Japanese Encephalitis Vaccine
Japanese encephalitis (JE) is caused by a flavivirus transmitted by the night-biting Culex mosquito. The risk of contracting severe JE is low, especially for travelers who will have a brief stay in an endemic area, as the infection rate in Culex mosquitoes is 3% or lower, and only 1 in 200 infections with JE leads to neuroinvasive disease. The symptoms of JE include seizures, paralysis, coma, and mental status changes; residual neurological damage occurs in 50% of those with clinical disease (see Chapter 40). The case fatality rate is 30% in those with severe disease. Most symptomatic cases occur in children younger than 10 years and in the elderly. The areas at risk include most of Asia, Eastern Russia, some areas of the Western Pacific, and the Torres Strait Islands of Australia. The peak season is between April and October, during and just after the rainy season. The JE vaccine licensed and available for use in the United States is Ixiaro, an inactivated Vero cell culture-derived vaccine. It was approved in May 2013 for use in children aged 2 months of age and older. The primary series is two doses administered 28 days apart. Each dose is 0.5 mL for adults and children aged 3 years and older, and 0.25 mL for children aged 2 months to 2 years. The JE vaccine is recommended for travelers who plan to spend at least 1 month in endemic areas during the JE transmission season. Vaccine should also be considered in the following scenarios: 1) short-term travelers to non-urban areas who will participate in outdoor activities; 2) travelers to an area with an ongoing JE outbreak; 3) travelers to endemic areas who are uncertain of specific destinations, activities, or duration of travel.
Rabies is found worldwide and contracted through the bite or saliva-contaminated scratch of infected animals. Canine rabies is highly endemic in parts of Africa, Asia, and Central and South America (Rabnet—www.who.int/rabies/rabnet/en/—provides country-specific animal and human data), where 40% of rabies occurs in children younger than 14 years. This increased risk is because children are attracted to animals, are more likely to be bitten, and may not report minor encounters with animals. Most cases of rabies in travelers occur through the bite of an infected dog, cat, or monkey (particularly those that live near temples in parts of Asia). Bats, mongooses, and foxes are other animals that can transmit disease.
Rabies vaccine is available for pre-exposure and postexposure prophylaxis. It is recommended for travelers to areas in which rabies is endemic and for those who will have occupational or recreational exposure (such as cavers), especially if access to medical care will be limited when traveling. The risk of a bite from a potentially rabid animal is up to 2% for travelers to the developing world. The three types of inactivated virus vaccine available are administered prior to exposure in three doses at days 0, 7, and 21 or 28. Vaccination prior to exposure may not be completely protective; further doses are required if a high-risk bite occurs. The minimum age of administration is 1 year, and duration of protection is 2 years. Malaria chemoprophylaxis with mefloquine or chloroquine should begin 1 month after completing the rabies vaccine series to avoid interference with the immune response.
It is important to counsel travelers about animal avoidance, thorough cleansing of a bite wound with irrigation for at least 5 minutes, and the need for previously vaccinated individuals to seek additional vaccination on days 0 and 3 if an exposure occurs. In the event of a bite in a nonvaccinated individual, rabies immunoglobulin and four doses of vaccine at days 0, 3, 7, and 14 are required, ideally within 24–48 hours after contact. In a fully vaccinated child exposed to rabies, two booster doses should be given on days 0 and 3 of exposure, and rabies immunoglobulin is not required.
Yellow fever is a flavivirus transmitted by mosquitoes, found in urban and rural areas in sub-Saharan Africa and equatorial South America. Of those infected with the virus, 15% have moderate to severe infection. The licensed 17D strain live attenuated vaccine is highly effective. It must be administered 10 days before travel to an endemic region to allow for the development of protective antibodies. It is required by many countries for reentry after travel to an endemic area, and receipt of the vaccine should be documented in the International Certificate of Vaccination that became available in December 2007 (wwwnc.cdc.gov/travel/yellowbook provides an updated list of countries in which yellow fever vaccination is recommended). For this reason, it is only administered at certified clinics. The vaccine is given subcutaneously, and a single dose confers lifelong immunity. As of July 1, 2016, a completed International Certificate of Vaccination or Prophylaxis is valid for the entire lifetime of the vaccine and countries cannot require proof of revaccination as a condition of entry, even if the last vaccination was more than 10 years prior. The recommended minimum age of administration is 9 months, and vaccine should not be administered to at-risk infants younger than 6 months, because of the increased risk of encephalitis (0.5–4 per 1000 vaccines). The risk of severe vaccine-related disease is also higher in adult caretakers older than 60 years. The decision to immunize infants who are 6–8 months of age must balance the infant’s risk for exposure with the risk for vaccine-associated encephalitis. The vaccine is contraindicated in individuals with egg allergy or immunosuppression (including HIV with CD4 T-lymphocyte counts less than 200 cells/mm3) or a history of thymus disorder or thymectomy). A letter of medical exemption may be required for these travelers. In addition to age limitations, precautions to vaccination include asymptomatic HIV infection and CD4 T-lymphocyte count of 200–499 cells/mm3, pregnancy, and breast-feeding. Adverse effects include encephalitis (15 per million doses for those aged > 60 years) and multisystem disease (5 per million doses in older people).
Cholera is an acute, watery diarrheal illness caused by Vibrio cholerae (O1 or O139 serogroups). Global pandemics continue to occur in developing countries. In 2016, the oral cholera vaccine was recommended for travelers ≥18 years of age to cholera-affected areas. The only cholera vaccine available in the United States is the CVD 103-HgR, (Vaxchora), which is a live vaccine against serogroup O1. The vaccine is not indicated for use in children.
The risk of typhoid fever in travelers is 1–10:100,000, depending on the destination. Areas at risk include South Asia, West and North Africa, South America, and Latin America. Travelers to the Indian subcontinent are at greatest risk.
The vaccine is recommended for long-term travelers traveling to an endemic area, those traveling off standard tourist routes, immunocompromised travelers, those of south Indian ancestry, and patients with cholelithiasis. There are two vaccines available: a capsular polysaccharide (ViCPS) and a live attenuated (Ty21a) vaccine. The ViCPS is given intramuscularly 2 weeks prior to travel. The minimum age of administration for this vaccine is 2 years; efficacy is 75% over 2 years. Fever, headache, and severe local pain and swelling are reported with the ViCPS more frequently than with other vaccines. The Ty21a is an oral vaccine in capsule form given every other day for four doses. The schedule needs to be completed more than 1 week prior to travel to be effective. The capsules should be refrigerated but not frozen, and should not be taken with liquids warmer than 37°C. It is licensed for children older than 6 years; efficacy is 80% over 5 years. It is contraindicated in immunodeficient populations. Doses should be delayed for more than 72 hours after receipt of antibiotics, as they interfere with growth of the vaccine strain bacteria. Mefloquine, chloroquine, and prophylactic doses of atovaquone-proguanil can be given concurrently with the typhoid vaccine.
Tuberculosis risk is increased for travelers, especially when visiting Africa, Asia, Latin America, and the former Soviet Union. The risk is higher in long-term travelers to countries with a high incidence of tuberculosis and is highest among health care workers. Bacillus Calmette-Guérin (BCG) vaccination is given soon after birth in many countries, but not in the United States. It protects against miliary and meningeal tuberculosis, but not against pulmonary disease, with efficacy only established in children younger than 1 year. It may be considered in children younger than 5 years who will be in a high-risk area for a prolonged period and have a negative test for tuberculosis (tuberculin skin test [TST] or interferon-gamma release assay [IGRA]). It should not be given to immunosuppressed individuals. BCG is not widely available in the United States, but may be administered in the destination country. A preferred alternative is that travelers to high-prevalence areas have a test for tuberculosis prior to travel and 3 months after return. It should be noted that live virus vaccines can create an anergic state, in which tuberculosis testing can be falsely negative. Therefore, testing should be performed on the same day as any live vaccine administration, or at least 28 days later.
J: Cholera. Lancet 2017 Mar 10; 6736(17)30559-7
M: Rabies: prelevance, prevention, and management in travel medicine. Infect Dis Clin North Am 2012 Sep;26(3):739–753
et al: The practice of travel medicine: guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2006 Dec 15;43(12):1499–1539
et al: Vaccine administration decision making: the case of yellow fever vaccine. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. Clin Infect Dis 2012 Sep;55(6):837–843