Modifying the Immunization Schedule for Inadequately Immunized Infants and Younger Children Before International Travel
Several factors influence recommendations for the age at which a vaccine is administered, including age-specific risks of the disease and its complications, the ability of people of a given age to develop an adequate immune response to the vaccine, and potential interference with the immune response by passively transferred maternal antibody.
The routine immunization recommendations and schedules for infants and children in the United States do not provide specific guidelines for those traveling internationally before the age when specific vaccines and toxoids are routinely recommended. Recommended age limitations are based on potential adverse events (yellow fever), lack of efficacy or inadequate immune response (polysaccharide vaccines and influenza), maternal antibody interference (measles, mumps, rubella), or lack of safety data. In deciding when to travel with a young infant or child, parents should be advised that the earliest opportunity to receive routinely recommended immunizations in the United States (except for the dose of hepatitis B vaccine at birth) is at 6 weeks of age.
Routine Infant and Childhood Vaccinations
Hepatitis B Vaccine
Hepatitis B virus (HBV) is a cause of acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. There are more than 200 million chronically infected persons worldwide. The risk of chronic infection is highest when infection occurs in infancy or childhood and declines with age.
- Infants and children who have not previously been vaccinated and who are traveling to areas with intermediate and high HBV endemicity are at risk if they are directly exposed to blood (or body fluids containing blood) from the local population.
- Circumstances in which HBV transmission could occur in children include receipt of blood transfusions not screened for HBV surface antigen (HBsAg), exposure to unsterilized medical or dental equipment, or continuous close contact with local residents who have open skin lesions (impetigo, scabies, or scratched insect bites).
Hepatitis B vaccine is recommended for all infants in the United States, with the first dose administered soon after birth and before hospital discharge.
- Infants and children who will travel should receive three doses of HBV vaccine before traveling.
- The interval between doses one and two should be at least 4 weeks.
- Between doses two and three, the interval should be a minimum of 8 weeks; the interval between doses one and three should be at least 16 weeks. The third dose should not be given before the infant is at least 24 weeks of age.
- Adolescents not previously vaccinated with hepatitis B vaccine should be vaccinated at 11–12 years of age.
- For adolescents, the usual schedule is two doses separated by at least 4 weeks, followed by a third dose 4–6 months after the second dose.
- A two-dose series (Recombivax HB, 10 mcg) is licensed for 11- to 15-year-olds and can be given at 0 and 4 to 6 months later.
Diphtheria and Tetanus Toxoid and Pertussis Vaccine
Diphtheria, tetanus, and pertussis each occur worldwide and are endemic in countries with low immunization levels. Infants and children leaving the United States should be immunized before traveling.
- Optimum protection against diphtheria, tetanus, and pertussis is achieved with at least three but preferably four doses of diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP).
- Two doses of DTaP received at intervals at least 4 weeks apart can provide some protection; however, a single dose offers little protective benefit.
- Parents should be informed that infants and children who have not received at least three doses of DTaP might not be fully protected against pertussis.
The usual primary series includes four doses given at 2, 4, 6, and 15–18 months of age. A fifth (booster) dose is recommended when the child is 4–6 years of age. The fifth dose is not necessary if the fourth dose in the primary series was given after the child’s fourth birthday.
For infants and children <7 years of age, the schedule can be accelerated as soon as the infant is 6 weeks of age, with the second and third doses given 4 weeks after each preceding dose. The fourth dose should not be given before the infant is 12 months of age and should be separated from the third dose by at least 6 months. The fifth (booster) dose should not be given before the child is 4 years of age.
Haemophilus influenzae Type b Conjugate Vaccine
Haemophilus influenzae type b (Hib) is an endemic disease worldwide that can cause fatal meningitis, epiglottitis, and other invasive diseases. Infants and children should have optimal protection before traveling.
- Routine Hib vaccination beginning at 2 months of age is recommended for all U.S. children. The first dose may be given when an infant is as young as 6 weeks of age.
- Vaccination before age 6 weeks may induce immune tolerance to subsequent vaccines and should never be done.
A primary series consists of two or three doses (depending on the type of vaccine used) with a minimum interval of 4 weeks between doses.
- A booster dose is recommended when the infant is at least 12 months of age, at least 8 weeks after the previous dose.
- If Hib vaccination is started when the infant or child is 7 months of age or older, fewer doses are required.
- A shortage of Hib vaccine supply in the United States in 2008 may result in deferral of the booster dose at 12–15 months. When the supply is replenished, clinicians may need to review a child’s earlier vaccination history with Hib.
Considerations for Travel by Age
- If previously unvaccinated, infants <15 months of age should receive at least two vaccine doses before travel. An interval as short as 4 weeks between these two doses is acceptable.
- Unvaccinated infants and children 15–59 months of age should receive a single dose of Hib vaccine.
- Children >59 months of age, adolescents, and adults do not need to be vaccinated unless a specific condition exists such as functional or anatomic asplenia, immunodeficiency, immunosuppression, or HIV infection.
If different brands of vaccine are administered, a total of three doses of Hib conjugate vaccine completes the primary series. After completion of the primary infant vaccination series, any of the licensed Hib conjugate vaccines may be used for the booster dose when the infant is 12–15 months of age.
A shortage of Hib vaccine supply in the United States in 2008 may result in certain children’s being underimmunized. When the supply is replenished, clinicians may need to review a child’s earlier vaccination history with Hib.
Polio Vaccine
While polio has been eliminated in the United States, poliovirus continues to circulate in parts of Africa and Asia, including South Asia. In the United States, all infants and children should receive four doses of inactivated poliovirus vaccine (IPV) at 2, 4, 6–18 months, and 4–6 years of age.
- If accelerated protection is needed, the minimum interval between doses is 4 weeks.
- The minimum age for the fourth dose is 18 weeks.
- Infants and children who had initiated the poliovirus vaccination series with one or more doses of oral poliovirus vaccine (OPV) should receive IPV to complete the series.
Rotavirus Vaccine
Rotavirus is the most common cause of severe gastroenteritis in infants and young children worldwide. In developing countries rotavirus gastroenteritis is responsible for approximately 500,000 deaths per year among children <5 years of age. Routine rotavirus vaccination beginning at 2 months of age is recommended for all U.S. infants.
Two different rotavirus vaccines, Rotateq (RV5) and Rotarix (RV1), are licensed for use in U.S. infants. RV5 is to be administered orally in a 3-dose series with doses given at ages 2, 4, and 6 months. RV1 is to be administered orally in a 2-dose series with doses given at ages 2 and 4 months (see Table 7-5). The minimum age for the first dose of rotavirus vaccine is 6 weeks; the maximum age for the first dose is 14 weeks 6 days. Vaccination should not be initiated for infants aged 15 weeks 0 days or older because of insufficient data on safety of the first dose of rotavirus vaccine in older infants. The minimum interval between doses of rotavirus vaccine is 4 weeks. All doses should be administered by age 8 months 0 days.
Measles, Mumps, and Rubella Vaccine
Measles is an endemic disease in areas where measles immunization levels are low, and outbreaks occur even in developed countries. International travelers are at increased risk for measles exposure. Infants and children should be as well protected as possible against measles and one should try to complete the immunization series before traveling. While the risk for serious disease from either mumps or rubella is low, these diseases do circulate in many parts of the world and vaccination is recommended.
Monovalent and Combination Vaccines
In addition to the measles, mumps, and rubella vaccine (MMR), monovalent measles, monovalent mumps, monovalent rubella, and combinations of the components are available from the manufacturer. A combined measles, mumps, rubella, and varicella vaccine (MMRV) is also available for children age 12 months to 12 years. ACIP recommends that MMR or MMRV be administered when any of the individual components is indicated as part of the routine immunization schedule.
Dosing
Two doses of MMR are routinely recommended for all children, usually at age 12 months and again at age 4–6 years.
- The second dose of MMR can be given as soon as 28 days after the first dose. However, if MMRV is used, note that two varicella-containing vaccines should be separated by at least 3 months.
Children age 6–11 months, if they must travel outside the United States, should receive monovalent measles vaccine before departure if it is available, or MMR if monovalent measles vaccine is not available.
- MMR given before age 12 months should not be counted as part of the two-dose series.
- Children who receive MMR before age 12 months will need two more doses of MMR—the first of which should be administered at 12 months of age.
Varicella Vaccine
Varicella (chickenpox) is an endemic disease throughout the world. Two doses of varicella vaccine are recommended for all susceptible children 12 months of age and older. The first dose is recommended at age 12–15 months. The second dose is routinely recommended at age 4–6 years but can be given earlier, provided that at least 3 months have passed since the first dose.
Efforts should be made to ensure varicella immunity before age 13 years, because varicella disease can be more severe among older children and adults. Children 13 years of age and older should receive two doses of varicella vaccine 4–8 weeks apart.
Vaccination is not necessary for children with a history of documented chickenpox. When a prior history of chickenpox is uncertain, the vaccine should be given.
Meningococcal Vaccine
Meningococcal disease, caused by the bacterium Neisseria meningitidis, has high morbidity and mortality rates. Epidemics occur in sub-Saharan Africa during the dry season (December through June) (see Map 2-6), and CDC recommends that travelers be vaccinated before traveling to this region. Meningococcal vaccination is a requirement to enter Saudi Arabia when traveling to Mecca during the annual Hajj.
Two vaccines are available in the United States that protect against four serogroups of N. meningitidis (A, C, Y, and W-135): the meningococcal conjugate vaccine (MCV4) and the meningococcal polysaccharide vaccine (MPSV4).
- MCV4 is approved for use in persons 2–55 years of age and is recommended by the ACIP for routine vaccination of adolescents at 11–18 years of age. MCV4 is also recommended for persons 2–55 years of age who travel to or reside in areas where N. meningitidis is hyperendemic or epidemic.
- MPSV4 can be used when MCV4 is not available.
- Age considerations:
- The serogroup A polysaccharide in MPSV4 induces an antibody response in some children as young as 3 months. Thus, vaccinating infants traveling to high-risk areas can provide some degree of protection.
- For children vaccinated with either MPSV4 or MCV4 at <7 years of age, revaccination with MCV4 in 3 years is recommended if they remain at high risk for infection.
- For children vaccinated with either MPSV4 or MCV4 at ≥7 years of age and older, revaccination with MCV4 is recommended in 5 years if they remain at high risk.
(This section has been updated as of October 15, 2009). Pneumococcal Vaccines
Streptococcus pneumoniae is a leading cause of illness and death worldwide. Two vaccines are available for prevention of pneumococcal disease: the pneumococcal conjugate vaccine (PCV7) is recommended for routine use in children aged ≤5 years and the pneumococcal polysaccharide vaccine (PPSV23) for children aged ≥2 years who have certain underlying medical conditions and adults.
- All infants should be vaccinated with PCV7. Infant vaccination provides the earliest protection, and children aged <2 years have high rates of pneumococcal disease. The primary series for PCV7 includes three doses given at 2, 4, and 6 months of age with a fourth (booster) dose at 12–15 months of age.
- Children 24 months of age and older who are at high risk for pneumococcal disease (e.g., those with sickle cell disease, asplenia, HIV, chronic illness, or immunocompromising conditions) should receive a dose of PPSV23 at least 2 months following their last dose of PCV7.
- A second dose of PPSV23 is recommended 5 years after the first dose of PPSV23 for persons aged >2 years who are immunocompromised, have sickle cell disease, or functional or anatomic asplenia.
Age-based considerations for children who have not been completely vaccinated:
- Use of PCV7 in children aged 24–59 months:
- For all healthy children aged 24–59 months who have not completed any recommended schedule for PCV7, administer 1 dose of PCV7.
- For all children with underlying medical conditions aged 24–59 months who have received three doses, administer one dose of PCV7.
- For all children with underlying medical conditions aged 24–59 months who have received fewer than three doses, administer two doses of PCV7 at least 8 weeks apart.
- The PCV7 vaccine is not routinely recommended for persons aged >5 years.
Influenza Vaccine
Influenza vaccine can reduce the risk of influenza infection. Influenza circulation occurring predominantly in the winter months in temperate regions (typically November–April in the Northern Hemisphere, April–September in the Southern Hemisphere), but can occur year-round in tropical climates. The vaccine is prepared in two forms: an intramuscular trivalent inactivated vaccine (TIV) approved for persons ≥6 months and a live, attenuated, intranasal vaccine (LAIV) approved for only healthy, nonpregnant persons aged 2–49 years. A history of recurrent wheezing in children 2–4 years is a contraindication to LAIV.
All children 6 months through 18 years of age should receive influenza vaccination annually, as should all children at risk for complicated influenza infection due to chronic medical conditions, including but not limited to asthma, cardiac disease, sickle cell disease, HIV, and diabetes. In addition, all persons who have close contact with healthy children <5 years old (particularly contacts of infants <6 months of age since this group is at high risk for influenza complications but is not eligible for influenza vaccination) or with other persons at increased risk of influenza complications should be vaccinated annually.
- Children receiving TIV should be administered an age-appropriate dose (0.25 mL for those 6–35 months of age and 0.5 mL for those ≥36 months of age).
- One dose of influenza vaccine per season is recommended for most people. Children <9 years of age who are receiving influenza vaccine for the first time or who received only one dose the previous season (if it was their first vaccination season) should receive two doses (separated by a 4-week interval). Only one dose per year is needed in previously vaccinated children and in previously unvaccinated children ≥9 years of age.
Hepatitis A Vaccine or Immune Globulin for Hepatitis A
Hepatitis A virus (HAV) is endemic in most parts of the world, and infants and children traveling to these areas are at increased risk for acquiring HAV infection. Although HAV is often not severe in infants and children <5 years of age, infected children may transmit the infection to older children and adults, who are at higher risk of severe disease.
Hepatitis A Vaccine
Hepatitis A vaccine is now a routine immunization of childhood in the United States. It is recommended for all children at age 1 year (i.e., 12–23 months).
- Vaccination should be ensured for all susceptible children traveling to areas where there is an intermediate or high risk of HAV infection.
- The hepatitis A vaccine is not approved for children <1 year of age.
- The HAV vaccine series consists of two doses at least 6 months apart. One dose of monovalent hepatitis A vaccine administered at any time before departure can provide adequate protection for most healthy children. The second dose is necessary for long-term protection.
Immune Globulin
Children <1 year of age who are traveling to high-risk areas can receive immune globulin (IG). For optimal protection, children who are >1 year of age, immunocompromised or have chronic medical conditions, and are planning to depart to an area in <2 weeks should receive the initial dose of vaccine along with IG (0.02 mL/kg) at a separate anatomic injection site.
- IG does not interfere with the response to yellow fever vaccine but can interfere with the response to other live injected vaccines (e.g., measles, mumps, rubella [MMR], and varicella vaccines).
- Administration of MMR should be delayed for at least 3 months and varicella for more than 5 months after administration of IG.
- IG should not be administered for 2 weeks after measles-, mumps-, rubella-, and varicella-containing vaccines. If IG is given during this time, the child should be revaccinated with the live vaccine at least 3 months after administration of IG.
- When travel plans do not allow adequate time for administration of live vaccines and IG before travel, the severity of the diseases and epidemiology of the diseases at destination points will help determine the most appropriate course of preparation.
Other Vaccines
Yellow Fever Vaccine
Yellow fever, a disease transmitted by mosquitoes, is endemic in certain areas of Africa and South America (see Maps 2-3 and 2-4). Proof of yellow fever vaccination is required for entry into some countries (see the Yellow Fever Vaccine Requirements and Recommendations, by Country, section in Chapter 2). Infants and children ≥9 months of age can be vaccinated if they travel to countries within the yellow fever-endemic zone.
Infants are at high risk for developing encephalitis from yellow fever vaccine, a live virus vaccine. Vaccination of infants should be considered on an individual basis. Although the incidence of these adverse events has not been clearly defined, 14 of 18 reported cases of postvaccination encephalitis were in infants <4 months old. One fatal case confirmed by viral isolation was in a 3-year-old child.
Travelers with infants <9 months of age should be advised against traveling to areas within the yellow fever-endemic zone.
- The ACIP recommends that yellow fever vaccine never be given to infants <6 months of age.
- Infants 6–8 months of age should be vaccinated only if they must travel to areas of ongoing epidemic yellow fever and a high level of protection against mosquito bites is not possible.
- Physicians considering vaccinating infants <9 months of age should contact the Division of Vector-Borne Infectious Diseases (970-221-6400) or the Division of Global Migration and Quarantine (404-498-1600) at CDC for advice.
Typhoid Vaccine
Typhoid fever is caused by the bacterium Salmonella enterica Typhi. Vaccination is recommended for travelers to areas where there is a recognized risk of exposure to S. ser. Typhi.
Two typhoid vaccines are available: a Vi capsular polysaccharide vaccine (ViCPS) administered intramuscularly and an oral, live, attenuated vaccine (Ty21a). Both vaccines induce a protective response in 50%–80% of recipients.
- The ViCPS vaccine can be administered to children who are at least 2 years of age, with a booster dose 2 years later if continued protection is needed.
- The Ty21a vaccine, which consists of a series of four capsules (i.e., one ingested every other day) can be administered to children ≥6 years of age. A booster series for Ty21a should be taken every 5 years if indicated.
- The capsule cannot be opened for administration but must be swallowed whole.
- All four doses should be ingested at least 1 week before potential exposure.
Japanese Encephalitis Vaccine
Japanese encephalitis (JE) virus is transmitted by mosquitoes and is endemic throughout Asia. The risk can be seasonal in temperate climates, and year-round in more tropical climates. The risk to short-term travelers and those who confine their travel to urban centers is very low. Travelers who plan to take up residence in an endemic area should be vaccinated against JE. The decision to vaccinate a child should follow the recommendations of the Japanese Encephalitis section in Chapter 2.
JE vaccine is administered as a series of three injections on days 0, 7, and 30.
- Children 1–2 years of age receive 0.5 mL of vaccine per dose; those ≥3 years of age receive 1.0 mL of vaccine per dose. No data are available on vaccine efficacy for infants <1 year of age.
- For children who remain at risk, a booster can be given after 3 years.
- JE-VAX carries a risk of hypersensitivity reactions that range from 10 to 180 cases per 100,000 vaccinees. Hypersensitivity reactions can be delayed for 1 to 2 weeks after receipt of the vaccine. Children receiving the vaccine series should be observed for 30 minutes after immunization, and the series should be completed at least 10 days before departure.
The JE vaccine (JE-VAX) currently in use is no longer manufactured. A stockpile of vaccine will be made available until supplies are depleted. A new JE vaccine (IC51, trade name Ixiaro) has been submitted to the FDA for approval, which is anticipated to occur in late 2008 or early 2009. The IC51 vaccine will not initially be approved for use in children <18 years of age. Those children who need JE vaccine will still use the remaining JE-VAX.
Rabies Vaccine
Rabies virus causes an acute viral encephalitis that is virtually 100% fatal. Traveling children may be at increased risk of rabies exposure, mainly from street dogs in developing countries. Bat bites carry a potential risk of rabies throughout the world. There are two strategies for the prevention of rabies in humans.
- Prevention of rabies encephalitis is based on avoiding bite or scratch exposures to potentially infected mammals.
- A child can have a three-shot pre-exposure immunization series, on days 0, 7, and 21 to 28. In the event of a subsequent possible rabies virus exposure, the child will require two more doses of rabies vaccine on days 0 and 3. The decision as to whether to obtain pre-exposure immunization for children should follow the recommendations in the Rabies section of Chapter 2.
For children who have not been pre-immunized and have potentially been exposed to rabies, a weight-based dose of human rabies immune globulin and a series of five rabies vaccine injections are required on days 0, 3, 7, 14, and 28.
Beginning in 2007, there has been a limitation in the supply of rabies vaccine in the United States. Pre-exposure rabies immunization is currently unavailable until the supply of rabies vaccine can be increased. The available doses of vaccine are being prioritized for people undergoing postexposure immunoprophylaxis.
