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Adult Immunizations
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Vaccines recommended for routine use in US adults are reviewed here. Vaccines for travel have been reviewed separately.1

VACCINE PREPARATIONS

Live attenuated vaccines use a weakened form of the pathogen, which replicates after administration to induce an immune response. Compared to inactivated vaccines, live attenuated vaccines tend to have higher rates of adverse effects, particularly fever, but generally produce longer-lasting immunity.

Inactivated vaccines are prepared from whole bacteria or virus, or a fractional antigenic component of one. Fractional vaccines are usually either protein- or polysaccharide-based. Protein-based vaccines typically include subunits of microbiologic protein or inactivated bacterial toxins (toxoids). Polysaccharide-based vaccines are generally less immunogenic than protein-based vaccines; they may be conjugated to a protein to increase the immune response.

VACCINES

Eight vaccines are currently recommended by the US Advisory Committee on Immunization Practices (ACIP) for routine use in adults: tetanus-diphtheria alone (Td) or combined with acellular pertussis (Tdap), human papillomavirus (HPV), varicella, zoster, measles/mumps/rubella (MMR), influenza and pneumococcal. For some patients, hepatitis A and B and meningococcal vaccines are also recommended.2

TETANUS, DIPHTHERIA AND PERTUSSIS — A vaccine containing inactivated adsorbed (aluminum-salt-precipitated) tetanus and diphtheria toxoids (Td) was for many years the standard booster vaccine for adults. Adults were not re-immunized against pertussis because of concerns about reactions to the whole cell vaccine, but many pertussis cases occur each year in adults in whom vaccine-induced immunity has waned over time. Now 2 vaccines containing protein components of acellular pertussis combined with diphtheria and tetanus toxoids (Tdap) are FDA-approved as a one-time booster for adults.3

Recommendations for Use – The rationale for use of Tdap in adults is that waning immunity in adults has led to transmission of pertussis to un- and under-immunized infants, with some deaths. The ACIP recommends that adults with an uncertain history of primary vaccination receive 3 doses of a tetanus and diphtheria toxoids vaccine, one of which (preferably the first) should be Tdap. The first 2 doses should be administered at least 4 weeks apart and the third dose 6-12 months after the second. Adults who have completed a primary childhood series should be given a single dose of Tdap to protect against pertussis. Adults who require tetanus toxoid-containing vaccine as a booster (recommended every 10 years) or as a part of wound management should be given Tdap instead of Td if they have not previously received Tdap.

Pregnant women who have not received Tdap should receive it during the late second (after 20 weeks’ gestation) or third trimester to protect the newborn against pertussis through maternal antibodies. If Tdap is not administered during pregnancy, it should be given immediately postpartum. Pregnant women with an uncertain or incomplete history of primary vaccination should be given 3 doses of Td. The first 2 doses should be administered at least 4 weeks apart and the third 6-12 months after the second. Tdap should replace one of the doses, preferably during the late second or third trimester.

Adverse Effects – Local reactions around the injection site, such as erythema and induration, are common, but are usually self-limited. Arthus-type reactions with extensive painful swelling can occur in adults with a history of repeated vaccinations. Fever and injection-site pain have been more frequent with Tdap than with Td.

HUMAN PAPILLOMAVIRUS (HPV) — HPV is a common sexually transmitted infection often acquired soon after initiation of sexual activity. Although most HPV infections clear spontaneously without clinical sequelae, persistence of an oncogenic HPV type can cause abnormalities in the epithelium that may progress to cancer. Types 16 and 18 cause more than 70% of cervical cancers and about 80% of anal cancers. Types 6 and 11 cause 90% of genital warts. Two inactivated recombinant human papillomavirus-like particle vaccines are approved by the FDA. A bivalent vaccine (Cervarix) is approved for use in girls and young women 9-25 years old to prevent diseases associated with the oncogenic HPV types 16 and 18.4 A quadrivalent vaccine (Gardasil) is approved for use in both sexes (9-26 years old) to prevent diseases associated with HPV 6, 11, 16 and 18.5,6 The quadrivalent vaccine has been shown to reduce the rate of anal epithelial neoplasia among men who have sex with men.7 The bivalent vaccine can induce higher antibody levels than the quadrivalent vaccine for types 16 and 18; whether these higher levels lead to greater longterm protection is unknown.

Recommendations for Use – Routine HPV vaccination is recommended for girls (with Cervarix or Gardasil) and boys (with Gardasil) aged 11-12 years old, administered in 3 doses (0, 1 and 6 months for Cervarix; 0, 2 and 6 months for Gardasil). Vaccination is recommended in young women 13-26 years old (with Cervarix or Gardasil) and young men 13-21 years old (with Gardasil) who have not been vaccinated previously. Although it should ideally be administered before the onset of sexual activity, patients who have already been exposed to HPV or diagnosed with HPV (based on an abnormal Pap smear or presence of genital warts) should also be vaccinated because they may not have been exposed to all the HPV types in the vaccine. The duration of immunity is not known; booster doses are not currently recommended.

HPV vaccine has not been recommended for pregnant women due to limited data, but no adverse outcomes have been reported among women who became pregnant after receiving the vaccine.8

Adverse Effects – In clinical trials for both formulations of the vaccine, injection-site reactions included pain, swelling and erythema, but discontinuation of the vaccine series was uncommon. Syncope after vaccination has occurred in adolescents and young adults. Patients should be seated and observed for 15 minutes after the injection.

VARICELLA — Although universal childhood vaccination against varicella, introduced in the US in 1995, has resulted in a sharp decline in the incidence of varicella in both children and adults, susceptible adults should be vaccinated because primary varicella infection is much more severe in adults than in children.

Recommendations for Use – Persons born in the US before 1980 are considered immune to varicella, except for healthcare workers and pregnant women, who should have other evidence of immunity. Evidence of immunity to varicella is demonstrated by: a history of typical varicella diagnosed by a healthcare provider, laboratory evidence of immunity (not always reliable), documentation of vaccination or healthcare provider-diagnosed zoster. Adult vaccination programs should target healthcare workers, close contacts of immunosuppressed persons, college students, teachers, childcare workers, adults living with young children, international travelers and military personnel. Newly arrived adult immigrants from tropical countries may also be susceptible to varicella. Immunity after vaccination is probably permanent. Two doses of vaccine, separated by at least 4 weeks, are recommended for non-immune adults. Non-immune pregnant women should not be vaccinated until after delivery; they should receive the first dose of varicella vaccine postpartum before hospital discharge.

Adverse Effects – Local injection-site reactions are common in adults. Other adverse effects include fever and injection-site or, rarely, generalized varicella-like rash. Spread of vaccine virus from healthy vaccinees who develop a varicella-like rash to susceptible contacts has been reported, but is rare. Recipients who have a vaccine-related rash should avoid, if possible, contact with susceptible individuals who are at high risk of complications of varicella, such as immuno-compromised persons, pregnant women and neonates born to non-immune mothers.

Contraindications – Because it is a live vaccine, varicella vaccine is contraindicated in pregnant women and patients who are immunosuppressed as a result of disease, such as lymphoproliferative malignancies, or treatment (cytotoxic chemotherapy, systemic corticosteroids), except possibly HIV-infected patients without evidence of immunity to varicella who do not have evidence of severe underlying immunosuppression (CD4+ count <200 cells/mcL, ≤14% of total). It should not be given to patients with a history of anaphylaxis caused by neomycin.

ZOSTER — Following primary infection, varicellazoster virus (VZV) persists in a latent form in sensory ganglia; VZV-specific cell-mediated immunity (CMI) prevents latent virus from reactivating and multiplying to cause herpes zoster. When CMI falls below a critical threshold, as it can in older persons and immunosuppressed patients, latent VZV can reactivate and cause herpes zoster ("shingles"). An FDA-approved live attenuated vaccine (Zostavax)9 is available to prevent zoster in persons ≥50 years old.

Recommendations for Use – The ACIP recommends a single dose of Zostavax for all immunocompetent persons ≥60 years old. Some experts would exclude patients who have had a well-documented episode of zoster within the previous 3 years.

Adverse Effects – Reactions to the vaccine at the injection site (erythema, pain, tenderness, swelling and pruritus) are generally mild. Varicella-like rash has occurred at the injection site, but is less common than with varicella vaccination. Transmission of the vaccine virus from vaccine recipients to other susceptible persons has not been reported with Zostavax.

Contraindications – Because it is a live vaccine, Zostavax is contraindicated in pregnant women and persons who are immunosuppressed as a result of disease, such as lymphoproliferative malignancies, or treatment (cytotoxic chemotherapy, systemic corticosteroids). It is also contraindicated in patients with a history of anaphylaxis caused by neomycin.

MEASLES, MUMPS, RUBELLA (MMR) — Routine vaccination of children with MMR vaccine has almost eliminated measles, mumps and rubella in the US, although recent increases in measles cases in Europe and Southeast Asia have led to an increasing number of measles cases in the US.10 Sporadic mumps outbreaks also continue to occur.

The MMR vaccine is recommended for routine adult immunization. Each 0.5-mL subcutaneous dose contains live attenuated measles virus and mumps virus, both derived from chick embryo cell culture, and rubella virus derived from human diploid cell culture.

Recommendations for Use – In most adults, one dose of MMR is sufficient. A second dose, given at least 28 days after the first, may be required in some situations to ensure protection against measles or mumps.

Adults born before 1957 (1970 in Canada) can be considered immune to measles, mumps and rubella. All other adults who lack documentation of vaccination should receive at least 1 dose of MMR vaccine unless they have a physician-documented history of measles and mumps or laboratory evidence of immunity. Two doses of vaccine, separated by at least 28 days, are recommended for adults living in communities experiencing a major outbreak, students in postsecondary educational institutions, healthcare workers, travelers to countries where measles or mumps is endemic and those with a recent exposure. Adults previously vaccinated with the killed (or an unknown) measles vaccine used in the 1960s should receive 2 doses of the vaccine.

One dose of MMR vaccine should be administered to nonpregnant women of childbearing age who lack serologic evidence of immunity to rubella. Pregnant women who do not have evidence of immunity to rubella should receive MMR vaccine postpartum, ideally before discharge from the healthcare facility.

MMR vaccination should be considered for healthcare workers born before 1957 if they do not have serologic or other evidence of immunity to measles, mumps and rubella.

Adverse Effects – Adverse events associated with MMR vaccination include pain and erythema at the injection site, fever and rash and transient arthralgias (up to 25% of women). Systemic anaphylactic reactions and thrombocytopenia occur very rarely. There is no evidence to support a causal link between MMR vaccination and autism.11

Contraindications – Because MMR is a live vaccine, it is contraindicated in pregnant women (the risk may be only theoretical; congenital rubella syndrome has not been reported among the thousands of women vaccinated inadvertently during pregnancy) and in patients with moderate-to-severe immunodeficiency. HIV-infected patients who do not have evidence of severe underlying immunosuppression (CD4+ count <200 cells/mcL, ≤14% of total) are an exception and should be vaccinated if otherwise indicated. Patients with a history of anaphylaxis caused by neomycin should not receive the vaccine. Patients with a history of egg allergy without anaphylaxis can be vaccinated.

INFLUENZA — Influenza vaccine is about 70% effective (less in the elderly) in preventing infection; effectiveness varies annually depending on the match between the vaccine and circulating strains. All influenza vaccines contain two influenza A strains and one influenza B strain, selected annually based on surveillance data from the CDC. Both inactivated and live attenuated vaccines are available in the US.

No commercial vaccine is available for pathogenic strains of avian influenza (H5N1, H7N2, H9N2, H7N3, H7N7), but an inactivated vaccine against avian H5N1 influenza is FDA-approved and is included in the US Strategic National Stockpile. The 2009 pandemic influenza A (H1N1) antigen remains in this season’s trivalent vaccine.12

Recommendations for Use – Based on the duration of protective antibodies and the timing of influenza circulation, the optimal time for annual vaccination in the US is in October or November, but the vaccine should be offered until the end of the influenza season in the late spring. Routine vaccination should be offered to all adults without a specific contraindication, including pregnant women. One study found that vaccinating women during the third trimester reduced proven influenza illness in infants <6 months old by 63%.13 Vaccination against influenza is especially important for healthcare workers and close contacts of high-risk persons.

The live attenuated intranasal vaccine (FluMist) is approved for healthy, non-pregnant adults <50 years old. It should not be used in patients who are immunosuppressed and is not recommended for those with asthma, reactive airway disease or chronic cardiovascular, pulmonary, renal or metabolic disease.12

In comparative clinical trials in children, the live attenuated vaccine was more effective than the inactivated vaccine, even against antigenically drifted strains of influenza A and B,14 but the inactivated vaccine appears to be more effective than the live attenuated vaccine in previously immunized adults.15

The standard-dose inactivated influenza vaccine produces lower antibody titers in people ≥65 years old than in younger people. The higher-dose vaccine produces significantly higher antibody levels than the standard dose vaccine in this age group, but whether it offers greater protection against infection or illness is unknown.

Adverse Effects – Except for soreness at the injection site, adverse reactions to inactivated influenza vaccine are uncommon. Fever, myalgia and malaise can occur. Rarely, vaccination has been associated with Guillain-Barré syndrome. The live attenuated intranasal vaccine is generally well tolerated, but can cause rhinorrhea, nasal congestion and sore throat. After receiving the live-virus vaccine, healthcare workers, family members and other close contacts of severely immunosuppressed patients (in special care units) should avoid contact with the immunosuppressed person for 7 days because of the theoretical risk of transmission of vaccine-strain virus.

Contraindications – A history of a severe allergic reaction to any influenza vaccine is a contraindication to vaccination. Since both the live and inactivated vaccines are made from virus grown in eggs, hypersensitivity reactions to egg protein could occur. Persons being vaccinated who report a history of hives related to egg exposure should receive inactivated rather than live attenuated vaccine, and should be observed for 30 minutes following vaccine administration for signs of an allergic reaction. Persons with a history of a more severe reaction to eggs should be referred for allergy evaluation prior to vaccination.

PNEUMOCOCCAL — A 23-valent inactivated pneumococcal polysaccharide vaccine (PPSV23; Pneumovax 23) has been available for many years for use in adults. The serotypes contained in the vaccine account for 66-78% of the strains that cause invasive disease,16 but randomized controlled trials and cohort studies have not consistently shown a decrease in bacteremic pneumococcal pneumonia among vaccinees.17,18

A conjugate vaccine that contains 13 serotypes of pneumococcus (PCV13; Prevnar13 – Pfizer) is FDA-approved only for use in infants and toddlers. Use of an earlier vaccine (PCV7; Prevnar 7) substantially decreased rates of invasive pneumococcal disease in young children.19 Vaccination of children with PCV7 has also been shown to decrease pneumococcal carriage of vaccine serotypes in unvaccinated contacts of vaccine recipients.20 Rates of invasive pneumococcal disease in adults have also decreased since childhood immunization began.21 A 13-valent conjugate vaccine is currently under investigation for the prevention of pneumococcal pneumonia in adults.

Recommendations for Use – A one-time dose of PPSV23 vaccine has been recommended by the ACIP for all adults ≥65 years of age. The vaccine is also recommended for persons of any age who smoke, reside in long-term healthcare facilities or have chronic illnesses that place them at moderate or high risk for invasive pneumococcal disease, such as those with diabetes, heart disease, pulmonary disease, liver disease, kidney disease, asplenia or other immunocompromising conditions, and for recipients of organ or bone marrow transplants or cochlear implants.

Persons who receive an initial dose of PPSV23 before 65 years of age should be revaccinated once at or after age 65, at least 5 years after initial vaccination. A second dose should be given after 5 years to persons with chronic renal failure or nephrotic syndrome, asplenia or other underlying immunosuppression regardless of age. No additional doses are recommended.

Adverse Effects – Mild to moderate soreness and erythema at the injection site are common.

HEPATITIS A — Hepatitis A virus (HAV) infection occurs frequently in the US and is endemic in certain communities in the western and southwestern states and in Alaska. In the US, the prevalence of anti-HAV antibodies ranges from about 10% in preadolescent children to about 75% in elderly adults.22 Hepatitis A vaccination is now (since 1996) part of routine pediatric immunization in the US. Two inactivated hepatitis A whole-virus vaccines (Vaqta, Havrix) are available in the US. Twinrix, the combination hepatitis A and B vaccine, contains the same hepatitis A component as in Havrix, but at half the dose. All 3 vaccines are equally effective.

Recommendations for Use – Hepatitis A vaccine is recommended for adults with a medical, occupational or behavioral risk of infection. Medical indications include clotting factor disorders or chronic liver disease, such as chronic active hepatitis C and/or B virus infection. Occupational indications include work with HAV in a laboratory setting. Behavioral indications include illicit (injection and non-injection) drug users and men who have sex with men. Hepatitis A vaccine is also recommended for close contacts of adopted children from countries with high rates of hepatitis A and for susceptible travelers going anywhere other than Canada, Australia, New Zealand, Japan or western Europe.

Hepatitis A vaccination in adults usually consists of 2 doses separated by at least 6 months. After a single dose, Havrix provides protection for at least 12 months, and Vaqta for at least 18 months. Patients who receive Twinrix need 3 doses at 0, 1 and 6 months. An accelerated 4-dose schedule is also licensed for Twinrix with doses at 0, 7 and 21-30 days and a fourth dose at 12 months. Patients who have received a first dose of one vaccine will respond to a second dose of the other. Booster doses are not recommended for immunocompetent adults who have completed a primary immunization series.

Adverse Effects – Local injection-site reactions such as pain, swelling or erythema occur in 20-50% of vaccine recipients. Mild systemic complaints such as malaise, low-grade fever or fatigue occur in less than 10%.

HEPATITIS B — Universal vaccination of infants against hepatitis B has been standard in the US since 1991. Available formulations of hepatitis B vaccine contain hepatitis B surface antigen (HBsAg) protein. Each 1-mL dose of Engerix-B contains 20 mcg of HBsAg, while each 1-mL dose of Recombivax HB contains 10 mcg of HBsAg. The hepatitis B component in the combined hepatitis Aand B vaccine (Twinrix) is the same as in Engerix-B. All available vaccines are equally effective.

Recommendations for Use – Hepatitis B immunization is recommended for adults with a medical, occupational or behavioral risk of infection. Medical indications include hemodialysis, treatment with clotting-factor concentrates or HIV infection. Occupational indications include healthcare or public safety work with potential exposure to blood or body fluids. Behavioral indications include injection drug use, sex with more than one partner in the previous 6 months, recently acquired sexually transmitted infection and men who have sex with men.

Other populations who should receive hepatitis B vaccination include unvaccinated adults with diabetes, clients of facilities that treat sexually transmitted infections, HIV or drug abuse, residents and staff members of institutions for the developmentally disabled, inmates of correctional facilities, household contacts and sex partners of those with chronic hepatitis B infection, travelers who will be in countries with intermediate or high prevalence of hepatitis B infection for more than 6 months, or who may undergo medical or dental procedures in such countries.

Primary immunization with hepatitis B vaccine usually consists of 3 doses given at 0, 1 and 6 months. An alternate schedule of 3 doses given at 0, 1 and 2 months, followed by a fourth dose at 12 months, is approved only for Engerix-B in the US and is intended for use in certain populations, including those who have been recently exposed to the virus and travelers to high-risk areas. An interrupted hepatitis B vaccination series does not have to be restarted. A 3-dose series started with one vaccine may be completed with the other. Patients who receive Twinrix need 3 doses at 0, 1 and 6 months. An accelerated 4-dose schedule is also licensed for Twinrix with doses at 0, 7 and 21-30 days and a fourth dose at 12 months. Booster doses are not recommended for most adults who have completed a primary immunization series.

Adverse Effects – The most common adverse effect of hepatitis B vaccination is pain at the injection site. Fever occurs in <10% of recipients.

MENINGOCOCCAL — About 1000-2000 cases of meningococcal disease occur in the US each year. The case fatality rate is 10% for meningitis and up to 40% for meningococcemia. Rates of meningococcal disease are highest in infancy, but a second peak occurs in adolescents and young adults, especially freshmen living in dormitories. Five major serogroups of Neisseria meningitidis—A, B, C, Y and W-135—cause most human infection.

Three quadrivalent inactivated vaccines are available against N. meningitidis serogroups A, C, Y, and W-135. Menomune contains meningococcal capsular polysaccharides. Menactra and Menveo both contain the same capsular polysaccharides, each conjugated to different diphtheria toxoid proteins, and are approved for adults ≤55 years old.23 None of the vaccines provide protection against serogroup B, which has a polysaccharide capsule with some antigenic similarity to human neural glycoprotiens. In adults, all three vaccines are effective and induce serotype-specific antibody responses in more than 90% of recipients.24

Recommendations for Use – Vaccination is recommended for adolescents 11-18 years old, adults with anatomic or functional asplenia or terminal complement component deficiencies, first-year college students living in dormitories, laboratory personnel routinely exposed to isolates of N. meningitidis, military recruits, and persons who travel to or reside in countries in which meningococcal disease is hyperendemic or epidemic, particularly those in the "meningitis belt" of sub-Saharan Africa. The government of Saudi Arabia also requires vaccination for pilgrims during the annual Hajj.

For adults ≤55 years old with asplenia, terminal complement deficiencies or HIV infection, two doses of conjugated vaccine at 0 and 2 months are recommended; only 1 dose of unconjugated vaccine is recommended for adults >55 with these comorbidities. For all others, a single dose of vaccine is recommended (either conjugated if ≤55 years old or unconjugated if >55). For adults previously vaccinated who remain at high risk, revaccination every 5 years (with the conjugate vaccine for adults ≤55 years old or unconjugated if >55) is recommended.25 Published data are not yet available, but according to some experts, immunity after conjugate vaccine administration wanes substantially after 3 years.

Adverse Effects – The most common adverse reactions to Menactra and Menveo have been headache, fatigue and malaise, in addition to pain, redness and induration at the site of injection. The rates of these reactions are higher than with Menomune, but similar to those with tetanus toxoid. Guillian-Barré syndrome has been reported rarely in adolescents who received Menactra, but a cause-and-effect relationship has not been established.

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