Immunizations and Postexposure Therapies

Immunizations and Postexposure Therapies is a topic covered in the Washington Manual of Medical Therapeutics.

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Introduction

  • Active immunization promotes the development of a durable primary immune response (B-cell proliferation, antibody response, T-cell sensitization) directed toward a specific pathogen such that subsequent exposure to that pathogen results in a secondary immune response that protects against infection (Table A.1).
    Table A.1: Selected Adult Immunization Recommendations in the United States
    Vaccine, DoseIndications & DosingContraindicationsPrecautions
    Haemophilus influenzae type b (Hib)
    Hib conjugate vaccine: 0.5 mL IM
    Unvaccinated adults with anatomic or functional asplenia (including sickle cell disease) or undergoing elective splenectomy (preferably 14 d before surgery): Administer 1 dose
    Hematopoietic stem cell transplant recipients 6–12 mo after successful transplant: Administer three doses (4 wk apart)
    Severe allergic reaction to any vaccine component or after a previous doseModerate or severe acute illness with or without fever
    Hepatitis A
    Single-antigen hepatitis A vaccine (HepA; Havrix, Vaqta): 1 mL IM
    Combined hepatitis A/hepatitis B vaccine (HepA-Hep B; Twinrix): 1 mL IM
    Any adult seeking protection from hepatitis A virus (HAV)
    Specific indications: travel to countries with high or intermediate HAV endemicity (including infants 6 mo and older); men who have sex with men (MSM); injection or noninjection drug use; laboratory workers exposed to HAV; clotting factor disorders; chronic liver disease; persons who anticipate close personal contact with an adoptee from a country with high or intermediate HAV endemicity during the first 60 d after arrival in the United States; healthy persons ages 12 mo and older recently exposed to HAV (adults >40 yr may also receive HAV immunoglobulin).
    Standard dosing:
    • Havrix: Administer two doses at 0 and 6–12 mo
    • Vaqta: Administer two doses at 0 and 6–18 mo
    • Twinrix: Administer three doses at 0, 1, and 6 mo
    Severe allergic reaction to any vaccine component or after a previous doseModerate or severe acute illness with or without fever
    Hepatitis B
    Single-antigen hepatitis B vaccine (HepB; Recombivax HB), standard (10 μg/mL) & high-dose (40 μg/mL) formulations: 1 mL IM
    Single-antigen hepatitis B vaccine (HepB; Engerix-B) (20 μg/mL): 1 mL IM
    Combined hepatitis A/hepatitis B vaccine (HepA-Hep B; Twinrix): 1 mL IM
    Any adult seeking protection from hepatitis B virus (HBV)
    Specific indications: chronic liver disease; HIV infection; percutaneous or mucosal risk of exposure to blood (e.g., household contacts of persons with chronic HBV infection; persons age <60 yr with diabetes mellitus and those ≥60 yr at discretion of treating clinician; adults with ESRD including those receiving dialysis; injection drug users; health care and public safety workers at risk for exposure to blood or body fluids); sexual exposure risk (e.g., sex partners of persons with chronic HBV infection; sexually active persons not in long-term, mutually monogamous relationship; persons seeking evaluation or treatment for a sexually transmitted disease; MSM); persons receiving care in settings where risk of HBV infection is high (e.g., facilities providing STD treatment, HIV testing and treatment, or drug abuse treatment and prevention services; health-care settings targeting services to injection drug users or MSM; correctional facilities; ESRD and hemodialysis programs; institutions for persons with developmental disabilities); travelers to countries with high or intermediate HBV endemicity
    Standard dosing: Administer three doses of standard-dose Recombivax HB, Engerix-B, or Twinrix at 0, 1, and 6 mo
    HD patients or other immunocompromised: Administer three doses of high-dose Recombivax HB at 0, 1, and 6 mo, or eight doses of Engerix-B as four two-dose (2 mL) injections at 0, 1, 2, and 6 mo
    Severe allergic reaction to any vaccine component or after a previous doseModerate or severe acute illness with or without fever
    Human papillomavirus (HPV)
    9-valent vaccine (9vHPV; Gardisil 9): 0.5 mL IM
    Females through age 26 yr (including immune compromised) and males through age 21 yr (males aged 22 through 26 yr if MSM or immune compromised):
    • If age <15 yr, administer two doses at 0 and 6–12 mo
    • If age ≥15 yr, administer three doses at 0, 1–2, and 6 mo
    Severe allergic reaction to any vaccine component or after a previous doseModerate or severe acute illness with or without fever; pregnancy
    Influenza
    Inactivated or recombinant influenza vaccine (IIV or RIV): 0.5 mL IM (5 mL if multidose vial used)
    Intradermal IIV3 0.5 mL (only aged 18–64 yr)
    Live attenuated influenza vaccine (LAIV): 0.2 mL intranasal
    Available in quadrivalent (4) and trivalent (3). Quadrivalent contains the same three influenza viruses (A/A/B) and an additional influenza B vaccine virus
    Annual vaccination is recommended for all persons aged ≥6 mo who do not have contraindications.
    Age 6 mo through 8 yr: IIV4 (LAIV4 option for age ≥2 yr)
    Pregnancy: IIV4 or RIV4
    Age ≥65 yr: High-dose IIV3
    All others: Standard-dose IIV4 or IIV3
    Egg allergy: RIV4 preferred
    Cell culture-based IIV4 or RIV4 should only be administered if age ≥18 yr
    Health-care personnel who receive LAIV should avoid providing care for severely immune-suppressed persons (i.e., requiring protective environment) until 7 d postvaccination
    Severe allergic reaction to any vaccine component or after a previous dose
    Persons with a history of egg allergy of any severity may receive any licensed, recommended, and age-appropriate influenza vaccine
    LAIV: pregnancy, immune suppression (includes close contacts), children aged 2–4 yr with asthma, children/adolescents on salicylate therapy (aspirin), persons who have taken influenza antiviral medications within previous 48 h
    Moderate to severe illness with or without fever; history of Guillain-Barré syndrome (GBS) within 6 wk of previous influenza vaccination
    LAIV: asthma; chronic medical conditions that may predispose to higher risk of influenza-related complications (e.g., lung disease, cardiovascular disease, diabetes, renal or hepatic disease)
    Measles, mumps, rubella
    Live measles, mumps, and rubella (MMR) vaccine: 0.5 mL SC
    Anyone without evidence of immunity: Administer one dose
    Evidence of immunity:
    • Born before 1957 (except for health-care personnel)
    • Documented vaccination
    • Laboratory confirmation of immunity or disease
    HIV infection with CD4+ >200 cells/µL for at least 6 mo without evidence of immunity: Administer two doses ≥28 d apart
    Students in postsecondary educational institutions, international travelers, and household contacts of immune compromised persons: Administer two doses ≥28 d apart
    Women of childbearing age: Rubella immunity should be determined. If no immunity and nonpregnant, administer 1 dose of MMR; pregnant women with no rubella immunity: administer 1 dose on completion or termination of pregnancy and before discharge from the health-care facility
    Health-care personnel born in 1957 or later: If no documentation of vaccination or laboratory confirmation of immunity or disease, administer vaccination (two doses if measles or mumps nonimmune ≥28 d apart; one dose if rubella nonimmune)
    Adults who previously received ≤2 doses of MMR identified to be at increased risk for mumps during an outbreak: Administer one dose
    Severe allergic reaction to any vaccine component or after a previous dose; current febrile respiratory or other febrile infection; known severe immunodeficiency (e.g., hematologic and solid tumors, receipt of chemotherapy, congenital immunodeficiency, long-term immunosuppressive therapy, HIV infection with CD4+ <200 cells/μL); pregnancyModerate or severe acute illness with or without fever; recent (≤11 mo) receipt of antibody-containing blood product; history of thrombocytopenia or thrombocytopenic purpura; need for tuberculin skin testing within 4 wk of vaccination (measles component may temporarily suppress reactivity)
    Meningococcal (Neisseria meningitidis)
    Quadrivalent meningococcal conjugate vaccine-diphtheria toxoid carrier (MenACWY; Menactra, Menveo): 0.5 mL IM
    Meningococcal serogroup B vaccine (MenB-4C, Bexsero; MenB-FHbp, Trumenba): 0.5 mL IM
    Adults with anatomical or functional asplenia, HIV infection, persistent complement component deficiency, or eculizumab use: Administer two doses of MenACWY ≥8 wk apart; revaccinate with 1 dose of MenACWY every 5 yr if risk persists
    Adults traveling to living in countries where meningococcal disease is hyperendemic or epidemic, microbiologists routinely exposed to N. meningitidis, military recruits, first-year college students living in residence halls if no vaccination at age 16 yr or older: Administer one dose of MenACWY; revaccinate with one dose of MenACWY every 5 yr if risk persists
    Adults with anatomical or function asplenia, persistent complement component deficiency, eculizumab use, microbiologists routinely exposed to N. meningitidis, or at risk for meningococcal disease outbreak attributed to serogroup B: Administer two doses of MenB-4C ≥1 mo apart or three doses of MenB-FHbp at 0, 1–2, and 6 mo
    Severe allergic reaction to any vaccine component or after a previous doseModerate or severe acute illness with or without fever
    Pneumococcal (Streptococcus pneumoniae)
    13-Valent pneumococcal conjugate vaccine (PCV13): 0.5 mL IM
    23-Valent pneumococcal polysaccharide vaccine (PPSV23): 0.5 mL IM or SC
    Immunocompetent adults ≥65 yr: Administer one dose of PCV13 (if not previously received), followed by one dose of PPSV23 ≥1 yr later. If PPSV23 previously administered but not PCV13, administer PCV13 at least 1 yr after PPSV23
    Adults 19–64 yr AND chronic heart disease (including hypertension), chronic lung disease, chronic liver disease, alcoholism, diabetes mellitus, or tobacco dependence: Administer one dose of PPSV23. At age ≥65 yr, administer one dose of PCV13 (if not previously received), followed by another dose of PPSV23 ≥1 yr after PCV13 and ≥5 yr after last PPSV23
    Adults 19–64 yr AND immune compromise, HIV infection, anatomic or functional asplenia, chronic kidney disease, or nephrotic syndrome: Administer one dose of PCV13, followed by one dose PPSV23 at ≥8 wk and second dose at ≥5 yr after 1st PPSV23. If last PPSV23 received before age 65 yr, at age 65 yr, administer another dose of PPSV23 ≥5 yr after last dose
    • Adults 19–64 yr AND cerebrospinal fluid leak or cochlear implant: Administer one dose of PCV13, followed by one dose of PPSV23 at ≥8 wk. If PPSV23 received before age 65 yr, at age 65 yr, administer another dose of PPSV23 ≥5 yr after last dose
    Severe allergic reaction after a previous dose or to a vaccine component
    PCV13: severe allergic reaction to any vaccine containing diphtheria toxoid
    Moderate or severe acute illness with or without fever
    Tetanus, diphtheria, pertussis
    Tetanus & diphtheria toxoids vaccine (Td): 0.5 mL IM
    Tetanus, diphtheria & acellular pertussis vaccine (Tdap; Adacel, Boostrix): 0.5 mL IM
    Other formulations [e.g., diphtheria and tetanus toxoids and acellular pertussis (DTaP)] not recommended for adult use
    Everyone:
    • Td: Administer every 10 yr
    • Tdap: Administer one dose after age 18 yr as substitute for 1 Td booster
    Pregnant women: Administer one dose every pregnancy (preferably at 27–36 wk gestation)
    Adults not previously vaccinated: Administer three-dose series consisting of Tdap followed by Td 4 wk later and Td 6–12 mo later
    Postexposure prophylaxis: See Table A.2
    Severe allergic reaction to any vaccine component or after a previous dose
    Tdap:
    encephalopathy (e.g., coma, prolonged seizures) not attributable to other cause within 7 d of administration of previous dose
    Moderate or severe acute illness with or without fever; GBS within 6 wk after previous dose of tetanus toxoid-containing vaccine; history of Arthus-type (type III) hypersensitivity reactions after previous dose of diphtheria toxoid–containing vaccine
    Tdap: progressive or unstable neurologic disorder, uncontrolled seizures, or progressive encephalopathy until treatment regimen established and condition stabilized
    Varicella (chickenpox)
    Live varicella vaccine (VAR, Varivax):
    0.5 mL SC
    Anyone without evidence of immunity: Administer
    two doses (4–8 wks apart); if one dose given previously, only give second dose
    Evidence of immunity:
    • Documented vaccination (two doses >4 wk apart)
    • US born before 1980 except if pregnant or health-care personnel
    • Varicella or zoster infection documented by health-care provider
    • Laboratory confirmation of immunity or disease
    Severe allergic reaction to any vaccine component or after a previous dose; known severe immunodeficiency (e.g., hematologic and solid tumors, receipt of chemotherapy, congenital immunodeficiency, long-term immunosuppressive therapy, HIV infection with CD4+ <200 cells/μL); pregnancyModerate or severe acute illness with or without fever; simultaneous or recent (≤2 wk) receipt of antibody-containing blood product; receipt of specific antivirals (i.e., acyclovir, famciclovir, valacyclovir) 24 h before vaccination; avoid antiviral use for 14 d after vaccination
    Herpes zoster (shingles)
    Recombinant zoster vaccine (RZV; Shingrix): 0.5 mL IM
    Zoster vaccine live (ZVL; Zostavax): 0.65 mg SC
    Adults ≥50 yr: Administer two doses of RZV 2–6 mo apart regardless of prior episode of herpes zoster or receipt of ZVL (give RZV at least 2 mo after ZVL)
    Adults ≥60 yr: Administer either two doses of RZV as above (preferred) or single dose of ZVL
    Severe allergic reaction to a vaccine component
    ZVL: known severe immunodeficiency (e.g., hematologic and solid tumors, receipt of chemotherapy, congenital immunodeficiency, long-term immunosuppressive therapy, HIV infection with CD4+ <200 cells/μL); pregnancy
    Moderate or severe acute illness with or without fever
    ZVL: receipt of specific antivirals (i.e., acyclovir, famciclovir, valacyclovir) 24 h before vaccination; avoid antiviral use for 14 d after vaccination

    Adapted from Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices recommended immunization schedule for adults aged 19 years or older—United States, 2018. MMWR Morb Mortal Wkly Rep. 2018;67(5):158-160. https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html.

    ESRD, end stage renal disease

  • Passive immunization involves the administration of immune globulin resulting in transient protection against infection. It is usually employed in a host with limited capacity to mount a primary immune response, when exposure to a pathogen occurs in a previously unvaccinated host, or to protect against toxin-mediated disease.
  • Postexposure prophylaxis is therapy given following exposure to a pathogen to prevent the development of disease. This can include active immunization, passive immunization, and/or antimicrobial therapy (Tables A.2 and A.3).
    Table A.2: Selected Adult Postexposure Prophylaxis Recommendations
    DiseaseIndications and Therapy
    AnthraxIndicated for all contacts. Either ciprofloxacin 500 mg PO q12h (preferred for pregnant women), or doxycycline 100 mg PO q12h for 60 days and anthrax vaccine absorbed (AVA) SC series (obtained from the CDC): First dose administered as soon as possible, second and third doses administered at 2 and 4 wk after the first dose. (Alternative antibiotic regimens available; see CDC website.)
    Botulinum toxinClose observation of exposed person; treat with heptavalent botulinum antitoxin (equine immunoglobulin) at first sign of illness (obtained via consultation with state health department).
    DiphtheriaIndicated for close (e.g., household) contacts: Benzathine penicillin G 1.2 million units IM once or erythromycin (base) 500 mg PO q12h for 7–10 d and tetanus and diphtheria (Td) booster vaccine (see Table A.1). Diphtheria antitoxin (DAT) 10,000 units IM/IV (after appropriate sensitivity testing) used for prophylaxis only in exceptional circumstances, obtained in consultation with the CDC (770-488-7100).
    Hepatitis AIndicated for unvaccinated household and sexual contacts of infected individual; persons who have shared illicit drugs with the infected individual; coworkers of infected food handlers; all staff and children at day care centers caring for diapered children where ≥1 case has occurred or when cases occur in ≥2 households of center attendees; only classroom contacts in centers not caring for diapered children.
    For healthy persons <40 yr: Administer single-antigen hepatitis A vaccine (see Table A.1).
    For persons ≥40 yr, immune compromised, or with chronic liver disease: Administer single-antigen hepatitis A vaccine (see Table A.1) and immune globulin (IG), 0.1 mL/kg IM, once within 14 d of exposure.
    Hepatitis BNonoccupational: If exposure source is known surface antigen positive, unvaccinated or incompletely vaccinated persons should receive vaccine (see Table A.1) and hepatitis B immune globulin (HBIG) 0.06 mL/kg IM once. Vaccinated persons without serologic confirmation of immunity should receive 1 vaccine dose. If exposure source antigen status is unknown, unvaccinated persons should receive the vaccine series, and incompletely vaccinated persons should receive the remaining doses. Vaccinated persons require no further treatment.
    Occupational: See Table A.3.
    HIVNonoccupational: Indicated within 72 h of exposure to HIV-infected blood, urogenital secretions, or other body fluids (e.g., condomless sexual intercourse, needle sharing). Administer tenofovir-emtricitabine 300/200 mg (1 tablet) PO daily and raltegravir 400 mg PO q12h for 28 d. Test for HIV at presentation and ensure follow-up for repeat HIV testing at 6 wk. See https://www.cdc.gov/hiv/pdf/programresources/cdc-hiv-npep-guidelines.pdf. If alternative regimens desired, recommend consultation with an HIV specialist.
    Occupational: See Table A.3.
    MeaslesNonoccupational: If nonimmune (see Table A.1), give measles, mumps, rubella (MMR) vaccine within 72 h of initial exposure. For pregnant women (if nonimmune) or severely immunocompromised (regardless of prior immunity), give immunoglobulin 400 mg/kg IV (IVIG) once within 6 d of exposure. Monitor for signs/symptoms for at least 1 incubation period.
    Occupational: See Table A.3.
    Meningococcus (Neisseria meningitidis)Indicated for close contacts of patients with invasive meningococcal disease, including household contacts, child care center contacts, and persons directly exposed to the patient’s oral secretions. Administer ciprofloxacin 500 mg PO once, rifampin 600 mg PO q12h for 2 d, or ceftriaxone 250 mg IM once (preferred in pregnancy).
    Pertussis (Bordetella pertussis, whooping cough)Indicated for close contacts of symptomatic patients (face-to-face exposure ≤3 ft), persons with direct contact with infected respiratory or oral secretions, persons with high risk of severe illness (e.g., immunocompromised, third trimester of pregnancy, asthma), or those who will have contact with high-risk persons (including infants age <12 mo). Administer a macrolide antibiotic (azithromycin 500 mg PO day 1, 250 mg PO daily days 2–5; erythromycin 500 mg PO q6h for 14 d; clarithromycin 500 mg PO q12h for 7 d) within 21 d of onset of cough in exposure source.
    PlagueIndicated for close contacts of pneumonic plague patients (face-to-face exposure ≤3 ft) that have received ≤48 h of effective antibiotic therapy or persons with direct contact with infected body fluids or tissues (for pregnant women, weigh prophylactic benefits with antibiotic risks). Administer doxycycline 100 mg PO q12h or ciprofloxacin 500 mg PO q12h for 7 d.
    RabiesSee Rabies Postexposure Prophylaxis section of this Appendix.
    TetanusFor clean, minor wounds: If vaccination history unknown or <3 doses tetanus toxoid-containing vaccine, give Tdap and complete catch-up vaccination (see Table A.1). If ≥3 doses and >10 yr since last dose, give Tdap (if not yet received) or Td.
    For all other wounds: If vaccination history unknown or <3 doses tetanus toxoid-containing vaccine, give tetanus immune globulin 250 units IM once, as well as Tdap (at separate site) and complete catch-up vaccination. If ≥3 doses and >5 yr since last dose, give Tdap (if not yet received) or Td.
    TularemiaRoutine prophylaxis not recommended. If exposure in bioterrorism or mass casualty setting, give doxycycline 100 mg PO q12h or ciprofloxacin 500 mg PO q12h (preferred in pregnant women) for 14 d.
    SmallpoxIndicated in setting of intentional release of smallpox (variola virus) for exposed persons and persons with contact with infectious materials from smallpox patients, weighing risks and benefits for those with relative contraindications. Administer smallpox (vaccinia) vaccine (ACAM2000; available from the CDC Drug Service at 404-639-3670) ideally within 3 d of exposure; vaccination 4–7 d after exposure may offer some protection.
    VaricellaIndicated for exposed persons without evidence of immunity. Vaccinate (see Table A.1) within 3 d of exposure (possibly effective up to 5 d of postexposure). If contraindication to vaccination and at high risk of severe infection (e.g., pregnant women, immunocompromised, malignancy), give varicella-zoster immune globulin (VariZIG) 12.5 international units (IU)/kg IM once (minimum, 125 IU; maximum, 625 IU) within 10 d of exposure, which can be obtained from FFF Enterprises (800-843-7477, http://www.fffenterprises.com).

    CDC, Centers for Disease Control and Prevention; Tdap, tetanus, diphtheria, pertussis.

    Table A.3: Selected Postexposure Guidelines for Health Care Personnela
    PathogenTreatment
    HIVIndicated for exposure to HIV-infected blood, tissue, or body fluids (e.g., semen, vaginal secretions, amniotic fluid)b via percutaneous injury, contact with mucous membranes, or contact with nonintact skin. Administer as soon as possible within 72 h after exposure (can consider up to 1 wk in very–high risk cases). Preferred regimen is tenofovir-emtricitabine 300/200 mg (1 tablet) PO daily and raltegravir 400 mg PO bid for 28 d or until exposure source tests negative for HIV (unless acute seroconversion is suspected).c Test exposed workers at baseline, 6 wk, 12 wk, and 6 mo for HIV (baseline, 6 wk, and 4 mo if using fourth-generation test). Assistance with choosing a regimen may be obtained by calling the National Clinicians’ Post-Exposure Prophylaxis Hotline (PEPline) at 1-888-448-4911 or consulting an HIV expert.
    Hepatitis BFor percutaneous injury with blood or blood-contaminated fluids from known surface antigen–positive source:
    Unvaccinated health-care worker: Administer hepatitis B immunoglobulin (HBIG), 0.06 mL/kg IM, within 96 h of exposure AND start hepatitis B vaccine series (see Table A.1).
    Vaccinated health-care worker:
    • Known responder: no treatment
    • Nonresponder after one complete series: HBIG × 1 and repeat series
    • Nonresponder after two complete series: HBIG × 2 doses 1 mo apart
    • Antibody response unknown: check anti-HBs titer; if ≥10 IU/mL: no therapy; if <10 IU/mL: HBIG × 1 and vaccine booster.
    Hepatitis CImmunoglobulin and postexposure prophylaxis not effective. Ensure occupational health follow-up for baseline and subsequent follow-up testing.
    MeaslesIf no documented evidence of immunity, give MMR vaccine within 72 h of initial exposure. For pregnant women (if nonimmune) or severely immunocompromised (regardless of prior immunity), give immunoglobulin 400 mg/kg IV (IVIG) once within 6 d of exposure. Monitor for signs/symptoms for at least one incubation period. Health-care personnel without evidence of immunity should be off duty from day 5 after first exposure to day 21 after last exposure, regardless of whether prophylaxis was given.

    aAll blood and body fluid exposures should be reported to the occupational health department. Source patients should be tested for HIV (with consent), hepatitis B surface antigen (HbsAg), and hepatitis C antibody (anti-HCV).

    bBody fluids not considered infectious include feces, urine, vomitus, saliva, and tears, unless these are visibly contaminated with blood.

    cMultiple alternative antiretroviral regimens are available if exposed worker has contraindications to or is otherwise unable to use the preferred regimen, or if the exposure source is known to have resistant virus. See Infect Control Hosp Epidemiol. 2013;34:875. Consultation with an HIV specialist is recommended in such cases.

  • Adverse events potentially related to vaccination should be reported through the Vaccine Adverse Event Reporting System at http://vaers.hhs.gov/ or 1-800-822-7967.
  • More information, including adult vaccination schedules, recommendations regarding travel, and up-to-date guidelines can be found at the Centers for Disease Control and Prevention (CDC) website, http://www.cdc.gov/. Additional guidance for specific clinical questions can be obtained by contacting the CDC directly at 1-800-232-4636 (1-800-CDC-INFO) or via e-mail at NIPINFO@cdc.gov.

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