66.  Adult Immunizations_Including Chemoprophylaxis Against Influenza A



RECOMMENDATION



Annual influenza vaccine is recommended for all persons aged 65 and older and persons in selected

high-risk groups (see Clinical Intervention). Pneumococcal vaccine is recommended for all

immunocompetent individuals who are age 65 years and older or otherwise at increased risk for

pneumococcal disease (see Clinical Intervention). There is insufficient evidence to recommend for

or against pneumococcal vaccine for high-risk immunocompromised individuals, but

recommendations for vaccinating these persons may be made on other grounds. The series of

combined tetanus-diphtheria toxoids (Td) should be completed for adults who have not received the

primary series, and all adults should receive periodic Td boosters. Vaccination against measles and

mumps should be provided to all adults born after 1956 who lack evidence of immunity. A second

measles vaccination is recommended for adolescents and young adults in settings where such

individuals congregate (e.g., high schools and colleges). See Chapter 32 for recommendations for

rubella vaccine. Hepatitis B vaccine is recommended for all young adults not previously

immunized and for all persons at high risk for infection (see Clinical Intervention). Hepatitis A

vaccine is recommended for persons at high risk for hepatitis A virus (HAV) infection (see

Clinical Intervention). Varicella vaccine is recommended for susceptible adults (see also Chapter

65). See Chapter 25 for recommendations regarding the Bacille Calmette-Gurin (BCG) vaccine.

Recommendations for postexposure prophylaxis against selected infectious diseases are in Chapter

67; see also Chapter 24, Screening for Hepatitis B Virus Infection.



INFLUENZA



Burden of Suffering



Influenza, which frequently causes incapacitating malaise for several days, is responsible for

significant morbidity and decreased productivity during epidemics. Twenty thousand or more

excess deaths have been reported during each of 10 different epidemics from 1972-1973 to

1990-1991; more than 40,000 excess deaths occurred in each of three of these epidemics.1

During severe pandemics (e.g., 1957 and 1968), there are often high attack rates across all age

groups, and mortality usually is markedly 



increased. Elderly persons and persons of all ages with certain chronic medical disorders (see

Clinical Intervention) are at increased risk for complications from influenza infections. More

than 90% of the deaths attributed to pneumonia and influenza in these epidemics occurred among

persons aged 65 and older.1 Influenza has been estimated to cause a yearly average of 4.1-4.4

million excess respiratory illnesses and 16.6-17.9 million excess bed and restricted activity

days in persons over 20 years of age.2 Excess rates of hospitalization have also been documented

for children with influenza who have chronic conditions such as severe asthma, cystic fibrosis,

and diabetes.3



Efficacy of Vaccine



Inactivated (killed-virus) influenza vaccine containing antigens identical or similar to currently

circulating influenza A and B viruses has been shown in controlled trials to be 70-80% effective

in preventing influenza illness or reducing severity of influenza illness in healthy children,

adolescents, and adults under age 65.4-8 The vaccine has also been reported to reduce clinical

symptoms in health care workers,9 which may translate into a reduction in transmission to

high-risk patients.



Only one randomized placebo-controlled trial has studied vaccine efficacy in high-risk persons for

whom the vaccine is generally recommended. This trial enrolled 1,838 persons aged 60 years and

older, three fourths of whom had no risk factors other than age.10 During the influenza season,

the vaccine significantly reduced the proportion with influenza-like illness (from 3% to 2%) and

with serologically diagnosed infections (from 9% to 4%). In stratified analyses, protective

efficacy was similar in healthy older adults and those with chronic disease but was reduced in

subjects 70 years of age. In a poorly reported randomized controlled trial comparing different

types and dosages of influenza vaccine in elderly persons living in the community,11 one of the

vaccines reduced clinical illness rates by 50-70% compared with other vaccine types and dosages.

Illness rates were also substantially reduced compared to an unvaccinated cohort not enrolled in

the trial. In a large serial cohort study of community-dwelling elderly persons, influenza

vaccination reduced hospitalization rates by 48-57% for pneumonia and influenza and by 27-

39% for all acute and chronic respiratory conditions, after adjustment for covariates.12

Case-control studies in persons who are 65 years or older have reported that during epidemic

periods when there was a good antigenic match between vaccine and virus, influenza vaccination

prevented 31-45% of hospitalizations for pneumonia and influenza13-15 and 43-49% of deaths

due to all respiratory conditions.13 In a separate analysis using vital statistics data, influenza

vaccination reduced total mortality by 27-30% among individuals aged 45 years or older.13



Adequately designed and performed observational studies conducted during influenza outbreaks also

generally support the efficacy of influenza vaccine in preventing illness, hospitalization, and

mortality in the institutionalized elderly population and in community-dwelling elderly persons

with high-risk chronic conditions, although efficacy estimates vary widely (e.g., 24-58%

efficacy against pneumonia).16-22 Vaccination of nursing home residents also may prevent

institutional outbreaks.23 Randomized controlled trials in nursing homes have suggested that

greater protection may be offered by other, as yet unlicensed, vaccine formulations or

combinations (e.g., diphtheria toxoid conjugate vaccine or addition of live intranasal

vaccine).24,25 Data are more limited for younger high-risk persons. One cohort study in

children with moderate to severe asthma demonstrated 49% vaccine efficacy against clinical

illness despite a poor antigenic match with the epidemic influenza A virus, but no effect was seen

on hospitalizations or asthma attack rates or severity.26



Because of frequent seasonal variation in the hemagglutinin and neur-aminidase antigens of

circulating viruses ("antigenic drift"), it is necessary to administer the vaccine annually each

fall, prior to the epidemic season. This schedule allows the annually reformulated influenza

vaccine to include antigens detected from recent global viral surveillance, which are likely to be

circulating during the subsequent season. Although allergic reactions have been described,

principally in patients with hypersensitivity to eggs, serious adverse effects from influenza

vaccine are quite uncommon.1 Randomized placebo-controlled trials of influenza vaccine have

reported no difference in systemic reactions, but mild local side effects were more common after

vaccine and occurred in up to 20% of patients.27,28



Amantadine and rimantadine are 70-90% effective in preventing illness caused by outbreaks of

naturally occurring strains of influenza A viruses when used prophylactically in healthy

community-living or institutionalized persons.29-34 Several trials have shown much lower

protection rates,35,36 however, possibly due to late initiation of chemoprophylaxis or inadequate

compliance. No controlled trials of these medications have been conducted in nursing home

populations, but observational studies support the efficacy of chemoprophylaxis as an adjunct to

vaccination during influenza A outbreaks in these institutions.21,37,38 Neither drug is effective

as prophylaxis against influenza A for household members of simultaneously treated index

cases,39,40 although amantadine has been proven efficacious in preventing influenza A disease

when the index case is not treated.41 Transmission of resistant viruses from treated patients may

reduce the efficacy of chemoprophylaxis in household or institutional contacts.22,39 Neither drug

prevents influenza B infection, so they are appropriate only in presumed influenza A epidemics.



Amantadine and rimantadine produce transient insomnia, anxiety, nausea, dizziness, and impaired

concentration in 5-25% of patients.42-47 The risk of adverse central nervous system effects has

been shown to be significantly lower with rimantadine.33 Adverse effects occur more frequently

and with greater severity in older persons and have been associated with increased risk of

falls.48,49 Toxic levels resulting from reduced drug clearance have been identified in elderly

persons.42,49



PNEUMOCOCCAL DISEASE



Burden of Suffering



Pneumococcal disease is a significant cause of morbidity and mortality in the U.S. Although

pneumococcal infection is not a reportable disease, population-based surveillance studies have

reported annual invasive pneumococcal disease rates of at least 15-19/100,000 population and

pneumococcal meningitis rates of 0.3-1.2/100,000.50-54 Significantly higher incidence rates

are reported for persons less than 5 years of age or over age 65; blacks, Native Americans, and

Alaska Natives; nursing home residents; alcoholics; and those with underlying chronic medical or

immunodeficient conditions.50-57 Pneumococcal disease accounts for about 15% of severe

community-acquired pneumonia, which has a case-fatality rate (proportion of cases resulting in

death) of 9-26%.58-63 Pneumococcal bacteremia and meningitis are also associated with high

case-fatality rates.50-54,63,64 The highest case-fatality rates from invasive pneumococcal

infection occur in elderly persons (30-43%) and patients with co-morbid conditions (25-

27%), and the lowest occur in healthy children (0-3%).50-53,63 In recent years,

drug-resistant strains of Streptococcus pneumoniae have emerged; recent estimates suggest that

in some locales 15% or more of pneumococcal isolates are drug resistant.50,65,65a The

emergence of drug-resistant strains underscores the importance of preventing pneumococcal

disease by vaccination.



Efficacy of Vaccine



The 14-valent polysaccharide pneumococcal vaccine, which was licensed in 1977, was replaced in

1983 by a 23-valent polysaccharide vaccine.66 The latter contains purified capsular materials

from 88% of the strains of S. pneumoniae causing bacteremic pneumococcal disease reported in

the U.S.67 In randomized controlled trials, 4- to 13-valent pneumococcal vaccines were 76-92%

efficacious in preventing pneumococcal pneumonia in healthy young adult populations living in

epidemic conditions.68-70 A 14-valent vaccine was also efficacious in reducing respiratory

mortality in a population from a developing country.71 The efficacy of pneumococcal vaccine in

the general U.S. population has not been determined with certainty. Controlled trials in the U.S.

involving low-risk middle-aged and older adults failed to demonstrate protective efficacy,72

although the relatively low incidence of pneumococcal infection in healthy U.S. adults makes

efficacy difficult to establish in a prospective clinical trial. A meta-analysis combining the most

recent trials (follow-up periods of 16-36 months) in low-risk populations in the U.S. and

elsewhere reported significant reductions in definitive and presumptive pneumococcal pneumonia

with vaccination.73 Vaccinated individuals had 11 fewer episodes of definitive pneumococcal

pneumonia and 25 fewer episodes of presumptive pneumococcal pneumonia per 1,000 subjects.

Results were similar for definitive and presumptive pneumonia due to vaccine types only. Small

reductions in mortality were not statistically significant.



Trials in relatively healthy institutionalized elderly (50-55 years of age) have demonstrated

significant reductions in the incidence of pneumonia, and in mortality in one study, with 3- and

14-valent vaccines, although these trials were limited by flaws in design and conduct.74,75 Other

trials of 14- to 17-valent vaccines in high-risk populations, all adequately designed and

conducted, have been unable to detect significant reductions in pneumococcal or all-cause

pneumonia or mortality.76-79 A meta-analysis combining five trials in high-risk populations

also reported no effects of vaccine on pneumococcal pneumonia, all-cause pneumonia, or

mortality.73 The sample sizes were much smaller than for the analyses in low-risk populations,

but effect estimates for most outcomes did not suggest important benefits.



One possible explanation for the lack of vaccine efficacy in trials in high-risk populations is that

the trials may have included subsets of individuals for whom the vaccine has little benefit.

Case-control studies and indirect cohort studies (comparing the distribution of pneumococcal

serotypes in the blood of vaccinated and unvaccinated persons) have been much more feasible to

perform than controlled trials, although such observational studies may be more prone to bias.

These studies support the protective value of pneumococcal vaccine in immunocompetent

recipients, with vaccine efficacy estimates of 60-75% reported but not in severely or relatively

immunocompromised individuals, including those with alcoholism, chronic renal failure,

immunoglobulin deficiency, nephrotic syndrome, sickle cell disease, multiple myeloma,

metastatic or hematologic malignancies, or systemic lupus erythematosus.80-86 For some of

these disorders, efficacy point estimates suggest a benefit, but confidence intervals are wide and

include the possibility of no benefit. Additional research is needed to obtain more definitive data on

the efficacy of pneumococcal vaccine and to develop vaccines that have better efficacy in both

immunocompetent and immunocompromised individuals, as well as in high-risk children under 2

years of age.



The total duration of antibody protection from pneumococcal vaccination is unknown; elevated

titers appear to persist in adults for at least 5 years after immunization, but in some persons,

they may fall to prevaccination levels within 10 years.66 A case-control study reported a

statistically significant decline in protective efficacy with increasing time since vaccination (e.g.,

from 88% within 3 years to 75% if 5 years since vaccination in persons aged 55-64).81 On the

other hand, an indirect cohort study reported that clinical efficacy persisted at least 7-10

years.84



There is little evidence of serious adverse effects from this vaccine, although erythema,

induration, or pain at the injection site occur in about one third to one half of patients. Fever,

myalgia, and severe reactions occur in no more than 1% of patients.66,72 Most evidence indicates

little difference in adverse reactions to revaccination compared to initial vaccination.66



TETANUS AND DIPHTHERIA



Burden of Suffering



Largely as a result of routine immunization, tetanus and diphtheria have become uncommon

diseases in the U.S.: 51 cases of tetanus (0.02/100,000) and 2 cases of diphtheria were reported

in 1994.86a In 1948, before tetanus and diphtheria toxoids were widely introduced, there were

over 600 cases of tetanus and about 9,500 cases of diphtheria in the U.S.87 The prevalence of

immunity to tetanus in the U.S. population, as measured by serum antibodies, declines with age

beginning at age 40 and is only 28% among persons ages 70 or older.88 Adults ages 50 and older

account for the majority of cases of tetanus.87,88 Tetanus remains a serious infection, with death

occurring in 19-24% of cases.88,89 Reports may underrepresent tetanus mortality by as much

as 60%.90 The tetanus case-fatality rate increases with age and is 26% for persons ages 70 and

older.88 The case-fatality rate is also high in neonates, indicating the need to adequately immunize

women of childbearing age against tetanus. Diphtheria is a potentially severe illness, with a

case-fatality rate of 5-10% in unvaccinated individuals. The disease is rare in the U.S., but large

outbreaks have occurred in other developed countries despite relatively high rates of childhood

immunization.91-94



Efficacy of Vaccine



The efficacy of the tetanus and diphtheria toxoids is established on the basis of clinical studies and

decades of experience with universal childhood immunization.95,96 A primary series of three

doses of Td, followed by a booster dose, is highly effective in producing protective antibody titers

lasting as long as 15-25 years and results in anamnestic responses with booster immunization as

much as 20-30 years later.97-104 In Sweden, a five-dose regimen (primary series plus

boosters at age 8-10 and 18 years) resulted in greater than 90% of subjects having protective

tetanus antitoxin levels at age 50 years, slightly fewer than at age 30.105 Tetanus is unlikely in

Americans who have received a primary vaccination series,89,90,106 although clinical

immunity may wane somewhat after 10-20 years.89 Td often produces mild local inflammation,

occasionally Arthus-type reactions and peripheral neuropathy (following frequent boosters), and

rarely, anaphylaxis.107-110



MEASLES, MUMPS, AND RUBELLA



Burden of Suffering



Measles, a childhood illness, was reported in 232 (0.1/100,000) American adults (aged 20 or

older) in 1994, a substantial decline from the recent peak of 6,210 cases (3.9/100,000)

reported in 1990.87,111 Adults accounted for nearly one fourth of all cases with known age

reported in 1994.111 About one third of adult infections occur among persons ages 20-24,87

often in places where young adults congregate, such as schools or college campuses.111

Hospitalization for measles and complications such as pneumonia and encephalitis are more

common in adults than in school-aged children. Mumps infection was reported in 319 persons 20

years of age in 1993 (0.2/100,000), accounting for 20% of reported cases with known age.87

Mumps outbreaks continue to occur periodically in schools and similar settings; in several recent

outbreaks, most of those infected had previously been vaccinated against mumps.111a Rubella

infection is discussed in Chapter 32.



Efficacy of Vaccine



A single dose of measles vaccine is 95% effective in producing long-term immunity.112,113

Seropositivity rates remain high at least 10-15 years following vaccination,114,115 and cohorts

of known seroconverters have shown little evidence of increasing disease incidence with time since

immunization.115 Adult infections occur primarily in persons who have not been naturally

infected or appropriately vaccinated in the past,111 as well as those who were vaccinated before

age 15 months.116,117 Persons born before 1957 are likely to have been naturally infected and

need not be considered susceptible.118 Based on the age distribution and location of recent measles

outbreaks,111,117 revaccination of young adults in settings such as colleges and the workplace is

likely to be most effective in reducing incidence in adults. Measles outbreaks are less common at

colleges where two doses of vaccine are required prior to matriculation.119 When outbreaks do

occur in these settings, attack rates are lower among persons who have had two doses of

vaccine.117,120,122-124 Measles has been virtually eliminated among military recruits by

revaccinating those whose screening sera suggest they are susceptible despite a history of

vaccination.125



Since the introduction of mumps vaccine in the United States in 1967, there has been a 99%

decline in the incidence of mumps, supporting the efficacy of this vaccine.111a The incidence of

mumps in adults declined 50% between 1988-1990 and 1991-1993.111a Recommendations

issued in 1989 for a two-dose measles vaccination schedule, with MMR recommended as the

preferred vaccine, may have contributed to this recent decline. The age distribution and location of

recent mumps outbreaks also suggests that revaccinating young adults in settings such as schools

and colleges may be effective in reducing the incidence in adults. As with measles, persons born

before 1957 can generally be considered immune to mumps and need not be vaccinated. Rubella

screening and immunization are discussed in Chapter 32.



Adverse effects of measles or combined measles-mumps-rubella (MMR) vaccine in adults are

usually mild and self-limited.118,126 Administration of MMR vaccine is not associated with

adverse effects in persons already immune to these diseases, and thus the combined MMR vaccine

is preferable to individual vaccines such as measles vaccine, since many recipients may be

susceptible to more than one of the three diseases MMR prevents.



HEPATITIS B



Burden of Suffering



An estimated 200,000-300,000 persons become infected with hepatitis B virus (HBV) in the

U.S. each year and more than 10,000 require hospitalization.127,128,188 The risk of developing

a chronic HBV infection (i.e., carrier state) after acute infection is about 6-10% in

adults.127,130,131 Some 1-1.25 million persons in the U.S. are chronic HBV carriers.188

About one quarter of carriers develop chronic active hepatitis, which can progress to cirrhosis;

carriers are also at risk for developing hepatocellular carcinoma.128,132,133 Some 5,000

hepatitis B-related deaths occur each year as a result of cirrhosis and liver cancer.128 Persons

with acute or chronic HBV infection are also at risk for infection with hepatitis delta virus (HDV),

which can itself cause acute, possibly fulminant, hepatitis or chronic hepatitis that may progress

to cirrhosis.128 Since HDV cannot be transmitted in the absence of HBV infection, measures to

prevent HBV infection will also prevent the complications of HDV infection.



Efficacy of Vaccine



Plasma-derived hepatitis B vaccine, which became available in 1982, has 85-95% protective

efficacy when administered in three intramuscular doses to immunocompetent patients.134-138

Controlled trials and time series in adult responders to plasma-derived vaccine indicate persistent

protection against clinical HBV infection and chronic carriage lasting at least 7-9 years despite

declines in protective antibody levels.139-141,147 The recombinant vaccines licensed in 1986

and currently in use in the U.S. induce antibody responses and short-term efficacy (up to 5 years)

similar to those of the plasma-derived vaccine.142-145 Information on longer-term efficacy is

not yet available for recombinant vaccines. The possible need for booster doses after longer

intervals will be assessed as additional data become available.



Compared to healthy young persons, older adults, overweight persons, smokers, chronic

hemodialysis patients, injection drug users, and human immunodeficiency virus (HIV)-infected

patients are significantly less likely to have an adequate antibody response to the vaccine; those

who do respond have a more rapid decline in antibody levels.142,146-155 A repeat vaccination

series in persons who fail to respond to the first series results in moderate antibody response in

up to 50%.156 Injection into the buttocks has been associated with a suboptimal immune

response, and therefore the deltoid muscle is the preferred injection site.128,146 Local soreness

at the injection site is a common side effect.145 There have been several case reports of nonfatal

anaphylaxis from recombinant hepatitis B vaccine.157



HEPATITIS A



Burden of Suffering



Almost 27,000 cases of hepatitis A were reported in the U.S. in 1994 (10.3/100,000),86a

although the actual number of cases is estimated to be several times higher.128 Adults aged 20-

39 years account for 43% of reported cases.87 About half of reported hepatitis cases in the U.S.

are attributable to hepatitis A.128 The case-fatality rate and clinical severity of hepatitis A

increase with increasing age.128,158 Groups at high risk for hepatitis A include certain Alaska

Native, Pacific Islander, and Native American populations, institutionalized persons and workers

in these institutions, men who have sex with men, users of injection or street drugs (depending on

local epidemiology), certain laboratory workers, some religious communities, and travelers to

countries where hepatitis A has intermediate or high endemicity.128,159,160 For susceptible

travelers visiting developing countries, the incidence rate of hepatitis A has been estimated at 300

cases per 100,000 persons per month and the mortality rate at 3 deaths per 100,000 per

month.160



Efficacy of Vaccine



Inactivated hepatitis A vaccine, now licensed in the U.S., has been proven efficacious against

hepatitis A in randomized controlled trials in children (see Chapter 65).161,162 Although trials

evaluating clinical outcomes have not been performed in adults, hepatitis A vaccine produces

seroconversion rates of 90-100% after one dose and 99-100% after two doses in healthy adult

volunteers, including Alaska Natives.163-169 The duration of immunity has not been established,

but in adults, protective levels of antibody have been shown to persist at least 4 years after

administration of three doses of vaccine.164,168,170,170a Estimates from models of antibody

decline after vaccination predict that protective levels could last at least 20 years.164 Vaccine

efficacy is low in the first week after vaccination, rising to 77-90% at 2 weeks and 90-100% at

3-4 weeks.162,165,171,172,176



To provide immediate protection for those at high risk of exposure (e.g., travelers to endemic

areas), giving immune globulin (IG) with the first vaccine dose may be necessary (see Chapter

67). Although several studies have reported lower mean antibody titers when the vaccine is

administered concomitantly with IG, vaccine seroconversion rates appear to be

comparable.173,176,181 Seroconversion rates do not appear to be adversely affected when

hepatitis A vaccine is given with hepatitis B vaccine.174



In direct comparisons with IG, traditionally used as preexposure prophylaxis against hepatitis A

for high-risk persons (see Chapter 67), the vaccine led to higher and longer-lasting antibody

titers.175-181 The reported protective efficacy of hepatitis A vaccine is higher than that

reported for IG (see Chapters 65 and 67), but the clinical efficacies of the two interventions have

not been directly compared.



Adverse effects of the vaccine, including mild local reactions (pain, tenderness, redness, and

swelling) and minor systemic symptoms such as fever, headache, and malaise, occur in 10-30%

of recipients and are more common after the second and third doses.161,162,169,170,182,183

Serious allergic reactions without long-term consequences have been reported rarely in temporal

association with hepatitis A vaccine.160



Recommendations of Other Groups



Guidelines on adolescent and adult immunizations have been published by the American College of

Physicians (ACP) and the Infectious Diseases Society of America (IDSA),184 the American

Academy of Family Physicians,185 the American Academy of Pediatrics,3 the Canadian Task Force

on the Periodic Health Examination,186 the American College of Obstetricians and Gynecologists

(ACOG),186a and the Advisory Committee on Immunization Practices (ACIP).187 ACIP has also

issued specific recommendations on the use of Td;96 pneumococcal,66 influenza,1 hepatitis

B,128,170a,188 rubella,189 measles,118 varicella,189a and hepatitis A189b vaccines; and the

use of vaccines in persons with altered immunocompetence.190 ACOG has issued detailed guidelines

on the use of vaccines during pregnancy.191



A few of these recommendations differ from those made in this chapter. The Canadian Task Force

recommends against pneumococcal vaccine in immunocompromised individuals and found

insufficient evidence to recommend for or against routine pneumococcal vaccination for healthy

community-living elderly persons.186 ACP184 recommends that a single Td booster at age 50 for

those who have completed the full five-dose pediatric series is an equally acceptable alternative

strategy to decennial Td boosters.96 ACIP and AAP recommend catch-up immunization with

hepatitis B vaccine for adolescents aged 11-12 who have not been vaccinated previously, but they

do not recommend routine hepatitis B vaccination for low-risk persons over 12 years, primarily

because of cost and implementation considerations.3,188,188a ACIP recommends two doses of live

measles vaccine or evidence of measles immunity for two groups in addition to those entering

schools or colleges: persons who travel abroad and medical personnel at the time they begin

employment.118 ACOG recommends routine influenza vaccine beginning at age 55 rather than 65

and hepatitis B vaccine only for high-risk groups.186a



Antiviral chemoprophylaxis against influenza A, using either rimantadine hydrochloride or

amantadine hydrochloride, has been recommended by the ACP, IDSA, and ACIP for high-risk

persons and their caretakers who cannot be or have very recently been vaccinated (i.e., within 2

weeks for adults; within 2 weeks of the second dose for children), immunodeficient individuals as

a supplement to vaccine, and residents and unvaccinated staff during outbreaks in

institutions.184,192



Discussion



Most adults have not been immunized in accordance with existing immunization guidelines.193

Perceptions that adult vaccine-preventable infections are not important health problems and that

available vaccines are not safe and efficacious193 can be readily refuted by the evidence already

described. The cost of vaccines is another possible barrier to widespread immunization, but

studies have shown that the prevention of morbidity and mortality from infectious diseases makes

immunization cost-effective. For example, analyses of routine influenza and pneumococcal

vaccination of persons aged 65 and older suggest that their cost-effectiveness is comparable to that

of other widely recommended preventive services such as mammography or screening for

hypertension.12,15,194,195 Hepatitis B vaccination of high-risk groups (those with HBV

incidence >5%), with or without prior screening for susceptibility, has been shown to be

cost-effective, even cost-saving in some analyses.196-198



Cost-effectiveness analysis may also provide guidance on appropriate vaccination strategies.

Vaccination of high-risk newborns and adults against hepatitis B has been ineffective in

eliminating the disease. One cost-effectiveness analysis reported that vaccinating all adolescents

against hepatitis B, in addition to the current strategy of screening pregnant women and

vaccinating high-risk newborns, would cost only $3,695 per year of life saved.198 While Td

booster vaccination every 10 years is efficacious in preventing disease, antibody studies suggest

that an interval of 15-30 years between boosters is likely to be adequate, especially given the

small absolute risk of either disease in the U.S. A recent cost-effectiveness analysis reported that

a decennial-booster strategy added a 2-minute survival advantage compared with a single booster

at age 65 years, at a cost of $281,748 per year of additional life saved,199 although potential

costs related to diphtheria were not incorporated into the analysis.200



Compared to IG, hepatitis A vaccine appears to have greater and longer-lasting efficacy against

infection with fewer adverse effects, but it is unclear whether the benefits outweigh the costs of

the vaccine. One cost-effectiveness analysis reported that for all age groups, use of IG for

post-exposure prophylaxis or for preexposure short-term (6 months) prophylaxis is less

expensive than vaccination.201 Testing for hepatitis A antibodies in groups with a high prevalence

of immunity (e.g., frequent travelers, military personnel, older persons) reduces vaccination

costs, however. An analysis for British soldiers calculated a more favorable cost-benefit ratio for

the vaccine than for IG if there were at least two exposures to areas endemic for hepatitis A in 4

years.202



CLINICAL INTERVENTION



Influenza vaccine should be administered annually to all persons ages 65 and older and to persons

6 months of age or older who are residents of chronic care facilities or suffer from chronic

cardiopulmonary disorders, metabolic diseases (including diabetes mellitus), hemoglobinopathies,

immunosuppression, or renal dysfunction ("B" recommendation). Influenza vaccine is also

recommended for health care providers for high-risk patients ("B" recommendation). In persons

at high risk for influenza A (e.g., during institutional outbreaks), amantadine or rimantadine

prophylaxis (200 mg/day orally) may be started at the time of vaccination and continued for 2

weeks ("B" recommendation). A lower dose (100 mg/day) of amantadine is recommended for

persons with reduced creatinine clearance and those 65 years of age and older. A reduced dosage

(100 mg/day) of rimantadine is indicated for those with reduced renal or hepatic function and for

elderly nursing home residents and may also be necessary in healthy persons 65 years and older

who experience side effects. Amantadine and rimantadine are most useful as short-term

prophylaxis for high-risk persons who have not yet received the vaccine or are vaccinated after

influenza A activity in the community has already begun; when the vaccine may be ineffective due

to major antigenic changes in the virus; for unimmunized persons who provide care for high-risk

persons; to supplement protection provided by vaccine in persons who are expected to have a poor

antibody response; and for high-risk persons in whom the vaccine is contraindicated (i.e., those

with anaphylactic hypersensitivity to egg protein). If vaccine is contraindicated, amantadine or

rimantadine should be started at the beginning of the influenza season and continued daily for the

duration of influenza activity in the community.



Pneumococcal vaccine is recommended for all immunocompetent individuals who are aged 65 years

and older or otherwise at increased risk for pneumococcal disease ("B" recommendation).

High-risk groups include institutionalized persons 50 years of age, persons 2 years of age with

certain medical conditions, including chronic cardiac or pulmonary disease, diabetes mellitus, and

anatomic asplenia (excluding sickle cell disease), and persons 2 years of age who live in special

environments or social settings with an identified increased risk of pneumococcal disease (e.g.,

certain Native American and Alaska Native populations). Routine revaccination is not

recommended, but it may be appropriate to consider revaccination in immunocompetent

individuals at highest risk for morbidity and mortality from pneumococcal disease (e.g., persons

75 years of age or with severe chronic disease) who were vaccinated more than 5 years

previously. Revaccination with the 23-valent vaccine may be appropriate for high-risk persons

who previously received the 14-valent vaccine. There is insufficient evidence to recommend for

or against pneumococcal vaccine as an efficacious vaccine for immunocompromised individuals,

but recommendations for vaccinating these persons may be made on other grounds, including high

incidence and case-fatality rates of pneumococcal disease and minimal adverse effects from the

vaccine ("C" recommendation). Immunocompromised conditions associated with high risk for

pneumococcal disease include alcoholism, cirrhosis, chronic renal failure, ne-phrotic syndrome,

sickle cell disease, multiple myeloma, metastatic or hematologic malignancy, acquired or

congenital immunodeficiency (including HIV infection), and other conditions associated with

immunosuppression, such as organ transplant. It may be appropriate to consider periodic

revaccination in these high-risk immunocompromised patients, who are likely to have poor initial

antibody response and rapid decline of antibodies after vaccination.



The Td vaccine series should be completed for patients who have not received the primary series,

and all adults should receive periodic Td boosters ("A" recommendation). For persons not

previously immunized, the recommended schedule for the primary Td series is 0, 2, and 8-14

months. The optimal interval for booster doses is not established. The standard regimen is to

provide a Td booster at least once every 10 years, but in the U.S., intervals of 15-30 years

between boosters are likely to be adequate in persons who received a complete five-dose series in

childhood (see Chapter 65). For international travelers, an interval of 10 years between boosters

is recommended.



MMR vaccine should be administered to all persons born after 1956 who lack evidence of

immunity to measles (receipt of live vaccine on or after the first birthday, laboratory evidence of

immunity, or a history of physician-diagnosed measles) ("A" recommendation). A second measles

vaccination is recommended for adolescents and young adults in settings where such individuals

congregate (e.g., high schools, technical schools, and colleges), if they have not previously

received a second dose (see Chapter 65) ("B" recommendation). The combined MMR vaccine is

preferable to monovalent measles vaccine, since many recipients may also be susceptible to

mumps or rubella due to inadequate vaccination or primary vaccine failure. Susceptible

individuals should be vaccinated against mumps ("B" recommendation). Administration of the

MMR or measles vaccine during pregnancy is not recommended. See Chapter 32 for

recommendations on rubella screening and vaccination.



Hepatitis B vaccine is recommended for all young adults not previously immunized ("A"

recommendation). Hepatitis B vaccine is also recommended for susceptible adults in high-risk

groups, including men who have sex with men, injection drug users and their sex partners,

persons who have a history of sexual activity with multiple partners in the previous 6 months or

have recently acquired another sexually transmitted disease, international travelers to countries

where HBV is of high or intermediate endemicity, recipients of certain blood products (including

hemodialysis patients), and persons in health-related jobs with frequent exposure to blood or

blood products ("A" recommendation). The recommended regimen for the recombinant hepatitis B

vaccine is to administer 10 or 20 mg (depending on vaccine product) intramuscularly in the

deltoid muscle at the current visit and at 1 and 6 months later. Clinicians should consider testing

antibody response to the vaccine in individuals at very high risk from hepatitis B who are likely to

have an inadequate antibody response (i.e., chronic renal dialysis patients, injection drug users,

HIV-infected patients). Recommendations on screening for HBV infection and prevention of

perinatal transmission are in Chapter 24. Recommendations for persons with possible

percutaneous or sexual exposure to individuals infected with hepatitis B virus are in Chapter 67.



Hepatitis A vaccine is recommended for all high-risk adults ("B" recommendation). High-risk

groups include persons living in, traveling to, or working in areas where the disease is endemic

and periodic hepatitis A outbreaks occur (e.g., Alaska Native, Pacific Islander, and Native

American communities, certain religious communities, countries with high or intermediate

endemicity), men who have sex with men, users of injection or street drugs (depending on local

epidemiology), military personnel, and certain hospital and laboratory workers. Hepatitis A

vaccine may also be considered for institutionalized persons (e.g., in prisons and institutions for

the developmentally disabled) and workers in these institutions and in day care centers. Where

tracking or identification of high-risk patients is not practical or cost-effective, universal

vaccination may be a reasonable policy given the minimal adverse consequences of the vaccine. At

this writing, the only licensed hepatitis A vaccine is Havrix (SmithKline Beecham

Pharmaceuticals).* Two doses (1,440 ELISA units/dose) at 0 and 6-12 months are recommended

for persons over age 18 years. The need for periodic booster doses of the vaccine has not been

established. For persons requiring immediate protection against hepatitis A (e.g., travelers to

high-risk areas who have not previously been vaccinated), clinicians may wish to consider giving

IG simultaneously with the first dose of hepatitis A vaccine, although the clinical efficacy of this

approach has not been established. IG can also be recommended as an efficacious intervention for

short-term (5-6 months) preexposure prophylaxis against hepatitis A (see Chapter 67). While

some evidence suggests that the vaccine may be more efficacious than IG, the clinical efficacies of

these two interventions have not been directly compared. Other factors to consider in choosing

between these two interventions include patient preference, the likely duration of exposure, the

need for immediate vs. long-term protection, and cost.



Two doses of varicella vaccine delivered 4-8 weeks apart are recommended for healthy adults with

no history of varicella infection or previous vaccination ("B" recommendation) (see Chapter 65

for the review of evidence regarding varicella vaccine). Vaccination efforts should be targeted to

susceptible health care workers and family contacts of immunocompromised individuals, and may

also be targeted to susceptible adults who live or work in environments with a high likelihood of

varicella transmission (e.g., day care centers, residential institutions, colleges, military bases).

Given the high prevalence of immunity in adults with no history of chickenpox and the results of

cost-effectiveness analysis (see Chapter 65), clinicians may wish to offer serologic testing for

varicella susceptibility to history-negative adults who are likely to comply with return visits.



See Chapter 25 for recommendations regarding the Bacille Calmette-Gurin (BCG) vaccine.

Recommendations on postexposure prophylaxis against selected infectious diseases, including

tetanus, hepatitis A, and hepatitis B, are given in Chapter 67.



The draft update of this chapter was prepared for the U.S. Preventive Services Task Force by

Carolyn DiGuiseppi, MD, MPH, based in part on background papers prepared for the U.S.

Preventive Services Task Force by Modena Wilson, MD, MPH, and Donald Robinson, MD, MPH

(measles vaccine), and for the Canadian Task Force on the Periodic Health Examination by Elaine

Wang, MD, CM, FRCPC (pneumococcal vaccine).



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