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Protection of Travelers
Pretravel management of an international traveler should be based on risk management principles. Prevention strategies and medical interventions need to be individualized according to both the itinerary and factors that are dependent on the traveler. A structured approach to patient interaction ( Table 318.1 ) is the most efficient way to cover the necessary educational and preventive interventions. Because many of these measures will not be initiated until much later at the traveler's destination, clearly printed instructions in lay language are advisable. The worldwide epidemiology of travel-related diseases is constantly changing. A body of knowledge in travel medicine has been published, and online and print resources ( Table 318.2 ) should be consulted frequently to keep current.
TABLE 318.1
Structured Approach to Pretravel Office Visit With a Traveler to the Developing World a
| Perform Risk Assessment |
The following must always be ascertained to determine appropriate preventive medical recommendations. Preprinted medical record forms may be used to record these.
|
| Administer Immunizations |
|
| Provide Malaria Prevention (if Indicated) |
|
| Educate on Traveler's Diarrhea |
|
| Vector-Borne Diseases |
|
| Teach Essential Preventive Behaviors |
|
| Discuss Other Applicable Health Issues |
|
TABLE 318.2
In-Depth Information Resources for Travel Medicine
| Authoritative Websites Updated Constantly With Epidemiologic and Outbreak Information |
|
| In-Depth References on Specialized Topics |
|
Epidemiology of Travel-Related Illness
In 2015 international tourist arrivals in all countries exceeded 1.2 billion people. In 2014 the total number of arrivals in countries with emerging markets nearly surpassed the number in developed countries. Depending on the destination, 6% to 87% of travelers become ill across all studies. Of four studies that provide the best estimate, 43% to 79% of travelers who frequently visited developing nations (e.g., India, Tanzania, and Kenya) became ill; most of these illnesses were mild and self-limited such as diarrhea, respiratory infections, and skin disorders. Some travelers return to their own countries with preventable life-threatening infections. Yet 20% to 80% of travelers do not seek pretravel health consultation. Data about the effect of pretravel advice are limited, although such advice has had a positive effect on the prevention of malaria. Travelers visiting friends and relatives in their country of origin constitute the group with the highest morbidity, especially from malaria and typhoid; this group requires special approaches to illness prevention and education. Rates are significantly higher in summer. Approximately 8% of travelers consult a physician either during or after a trip, but less than 1% require hospitalization. Infectious diseases account for up to 10% of morbidity during travel but only 1% of deaths, with malaria the most common disease. Causes of death vary according to the population studied. At destinations that attract elderly adults, cardiovascular events predominate, whereas in developing countries, motor vehicle accidents and drowning prevail.
Immunization
The choice of vaccines for an individual traveler is based on risk of exposure to vaccine-preventable diseases on the chosen itinerary; the severity of disease, if acquired; and any risks presented by the vaccine itself. Travelers differ in their tolerance of risk. Requests for immunization against diseases that are actually of negligible risk to the traveler but have the potential for poor outcome if acquired are often difficult for the physician to refuse because sporadic travel-related cases do occur each year. For vaccine-preventable diseases, the monthly incidence for nonimmune travelers to developing countries is most significant for symptomatic hepatitis A (HA), at 0.03% per month overall, and is still considerable for perceived low-risk destinations such as Mexico. The risk of symptomatic hepatitis B (HB) is most significant for long-stay travelers and expatriates, at 0.25% per month. Enteric fever (typhoid and paratyphoid) has a risk of 0.03% per month on the Indian subcontinent and is 10 times lower in Africa and parts of Latin America. Risk of yellow fever (YF) may be as high as 0.1% per month of travel to an area with current epidemic transmission, but the risk varies greatly between destinations encompassed by the endemic area map. The risk of meningococcal meningitis, rabies, cholera, polio, measles, varicella, and Japanese encephalitis in travelers is not known but is thought to be small (<0.0001%) even for travel to highly endemic areas.
Table 318.3 provides data on dosing, administration, need for boosters, and possible accelerated regimens for vaccines administered in the travel medicine setting. Details on vaccine composition, mechanism of action, use for routine adult and childhood primary vaccination, and adverse reactions can be found in Chapter 316 . The following discussion focuses on indications for each vaccine in the context of travel.
TABLE 318.3
Travel-Related Vaccines of Adults
| DISEASE | VACCINE | PRIMARY COURSE | ROUTE | FURTHER BOOSTERS |
|---|---|---|---|---|
| Vaccines to Consider for All Destinations | ||||
| Hepatitis A | Killed virus | 0, 6–18 mo a | IM | None |
| Hepatitis B | Recombinant viral antigen | 0, 1, 6 mo | IM | None |
| A: 0, 1, 2, and 12 mo | IM | None | ||
| A: 0, 1, 3 wk and 12 mo b | IM | |||
| Hepatitis B (CpG) | Recombinant viral antigen, adjuvanted | 0, 1 mo | IM | No |
| Hepatitis A/B | Combination of monovalent preparations | 0, 1, 6 mo | IM | None |
| A: 0, 1, 3 wk and 12 mo | IM | None | ||
| Typhoid | Capsular Vi polysaccharide | Single dose | IM | 2–3 yr |
| Live-attenuated Ty21a bacteria | 0, 2, 4, 6 d | Oral | 5 yr | |
| Influenza | Inactivated viral | Single dose | IM | Annual |
| Varicella | Live-attenuated virus | 0, 4–8 wk | SQ | None |
| Vaccines for Selected Destinations | ||||
| Yellow fever | Live-attenuated 17D virus | Single dose | SQ | 10 yr for high-risk travelers, long-term to lifelong protection for others c |
| Meningococcal | Quadrivalent conjugated polysaccharide (ACYW-135) | Single dose | IM | 5 y |
| Rabies | Inactivated cell culture viral | 0, 7, 21–28 d | IM d | None routinely but 2 doses after each exposure |
| Japanese encephalitis (Vero cell) | Inactivated viral | 0, 7–28 d | IM | 1 yr if at continued risk. S ubsequent doses >6 yr later. No definitive recommendation |
| Polio e | Inactivated viral | Single dose if adequate childhood series | SQ; IM acceptable | None |
| Cholera | Live-attenuated CVD 103-HgR bacteria | Single dose | Oral | No data; immunity beyond 6 mo uncertain |
| Killed bacteria + recombinant B toxin subunit f , g | 0, 1 wk | Oral | 2 y for cholera; 3 mo for ETEC | |
| Tick-borne encephalitis h | Inactivated viral | 0, 1–3 mo, 9–12 mo | IM | 3 yr |
| A: 0, 7, 21 d (protective 7 d after dose 3) | ||||
A, Accelerated regimen to be used for imminent departures; ETEC, enterotoxigenic Escherichia coli ; IM, intramuscular; SQ, subcutaneous.
a Second dose may be delayed up to 8 years without diminished efficacy.
b Regimen not approved by US Food and Drug Administration for monovalent hepatitis B vaccine but approved for combination hepatitis A/B vaccine containing the same quantity of hepatitis B antigen.
c A few countries that have mandatory entry requirements may require vaccination every 10 years; International Health Regulations require only 1 lifetime dose to meet entry requirements.
d Intradermal rabies preexposure vaccine is no longer produced, and IM 1.0-mL vials are not licensed for intradermal use in 0.1-mL dose.
e Oral polio vaccine is no longer produced in the United States.
f Not available in the United States but licensed in some countries including Canada for traveler's diarrhea due to ETEC .
g Also licensed in some countries for traveler's diarrhea due to ETEC .
h Not available in United States and Canada but available in endemic areas of Europe.
Update of Routine Immunizations
Because of the increased prevalence of many infections in the developing world, routine adult immunizations need to be current. Widespread outbreaks of measles, mumps, and pertussis are currently ongoing in developed and in developing countries.
Tetanus-Diphtheria–Acellular Pertussis
If no adult doses of tetanus-diphtheria–acellular pertussis (Tdap) have ever been given, a dose of Tdap should be given regardless of the time elapsed since the last tetanus/diphtheria vaccination. Travelers to remote areas where tetanus toxoid (indicated in cases of highly contaminated wounds) will be inaccessible should get boosters at 5-year intervals.
Measles-Mumps-Rubella
Persons (except traveling health care workers) born in the United States before 1957 or born anytime in the developing world are considered immune to measles. Other adult travelers should have received at least two doses of live measles-containing vaccine during their life, unless measles immunity can be documented.. One dose of measles-mumps-rubella (MMR) should be considered for health care or humanitarian workers without other evidence of immunity.
Influenza and Pneumococcal Vaccine
Influenza is the most common vaccine-preventable disease among travelers including passengers on cruise ships. Because of year-round circulation of influenza virus in tropical and subtropical regions and an influenza season that occurs in winter in temperate regions in the Southern Hemisphere (which is summer in the Northern Hemisphere), all travelers to the tropics at any time of year and to temperate destinations where it is currently winter should have received the most current influenza vaccine available in their home country before traveling. Evidence suggests that travelers immunized with the current vaccine formulation more than 6 months earlier should consider revaccination because immunity may have declined. Travelers may consider oseltamivir or baloxavir as standby therapy, especially travelers who are at high risk for complications from influenza or who are inadequately vaccinated. All individuals older than 6 months should receive the influenza vaccine. In China and Southeast Asia, avoiding poultry markets and farms may decrease risk of avian influenzas such as H7N9, H5N1, and H5N6. Unvaccinated persons who have the accepted routine indications for the pneumococcal vaccine, which includes most individuals with chronic disease and immunocompromising conditions (see Chapter 165 ) should receive this during the pretravel consultation.
Varicella
Varicella is primarily a disease of adolescents and young adults in tropical, nonindustrialized countries. Two doses of varicella vaccine, spaced by at least 4 weeks, should be considered for adult travelers without evidence of varicella immunity. Adults born before 1980 in the United States are considered immune.
Vaccines to Consider for All Destinations in the Developing World
Hepatitis A
HA vaccine is indicated for every nonimmune traveler to countries or areas with moderate-to-high risk of infection, which includes essentially everyone traveling outside the United States, Canada, Japan, Australia, New Zealand, Scandinavian countries, and developed countries in Europe. A single dose of HA vaccine given any time before travel provides adequate protection. The Centers for Disease Control and Prevention (CDC) recommends ancillary concomitant immune globulin for travelers older than 40 years who are planning to depart in 2 weeks or less, immunocompromised persons, those with chronic liver disease, and pregnant women traveling to intermediate or high-risk areas. Individuals born in the developing world are generally immune to HA. Persons with a history of hepatitis or who previously lived in an endemic country for a prolonged period may benefit from prevaccination serum antibody testing.
Hepatitis B
Travelers born in the United States after 1992 already have received an HB vaccine series. Pretravel HB vaccination is indicated for all nonvaccinated travelers with standard indications such as health care workers and all travelers with plans for long-term stays who will be visiting or residing in high-risk or moderate-risk areas. Transmission via routes such as sexual contact, blood transfusions, contaminated medical equipment, body piercing, tattooing, acupuncture, and sharing of cooking and bathroom facilities is difficult to control or predict in the context of travel. Vaccination is usually advocated for short-term travelers, especially younger travelers and travelers anticipating close contact with local populations, even if they have no specific risk factors. Adventure travelers (accident prone), backpackers, and travelers with underlying medical conditions are more likely to require contact with the medical system. Business and other regular travelers who fly internationally on multiple but short trips have a cumulative risk that increases with time, and such individuals should receive the HB vaccine. Accelerated and hyperaccelerated schedules of standard HB vaccines (see Table 318.3 ) are used widely in practice and are approved in many countries. These are helpful in administering all three primary doses necessary for high assurance of protection in the frequent circumstance in which the traveler is leaving in a very short time and is at risk of HB exposure. A novel adjuvanted HB vaccine approved in 2018 in the United States is fully protective after two doses spaced by 1 month.
Combination Hepatitis A and Hepatitis B Vaccine
The combined HA and HB vaccine provides convenience for travelers with an overlap of indications for use of the individual vaccines and has a licensed accelerated 3-week schedule (see Table 318.3 )
Typhoid
Typhoid vaccine is indicated for all travelers to the Indian subcontinent and considered for individuals traveling to other endemic areas ( Fig. 318.1 ) under all but the most deluxe and protected of conditions. Risk increases with trip duration, lodging or eating with local residents, and extent of travel off the usual tourist itineraries. In risk areas, food and water precautions should still be followed rigorously because typhoid vaccines are only 53% to 72% protective, and a large oral inoculum may overwhelm even an optimal antibody response. The increase in quinolone-resistant Salmonella enterica serovar Typhi in Asia has decreased the threshold for typhoid vaccination because infection, once acquired, may require inpatient parenteral therapy with ceftriaxone or a carbapenem, although high-dose oral azithromycin efficacy is generally effective. Ceftriaxone-resistant typhoid fever is currently restricted to Pakistan. Current typhoid vaccines do not protect against Salmonella enterica serovar Paratyphi, which is emerging in many areas. Adherence to the oral vaccine regimen may be as low as 70%.
Vaccines to Consider Only for Certain Destinations
Some vaccines are indicated solely because of a specific destination region regardless of whether the traveler has a specific risk behavior. Meningococcal and poliomyelitis vaccines are childhood vaccines that may require boosters in adult travelers with certain destinations.
Yellow Fever
Risk of Yellow Fever
The primary indication for YF vaccination is to prevent infection in individuals at risk. However, YF is currently the only vaccine that falls under the International Health Regulations that may necessitate vaccination purely for regulatory reasons. Neither YF vaccine nor any other vaccine is currently required for readmission to the United States. In general, all healthy adult travelers to areas with a risk of YF transmission (see Fig. 318.1 ) should be vaccinated. This endemic area may be restricted to only a portion of a country. Because of rare but serious vaccine-associated adverse side effects (see Chapter 153 ), persons who are not at any risk of exposure should not be vaccinated. Urban YF occasionally occurs in South America, and a number of urban areas are considered to have potential risk. Short-term travel that is restricted to very large urban areas in the endemic zone of South America carries negligible, if any, risk, but the situation is currently evolving in Brazil. Persons who have anything less than a definite, fixed itinerary and who will travel anywhere close to regions with risk of transmission should be vaccinated out of prudence.
Yellow Fever Entry Requirements
A number of African countries (Angola, Benin, Burkina Faso, Cameroon, Central African Republic, Congo, Côte d'Ivoire, Democratic Republic of Congo, Gabon, Ghana, Guinea-Bissau, Liberia, Mali, Niger, Rwanda, São Tomé, Sierra Leone, Togo) and one country in South America (French Guiana) require proof of YF vaccination from all arriving travelers. Other countries, both within and outside the risk zone, have submitted more complex requirements to the World Health Organization (WHO). They may require an official vaccination certificate only for individuals arriving directly from or via a country in the YF endemic zone, but not from arriving travelers from other countries. Such transits may include even an airplane connection in an affected country. These YF-free countries usually have the conditions and vectors to initiate a YF transmission cycle, and the purpose of the vaccine requirement is to prevent entry of viremic travelers. Current country-by-country YF entry requirements are available at https://www.who.int/ith/ith-country-list.pdf?ua=1 . The requirement often applies even if the arriving traveler has not visited an area within a country of departure that is endemic for YF.
A special permit, obtainable in the United States from state health departments, is required to legally stamp an international certificate of vaccination as from an authorized YF vaccine center. The International Health Regulations enable clinicians who decide that YF vaccine is contraindicated on medical grounds to provide the traveler with a letter stating the reasons for that opinion, which can be presented to immigration authorities on arrival at the destination. Acceptance of such waiver letters is at the complete discretion of the destination country. On arrival, the receiving country may also quarantine the traveler for up to 6 days or request that the traveler be placed under surveillance.
No specific format exists for written documentation of medical contraindication. Letters of waiver are most appropriate for individuals needing a certificate purely for regulatory reasons. Waiver letters should be given with great reluctance for individuals with medical contraindications to vaccination (see Chapter 153 ) who plan to visit an endemic area. The variable risk within the endemic regions of the world needs to be considered (in consultation with an expert, if necessary), and cancellation of travel should be recommended strongly if the risk is more than negligible. A YF certificate becomes valid for entry 10 days after it is stamped and dated.
Yellow Fever Booster Doses
Until more recently, the YF vaccine was uniformly considered to provide protection for 10 years. Currently the CDC recommends that for healthy, nonpregnant adults, 10-year boosters should be given to all travelers planning a long stay in any area where there is a risk of YF transmission, to all travelers spending any amount of time in high-risk areas such as West Africa, and to all persons traveling to an area with a current outbreak. On the basis of an analysis by CDC experts showing that 92% of vaccine recipients have virus-neutralizing antibody at 10 years and 80% have the antibody at 20 years, the CDC has concluded that most healthy persons can be considered to have long-term immunity. For the purposes of the International Health Regulations, a single dose of YF vaccine at any time previously is sufficient for entry to any country.
Meningococcal Disease
Meningococcal vaccine is recommended for travelers to Africa's sub-Saharan “meningitis belt” (see Fig. 318.1 ) during the dry season, from December through June, especially if prolonged contact with the local populace is likely. Out-of-season epidemics have occurred in Ethiopia, Somalia, and Tanzania, indicating possible changes in epidemiologic trends perhaps resulting from climate changes. Muslims undertaking Hajj and Umrah pilgrimages in Saudi Arabia are at a higher risk of meningococcal disease, and proof of current vaccination with quadrivalent vaccine is required to obtain pilgrimage visas. Immunity to some serotypes in the tropics may wane in 3 years. Meningococcal B vaccine is not indicated for travel.
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