viruses that have been weakened so that they are able to “infect” cells and stimulate an immune response, but not develop into the disease. The best examples of this are vaccines for measles, mumps and rubella; chickenpox; and the polio vaccine given orally, which is no longer used in the United States.

Q. What do people need to know about adult vaccines?

A. The most important thing for adults to know is that shots are not just for tots — vaccines are available to prevent many diseases that take a serious toll on adults in terms of lost productivity, hospitalization and lives lost.

Vaccine-preventable diseases in adults include influenza, pneumococcal diseases (pneumonia, sepsis and meningitis), tetanus (lockjaw) and hepatitis A and B. Vaccines are an important part of disease prevention across the lifespan. As we learn more about cancer, we have found that a number of common cancers are the end result of a remote infection. The best example of this is liver cancer, which is caused primarily by the hepatitis B virus. Prevention of the infection also means preventing cancer.

Q. Flu season is almost here again. What is the flu and what can adults do to protect themselves from it?

A. Influenza is a respiratory disease that causes about 20,000 deaths and just under 150,000 hospitalizations each year in the United States. The flu is often confused with the common cold, but it is not caused by the same organisms and is far more likely to lead to serious complications.

The flu tends to come on suddenly with symptoms that include muscle aches, fever, chills, headache, cough and runny nose. The most frequent complication of flu is pneumonia, but inflammation of the heart and worsening of chronic lung disease may also occur. Infants with the flu are vulnerable to croup.

The flu is spread through coughing and sneezing and indirect contact with respiratory secretions, which is why hand washing is important. It is highly contagious, especially in child care centers, schools and nursing homes. When there is a major change or mutation in the virus strain, epidemics or pandemics can occur. The worst flu pandemic of the 1900s caused 21 million deaths worldwide, 500,000 of them in the United States, from 1918 to 1919.

More recently, from 1957 to 1986 we experienced 19 different flu epidemics in the United States. Several of the most recent of these epidemics each caused more than 40,000 deaths.

Q. Who should get flu shots?

A. The recommendations from the Centers for Disease Control and Prevention have changed recently. Other than health care workers who are more likely to come into contact with influenza and possibly transmit it to susceptible patients, recommendations for annual influenza vaccination are intended to protect those who are more likely to suffer complications from influenza. The new recommendations have broadened the recommendations to include anyone age 50 years and over.

Other individuals who should be vaccinated include people who live in nursing homes or other facilities for people with chronic medical conditions; people who have chronic disorders of the lungs, heart or circulation (for example, asthma or cystic fibrosis); people who have metabolic diseases such as diabetes, or kidney or blood disorders; people with weakened immune systems including individuals with HIV; children over 6 months old who receive long-term aspirin therapy and women who will be in their second or third trimester of pregnancy during the flu season. Nursing mothers can be vaccinated against the flu.

Vaccination is also recommended for health care providers, employees of nursing homes or assisted living facilities, providers of home care to people in high-risk groups, and emergency response workers.

This year, the CDC also is encouraging vaccination for all children between 6 and 23 months old because they have been found to have the same risk of hospitalization as people over 65. (5)

Q. Who shouldn’t be vaccinated?

A. The flu vaccine should not be given to children younger than 6 months. Children younger than 4 years should not receive Fluvirin because it has not been tested in this population. Because the vaccine is made in eggs, people who have extreme allergic reactions to eggs or other components of the flu vaccine should not be vaccinated. If people can eat eggs then they are able to take the vaccine. For those who cannot take the vaccine, there are antiviral agents that doctors can prescribe as alternatives.

Q.What types of side effects to the flu vaccine have been observed?

A.Flu vaccines have been in use since 1945 with relatively few difficulties or side effects. Among those few who do experience side effects, the most common is soreness or tenderness at the site of the injection. Fewer than 1 percent of people immunized will experience fever, chills or a general sense of feeling unwell that may last one to two days. In very rare cases, serious reactions can occur. People who are allergic to eggs, which are used in making the vaccine, are at the greatest risk for an allergic reaction. One other very rare reaction is Guillain-Barré Syndrome, which affects about one person in 100,000, typically after a person has had symptoms of a respiratory or gastrointestinal viral infection, where the immune system attacks part of the peripheral nervous system. (18, 19) No vaccine is 100 percent effective, so some people who are vaccinated will develop the flu. When this occurs, the illness is usually less severe.

Q. What are some of the possibilities you see on the horizon for vaccines for adults?

A. Some of the most promising possibilities have to do with the way vaccines are delivered into the body. It’s likely that there will be new biotechnological applications for the delivery of vaccines, including nasal sprays and vaccines that are painted on the skin that could eliminate the need for shots in the future. Another encouraging possibility is work that is being done to develop DNA-based flu vaccines that would protect against more than one strain and therefore would not have to be altered yearly. And, as we learn more about the underlying causes of a broad range of diseases, there is the possibility of preventing diseases that are not traditionally considered to be vaccine preventable. The hepatitis B vaccine was the world’s first anti-cancer vaccine and there are others on the horizon. Our current understanding of cervical cancer is that it is caused by certain strains of human papilloma virus. A vaccine against HPV is in the final stages of testing and results should be available soon.

The Bioterrorism Threat

Escalating concerns about smallpox or other viruses as bioterror weapons highlight the importance of a public health system, including effective, safe and available vaccines, in protecting and maintaining people’s well being.

The last case of naturally occurring smallpox was reported in 1977. In 1980, the World Health Organization declared that smallpox had been eradicated worldwide and recommended that all countries stop vaccinating against smallpox because the risk of vaccination, though small, outweighs the risk of the disease. (13) The smallpox virus exists in WHO reference laboratories in Russia and the U.S. Centers for Disease Control and Prevention. In the wake of the anthrax attacks that occurred in the United States after last Sept. 11, concerns have arisen about possible renegade stockpiling and use of smallpox or other potentially deadly viruses in bioterrorist attacks.

Although the likelihood of contracting smallpox from a deliberate release of the virus in an act of terrorism is not known, it is thought to be low. (13) Concerns about possible bioterrorism, however, are high enough to have triggered a re-examination of public health preparedness and bioterrorism response plans.

The Centers for Disease Control and Prevention have developed an interim plan to provide guidance to the local, state and federal public health authorities who would respond to stop an outbreak of smallpox. (14) To respond quickly and effectively to a terrorist attack using the smallpox virus, the United States must have adequate supplies to stop an outbreak of the disease. As a precaution, the federal government has contracted with a pharmaceutical company to increase the CDC’s smallpox vaccine supply to 286 million doses, enough to stop an outbreak here. (15)

In addition, to effectively respond to a bioterrorist attack, says Craig Smith, M.D., an infectious disease expert and member of the Infectious Diseases Society of America’s Bioterrorism Work Group, public health surveillance must be improved. In the case of chemical warfare or hazardous materials, says Smith, detectors can be used to alert public health authorities about the existence of a threat. In contrast, in the case of biological agents such as the smallpox virus, there are no detectors. This makes planning and preparedness more complicated.

Smith, director of Infectious Disease Services at Phoebe Putney Memorial Hospital in Albany, Ga., maintains that public confidence is also a critical component of mounting an effective response to bioterrorism. Right now, in the wake of the anthrax attacks in the United States, public confidence in the health system’s ability to diagnose and respond to such attacks appears to be low. But improvements in the public health infrastructure, including the development of comprehensive response plans by local health departments and at other levels of government, are under way.

The federal government has set aside grants of $1 billion for public health agencies. (16) Part of strengthening the public health system, says Smith, is improving current systems to make real-time surveillance possible. This means improving individual surveillance of episodes of infectious disease by health care providers. It also means surveillance and monitoring in hospitals and medical centers will be critical.

Interview:

In the Best Interests of the Child: Vaccine Issues for Parents

Edgar Marcuse, M.D., M.P.H., F.A.A.P., is a childhood immunization expert and has served as chair of the National Vaccine Advisory Committee at the U.S. Department of Health and Human Services and numerous other national committees. He has written extensively on pediatric immunization and on ethics and vaccine policy and has served as a consultant to the Centers for Disease Control and Prevention. He is professor of pediatrics and adjunct professor of epidemiology at the University of Washington and director of medical services at Children’s Hospital and Regional Medical Center in Seattle, Wash.

Q. What do you think is most important for parents to know about vaccines and immunizations?

A. The risks and potential negative consequences of contracting vaccine-preventable diseases greatly outweigh the risks of routine childhood vaccinations. Although we have reduced the incidence of vaccine-preventable childhood diseases, many of these diseases are still in our communities or are just an airplane ride away.

This means that it is still important to be immunized against these diseases, even though they are rare in the United States now. For example, although measles is no longer endemic to the United States — the virus is not continuously transmitted here — people who visit from other countries who are infected with measles can spread the disease here to unimmunized individuals. This has been the case in recent outbreaks of measles on several college campuses and other school settings.

Q. Are there other gaps in information about childhood immunizations?

A. Most childhood diseases have the highest attack rates in the first two years of life. This means that early and complete immunization, as recommended by the CDC’s Advisory Committee on Immunization Practices, the American Academy of Pediatrics and the American Academy of Family Physicians, is essential.

The risks of whooping cough, for example, are greatest early in life, in the first six months. In the past decade, rates of whooping cough have gone up in adults, which means that it is not uncommon for infants to be infected by adults, but lots of people aren’t aware of this. This is just one example, though, of how important it is for small infants to get their full vaccinations on schedule.

Q. Does the number of vaccines children receive put them at risk?

A. A nationally representative survey of parents of children age 6 and younger indicated that about a quarter of parents believe that multiple vaccinations may overwhelm the immune system and leave children more vulnerable to infection. (11)

There is no evidence, however, that the number of vaccines currently recommended compromises children’s immune systems, either by overwhelming it or by putting children at greater risk of other infections. (12)

The number of vaccines that are recommended for children has risen dramatically in recent years — from the five vaccines that were routinely given 40 years ago (diphtheria, pertussis, tetanus, polio and smallpox) to the 11 vaccines that are routinely given today. But the actual number of antigens that are introduced in these vaccinations is less now than it was in the past when far fewer vaccinations were given.

Antigens are the component of the vaccine that produce a response from the immune system. Children today are exposed to far fewer antigens through vaccination in part because the smallpox vaccine is no longer given, but also because of changes in the formulation of the vaccines. The total number of antigens contained in the 11 vaccines that are now routinely given is about 130, but the smallpox vaccine alone contained about 200 antigens.

So children are receiving a greater number of vaccines and are being protected against more diseases, but they are actually receiving fewer antigens.

We also know that the capacity of the immune system is enormous and that there is really no possibility of overwhelming or overloading children’s immune systems given the currently recommended schedule.

Q. How do you advise parents who come to you with concerns about vaccinating their children?

A. It’s very important to be respectful of parents’ concerns about immunization while also communicating the very sound scientific evidence that supports current vaccination practices. We don’t know all of the answers about vaccines and we can’t know everything about potential consequences many years down the road.

But we do have a great deal of solid evidence about the safety and effectiveness of the childhood vaccines that are currently recommended. In helping people use this evidence in making vaccination choices, it is also very helpful to understand how individuals make decisions and what their beliefs are about health.

Making good choices about vaccination is based in part on the ability to understand fundamental scientific principles. It also depends on putting individual cases or case reports in a larger context — case reports of problems associated with vaccines can weigh very heavily when a parent is trying to make a decision, regardless of whether there is evidence of a causal relationship between the vaccine and the problem.

The weight of accumulated evidence, though, is that the risks of childhood vaccination are lower than the risks associated with contracting the diseases the vaccinations are designed to prevent. It is very important to have access to good information to help make good decisions.

Q. What role can physicians play in helping parents make decisions about vaccination?

A. People tend to trust their own physicians and their children’s physicians. I think that all health care providers — not just doctors and nurses, but medical technicians, lab technicians and office secretaries — can all play a big role in helping parents get the information they need and in helping them make good decisions.

It’s also the case that what parents want from their physicians varies — some want answers and some want options. This means, at least from my perspective, that it is useful for physicians and other health care providers to be able to switch gears depending on the needs and concerns of the different parents and children for whom they provide care.

This makes it possible to respond to patients’ specific situations and circumstances while also communicating reliable, scientifically supported information about vaccines and immunizations.

Q. Are there more general changes that have taken place that affect how parents make decisions?

A. Part of the challenge we face now is taking the time to provide enough information about vaccines and the diseases they prevent to help create a general cultural understanding that vaccines make sense. As immunization programs have become more successful, one result has been that the diseases they prevent have faded from memory.

Policymakers now are of an age that, although their parents and grandparents may have been familiar with diseases such as polio, measles and diphtheria and the ravages they can cause, the policymakers themselves have no firsthand knowledge of these diseases.

The control or near-elimination of so many diseases is a tremendous advance in public health, but it does make it more complicated to help people understand the value of vaccines and why they are so critical to maintaining and protecting the health of our population.

Q. Who should be involved in making decisions about vaccines and vaccine policy?

A. Society as a whole should make these decisions. We need to have a deep public understanding of the issues, including the risks and benefits involved. Otherwise there won’t be any resilience to the concept that vaccines make sense.

We need to talk about the types of risk people are willing to assume and develop a clearer consensus about what a public health risk is and what criteria we use for deciding how to respond to those risks.

As a clinician, I experience enormous sadness when I see thoughtful, concerned parents who take every other possible precaution to protect their young children choose for unwise reasons not to protect their children from diseases that are preventable.

The issues involved are complicated, but they can be systematically addressed and better decisions made.

How Safe Are Vaccines?

Concerns about the safety of vaccines, especially childhood vaccines, have become more pronounced and more public in the past decade. Safety issues such as the use of live virus in the oral polio vaccine, the potential effects of multiple vaccinations on the immune system and the possible impact of specific vaccines and mercury-containing preservatives in vaccines on children’s development have generated tremendous public attention and discussion. (11, 17)

In 1999, at the request of federal health agencies, the Institute of Medicine created the Immunization Safety Review Committee, an independent group of scientific experts charged with examining scientific evidence related to concerns about vaccine safety and examining the significance of vaccine safety issues in a broader social context.

Since its inception in 2001, the committee has examined four safety issues and published findings and recommendations. The issues are: thimerosal (mercury-containing preservative) in vaccines and neurodevelopmental disorders, measles-mumps-rubella (MMR) vaccine and autism, multiple immunizations and immune dysfunction and hepatitis B vaccine and neurological disorders. Findings suggest:

* Current scientific data do not show a link between thimerosal-containing vaccines and neurodevelopmental disorders in children, but the committee supports previous policies that encourage efforts to reduce thimerosal use as much as possible.

* The evidence does not support a causal relationship between the MMR vaccine and autism spectrum disorder, but this does not exclude the possibility that the MMR vaccine could contribute to the development of autism in a small number of children.

* The current childhood immunization schedule does not increase the risk of contracting diabetes mellitus type 1 or infections such as pneumonia and meningitis, but there is insufficient evidence on a relationship between multiple immunizations and an increased risk of allergic diseases such as asthma.

* The hepatitis B vaccine does not cause or trigger multiple sclerosis in adults.

The committee’s reports on these issues and related news releases are available at www.nationalacademies.org.

Preventing Child Vaccine Shortages

A report released Sept. 16 by the government’s General Accounting Office addresses recent shortages in childhood vaccine supplies and makes recommendations to the U.S. Secretary of Health and Human Services to “help promote the availability of vaccine products.”

The report notes that recent shortages of vaccines have “necessitated temporary modifications to the recommended immunization schedule and have caused states to scale back immunization requirements.”

To see the full report, go to www.gao.gov and search for report number GAO-02-1105T.

Resources and Information:
Vaccine-Preventable Diseases, Recommendations and Immunization Schedules

Common vaccine-preventable diseases include:

Diphtheria
Haemophilus influenza type b (Hib)
Hepatitis A
Hepatitis B
Influenza (flu)
Measles
Mumps
Pertussis (whooping cough)
Pneumococcal disease
Polio
Rubella (German measles)
Tetanus (lockjaw)
Varicella (chicken pox)

Centers for Disease Control and Prevention:

* National Immunization Program: Comprehensive information about vaccines, vaccine safety, immunization schedules, survey data, bioterrorism preparedness and planning for the public, health care providers, travelers and the media. (www.cdc.gov/nip) The CDC National Immunization Program also publishes an Influenza Vaccine Bulletin for Flu Season 2002-2003, covering vaccine supply and production, vaccine distribution and communications. (www.cdc.gov)

National Network for Immunization Information: Comprehensive resource for vaccine information, disease information, immunization schedules, state vaccine requirements for school entry. Information for the public, healthcare professionals, policy makers and the press. An educational program of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, the American Academy of Pediatrics and the American Nurses Association. (www.immunizationinfo.org)

American Medical Association:
* Vaccine information and recommendations oriented toward physicians.
* AMA Summary of Rules for Childhood Immunization
* AMA Summary of Recommendations for Adult Immunization

Every Child by Two: The Carter/Bumpers Campaign for Early Immunization, www.ecbt.org

National Partnership for Immunization:
partnersforimmunization.org

American College of Preventive Medicine: Adult Immunization Practice Policy Statement, acpm.org/adult.htm

The Research

Bibliography

1. Centers for Disease Control and Prevention, National Immunization Program: 2002 NIP Annual Report: Reaching for new heights in immunization: Mission and goals of the CDC National Immunization Program.

2. Centers for Disease Control and Prevention. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices. MMWR 1999, 48 (RR-4).

3. Centers for Disease Control and Prevention. Flu Season 2002-03: Flu Facts for Everyone.

4. Centers for Disease Control and Prevention. Reasons reported by Medicare beneficiaries for not receiving influenza and pneumococcal vaccinations–United States, 1996. MMWR 1999; 48(39); 556-90.

5. Centers for Disease Control and Prevention. Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices. MMWR, April 12, 2002; 51, RR03; 1-31.
Erratum: Vol51, No. RR-3; MMWR June28, 2002; 51(25); 563.

6. American Medical Association. Flu vaccine worries fade; focus shifts to future. American Medical News. August 12, 2002.

7. Katz, S.L. and Shine, K.I. Guaranteeing vaccines for all Americans. January 4, 2002. National Academies Office of News & Public Information, National Academies Op-Ed Service Archive.
www.nationalacademies.org.

8. Fingar, A.R. and Francis, B.J. Adult immunization: American College of Preventive Medicine Practice Policy Statement. American Journal of Preventive Medicine, Feb. 1998; 14(2):156-158.

9. Centers for Disease Control & Prevention, National Center for Health Statistics and National Immunization Program, National Immunization Survey.

10. National Partnership for Immunization. Report on the Feb. 20-21, 2002, Advisory Committee on Immunization Practices meeting.

11. Gellin, B.G., Maibach, E.W., Marcuse, E.K. Do parents understand immunizations? A national telephone survey. Pediatrics, Nov 2000; 106(5): 1097-102.

12. Offit, P.A., Quarles, J., Gerber, M.A. Hackett, C.J., Marcuse, E.K. et al. Addressing parents’ concerns: Do multiple vaccines overwhelm or weaken the infant’s immune system? Pediatrics 2002;109:124-129.

13. Centers for Disease Control & Prevention, National Immunization Program. Smallpox: Disease of the past and protection for the future.

14. Centers for Disease Control & Prevention, Interim smallpox plan and guidelines (updated June 20, 2002)

15. Centers for Disease Control & Prevention. Programs in Brief: Smallpox Vaccine: What is the public health problem?

16. Public Health System Undergoing Anti-Terrorism Overhaul. Newhouse News Service.

17. Consumers Union. Special Report. Vaccines: An issue of trust. Consumer Reports, Aug. 2001.
www.consumerreports.org

18. National Institute of Neurological Disorders and Stroke. Guillain-Barré Syndrome Fact Sheet. 19. Lasky, T., Terracciano, D.O., Magder, L. et al. Guillain-Barré syndrome and 1992-93 & 1993-94 influenza vaccines. New England Journal of Medicine, Dec. 17, 1998; 339(25): 1797-1802.

The Center for the Advancement of Health is an independent nonprofit organization that promotes greater recognition of how psychological, social, behavioral, economic and environmental factors influence health and illness. The Center advocates the highest quality research and communicates it to the medical community and the public. The fundamental aim of the Center is to translate into policy and practice the growing body of evidence that can lead to the improvement and maintenance of the health of individuals and the public. The Center was founded by the John D. and Catherine T. MacArthur Foundation and the Nathan Cummings Foundation, which continue to provide core funding. Funding for this series was provided by the Robert Wood Johnson Foundation.

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