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Chapter 2The Pre-Travel Consultation

General Recommendations for Vaccination & Immunoprophylaxis

Andrew T. Kroger, Raymond A. Strikas

Recommendations for the use of vaccines and other biologic products (such as immune globulin [IG] products) in the United States are developed by the Advisory Committee on Immunization Practices (ACIP) and other groups, such as the American Academy of Pediatrics, the American Academy of Family Physicians, and the American College of Physicians. ACIP recommendations are based on scientific evidence of benefits (immunity to the disease) and risks (vaccine adverse reactions) and, where few or no data are available, on expert opinion. The recommendations include information on general immunization issues and the use of specific vaccines. Box 2-01 provides more information about ACIP. This section is based primarily on the ACIP General Recommendations on Immunization.

Evaluation of people before travel should include a review and provision of routine vaccines recommended based on age and other individual characteristics. Additionally, some routine vaccines are recommended at earlier ages for international travelers. For example, MMR (measles-mumps-rubella) vaccine is recommended for infants aged 6–11 months who travel abroad to protect them from measles. Recommendations for specific vaccines related to travel will depend on itinerary, duration of travel, and host factors. Vaccinations against diphtheria, tetanus, pertussis, measles, mumps, rubella, varicella, poliomyelitis, hepatitis A, hepatitis B, Haemophilus influenzae type b (Hib), rotavirus, human papillomavirus (HPV), and pneumococcal and meningococcal invasive disease are routinely administered in the United States, usually in childhood or adolescence. Influenza vaccine is routinely recommended for all people aged ≥6 months, each year. A dose of herpes zoster (shingles) vaccine is recommended for adults aged ≥60 years. If a person does not have a history of adequate protection against these diseases, immunizations appropriate to age and previous immunization status should be obtained, whether or not international travel is planned. A visit to a clinician for travel-related immunizations should be seen as an opportunity to bring an incompletely vaccinated person up-to-date on his or her routine vaccinations.

Both the child and adolescent vaccination schedules, and an adult vaccination schedule, are published annually in the Morbidity and Mortality Weekly Report (MMWR). Clinicians should obtain the most current schedules from the CDC Vaccines and Immunization website (www.cdc.gov/vaccines/schedules). The text and many tables of this publication present recommendations for the use, number of doses, dose intervals, adverse reactions, precautions, and contraindications for vaccines and toxoids that may be indicated for travelers. Recommendations for travelers are not always the same as routine recommendations. For instance, most adults born after 1956 are recommended to receive 1 dose of MMR vaccine; however, international travelers of this age are recommended to receive 2 doses. One dose of MMR vaccine is also recommended for infants aged 6–11 months before they travel abroad. For specific vaccines and toxoids, additional details on background, adverse reactions, precautions, and contraindications, refer to the respective ACIP recommendations (www.cdc.gov/vaccines/acip/index.html).

Box 2-01. The Advisory Committee on Immunization Practices (ACIP)

In 1964, the Department of Health and Human Services chartered the Advisory Committee on Immunization Practices (ACIP) to provide guidance to CDC for making immunization policy. Guidance includes scheduling of vaccine doses, specific risk groups for whom vaccination is recommended, and vaccine contraindications and precautions.

The ACIP is composed of 15 voting members selected by the Secretary of Health and Human Services. ACIP chair, a consumer representative, and 13 members are balanced among various sectors, including academic immunology, medicine, and public health. In addition to the 15 voting members, the committee includes 8 ex officio members representing federal agencies and 26 nonvoting representatives of liaison organizations with broad responsibilities for vaccine development, administration of vaccines to various segments of the population, and operation of immunization programs. ACIP is subdivided into 4 permanent workgroups that address child/adolescent immunization schedules, adult immunization schedules, influenza vaccine, and general immunization issues. In addition to the 4 permanent workgroups, 7 additional workgroups focus on particular vaccines. Input into the development of immunization schedules is shared with professional organizations, including the American Academy of Pediatrics, American College of Physicians, American Academy of Family Physicians, American Congress of Obstetricians and Gynecologists, and American College of Nurse-Midwives.

ACIP workgroups are led by a member of ACIP who works in close collaboration with a CDC workgroup lead staff member. Members of the vaccine pharmaceutical industry may not serve as workgroup members. The workgroup develops consensus on various policy points, then the CDC workgroup lead writes specific content for presentation to the ACIP at large. When it is difficult to achieve consensus, options with plans are developed and presented to the ACIP at large for a vote.

The ACIP meets 3 times a year in a public meeting during which the various workgroups present content that has been developed and is ready for ACIP discussion or voting. Sometimes ACIP members are involved in academic vaccine research supported by the pharmaceutical industry. These members must state these conflicts and must recuse themselves from votes regarding vaccines manufactured by companies from which they receive support. The end result of various discussions and votes is an ACIP document published in CDC’s Morbidity and Mortality Weekly Report (www.cdc.gov/mmwr), representing the official policy of the Department of Health and Human Services.

SPACING OF IMMUNOBIOLOGICS

Simultaneous Administration

All commonly used vaccines can safely and effectively be given simultaneously (on the same day) at separate sites without impairing antibody responses or increasing rates of adverse reactions. This knowledge is particularly helpful for international travelers, for whom exposure to several infectious diseases might be imminent. Simultaneous administration of all indicated vaccines is encouraged for people who are the recommended age to receive these vaccines and for whom no contraindications exist. If not administered on the same day, an inactivated vaccine may be given at any time before or after a different inactivated vaccine or a live-virus vaccine.

The immune response to an injected or intranasal live-virus vaccine (such as MMR, varicella, yellow fever, or live attenuated influenza vaccine) might be impaired if administered within 28 days of another live-virus vaccine (within 30 days for yellow fever vaccine). Whenever possible, injected live-virus vaccines administered on different days should be given ≥28 days apart (≥30 days for yellow fever vaccine). If 2 injected or intranasal live-virus vaccines are not administered on the same day but <28 days apart (<30 days for yellow fever vaccine), the second vaccine should be readministered ≥28 days (≥30 days for yellow fever vaccine) after the second vaccine was administered.

Measles and other live-virus vaccines may interfere with the response to tuberculin skin testing and the interferon-γ release assay. Tuberculin skin testing, if otherwise indicated, can be done either on the day that live-virus vaccines are administered or 4–6 weeks later. Tuberculin skin testing is not a prerequisite for administration of any vaccine. Oral typhoid vaccine, a live attenuated bacterial vaccine, has not been associated with suppressing the response to tuberculosis testing.

Missed Doses and Boosters

All vaccines require a primary dose or series to ensure immunity, and some require periodic repeat, or booster, doses to maintain immunity. Travelers may forget to return to complete a series or for a booster at the specified time. Occasionally, the demand for a vaccine may exceed its supply, and providers may have difficulty obtaining vaccines. Information on vaccine shortages and recommendations can be found on the CDC Vaccines and Immunization website at www.cdc.gov/vaccines/vac-gen/shortages/default.htm.

In some cases, a scheduled dose of vaccine may not be given on time. If this occurs, the dose should be given at the next visit. Available data indicate that intervals between doses longer than those routinely recommended do not affect seroconversion rate or titer when the schedule is completed. Consequently, it is not necessary to restart the series or add doses of any vaccine because of an extended interval between doses. The only exception to this rule is oral typhoid vaccine in some circumstances. Some experts recommend repeating the series of oral typhoid vaccine if the 4-dose series is extended to more than 3 weeks. Information on revaccination (booster) doses of vaccines is listed in Table 2-04.

Antibody-Containing Blood Products

Antibody-containing blood products, such as IG products, from the United States do not interfere with the immune response to yellow fever vaccine and are not believed to interfere with the response to live typhoid, live attenuated influenza, rotavirus, or zoster vaccines. When MMR and varicella vaccines are given shortly before, simultaneously with, or after an antibody-containing blood product, response to the vaccine can be diminished. The duration of inhibition of MMR and varicella vaccines is related to the dose of IG in the product. MMR or its components and varicella vaccines either should be administered ≥2 weeks before receipt of a blood product, or should be delayed 3–11 months after receipt of the blood product, depending on the vaccine (Table 2-05).

IG administration may become necessary for another indication after MMR or its individual components or varicella vaccines have been given. In such a situation, the IG may interfere with the immune response to the MMR or varicella vaccines. Vaccine virus replication and stimulation of immunity usually occur 2–3 weeks after vaccination. If the interval between administration of one of these vaccines and the subsequent administration of an IG preparation is ≥14 days, the vaccine need not be readministered. If the interval is <14 days, the vaccine should be readministered after the interval shown in Table 2-05, unless serologic testing indicates that antibodies have been produced.

If administration of IG becomes necessary, MMR or its components or varicella vaccines can be administered simultaneously with IG, with the recognition that vaccine-induced immunity can be compromised. The vaccine should be administered at a body site different from that chosen for the IG injection. Vaccination should be repeated after the interval noted in Table 2-05, unless serologic testing indicates antibodies have been produced.

When IG is given with the first dose of hepatitis A vaccine, the proportion of recipients who develop a protective level of antibody is not affected, but antibody concentrations are lower. Because the final concentrations of antibody are many times higher than those considered protective, this reduced immunogenicity is not expected to be clinically relevant.

IG preparations interact minimally with other inactivated vaccines and toxoids. Other inactivated vaccines may be given simultaneously, or at any time interval before or after an antibody-containing blood product is used. However, such vaccines should be administered at different sites from the IG.

Table 2-04. Revaccination (booster) schedules

VACCINE RECOMMENDATION
Hepatitis A Booster doses not recommended for adults and children who have completed the primary series (2 doses) according to the routine schedule.1
Hepatitis B Booster doses not recommended for adults and children who have completed the primary series (3 doses) according to the routine schedule.1, 2
Influenza 1 annual dose (children aged 6 months to 9 years, and certain incompletely vaccinated children should receive 2 doses separated by ≥4 weeks the first time that influenza vaccine is administered). Live attenuated influenza vaccine is approved only for healthy, nonpregnant people aged 2–49 years.
Japanese encephalitisn (JE)
(Vero cell formulation)
For people aged ≥17 years, if the primary series of Ixiaro was administered ≥1 year previously, a booster dose should be given before potential reexposure or if there is a continued risk for JE virus infection. There are no data on the use of Ixiaro as a booster dose after a primary series with JE-Vax. People who have received JE-Vax previously and require further vaccination against JE virus should receive a 2-dose primary series of Ixiaro. See the booster dose information in Chapter 3, Japanese Encephalitis.
Measles, mumps, and rubella (MMR) Two doses of MMR vaccine separated by ≥4 weeks or other evidence of immunity (such as serologic testing) are recommended for people born after 1956 who travel outside the United States. Revaccination is not recommended.
Meningococcal quadrivalent A,C,Y, W-135 Revaccination for people who received meningococcal polysaccharide vaccine or meningococcal conjugate vaccine, and who remain at increased risk for meningococcal disease (including some international travelers): Revaccination with meningococcal conjugate vaccine is recommended after 3 years for children who were previously vaccinated at ages 9 months to 6 years. Revaccination with meningococcal conjugate vaccine is recommended after 5 years for people who were previously vaccinated at ages 7–55 years, and every 5 years thereafter for people who are at continued risk.3 Revaccination with meningococcal polysaccharide vaccine is recommended for adults >55 years who remain at increased risk 3–5 years after the last dose.
Pneumococcal (polysaccharide) One-time revaccination 5 years after original dose for people with certain underlying medical conditions (such as asplenia) or people who were first vaccinated at <65 years of age.
Polio vaccine, inactivated (IPV) For adults traveling to areas where poliomyelitis cases are still occurring, a single lifetime booster dose is recommended for those who have documentation of having completed a primary series.
Rabies preexposure vaccine No serologic testing or boosters recommended for travelers. For people in high-risk groups (such as rabies laboratory workers), serologic testing and booster doses are recommended. See Table 3-15.
Rotavirus Booster doses not recommended.
Tetanus, diphtheria, and acellular pertussis (Td, Tdap) Tetanus and diphtheria booster dose is recommended every 10 years. A single dose of adolescent/adult formulation Td that includes acellular pertussis vaccine (Tdap) is recommended to replace 1 Td booster dose for people aged 11–64 years. Adults aged ≤65 years who have or who anticipate having close contact with an infant aged <12 months and who previously have not received Tdap should receive a single dose of Tdap to protect against pertussis and reduce the likelihood of transmission; all other adults aged ≥65 years who have not previously received Tdap may be given a single dose of Tdap instead of Td. See ACIP statement for details.
Typhoid intramuscular Booster dose every 2 years for those who remain at continued risk.
Typhoid oral Repeat series every 5 years for those who remain at continued risk.
Varicella Revaccination is not recommended.
Yellow Fever Repeat vaccination every 10 years for those who remain at risk.
Zoster Revaccination is not recommended.
1A 3- or 4-dose series of combination hepatitis A-hepatitis B vaccine (HepA-HepB) is also available.
2Booster dosing may be appropriate for certain populations, such as hemodialysis patients.
3See: CDC. Updated recommendation from the Advisory Committee on Immunization Practices (ACIP) for revaccination of persons at prolonged increased risk for meningococcal disease. MMWR Morb Mortal Wkly Rep. 2009 Sep 25;58(37):1042–3.

VACCINATION OF PEOPLE WITH ACUTE ILLNESSES

Every opportunity should be taken to provide needed vaccinations. The decision to delay vaccination because of a current or recent acute illness depends on the severity of the symptoms and their cause. Although a moderate or severe acute illness is sufficient reason to postpone vaccination, minor illnesses (such as diarrhea, mild upper respiratory infection with or without low-grade fever, other low-grade febrile illness) are not contraindications to vaccination.

People with moderate or severe acute illness, with or without fever, should be vaccinated as soon as the condition improves. This precaution is to avoid superimposing adverse effects from the vaccine on underlying illness, or mistakenly attributing a manifestation of underlying illness to the vaccine. Antimicrobial therapy is not a contraindication to vaccination, with 3 exceptions:

  • Antibacterial agents may interfere with the response to oral typhoid vaccine.
  • Antiviral agents active against herpesviruses (such as acyclovir) may interfere with the response to varicella-containing vaccines.
  • Antiviral agents active against influenza virus (such as zanamivir and oseltamivir) may interfere with the response to live attenuated influenza vaccine.

A physical examination or temperature measurement is not a prerequisite for vaccinating a person who appears to be in good health. Asking if a person is ill, postponing a vaccination for someone with moderate or severe acute illness, and vaccinating someone who does not have contraindications are appropriate procedures for clinic immunizations.

ALTERED IMMUNOCOMPETENCE

Altered immunocompetence is a general term that is often used interchangeably with the terms immunosuppression, immunodeficiency, and a weakened immune system. It can be caused either by a disease (leukemia, HIV infection) or by drugs or other therapies (cancer chemotherapy, radiation therapy, prolonged high-dose corticosteroids). It can also include conditions such as asplenia and chronic renal disease.

Determination of altered immunocompetence is important because the incidence or severity of some vaccine-preventable diseases is higher in people with altered immunocompetence. Therefore, certain vaccines (such as inactivated influenza vaccine, pneumococcal vaccines) are recommended specifically for people with altered immunocompetence. Inactivated vaccine may be safely administered to a person with altered immunocompetence, although response to the vaccine may be suboptimal. The vaccine may need to be repeated after immune function has improved.

People with altered immunocompetence may be at increased risk for an adverse reaction after administration of live attenuated vaccines because of reduced ability to mount an effective immune response. Live vaccines should generally be deferred until immune function has improved. This is particularly important when planning to give yellow fever vaccine (see Chapter 3, Yellow Fever). For HIV-infected people with mild or moderate immunosuppression, MMR is recommended and varicella vaccine can be considered.

For an in-depth discussion, see Chapter 8, Immunocompromised Travelers.

Table 2-05. Recommended intervals between administration of antibody-containing products and measles-containing vaccine or varicella-containing vaccine1

INDICATION DOSE RECOMMENDED INTERVAL BEFORE MEASLES OR VARICELLA VACCINATION
Tetanus (TIG) 250 units (10 mg IgG/kg) IM 3 months

Hepatitis A (IG), duration of international travel

  < 3-month stay

  ≥ 3-month stay

 

0.02 mL/kg (3.3 mg IgG/kg) IM

0.06 mL/kg (10 mg IgG/kg) IM

 

3 months

3 months

Hepatitis B prophylaxis (HBIG) 0.06 mL/kg (10 mg IgG/kg) IM 3 months
Rabies prophylaxis (HRIG) 20 IU/kg (22 mg IgG/kg) IM 4 months
Varicella prophylaxis (VZIG) 125 units/10 kg (60–200 mg IgG/kg) IM (maximum 625 units) 5 months

Measles prophylaxis (IG)

  Immunocompetent contact

  Immunocompromised contact

 

0.25 mL/kg (40 mg IgG/kg) IM

0.50 mL/kg (80 mg IgG/kg) IM

 

5 months

6 months

Botulism immune globulin, intravenous 1.5 mL/kg (75 mg IgG/kg) IV 6 months

Blood Transfusion

  Red blood cells (RBCs), washed

  RBCs, adenine-saline added

  Packed RBCs (hematocrit 65%)2

  Whole blood (hematocrit 35%–50%)2

  Plasma/platelet products

 

10 mL/kg (negligible IgG/kg) IV

10 mL/kg (10 mg IgG/kg) IV

10 mL/kg (60 mg IgG/kg) IV

10 mL/kg (80–100 mg IgG/kg) IV

10 mL/kg (160 mg IgG/kg) IV

 

None

3 months

6 months

6 months

7 months

Cytomegalovirus prophylaxis (CMV IGIV) 150 mg/kg (maximum) 6 months
Respiratory syncytial virus (RSV) monoclonal antibody3 15 mg/kg IM None

Intravenous immune globulin (IVIG)

  Replacement therapy

  Immune thrombocytopenic purpura (ITP)

  Postexposure varicella prophylaxis4

  ITP

  ITP or Kawasaki disease

 

300-400 mg/kg IV

400 mg/kg IV

400 mg/kg IV

1 gm/kg IV

1.6–2 gm/kg IV

 

8 months

8 months

8 months

10 months

11 months

Abbreviations: IG, immune globulin; IM, intramuscular; IV, intravenous.
1Adapted from Table 5, Kroger AT, Sumaya CV, Pickering LK, Atkinson WL. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011 Jan 28;60(RR-2):1–61. This table is not intended for determining the correct indications and dosage for the use of IG preparations. Unvaccinated people may not be fully protected against measles during the entire recommended interval, and additional doses of IG or measles vaccine may be indicated after measles exposure. Concentrations of measles antibody in an IG preparation can vary by manufacturer’s lot. For example, more than a 4-fold variation in the amount of measles antibody titers has been demonstrated in different IG preparations. Rates of antibody clearance after receipt of an IG preparation can also vary. Recommended intervals are extrapolated from an estimated half-life of 30 days for passively acquired antibody and an observed interference with the immune response to measles vaccine for 5 months after a dose of 80 mg IgG/kg. Does not include zoster vaccine. Zoster vaccine may be given with antibody-containing products.
2Assumes a serum IgG concentration of 16 mg/mL.
3Contains only antibody to respiratory syncytial virus.
4IVIG is an alternative to VZIG for postexposure varicella prophylaxis. Both VZIG and IVIG should be administered within 96 hours of varicella exposure. Unlike VZIG, IVIG is a licensed product and in some situations might be obtained more quickly. For pregnant women who cannot obtain VZIG within 96 hours, monitoring for signs and symptoms of varicella disease and instituting treatment with acyclovir are an alternative to IVIG.

VACCINATION SCHEDULING FOR LAST-MINUTE TRAVELERS

As noted, for people anticipating imminent travel, most vaccine products can be given during the same visit. Unless the vaccines given are booster doses of those typically given during childhood, vaccines may require a month or more to induce a sufficient immune response, depending on the vaccine and the number of doses in the series. Some vaccines require more than 1 dose for best protection. Recommended spacing should be maintained between doses (Table 2-06). Doses given at less than minimum intervals can lessen the antibody response. It is important to note that if a traveler needs yellow fever vaccination to meet a country requirement under the International Health Regulations, the yellow fever vaccine is not considered valid until 10 days after administration. Intervals between doses longer than those routinely recommended do not affect the immune response when the schedule is completed. Consequently, it is not necessary to restart the series or add doses of any vaccine because of an extended interval between doses.

Administration of a vaccine earlier than the recommended minimum age or at an interval shorter than the recommended minimum is discouraged. Table 2-06 lists the minimum age and minimum interval between doses for vaccines routinely recommended in the United States.

Because some travelers visit their health care providers at the last minute, studies have been performed to determine whether accelerated scheduling is adequate. This concern is primarily the case for hepatitis B vaccine or the combined hepatitis A and B vaccine. An accelerated schedule for combined hepatitis A and B vaccine has been approved by the Food and Drug Administration (FDA). It is unclear what level of protection any given traveler will have if he or she does not complete a full series of multidose vaccination.

ALLERGY TO VACCINE COMPONENTS

Vaccine components can cause allergic reactions in some recipients. These reactions can be local or systemic and can include anaphylaxis or anaphylactic-like responses. The vaccine components responsible can include the vaccine antigen, animal proteins, antibiotics, preservatives (such as thimerosal), or stabilizers (such as gelatin). The most common animal protein allergen is egg protein in vaccines prepared by using embryonated chicken eggs (influenza and yellow fever vaccines). Generally, people who can eat eggs or egg products safely may receive these vaccines, while those with histories of anaphylactic allergy (swelling of the mouth and throat, difficulty breathing, hypotension, shock) to eggs or egg proteins ordinarily should not. Screening people by asking whether they can eat eggs without adverse effects is a reasonable way to identify those who might be at risk from receiving yellow fever and influenza vaccines. Protocols have been developed for testing and vaccinating people with anaphylactic reactions to egg ingestion. Recent studies have indicated that other components in vaccines in addition to egg proteins (such as gelatin) may cause allergic reactions, including anaphylaxis in rare instances.

Some vaccines contain a preservative or trace amounts of antibiotics to which people might be allergic. Providers administering the vaccines should carefully review the prescribing information before deciding if the rare person with such an allergy should receive the vaccine. No recommended vaccine contains penicillin or penicillin derivatives. Some vaccines (MMR and its individual component vaccines, inactivated polio vaccine [IPV], varicella, rabies) contain trace amounts of neomycin or other antibiotics; the amount is less than would normally be used for the skin test to determine hypersensitivity. However, people who have experienced anaphylactic reactions to this antibiotic generally should not receive these vaccines. Most often, neomycin allergy is a contact dermatitis—a manifestation of a delayed-type (cell-mediated) immune response rather than anaphylaxis. A history of delayed-type reactions to neomycin is not a contraindication to receiving these vaccines.

Thimerosal, an organic mercurial compound in use since the 1930s, has been added to certain immunobiologic products as a preservative. Thimerosal is present at preservative concentrations (trace quantities) in multidose vials of some brands of vaccine. Receiving thimerosal-containing vaccines has been postulated to lead to induction of allergy. However, there is limited scientific evidence for this assertion. Allergy to thimerosal usually consists of local delayed-type hypersensitivity reactions. Thimerosal elicits positive delayed-type hypersensitivity patch tests in 1%–18% of people tested, but these tests have limited or no clinical relevance. Most people do not experience reactions to thimerosal administered as a component of vaccines, even when patch or intradermal tests for thimerosal indicate hypersensitivity. A localized or delayed-type hypersensitivity reaction to thimerosal is not a contraindication to receipt of a vaccine that contains thimerosal.

Since mid-2001, vaccines routinely recommended for infants have been manufactured without thimerosal as a preservative. Additional information about thimerosal and the thimerosal content of vaccines is available on the FDA website (www.fda.gov/cber/vaccine/thimerosal.htm).

Table 2-06. Recommended and minimum ages and intervals between vaccine doses1,2

VACCINE AND DOSE NUMBER RECOMMENDED AGE FOR THIS DOSE MINIMUM AGE FOR THIS DOSE MINIMUM INTERVAL TO NEXT DOSE3
Diphtheria and tetanus toxoids and acellular pertussis vaccine, pediatric (6 weeks through 6 years) (DTaP)-14 2 months 6 weeks 4 weeks
DTaP-2 4 months 10 weeks 4 weeks
DTaP-3 6 months 14 weeks 6 months5,6
DTaP-4 15–18 months 12 months 6 months5
DTaP-5 4–6 years 4 years NA
Haemophilus influenzae type b (Hib)-14,7 2 months 6 weeks 4 weeks
Hib-2 4 months 10 weeks 4 weeks
Hib-38 6 months 14 weeks 8 weeks
Hib-4 12–15 months 12 months NA
Hepatitis A (HepA)-1 12–23 months 12 months 6 months5
HepA-2 ≥18 months 18 months NA
Hepatitis B (HepB)-14 Birth Birth 4 weeks
Hep B-2 1–2 months 4 weeks 8 weeks
Hep B-39 6–18 months 24 weeks NA
Herpes zoster10 ≥60 years 60 years NA
Human papillomavirus (HPV)-111 11–12 years 9 years 4 weeks
HPV-2 2 months after dose 1 9 years, 4 weeks 12 weeks12
HPV-312 6 months after dose 1 9 years, 24 weeks NA
Inactivated poliovirus (IPV)-14 2 months 6 weeks 4 weeks
IPV-2 4 months 10 weeks 4 weeks
IPV-3 6–18 months 14 weeks 6 months
IPV-413 4–6 years 4 years NA
Influenza, inactivated14 ≥6 months 6 months15 4 weeks
Influenza, live attenuated14 2–49 years 2 years 4 weeks
Japanese encephalitis, Vero cell (Ixiaro)-116 ≥17 years ≥17 years 28 days
Ixiaro-2 28 days after dose 1 ≥17 years, 28 days NA
Measles-mumps-rubella (MMR)-117 12–15 months 12 months 4 weeks
MMR-217 4–6 years 13 months NA
Meningococcal conjugate (MenACWY-1)18 11–12 years 9 months (Menactra) or 2 years (Menveo) 8 weeks19
MenACWY-2 16 years 11 months (Menactra) or 2  years, 8 weeks (Menveo) NA
Meningococcal polysaccharide (MPSV4)-118 NA 2 years 5 years
MPSV4-2 NA 7 years NA
Pneumococcal conjugate (PCV)-17 2 months 6 weeks 4 weeks
PCV-2 4 months 10 weeks 4 weeks
PCV-3 6 months 14 weeks 8 weeks
PCV-4 12–15 months 12 months NA
Pneumococcal polysaccharide (PPSV)-1 NA 2 years 5 years
PPV-220 NA 7 years NA
Rabies-1 (preexposure) See footnote 21 See footnote 21 7 days
Rabies-2 7 days after dose 1 7 days after dose 1 14 days
Rabies-3 21 days after dose 1 21 days after dose 1 NA
Rotavirus (RV)-122 2 months 6 weeks 4 weeks
RV-222 4 months 10 weeks 4 weeks
RV-322 6 months 14 weeks NA
Tetanus and reduced diphtheria toxoids (Td) 11–12 years 7 years 5 years
Tetanus toxoid, reduced diphtheria toxoid, and reduced acellular pertussis vaccine (Tdap)23 ≥11 years 7 years NA
Typhoid, inactivated (ViCPS) ≥2 years ≥2 years NA
Typhoid, live attenuated (Ty21a) ≥6 years ≥6 years See footnote 24
Varicella (Var)-117 12–15 months 12 months 12 weeks25
Yellow Fever >9 months26 >9 months26 10 years

1Adapted from Table 1, Kroger AT, Sumaya CV, Pickering LK, Atkinson WL. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011 Jan 28;60(RR-2):1–61.
2Combination vaccines are available. Use of licensed combination vaccines is generally preferred over separate injections of their equivalent component vaccines (CDC. Combination vaccines for childhood immunization. MMWR Recomm Rep. 1999 May 14;48(RR-5):1–14.). When administering combination vaccines, the minimum age for administration is the oldest age for any of the individual components; the minimum interval between doses is equal to the largest interval of any of the individual components.
3See Table 2–4 for recommended revaccination (booster) schedules.
4 Combination vaccines containing the HepB component are available (HepB-Hib, DTaP-HepB-IPV, HepA-HepB). These vaccines should not be administered to infants aged <6 weeks because of the other components (Hib, DTaP, IPV). HepA-HepB is not licensed for children aged <18 years in the United States.
5 Calendar months.
6 The minimum recommended interval between DTaP-3 and DTaP-4 is 6 months. However, DTaP-4 need not be repeated if administered ≥4 months after DTaP-3.
7 For Hib and PCV, children receiving the first dose of vaccine at ≥7 months of age require fewer doses to complete the series (see the current childhood and adolescent immunization schedule at www.cdc.gov/vaccines).
8 If PRP-OMP (Pedvax-Hib, Merck Vaccine Division) was administered at 2 and 4 months of age, a dose at 6 months of age is not indicated.
9 HepB-3 should be administered ≥8 weeks after Hep B-2 and ≥16 weeks after Hep B-1; it should not be administered before age 24 weeks.
10 Herpes zoster (shingles) vaccine is approved as a single dose for people aged ≥60 years.
11 Bivalent HPV vaccine is approved for girls/women aged 10–25 years. It is recommended to prevent cervical and other anogenital cancers and precursors for girls/women aged 11–26 years. Quadrivalent HPV vaccine is approved for boys/men and girls/women aged 9–26 years. It is recommended to prevent cervical and other anogenital cancers, precursors, and genital warts for girls/women aged 11–26 years. It may be given to girls aged 9–10 years to prevent the same diseases, and to boys/men aged 9–26 years to prevent genital warts.
12 The third dose of HPV should be administered ≥12 weeks after the second and ≥24 weeks after the first. Dose 3 need not be repeated if administered ≥16 weeks after dose 1.
13 For people receiving an all-IPV or all-OPV series, if the third dose is given after the fourth birthday, a fourth dose is not needed.
14 Two doses of influenza vaccine are recommended for children aged <9 years who are receiving the vaccine for the first time, and for certain incompletely vaccinated children (see reference 4). All others need only 1 dose annually. The doses of inactivated influenza vaccine are 0.25 mL for children aged 6–35 months and 0.5 mL for people aged ≥3 years.
15 The minimum age for inactivated influenza vaccine varies by vaccine manufacturer. See package insert for vaccine specific minimum ages.
16 Ixiaro is approved by the Food and Drug Administration for people aged ≥17 years.
17 Combination MMR-varicella can be used for children aged 12 months through 12 years. Also see footnote 25.
18 Revaccination with meningococcal vaccine is recommended for people previously vaccinated who remain at high risk for meningococcal disease (see Table 2–4). MenACWY is preferred when revaccinating people aged 2–55 years (Bilukha OO, Rosenstein N. Prevention and control of meningococcal disease. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2005 May 27;54(RR-7):1–21.).
19 Children aged 9–23 months who are vaccinated using Menactra (Sanofi Pasteur) should receive a 2-dose primary series administered 3 months apart (CDC. Recommendation of the Advisory Committee on Immunization Practices [ACIP] for use of quadrivalent meningococcal conjugate vaccine [MenACWY-D] among children aged 9 through 23 months at increased risk for invasive meningococcal disease. MMWR 2011: 60(40);1391–2.) People aged 2–55 years with persistent complement component deficiency (such as C5–C9, properdin, factor H, or factor D) and functional or anatomic asplenia, and for adolescents with human immunodeficiency virus (HIV) infection should receive a 2-dose primary series administered 2 months apart (CDC. Updated recommendations for use of meningococcal conjugate vaccines—Advisory Committee on Immunization Practices [ACIP], 2010. MMWR 2011;60(03); 72–6).
20 A second dose of PPSV is recommended for people aged ≥65 years who received a first dose at an age <65 years and at a five year minimum interval. A second dose is also recommended for people aged <65 years at highest risk for serious pneumococcal infection and those who are likely to have a rapid decline in pneumococcal antibody concentration (CDC. Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1997 Apr 4;46(RR-8):1–24.).
21 There is no minimum age for preexposure immunization for rabies (Manning SE, Rupprecht CE, Fishbein D, Hanlon CA, Lumlertdacha B, Guerra M, et al. Human rabies prevention—United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2008 May 23;57(RR-3):1–28.).
22 The first dose of RV must be administered by 14 weeks and 6 days of age. The vaccine series should not be started at ≥15 weeks of age. The final dose in the series should be administered by age 8 months, 0 days. If Rotarix rotavirus vaccine is administered at 2 and 4 months of age, a dose at 6 months of age is not indicated.
23 Only 1 dose of Tdap is recommended. Subsequent doses should be given as Td. Children aged 7–10 years who are not fully vaccinated against pertussis and for whom no contraindication to pertussis vaccine exists should receive a single dose of Tdap. If additional doses of tetanus and diphtheria toxoid-containing vaccines are needed, then children aged 7–10 years should be vaccinated according to catch-up guidance, with Tdap preferred as the first dose. Tdap vaccine, when indicated, should be administered regardless of the interval since the last dose of Td vaccine. For management of a tetanus-prone wound, the minimum interval after a previous dose of any tetanus-containing vaccine is 5 years.
24 Oral typhoid vaccine is recommended to be administered 1 hour before a meal with a cold or lukewarm drink (temperature not to exceed body temperature—98.6°F [37°C]) on alternate days, for a total of 4 doses.
25 The minimum interval from Var-1 to Var-2 for people beginning the series at ≥13 years of age is 4 weeks.
26Yellow fever vaccine may be administered to children aged <9 months in certain situations (Staples JE, Gershman M, Fischer M. Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR Recomm Rep. 2010 Jul 30;59[RR-7]:1–27.).

REPORTING ADVERSE EVENTS AFTER IMMUNIZATION

Modern vaccines are extremely safe and effective. Benefits and risks are associated with the use of all immunobiologics—no vaccine is completely effective or completely free of side effects. Adverse events after immunization have been reported with all vaccines, ranging from frequent, minor, local reactions to extremely rare, severe, systemic illness, such as that associated with yellow fever vaccine. Adverse events following specific vaccines and toxoids are discussed in detail in each ACIP statement. In the United States, clinicians are required by law to report selected adverse events occurring after vaccination with tetanus vaccine in any combination; pertussis in any combination; measles, mumps, or rubella, alone or in any combination; oral polio vaccine (OPV); IPV; hepatitis A; hepatitis B; varicella; Hib (conjugate); influenza; pneumococcal conjugate; rotavirus vaccines; HPV; and meningococcal vaccines (conjugate and polysaccharide). In addition, CDC strongly recommends that all vaccine adverse events be reported to the Vaccine Adverse Event Reporting System (VAERS), even if a causal relation to vaccination is not certain. VAERS reporting forms and information are available electronically at www.vaers.hhs.gov, or they may be requested by telephone: 800-822-7967 (toll-free). Clinicians are encouraged to report electronically at https://vaers.hhs.gov/esub/step1.

INJECTION ROUTE AND INJECTION SITE

Injectable vaccines are administered by intramuscular, intradermal, and subcutaneous routes. The method of administration of injectable vaccines depends in part on the presence of an adjuvant in some vaccines. The term adjuvant refers to a vaccine component distinct from the antigen, which enhances the immune response to the antigen. Vaccines containing an adjuvant (DTaP, DT, HPV, Td, Tdap, pneumococcal conjugate, Hib, hepatitis A, hepatitis B) should be injected into a muscle mass, because administration subcutaneously or intradermally can cause local irritation, induration, skin discoloration, inflammation, and granuloma formation.

Routes of administration are recommended by the manufacturer for each immunobiologic. Deviation from the recommended route of administration may reduce vaccine efficacy or increase local adverse reactions. Detailed recommendations on the route and site for all vaccines have been published in ACIP recommendations; a compiled list of these publications is available on the CDC website at www.cdc.gov/vaccines/pubs/ACIP-list.htm (also see Table C-01 in Appendix C).

BIBLIOGRAPHY

  1. Ball LK, Ball R, Pratt RD. An assessment of thimerosal use in childhood vaccines. Pediatrics. 2001 May;107(5):1147–1154.
  2. Bilukha OO, Rosenstein N. Prevention and control of meningococcal disease. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2005 May 27;54(RR-7):1–21.
  3. CDC. Combination vaccines for childhood immunization. MMWR Recomm Rep. 1999 May 14;48(RR-5):1–14.
  4. CDC. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP)—United States, 2012–13 influenza season. MMWR Morb Mortal Wkly Rep. 2012 Aug 17;61:613–8.
  5. CDC. Updated recommendations for prevention of invasive pneumococcal disease among adults using the 23-valent pneumococcal polysaccharide vaccine (PPSV23). MMWR Morb Mortal Wkly Rep. 2010 Sep 3;59(34):1102–6.
  6. CDC. Updated recommendations for use of meningococcal conjugate vaccines—Advisory Committee on Immunization Practices (ACIP), 2010. MMWR 2011;60(03):72–6.
  7. CDC. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine from the Advisory Committee on Immunization Practices, 2010. MMWR Morb Mortal Wkly Rep. 2011 Jan 14;60(1):13–5.
  8. Kretsinger K, Broder KR, Cortese MM, Joyce MP, Ortega-Sanchez I, Lee GM, et al. Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel. MMWR Recomm Rep. 2006 Dec 15;55(RR-17):1–37.
  9. Kroger AT, Sumaya CV, Pickering LK, Atkinson WL. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011 Jan 28;60(RR-2):1–61.
  10. Manning SE, Rupprecht CE, Fishbein D, Hanlon CA, Lumlertdacha B, Guerra M, et al. Human rabies prevention—United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2008 May 23;57(RR-3):1–28.
  11. Nuorti JP, Whitney CG. Prevention of pneumococcal disease among infants and children—use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010 Dec 10;59(RR-11):1–18.
  12. Plotkin SA. Vaccines: correlates of vaccine-induced immunity. Clin Infect Dis. 2008 Aug 1;47(3):401–99.
  13. Staples JE, Gershman M, Fischer M. Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010 Jul 30;59(RR-7):1–27.
  14. Varricchio F, Iskander J, Destefano F, Ball R, Pless R, Braun MM, et al. Understanding vaccine safety information from the Vaccine Adverse Event Reporting System. Pediatr Infect Dis J. 2004 Apr;23(4):287–294.
  15. Watson JC, Hadler SC, Dykewicz CA, Reef S, Phillips L. Measles, mumps, and rubella—vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1998 May 22;47(RR-8):1–57.
  16. Wood RA, Berger M, Dreskin SC, Setse R, Engler RJ, Dekker CL, et al. An algorithm for treatment of patients with hypersensitivity reactions after vaccines. Pediatrics. 2008 Sep;122(3):e771–7.
 
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