Immunization Update: What’s New, What’s True?

From Infectious Disease in Primary Care: Evidence-based Primary Prevention and Treatment, sponsored by the Cleveland Clinic Foundation, Cleveland, OH

 Doug Campos-Outcalt, MD, Associate Chair, Department of Family and Community Medicine, University of Arizona College of Medicine, Phoenix

Educational Objectives

The goal of this program is to improve immunization practice in primary care medicine. After hearing and assimilat­ing this program, the clinician will be better able to:

1.   Describe new, established, and current concepts in immunization practice for adolescents and adults.

2.   Describe current concepts in immunizations for travelers.

3.   Customize vaccination programs to suit individual patient's needs.

4.   Design and implement clinical vaccination programs based on the prevalence in a particular community.

5.   Explain why current recommendations for administration of the pneumococcal polysaccharide vaccine in smokers are controversial.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning com­mittee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and planning committee reported nothing to disclose.

Acknowledgments

Dr. Campos-Outcalt spoke in Beachwood, OH, at Infectious Disease in Primary Care: Evidence-Based Primary Prevention and Treatment, presented July 9, 2009, by the Cleveland Clinic Foundation. The Audio-Digest Foundation thanks Dr. Cam­pos-Outcalt and the Cleveland Clinic Foundation for their cooperation in the production of this program.

Vaccines for Adolescents and Preadolescents

Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices [ACIP] guidelines: patient  —  girl 12 yr of age presents with sports injury; no chronic illnesses; good health; all childhood vaccines by age 5 yr; recommended vaccines  —  tetanus and diphtheria toxoids and acellular pertussis (Tdap) for ad­olescents; influenza (universal annual administration 6 mo through 18 yr of age); varicella (catch-up if second dose not received); quadrivalent meningococcal conjugate vaccine (all children 11-12 yr of age); human papillomavirus (HPV; all girls 11-12 yr of age); hepatitis A (catch-up for ages 11-12 yr [depending on state regulations] and uni­versally for ages 1-2 yr)

Catch-up vaccines for adolescents (11-18 yr of age): Tdap; HPV; meningococcal conjugate; combination mumps measles rubella (MMR), varicella; hepatitis B; inactivated polio virus; past immunizations will indicate necessary catch-up vaccines; based on risk  —  pneumococcal polysaccharide; hepatitis A; immunization schedules for child, adolescent, adult, and catch-up on CDC website

Pertussis: difficult to eradicate; now affects older children and young adults, who can transmit to infants before full immunity achieved; Tdap vaccine  —  recommended for universal use for children, so now part of federal govern­ment’s Vaccines for Children program; 2 products available, both licensed for same age group; contraindications to Tdap  —  history of anaphylaxis to vaccine or vaccine components; encephalopathy within 7 days for all pertussis vaccines; precautions  —moderate to severe illness; Guillain-Barré Syndrome within 6 wk of receiving tetanus tox­oid product in past; pearl  —  DTaP (for young children) has higher proportion of diphtheria toxoid than Tdap (for adolescents and adults)

HPV vaccine: protection better when vaccine administered before start of sexual activity; rapid rate of HPV infection once girls become sexually active; when given after infection with high-risk HPV types in vaccine, vaccine does not protect; pregnancy test  —  not required before administration of vaccine (not approved for use during pregnancy, but if administered inadvertently, no intervention needed); cervical cytology  —  Papanicolaou (Pap) tests recom­mended; vaccine active against high-risk strains 16 and 18, but cytology needed for remaining 20% and for patients infected before receiving vaccine; licensed only for boys in the United States (licensed for boys and girls overseas)

Human papillomavirus: associated with cervical, anal, vulvar, vaginal, penile, oral cavity, and pharyngeal cancers; epidemiology  —  difficult to study; requires cervical sample or serology; in cervical infections, blood test positive only 50% of time; most HPV infections clear quickly, so possible to have been infected and not show positivity in serology or cervical sample; studies about HPV prevalence or incidence must be interpreted carefully; Gardasil vaccine  —  quadrivalent; strains 6 and 11 (cause 80%-90% of genital warts) and strains 16 and 18 (cause »70% of cervical cancer); licensed for females 9 to 26 yr of age; Cervarix vaccine (GSK)  —  not licensed as of July 2009; covers strains 16 and 18; some cross-protection against other HPV types; ACIP recommended vaccination schedule  —  3-dose series for girls 11 to 12 yr of age (can start at age 9 yr); catch-up age 13 to 26 yr of age; efficacy decreases with age; doses at 0, 2, and 6 mo; minimal interval 4 wk between first and second dose and 12 wk be­tween second and third dose; pregnancy  —  avoid vaccine; if patient has started series, defer remaining doses until after pregnancy (no need to start over); vaccine safety  —  CDC monitors adverse events through physician and pa­tient reporting (passive system); active surveillance of 8 million people in health maintenance organizations for ad­verse events post-marketing; barriers to use  —  only 25% of age group has received vaccine; cost; parental concern about “sending the wrong message”; safety; physician misperceptions; adverse events  —  slightly higher rates of syncope immediately following vaccination (keep patient in clinic for 15-30 min after injection)

Meningococcal meningitis: rare; incidence (1 in 500,000 persons); considered epidemic if incidence 1 in 100,000 persons or higher; high mortality and morbidity rates; »2000 cases per year; case fatality 10% to 15%; rate of neu­rologic sequelae 20%; peak in children <1 yr of age and in adolescents at present; no good vaccine for infants; me­ningococcal conjugate vaccine  —  quadrivalent (antigens against 4 types); missing type B (affects infants) licensed for ages 2 to 55 yr; recommended for routine use in ages 11 to 12 yr; use in ages 2 to 10 yr if at high risk (eg, sickle cell disease, asplenia); catch-up at ages 12 to 18 yr if not previously vaccinated; meningococcal polysaccharide vaccine  —  licensed for age >55 yr if traveling to endemic areas; protection may not last as long as conjugate; vac­cines recommended for high-risk categories (eg, freshmen in college dormitories, molecular biologists who work with meningococcal bacteria, military recruits, travelers, those with immunodeficiencies); ACIP recommends booster after 5 yr for those in high-risk categories; contraindications  —  allergies to vaccine components; history of Guillain-Barré syndrome history (conjugate contains tetanus toxoid); coadministration  —  permitted, or separate ad­ministrations by 1 mo

Influenza: recommended for ages £18 yr and ³50 yr; use in other adults based on risk; trivalent inactivated vaccine  —dead virus; injection; made in eggs (long production time); must be refrigerated; contraindications  —  anaphylactic reaction to eggs; precautions  —  moderate to severe illness; live attenuated vaccine  —  nasal spray; must be refrigerated; licensed for ages 2 to 49 yr; not licensed for high-risk categories; contraindications  —  chronic illness; long-term aspirin therapy; history of Guillain-Barré syndrome; pregnancy; caregiving to severely immuno­suppressed person

Varicella (chickenpox): previously universal childhood disease; not eradicated, but shifted to older age groups; rec­ommended vaccination schedule  —  2 doses to correspond with MMR; age 12 to 16 mo; catch-up age 4 to 6 yr; can be given to HIV-positive patients if no evidence of immune dysfunction; epidemiology  —  those born before 1980 are immune; those who have had chickenpox diagnosed by clinician; history of shingles indicates varicella immu­nity; combination mumps, measles, rubella, and varicella vaccine (MMRV)  —makes 2-dose schedule more conve­nient; 1 injection instead of 2; causes 1 excess case of febrile seizures for every 1000 children vaccinated (at first dose, not second)

Hepatitis B vaccine: age 11 to 12 yr, based on risk; 3-dose schedule; recombinant Hepatitis B vaccine (Recombivax)  —approved for 2-dose schedule for ages 11 to 15 yr

Polio virus vaccines: oral vaccine no longer available; 4-dose schedule; 3 doses acceptable if third dose administered after age 4 yr; can include combination of oral and injection

MMR vaccine: 2 doses at 4-wk intervals, beginning at age >1 yr; if first dose given at age <1 yr, not considered full series

Tdap vaccine: catch-up ages 13 to 18 yr; if last tetanus diphtheria vaccine (TD) dose ³5 yr ago, Tdap catch-up rec­ommended; catch-up sooner if caregiver to infant

Pneumococcal polysaccharide vaccine: age 11 to 12 yr; for high-risk patients, ie, those with chronic heart or lung disease, metabolic diseases, or immunocompromising diseases

Hepatitis A vaccine: 2 doses universally recommended at age 1 yr; may need catch-up during adolescence, depend­ing on risk in state; 6000 cases reported per year; 24,000 to 30,000 cases per year in United States; children trans­mit to adults (daycare centers); catch-up ages 2 to 18 yr; high-risk categories  —  men who have sex with men; travelers; illicit drug users; close contact with adoptees from other countries (eg, Guatemala, some South American countries); 2-dose series vaccination of all family members recommended before arrival of foreign adoptee; barri­ers to use  —  parental consent; cost; adolescents not visiting doctor as frequently as infants; inconsistent state laws

Methods for increasing vaccination rates  —  school requirements most effective; availability of vaccines  —  public health  clinics; Women, Infants, and Children clinics; helping parents with costs (Vaccines for Children Program); home visits to administer vaccines; education

Immunizations for Adults

Case: patient  —  man 61 yr of age; smoker; last tetanus vaccine 15 yr ago; never given Tdap; his daughter adopting from Guatemala in 1 mo; tetanus booster due; recommended vaccines  —  Tdap based on high risk (smoker) and need for tetanus booster; pneumococcal polysaccharide based on age and high risk (smoker); inactivated influenza vaccine; herpes zoster based on age; hepatitis A, based on daughter adopting from Guatemala; varicella not indi­cated (born before 1980); hepatitis B risk not identified; meningococcal conjugate not indicated

Adult immunization recommendations: Tdap  —  through age £64 yr; HPV  —  through age 26 yr; varicella  —  age >30 yr immune (catch-up if born after 1980); varicella zoster vaccine live (Zostavax; Merck)  —  age ³60 yr; MMR  —catch-up; influenza  —  age ³50 yr (younger if at risk); pneumococcal polysaccharide  —  age ³65 yr (younger if at risk); hepatitis A  —  based on risk; hepatitis B  —  based on risk; Japanese encephalitis  —  before travel

Shingles (herpes zoster): incidence increases with age; lifetime risk 25% (will decrease as varicella vaccine recipi­ents grow older); risk of developing postherpetic neuralgia 25% (will decrease as more people become immune); Zostavax  —  live attenuated vaccine; higher content of varicella antigens than childhood vaccine; recommend 1 dose at age ³60 yr; efficacy best at younger ages; 50% effectiveness; prevents herpes zoster and postherpetic neuralgia; contraindications  —  previous anaphylactic reaction to contents (eg, gelatin, neomycin); immunodeficiency; immu­nosuppressive therapy; active tuberculosis; pregnancy; precautions  —  daily use of topical or inhaled corticosteroids and low-dose oral corticosteroids; moderate to severe illness; barriers to use  —reimbursement (Medicare part D); must be stored frozen; access  —  available at 50% of primary care clinics; 39% of clinics refer patients to pharmacy for vaccine and administration at clinic (discouraged; vaccine must be kept frozen); 33% of clinics refer to phar­macy for administration of vaccine; 23% of clinics refer to public health department; 41% of clinics strongly rec­ommending vaccine

Varicella-containing vaccines: MMRV; single-antigen varicella vaccine; zoster vaccine

HPV vaccine (Cervarix): effective against HPV strains 16 and 18 (cause 70% of cervical cancers); highly effective if given before infection with HPV (strains 16, 18; »100% effective in preventing precancerous lesions or cancer after 5 yr); in intent to treat, effectiveness lower (50%-60%) when vaccine given after HPV infection

Pertussis vaccine (Tdap): recommended schedule  —  age £64 yr, Tdap should be boosted every 10 yr; can be given <10 yr for wound management; every 2 yr for adult caregiver of infant; optimal interval between last TD and Tdap 2 yr; <2 yr acceptable if, during pertussis outbreak, caregiver at risk and at risk of transmitting to infant; Tdap dur­ing pregnancy  —  not approved; given preconception or postpartum if not previously received; ACIP unclear on Tdap immunity passed from mother to infant and infant’s reaction to full vaccine series; wound management  —  acceptable to administer Tdap if vaccine history unknown, tetanus vaccination incomplete, or last pertussis vacci­nation >10 yr ago; precautions  —  history of Guillain–Barré syndrome; Arthus reaction to diphtheria or tetanus tox­oid; unstable or progressive neurologic disorder

Varicella vaccine: recommended 2-dose schedule; catch-up for adults; can be used in HIV-positive patients if not se­verely immunosuppressed

Hepatitis A (HAV) vaccine: recommended for adults based on risk (eg travelers, men who have sex with men, in in­travenous drug users, people with chronic liver disease, and those in certain occupations); 2 doses 6 mo apart; post­exposure prophylaxis  —  for patients 1 to 40 yr of age exposed to hepatitis A; after 40 yr of age, immune globulin (IG) preferred; travelers  —  pretravel vaccination preferred; IG reserved for groups outside of vaccine licensure and those with chronic illnesses that render vaccine less effective; foreign adoption  —  hepatitis A often not diagnosed immediately in children; adults and children exposed to infected adoptee at risk and will transmit to others; 85% of US international adoptions age <5 yr of age (1%-6% of adoptees infectious at time of arrival); HAV recommended for all unvaccinated persons who anticipate close personal contact with international adoptee during first 60 days after arrival from countries of high or intermediate hepatitis A endemicity; administer ³2 wk before arrival of adoptee

Hepatitis B vaccine (HBV): incidence of hepatitis B decreasing with time; recommendations  —  based on risk (be­havior and occupation); universal vaccination for unvaccinated adults who receive care at health care facilities serv­ing high-risk populations (eg, sexually transmitted disease [STD] clinics, HIV testing and treatment centers, drug treatment centers, correctional facilities); for high-risk populations and anyone who requests vaccine; HAV and HBV combination vaccine  —4- or 3-dose schedules; 4-dose schedule at 0, 7, 21, and 365 days; 3-dose schedule at 0, 1, and 6 mo

Influenza vaccine: trivalent  —  3 influenza virus strains carefully picked each year to match circulating strains; recommendations  —  age 18 to 50 yr, based on risk; not contraindicated in pregnancy; high-risk groups  —  residents of long-term care facilities; household contact or caregivers of children age <6 yr; chronic medical conditions (eg, heart disease, lung disease, diabetes, kidney disease, immunodeficiencies, hemoglobinopathy, anyone with inability to clear secretions); health care workers

Pneumococcal polysaccharide vaccine (Pneumovax)  —ACIP recommendations  —  smokers 19 to 64 yr of age; rela­tive risk for pneumococcal invasive disease higher in smokers; smoking, diabetes, and asthma have comparable risk; among smokers, risk 1 per 10,000; problems  —  when to administer and frequency; vaccine wears off with time; hyporesponsiveness occurs after second dose; if smokers revaccinated every 5 to 10 yr, low responsiveness expected by age 65 yr

Japanese encephalitis vaccine  —  travelers to Asian countries at highest risk; licensed in 1992 for children and adults; provided exclusively through travel clinics; production being phased out; currently reserved for children <18 yr of age; new product for adults only

Suggested Reading

Brabin L et al: A survey of adolescent experiences of human papillomavirus vaccination in the Manchester study. Br J Cancer [Epub ahead of print], 2009; Broder KR et al: Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immuniza­tion Practices (ACIP). MMWR Recomm Rep 24:55, 2006; Centers for Disease Control and Prevention (CDC), Advisory Committee on Immunization Practices (ACIP): Updated recommendations from the Advisory Committee on Immunization Practices (ACIP) for use of hepatitis A vaccine in close contacts of newly arriving international adoptees. MMWR Morb Mortal Wkly Rep 36:58, 2009; Lam S, Jodlowski TZ: Vaccines for older adults. Consult Pharm 5:24, 2009; Medeiros LR et al: Effi­cacy of human papillomavirus vaccines: a systematic quantitative review. Int J Gynecol Cancer 7:19, 2009; Weston WM et al: Safety and immunogenicity of a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine when co-adminis­tered with influenza vaccine in adults. Hum Vaccin 5:12 [Epub ahead of print], 2009.