Vaccine-preventable disease causes significant morbidity and mortality among adults. More than 50,000 American adults die each year of influenza, pneumococcal infection and hepatitis B - a marked contrast to the 500 annual deaths from vaccine-preventable diseases of childhood. The American College of Physicians and the Infectious Diseases Society of America have developed a set of guidelines for the immunization of adults.^, The United States Preventive Services Task Force has also published recommendations for adult immunization, and the CDC Advisory Committee on Immunization Practices (ACIP) provides annual updates. Recommendations for vaccination are based upon estimated risk of disease and of exposure and are summarized in Table 1. This chapter will focus on routine immunizations; information about post-exposure prophylaxis and vaccinations recommended for travel can be found in reference 1. The CDC web site is an excellent and updated source for those interested in travel medicine (www.cdc.gov/travel) and vaccination information (www.cdc.gov/nip).

There are many misconceptions among patients (and physicians) about contraindications to and complications from vaccines. While no vaccine is completely free from risk, modern vaccines are extremely safe. The following situations are not contraindications to vaccination:

• recent exposure to an infectious disease
• mild acute illness, including URI
• current antibiotic therapy
• breast feeding

Live vaccines (MMR, varicella) should not be given to pregnant women, patients with HIV or severely immunocompromised patients (including those with solid organ transplants). Simultaneous administration of vaccines does not decrease efficacy or increase the incidence of adverse reactions.⁴

While physicians often presume that adults have received all their childhood vaccines, persons without previous access to health care and those who have immigrated from other countries may not have been completely immunized. It is important to review vaccination histories with all adults; in immigrants and refugees it may be wise to assume that they have not been vaccinated unless evidence exists to the contrary.

Epidemic influenza has caused millions of deaths in the twentieth century, and is responsible for an average of 20,000 deaths a year in the United States. The virus is estimated to cause a yearly average of 4.1-4.4 million excess respiratory illnesses and 16.6-17.9 million excess sick days in Americans over the age of 20. The attack rate of the virus is extremely high, and antigenic shift and drift prevent long-term immunity. While approximately 90 percent of the mortality associated with non-pandemic influenza occurs in those over 65, temporary morbidity can be high even in younger patients.

Influenza vaccine is made from egg-grown inactivated virus which cannot cause infection. The vaccine is modified annually to match the latest strains of influenza A and B and now contains three virus strains. It takes about two weeks for patients to develop protective antibody levels, and these last for roughly four months. The optimal time to vaccinate against influenza is, therefore, October to November.

The efficacy of influenza vaccination has been demonstrated in healthy subjects to be approximately 70 percent. One randomized placebo-controlled trial in high-risk patients demonstrated a significant reduction in the numbers of patients diagnosed with influenza; cohort and case-control studies have suggested that the virus can also decrease hospitalization rates and mortality.^,,, As pneumonia and influenza are the fifth leading cause of death in Americans over 65, vaccination is an important part of health care maintenance.^7,

People with documented egg allergy should not be given the influenza vaccine. Immunizations of all types have been shown to increase viral load in patients with HIV for weeks; while there is no consensus about influenza vaccination in patients with AIDS, many practitioners reserve flu shots for patients with over 100 CD4 cells. The CDC maintains a useful influenza website at www.cdc.gov/ncidod/diseases/flu/fluvirus.htm.

Pneumococcal infections cause an estimated 40,000 deaths a year in the United States, predominantly from pneumonia (approximately 500,000 cases/year), sepsis (50,000 cases/year) and meningitis (3,000 cases/year). Vaccination rates among minorities are, disturbingly, significantly lower than those among non-Hispanic whites. People over the age of 65 and those with co-morbid conditions have the highest case-fatality rates. The emergence of drug-resistant pneumococcus highlights the importance of prevention.

The 23-valent pneumococcal vaccine (Pneumovax), licensed in 1983, contains capsular polysaccharide from 85 to 90 percent of the strains of S. pneumoniae causing invasive disease in the US. The polysaccharide antigen is T-cell independent, triggering mature B-cells to opsonize pneumococcus for phagocytosis by neutrophils. The exact duration of antibody protection is unknown, but is estimated to be at least five to ten years. In patients with nephrotic syndrome, renal failure or solid organ transplant, levels drop particularly quickly, and the ACP guidelines suggest revaccination every six years. Patients vaccinated with the 14-valent vaccine (prior to 1983) should be revaccinated with the newer 23-valent vaccine. Some experts believe that all patients over age 65 should be revaccinated every five years, given the demonstrated attenuation of protective effect. We leave the decision about revaccination to the discretion of patient and provider.

While the efficacy of the Pneumovax has been demonstrated in low-risk populations (where it is estimated to be 60 to 75 percent protective), there are less data to has support a protective effect in those at highest risk - the elderly and immunocompromised. This may be due to the T-cell independent nature of the antibody response, which does not induce immunologic memory. Antigenic response to the vaccine among normal subjects varies widely. Newer vaccines, such as pneumococcal conjugate vaccines in which the polysaccharide is coupled to a protein carrier, are in clinical phase III trials.

While 75,000 to 125,000 cases of acute hepatitis A occur annually in the United States, only 100 deaths a year are associated with the virus, which does not cause a chronic carrier state or chronic hepatitis. Specific risk factors have been identified - including contact with a person with hepatitis, employment at a daycare center, recent international travel and injection drug use - but in 42 percent of reported cases no risk factor has been identified.

The hepatitis A vaccine (Havrix, Vaqta) consists of killed formalin-inactivated virus. Immunization requires an initial IM injection followed by a booster shot 6 to 12 months later. Protective levels of antibodies develop in two weeks in 80 to 90 percent receiving the first shot and in close to 100 percent of those receiving both shots. Protective efficacy has been demonstrated in several pediatric studies - including a double-blind randomized controlled trial in 40,119 children in Thailand - but has not been studied in adults. Routine vaccination of children in states and communities with high levels of hepatitis A has been recommended by the CDC since 1996.

Unlike hepatitis A, hepatitis B infection can lead to a chronic carrier state, as well as to cirrhosis and to hepatocellular carcinoma. There are an estimated 200,000 to 300,000 cases of hepatitis B in the United States each year, leading to more than 10,000 hospitalizations and 5,000 hepatitis B-related deaths.

Plasma-derived hepatitis B vaccines were introduced in 1982; these have been replaced by recombinant hepatitis B vaccines (Recombivax, Engerix) which became available in 1986. The recombinant vaccines contain hepatitis B surface antigen (HBsAg) and stimulate neutralizing anti-HBs antibody production. Immunization involves a series of intramuscular injections at one, two and six months.

Protective serum antibody titers develop in 96 to 99 percent of healthy patients who receive all three doses of hepatitis B vaccine, but older and immunocompromised patients may have a reduced antibody response. Higher doses of vaccine are recommended for immunocompromised adults, particularly those undergoing hemodialysis. Immunization has been studied in controlled trials of at-risk cohorts of homosexual men and health care workers and has been shown to reduce the risk of infection by 90 to 95 percent. The duration of protection from plasma-derived vaccines appears to be at least seven to nine years, although antibody levels may fall before that time. The more recently introduced recombinant vaccines produce similar antibody responses and short-term protection, although information on longer-term protection is not yet available. Booster doses produce a rapid anamnestic response but are not routinely recommended. They should be considered in patients at high risk for exposure to blood (health care workers) and in patients on hemodialysis whose antibody levels have dropped.

As immunizing patients who have already been infected with hepatitis B confers no added protection, it may be cost-effective to test serology prior to the three-vaccine series.

While approximately 90 percent of adults are immune to varicella, infections in adults tend to be more serious than those in children, with a higher incidence of central nervous system and pulmonary complications. Varicella vaccine (Varivax) was licensed for use in the United States in 1995, after years of experience with its use in other countries. The vaccine is a live attenuated virus given as two subcutaneous doses four to eight weeks apart. Immunogenicity approximates 99 percent and persists for several years at least. In efficacy studies in children, varicella vaccine is estimated to be 95 percent effective at least seven years after vaccination.^, The incidence of herpes zoster in vaccinated children appears to be slightly less than that in children after natural infection, although follow-up studies are still underway. Efficacy studies in adults have also demonstrated a protective effect; adults who received the vaccine were less likely to develop varicella when exposed, and those who did develop the infection had milder disease than unvaccinated adults.

Adults with a documented history of varicella infection are assumed to be immune. In fact, most adults without a documented history of varicella have been exposed and are immune. Nonetheless, varicella serology and vaccination of those with negative serology are recommended for adults with no history of chickenpox who are in the following categories:

Tetanus is a rare disease, but one which is completely preventable through vaccination and appropriate management of high risk wounds. Adults who have received the three-dose primary immunization are at extremely low risk for contracting tetanus. Traditional recommendations call for a Td booster shot every ten years; the ACP also endorses a strategy of giving a single booster shot at age 50 years.

Patients receiving vaccinations should be told that there is a small risk of local pain and swelling at the site and counseled about use of symptomatic treatment, such as acetominophen and heating pads. Influenza and pneumococcal vaccines are routinely available from the nurse practitioners; hepatitis and varicella vaccines require a prescription. The lot number and expiration date of each vaccine should be documented by the clinician who administers it. Vaccine Information Sheets (VIS) are published by the CDC – providers are required by law to give patients the appropriate VIS when giving certain vaccines (including the HBV vaccine). These are available in English and Spanish in the PIC rooms and from the nursing staff.