Yellow Fever Vaccine

Yellow fever (YF) is a viral infection transmitted by mosquitoes in equatorial South America and Africa (Figure 84-1, online). The YF vaccine is a live attenuated viral vaccine that is highly protective.^112,188 The YF vaccine is given as a single dose for primary immunization; the booster interval is 10 years. Because of age-related risk of encephalitis after immunization, most authorities agree that the YF vaccine is contraindicated in infants less than 6 months of age, and immunization should usually be delayed until the infant is 9 months of age or older.⁴² The vaccine is generally not recommended for persons who are immunocompromised or during pregnancy. If the pregnant traveler cannot avoid or postpone travel to a highly endemic area, then risk of the disease should be greater than the theoretical risk of adverse effects from the vaccine.

FIGURE 84-1 A, Yellow fever endemic zones in Africa. B, Yellow fever endemic zones in the Americas.

(From CDC Health Information for International Travel, 2009. http://wwwnc.cdc.gov/travel/yellowbook/2010/chapter-2/yellow-fever.aspx.)

The vaccine virus is cultured in eggs and is contraindicated in persons with a history of an anaphylactic reaction to eggs. If a person can eat eggs without a reaction, they can receive the YF vaccine.

Vaccine-associated viscerotropic disease has been reported in a small number of first-time recipients of the YF vaccine.³¹ Many of the subjects died with fulminant multiorgan failure. Altered thymic function or thymectomy was documented in 4 of 23 cases, and the syndrome may occur more frequently in persons older than age 60 years; however, the small number of cases makes accurate risk factor assessment impossible.¹³ The disease is felt to be an infection by the attenuated vaccine strain facilitated by an altered host response rather than a change in virulence of the vaccine strain. Persons who have successfully received a first dose of YF vaccine are unlikely to be at risk with a booster dose if they have remained immunocompetent hosts.

Although YF vaccine-associated viscerotropic disease is rare (approximately one event per 250,000 to 350,000 doses), the potentially deadly outcome prompts careful risk assessment, especially when considering first-time vaccination in elder travelers. Some countries may be listed as endemic for YF, but certain locations within the country may pose no risk. If a person for whom the vaccine is contraindicated (or ill-advised because the person is not truly at risk) must travel to a country where yellow fever vaccine is required for entry, then according to WHO regulations a signed statement indicating that the YF vaccine could not be given because of medical contraindications should be acceptable in lieu of documented vaccination. The statement should be written, if feasible, on letterhead stationery and accompanied by authoritative stamps or seals. Contacting the embassy or consulate of the country may be necessary to help guarantee that the letter of waiver will be accepted.

Cholera Vaccine

The injectable cholera vaccine is not highly efficacious, even when the primary series of two doses given a week or more apart is received.¹⁴² The WHO no longer endorses a requirement for this vaccine for entry into any country. For countries that might still require cholera vaccination for travelers arriving from cholera-endemic areas, recording a single cholera dose in the traveler’s International Certificate of Vaccination should suffice to meet this requirement.

Travelers going to areas endemic or epidemic for cholera are encouraged to follow food and water precautions gauged to prevent all forms of travel-associated diarrhea. Oral killed and live-attenuated vaccines¹³³ are available in some countries, but at present, there are no standardized recommendations for use of cholera vaccines, although health care workers and relief workers going to outbreak areas might be suitable candidates. Likewise, travelers to cholera-endemic areas, who are achlorhydric or have had a partial gastric resection, are logical candidates for cholera vaccine.

Smallpox Vaccine

The requirement for smallpox vaccine for international travel was removed from the WHO regulations in 1982. The CDC has embarked on an initiative to immunize health care providers, first responders, and others involved in bioterrorism preparedness, but the vaccine is not otherwise available and travel is not considered a sufficient reason for vaccination.¹⁰⁹

Hepatitis A Vaccine

Hepatitis A virus (HAV) infection is the most common vaccine-preventable disease in international travelers to the developing world.^165,187 In the absence of vaccination, HAV infection occurs in 1 to 10 persons per 1000 travelers at risk during 2 to 3 weeks of travel. Risk is high even among those residing in “first class” accommodations. Adventure travelers who venture off usual tourist routes may be at increased risk compared with other groups of travelers. Although HAV infection is asymptomatic in young children and self-limited in most adults, it causes greater than 2% mortality in infected adults older than age 40 years, considerable morbidity during travel, and lost productivity after travel. Vaccination against HAV should be considered for all travelers to regions where sanitation and hygiene are poor.

Individuals with a history of jaundice, who were born prior to the 1950s, or who were born or resided for lengthy periods in endemic regions are likely to have natural immunity to HAV.¹⁷³ They should be screened for IgG antibodies against HAV, because if these are present, it is possible to avoid the cost of vaccination, which is usually more expensive than serologic testing. However, because vaccination of HAV-immune persons is not associated with adverse consequences, a traveler who does not have time prior to departure to receive the testing results should be vaccinated.

A single dose of monovalent hepatitis A vaccine affords adequate protection by 7 to 10 days following vaccination.^47,178 Amelioration of HAV clinical infection occurs if serum immune globulin is administered up to 14 days after exposure to HAV. HAV challenge experiments in a simian model and indirect evidence in humans suggest that immunization with monovalent vaccine immediately prior to travel obviates the need for serum immune globulin.^47,165 Some authorities continue to advocate a dose of serum immune globulin if HAV vaccination cannot be given sooner than 2 weeks before travel. Others feel ISG is seldom indicated except in immunocompromised persons who might not respond to the hepatitis A vaccine.⁴⁷

HAV vaccine products are thought to be interchangeable. After two full doses separated by 6 to 12 months, protection is likely life long, so booster doses are not recommended in immunocompetent travelers.¹⁷⁸ Travelers who fail to receive their second dose of HAV vaccine within 6 to 12 months should simply receive one full dose of monovalent vaccine with the anticipation of life-long immunity. Protective antibody levels have been produced even when second doses were given 8 years after the first dose.⁸⁶

Hepatitis B Vaccine

Hepatitis B vaccine was added to the list of vaccines recommended for routine immunization of children in the United States in 1991, and consideration should be given to vaccinating all U.S. adults regardless of travel. Risk to short-term travelers is low; however, travelers should be vaccinated when they might have contact with body fluids or blood (e.g., through sex or medical work), when they anticipate receiving medical care in a developing country or when they are frequent short-term travelers. Long-term travelers and expatriates should be vaccinated.⁸⁵

Two recombinant vaccines are available and are thought to be interchangeable. The standard regimen for both vaccines is doses at 0, 1, and 6 months. One of them, Engerix-B, is FDA approved for an accelerated dosage schedule of 0, 1, and 2 months with a booster dose at 12 months for long-lasting protection. Although a highly accelerated 3-week schedule is not approved, literature supports dosing at 0, 7, and 21 days with a 12-month booster.^25,103 This regimen affords 65% protection at the end of 1 month and is an attractive option for at-risk travelers who plan to depart in the next 3 to 4 weeks.

A combined hepatitis A and hepatitis B vaccine is now available and is dosed at 0, 1, and 6 months. Because a smaller dose of HAV antigen is used in this preparation, travelers must receive their second dose prior to travel for reliable protection. Literature also supports a highly accelerated 3-week dosing regimen with a 12-month booster.¹²¹

After any of the HBV vaccination regimens, additional boosters are not recommended for normal hosts. A protective amnestic response after exposure to wild-type virus can be expected even after serum concentrations of antibody have fallen to undetectable levels. An interrupted hepatitis A or B vaccine series can be completed without restarting.

Typhoid Fever Vaccine

The incidence of typhoid fever among American travelers is relatively low (1 to 10 cases per 100,000 travelers, in contrast to >100 cases per 100,000 native population in certain parts of the Indian subcontinent¹³⁰); but among reported cases in the United States, the majority were acquired during international travel.^99,111 Risk is highest among visitors to the Indian subcontinent and particularly high among those visiting friends and relatives. Visitors to Central and South America, Africa, and Asia should be considered for typhoid vaccination when they might be exposed to conditions of poor sanitation and hygiene, even for short periods of time.^48,169

Increasing antibiotic resistance among Salmonella enterica serotype Typhi is another reason to be vaccinated.^1,16 However, the current vaccines afford only 50% to 70% protection, and emergence of S. enterica serotype Paratyphi, against which protection is not afforded by the current vaccines, underscores the importance of hygienic food and beverage choices among travelers.⁶¹

Two vaccines are currently available and offer a similar degree of protection. The parenteral purified Vi polysaccharide typhoid vaccine is administered as a single injection with a booster recommended every 2 years. The oral Ty21a typhoid vaccine uses a live-attenuated strain of S. enterica serotype Typhi. One capsule is taken every other day for four doses (three doses in Europe).¹⁹ A booster regimen is recommended every 5 years.

Meningococcal Vaccine

Vaccine protection against meningococcal meningitis is recommended for long-term travelers to the sub-Saharan “meningitis belt” (Figure 84-2, online).^7,38,138 Short-term travelers to this region should receive vaccine if they will travel during the dry season (December to June) or have extensive contact with local people. Meningococcal vaccine is required for travel to Saudi Arabia during the time of the annual Hajj and Umrah religious pilgrimages. Regardless of travel, the classic recommendation has been that young adults who will live in school dormitories, those with complement deficiencies, those who will have prolonged contact with a local population such as in a refugee camp, and persons with surgical or functional asplenia should be vaccinated. Travelers to regions where outbreaks are occurring should be vaccinated. Practitioners who do not subscribe to commercial information services that are routinely updated should check the CDC website (http://www.cdc.gov/travel) periodically to determine where epidemic disease is occurring.

FIGURE 84-2 Meningitis belt. Consult details in the CDC Yellow Book for locations within each country where, and seasons when, pretravel vaccination is recommended.

(From CDC Health Information for International Travel, 2009. http://wwwnc.cdc.gov/travel/yellowbook/2010/chapter-2/meningococcal-disease.aspx.)

The quadrivalent meningococcal polysaccharide vaccine induces immunity against serogroups A, C, Y, and W-135. A single dose appears to provide immunity for 5 years. A single-dose quadrivalent meningococcal polysaccharide-protein conjugate vaccine is the preferred vaccine for age group >2 years, with a booster recommended every 5 years⁴⁵ for ongoing risk. However, neither vaccine provides immunity against serogroup B.

Travelers who had previously been vaccinated with polysaccharide vaccine and need revaccination should receive conjugate vaccine.

Japanese Encephalitis Virus Vaccine

Japanese encephalitis ( JE) is a mosquito-transmitted viral infection prevalent in Asia and Southeast Asia. Transmission is year round in tropical and subtropical areas and during the late spring, summer, and early fall in temperate climates. JE virus is not considered a risk for short-term travelers visiting the usual tourist destinations in urban and developed resort areas.²⁸

Risk of infection can be greatly decreased by personal protective measures that prevent mosquito bites. For visitors to rural areas during the transmission season, the estimated risk for JE during a 1-month period is 1 : 5000, so vaccination should probably be offered to both long- and short-term visitors to rural areas during transmission season, particularly when mosquito exposure might be intense and rice and pig farming occurs nearby.

The standard schedule for the inactivated viral vaccine (mouse brain preparation) has been doses injected at 0, 7, and 30 days. An accelerated schedule of doses at 0, 7, and 14 days results in a lower rate of seroconversion. When risk of exposure continues, a booster dose of vaccine may be given every 2 to 3 years.

Adverse reactions to the mouse brain preparation of JE vaccine include local pain and swelling at the injection site in about 20% of recipients, systemic symptoms (fever, headache, malaise, rash) in about 10%, and hypersensitivity reactions at a rate of 0.1 to 5 per 1000 administrations.²³ The hypersensitivity reactions can rarely be fatal and may occur immediately or with delays of up to 2 weeks. Limited data suggest that persons who have had urticarial reactions to hymenopteran envenomation and to other stimuli might be at greater risk of JE vaccine–induced hypersensitivity reactions. JE vaccine recipients should be directly observed for 30 minutes after injection and should not travel until 10 days after their last dose because of the risk of delayed adverse reactions. A recently approved non–mouse brain vaccine appears considerably safer and as effective as the older vaccine⁵⁰ This new vaccine requires only 2 doses, but in the United States is restricted to adults older than age 17 years.

Rabies Vaccine (see Chapter 60)

Although rabies is endemic in much of the world, the risk of rabies for most travelers is very low.¹⁸⁵ Avoidance of dog bites eliminates much of the risk.²⁹ Other animal species important to the transmission of rabies to travelers include monkeys, mongooses, bats, and foxes. Preexposure rabies immunization should be considered for rural travelers, particularly adventure travelers who go to remote areas, persons with occupational (veterinarians) or recreational (spelunkers) exposure, and for expatriate workers, missionaries, and their families living in countries in which rabies is a recognized risk. Children should be targeted for preexposure vaccination in high-risk regions, because they may not tell their parents when they have been bitten or exposed to the rabies virus.

Any of the three tissue culture–derived inactivated virus rabies vaccines can be administered intramuscularly in the deltoid (not gluteal) muscle in a preexposure schedule of 0, 7, and 21 or 28 days.²⁹ For persons who continue to be at risk of exposure, a booster can be given every two years, or less frequently based on annual serology testing. In the event of an exposure, the vaccinated traveler must understand how to clean the wound thoroughly and immediately seek two additional doses of vaccine. Preexposure vaccination obviates the need for postexposure administration of rabies immune globulin (RIG), which is an important consideration because RIG may be very difficult to obtain.^92,131 Persons who are exposed without having had preexposure rabies vaccination require both RIG and a four-dose course of rabies vaccine given over 14 days, instead of 5 doses over 28 days, as recently recommended by the U.S. Advisory Committee on Immunization Practice.³ Persons with immunosuppression should still receive the five doses of the vaccine.⁷ Intradermal (ID) administration results in slightly lower and shorter-lasting protection, so it is not routinely recommended. Also, chloroquine impairs the immune response, so an ID-administered preexposure series should be completed well before chloroquine prophylaxis begins. Cell culture rabies vaccine available outside the United States, unlike neural tissue vaccines that have serious side effects, are acceptable alternatives.¹⁵³

Mild local reactions to rabies vaccine occur in about 20% of vaccinations and are self-limited over 1 to 3 days. Up to 10% of recipients may develop mild fever, myalgia, headache, dizziness, or gastrointestinal upset. Much less commonly, allergic reactions characterized by urticaria, angioedema and respiratory symptoms can develop with serum sickness-like syndrome possible after doses of human diploid cell–derived vaccine. Sudden death and encephalomyelitis are rare.