Immunizations for Travelers

Hepatitis A Vaccine as a Routine Immunization

Hepatitis A is the most common vaccine-preventable disease associated with travel and should be a high priority for those over the age of 1 year who have not previously received it or had the natural disease. In 1999, the ACIP recommended that hepatitis A vaccine be administered to all 2-year-olds living in 11 Western states in the United States, where heightened transmission of hepatitis A virus infections was occurring. In 2006, the ACIP issued a new recommendation for hepatitis A immunization of all children at 1 year of age. Thus, hepatitis A vaccine is now a standard immunization for children but should be considered a travel vaccine for older children and adults.

Hepatitis B Vaccine as a Routine Immunization

Hepatitis B vaccine was incorporated into the recommended childhood immunization schedule in 1990. Adults born before 1990 may require the full three-dose hepatitis B vaccine primary series as a catch-up vaccine for protection against inadvertent exposures associated with travel.

Influenza Vaccine

Annual immunization against viral influenza is recommended by the ACIP for all persons 6 months of age or older who do not have medical contraindications to the vaccine. The influenza viruses undergo minor mutations of surface antigens from season to season in a process termed “antigenic drift”; thus the influenza vaccine is re-formulated each year in between flu seasons, according to WHO guidelines, to provide protection against strains of the influenza virus predicted to be in circulation during the season ahead. The newly formulated influenza vaccines are usually released in the early fall.

Both inactivated influenza vaccine (IIV) and live attenuated influenza vaccine (LAIV) products are available. The inactivated influenza vaccines are given by intramuscular (IM) or intradermal (ID) injection. The LAIV is approved for use in persons 2-49 years old and is administered by intranasal application. Both IIV and LAIV are effective in adults. If the flu season has already started in the community, susceptible persons should be immunized with either flu vaccine type that is immediately available. (See Chapter 12 for details on pediatric recommendations.) An IIV administered by ID injection is approved for use in persons 18-64 years. The elderly >65 years old may have a decreased response to IIV; a high-dose IIV formulated for this age group should be used.

Despite the recommendation for universal immunization against viral influenza, flu vaccine coverage rates in the general population remain suboptimal. Flu vaccine should be recommended to all international travelers because prolonged air travel, fatigue, and exposure to crowds in various closed environments may predispose them to air-borne infections. The CDC identified a particular risk for viral influenza infections among travelers during the summer sailing season of Alaska cruise ship tours. The risk is thought to be associated with exposure of susceptible travelers to influenza-infected persons among the other travelers and tourist industry staff, particularly those from the Southern Hemisphere where the seasonal climate patterns are opposite to those in the Northern Hemisphere.

If flu vaccine is unavailable for travelers during their travel season, the inclusion in the traveler's medical kit of one of the antiviral drugs active against influenza virus, either oseltamivir (Tamiflu ^® , chemoprophylaxis or early treatment) or zanamivir (Relenza ^® , early treatment), should be discussed with the travelers who will be at potential risk.

Pneumococcal Vaccine

Immunization of adults ≥65 years of age against invasive pneumococcal disease is routinely recommended by the ACIP. The current recommendation is for the 13-valent pneumococcal conjugate vaccine (PCV13) to be given first in a series, with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) administered 6-12 months after. However, since this recommendation is relatively recent (2014), the following regimens are also acceptable: if PPSV23 was received first, administer PCV13 after an interval of at least 1 year or more; if the first dose of PPSV23 was received prior to 65 years of age, give the first dose of PCV13 at ≥65 years of age (at least 1 year after the first PPSV23), and then give a second dose of PPSV23 at 6-12 months after the PCV13.

Yellow Fever Vaccine

Yellow fever is a viral infection transmitted by Aedes aegypti mosquitoes in equatorial South America and Africa. The endemic zones are shown in Figure 5.1 . Immunization is required for entry into some countries within the endemic zones or may be recommended to travelers going to rural tropical areas within the endemic zones or to both rural and urban areas during yellow fever outbreaks.

Yellow Fever (YF) Vaccine

YF vaccine is a live attenuated viral vaccine prepared from the 17D strain of YF virus (YF Vax™, Sanofi). The WHO controls the production of YF vaccine, sets requirements, and approves certain laboratories for its manufacture. The vaccine leads to seroconversion rates of 95% or higher, a protection rate of over 99% in immunocompetent recipients, and a duration of immunity after one dose, which appears to be lifelong. The YF vaccine is given as a single dose for primary immunization, and the recommended booster interval is 10 years ( Table 5.3 ).

YF Vaccine Booster Doses

In 2015, the ACIP recommended that routine booster doses of YF vaccine are not necessary for travelers to endemic areas because of studies showing that the primary YF vaccination elicits sustained immunity and probable lifelong protection in healthy recipients. The ACIP recommendation is in agreement with an earlier 2013 recommendation from the WHO Strategic Advisory Group of Experts on Immunization. However, since the 10-year booster dose requirement is scheduled to be removed from WHO IHR by June 2016, in the interim some travelers may find that a YF vaccine booster is still necessary for entry into certain countries. Travelers and travel health advisors can find updated country-by-country YF vaccine requirements at the WHO and CDC websites.

YF Vaccine Precautions and Contraindications

The vaccine virus is cultured in eggs and is not recommended for persons with a history of severe allergy (anaphylaxis) to eggs. A review of reports submitted to the US Vaccine Adverse Events Reporting System from 1990 through 1997 found a rate of 1/131,000 for anaphylaxis after immunization with yellow fever vaccine. The package insert contains instructions for skin-testing persons with an uncertain history of allergy to eggs. YF vaccine is contraindicated in infants <6 months of age because of the significant but rare risk of vaccine-associated neurotropic disease in such young infants after immunization (estimated rate 1 per 8 million doses). If possible, YF immunization should be delayed until the infant is ≥9 months of age ( Chapter 12 ). YF vaccine is generally not recommended during pregnancy except when travel to a highly endemic area cannot be avoided or postponed by the pregnant traveler, and the risk of the actual disease is thought to be greater than the theoretical risk of adverse effects from the vaccine.

Additional contraindications to receiving the YF vaccine include immune suppression caused by underlying disease (e.g., malignancy, HIV infection, congenital immune deficiency) or by medical therapy (e.g., treatment with daily corticosteroids, cancer chemotherapy, radiation therapy, organ transplant therapy). Most travel experts would consider administering YF vaccine to travelers at risk if the CD4 cell count is > 400 µL in an HIV-infected person or if the corticosteroid dosage is < 20 mg prednisone/day.

YF Vaccine-Associated Viscerotropic Disease (YEL-AVD)

YEL-AVD is likely related to the transient viremia that normally occurs after receipt of this live attenuated virus vaccine. In cases reported to the WHO and CDC, YEL-AVD occurred 2-5 days after receiving YF vaccine and is a febrile illness leading to multiple organ system failure as manifested by fever, myalgia, arthralgia, hepatitis, thrombocytopenia, disseminated intravascular coagulation, lymphopenia, rhabdomyolysis, hypotension, and oliguria. Review of the reported cases shows that the risk of YEL-AVD is very rare (13 cases reported per >100 million vaccine doses) and that the risk involved first-time vaccine recipients. The risk increases with age, with a rate of 3.5/100,000 vaccine recipients reported for persons 65-74 years of age, and an almost three-fold increase in rate to 9.1/100,000 among vaccine recipients aged >75 years old. Thus, careful review of the proposed itinerary with regard to risks and benefits of YF vaccine is particularly important in advising senior travelers. However, the protection offered by the vaccine probably outweighs the risks in those who are traveling to regions endemic for yellow fever, regardless of age.

YF Vaccine Letter of Waiver

If a person for whom the vaccine is contraindicated must travel to a country where yellow fever vaccine is required for entry, a signed statement on letterhead stationery that states that the yellow fever vaccine could not be administered to the traveler because of medical contraindications will be accepted in lieu of the vaccination statement, according to WHO regulations. Alternately, the medical provider can complete the “Medical Contraindication to Vaccination” section of the International Certificate of Vaccination or Prophylaxis.

Meningococcal ACWY Vaccines

Due to outbreaks of meningococcal disease among Hajj pilgrims with secondary spread of meningococcal infections to family and friends after the pilgrims returned home, in 2003 Saudi Arabia implemented a requirement for meningococcal vaccine for all persons seeking to travel in Saudi Arabia during the annual Hajj. Either the quadrivalent meningococcal vaccine containing capsular polysaccharides from Neisseria meningitidis serogroups A, C, W, Y (MCPSV4) or one of the quadrivalent meningococcal conjugate vaccines containing the same capsular polysaccharides conjugated to a protein carrier (MCV4/MenACWY-D or MenACWY-CRM) will meet the requirement. In some countries, bivalent meningococcal polysaccharide or conjugate vaccines eliciting immunity against serogroups A and C may be commonly available; however, the A/C vaccine does not protect travelers in outbreaks involving serogroup Y or W-135 disease, such as has been the case in some of the Hajj outbreaks ( Fig. 5.2 ). Meningococcal vaccine is also recommended for travelers going to live and work in certain areas of Africa (sub-Saharan), South America (Brazil), or other parts of the world where meningococcal disease is hyperendemic or epidemic among the residents.

The ACIP recommends routine immunization against meningococcal disease with ACWY quadrivalent vaccine for young people 11-18 years old and for incoming college freshmen who will live in large residence halls on campus (some institutions require immunization for matriculation because of the increased risk of meningococcal transmission in such student populations). Meningococcal vaccination is also recommended for persons at increased risk of disease, such as microbiologists who may be routinely exposed to strains of N. meningitidis , military recruits, persons with complement component deficiencies, and persons with anatomic or functional asplenia. Meningococcal B vaccine is discussed under “Recommended Travel Vaccines” below.

The meningococcal conjugate vaccines promote eradication of the nasopharyngeal carrier state due to the high levels of mucosal antibodies elicited, and there is a strong antibody response to subsequent booster doses of the vaccine. Use of a meningococcal conjugate vaccine is preferred for those persons who need imminent as well as possible future protection against meningococcal disease because immunity can be effectively boosted by additional conjugate vaccine doses, although the meningococcal polysaccharide vaccine is sufficiently protective for use in travelers and others anticipating limited exposure to meningococcal disease.

The duration of immunity following immunization with a conjugate vaccine is estimated to be 7 years, although no formal booster interval has been recommended at this time. Persons who received the MPSV4 vaccine in the past and who remain at risk of exposure to meningococcal disease may be boosted with a conjugate vaccine.

Meningococcal ACWY-Diphtheria Toxin Protein Conjugate (MenACWY-D) Vaccine

MenACWY-D vaccine (Menactra ^® , Sanofi) is a quadrivalent vaccine derived from serogroups A/C/W-135/Y capsular polysaccharides conjugated to diphtheria toxin protein, which enables enhanced immunogenicity through activation of a strong T-cell immune response in vaccine recipients. The vaccine is licensed for use among persons 9 months through 55 years of age and given as a single dose administered by IM injection.

Meningococcal ACWY-CRM Conjugate (MenACWY-CRM) Vaccine

MenACWY-CRM vaccine (Menveo ^® , Novartis) is a quadrivalent vaccine derived from serogroups A/C/W-135/Y capsular polysaccharides conjugated to diphtheria toxin mutant CRM197. The vaccine is licensed for use among persons 2 months through 55 years of age and given as a single dose administered by IM injection.

Meningococcal Polysaccharide A/C/Y/W-135 Vaccine (MPSV4)

MPSV4 vaccine (Menimmune ^® , Sanofi) is a quadrivalent capsular polysaccharide vaccine inducing immunity against serogroups A/C/Y/W-135. A single dose administered by subcutaneous (SC) injection provides immunity for approximately 3-5 years among healthy recipients, although vaccine efficacy is variable in young children. A second dose of vaccine after 2 or 3 years is recommended for children living in high-risk areas who received the first vaccine dose at <4 years of age.

Polio Vaccine

Polio vaccine is given as part of the routine immunization series to infants and children in the United States. A four-dose series of inactivated poliovirus vaccine (IPV) administered by IM or SC injection is given at 2, 4, and 6-18 months of age, and at 4-6 years old ( Chapter 12 ). IPV (Ipol ^® , Sanofi) is the only polio vaccine used in the United States since 2000, when a policy decision to discontinue the use of oral polio vaccine was made in order to avoid the rare occurrence of vaccine-associated paralytic poliomyelitis from the attenuated live virus vaccine. Oral polio vaccine is still in use in countries outside the United States.

A single lifetime IPV booster dose is recommended for adult travelers 18 years and older who are traveling to countries with recognized circulation of WPV or to countries that border countries that have areas with WPV in circulation. WPV circulation has been reported in Afghanistan, Pakistan, Middle Eastern countries, Egypt, Nigeria, and other countries located in a belt across sub-Saharan Africa. Outbound long-term (≥4 weeks) travelers and residents of WPV-affected countries may be required to show proof of polio vaccination between 4 weeks and 12 months before departure under WHO IHR in order to prevent importation of polio into polio-free countries by infected travelers. The CDC regularly updates its website regarding which countries have ongoing transmission of polio and which countries may require proof of polio vaccination from exiting travelers.

Cholera Vaccine

There is no WHO regulation requiring cholera vaccine for entry into any country. Currently available cholera vaccines are discussed under “Recommended Travel Vaccines” below.