David O. Freedman

To prescribe optimal pre-travel advice, preventive measures, and education, travel health professionals must be aware of the absolute and relative magnitude of the many travel-related health risks. Such knowledge allows health-care providers to perform an epidemiologic and host-related risk assessment so that these measures can be appropriately prioritized for each traveler. Health problems are self-reported by 22%–64% of travelers to the developing world; most of these problems are mild, self-limited illnesses such as diarrhea, respiratory infections, and skin disorders. Approximately 8% of the more than 50 million travelers to developing regions, or 4 million persons, are ill enough to seek health care, either while abroad or upon returning home.

Limitations of Current Epidemiologic Knowledge

Knowledge of the precise risk for a specific disease in a specific location has proved elusive despite several decades of interest and investigation. (For additional discussion, see the Risks Travelers Face section later in this chapter.) A reasonably exact estimate of the number of cases of the disease or infection in all travelers over a time period at a location is difficult to determine, as many will have returned to their home countries by the time the disease manifests symptoms. Similarly difficult to obtain is an exact denominator reflecting the total numbers of travelers to that location, due to poor infrastructure in many destination countries. An accurate numerator must be divided by an accurate denominator to calculate a true incidence rate or risk. Even this standard population-based approach assumes that past experience predicts future risk. In addition, disease risks are not stable over time, and current or real-time data are rarely available. Much of the frequently quoted numerical data regarding the incidence of infection in travelers are based on extrapolations of limited data collected in limited samples of travelers anywhere from a few to more than 20 years ago. This knowledge base includes morbidity studies of various methodologic designs, each with its own set of strengths and weaknesses. These studies have mostly examined a few key individual diseases in all travelers regardless of destination; profiles of disease occurrence at a few specific high-risk destinations; and disease occurrence in certain types of travelers with certain behaviors. Many have been single-clinic or single-destination studies that can lead to conclusions that are not generalizable to groups of travelers with different local, national, or cultural backgrounds.

Incidence Rates and Estimates of Risk

A compilation of best available numerical incidence rate estimates, given the above limitations, is available and is frequently updated (Figure 1-1). With the notable exception of malaria, the major preventable travel-related diseases are associated with relatively low risks, ranging from 1 in 100 for influenza to less than 1 in 100,000 for several diseases that often concern travelers. Hepatitis A may be taken as an example of a prototypical vaccine-preventable disease, with an estimated overall uncorrected incidence of approximately 1 in 5,000 travelers to the developing world. Thus, the odds against acquiring hepatitis A on a single short trip are greatly in the traveler’s favor, and many travelers are sophisticated enough to realize this. Any considered vaccination should be presented in context as insurance against a relatively uncommon event but one that may result in significant illness or consequences.

For diseases with poor or fatal outcomes, the context of less tolerance of even small risks needs to be communicated to travelers to help them make informed decisions about all available interventions. The incidence rates in Figure 1-1 are reflective of aggregate data and studies and do not consider variations in risk behaviors, destination, season, duration of travel, or general style of travel. For many diseases, research into increased or decreased risk according to these variables is still in its infancy due to difficulties in tracking outcomes at remote destinations.

Surveillance Networks and Tracking of Disease Profiles

A more recent and novel approach to defining disease epidemiology in travelers has involved the use of collaborative networks of specialized travel medicine clinics to collect and aggregate data on large samples of ill travelers who have been exposed in many countries and who are seen after their return home. One such network, GeoSentinel, a collaborative effort of the International Society of Travel Medicine and CDC has developed a profile of the relative likelihood of travel-related disease stratified by region of travel in the developing world (Figure 1-2).

Based on 17,353 ill returned travelers seen at 31 clinical sites on six continents, the destination-specific differences in relative frequencies are apparent for most diseases. Figure 1-2 shows destination-specific proportions of ill returned travelers with each diagnosis and not numerical incidence rates, which can be used to assist with risk-profiling of prospective travelers during the pre-travel medical consultation. When individual diagnoses were collected into syndrome groups and examined for all regions together, 226 of every 1,000 ill returned travelers seen by participating clinicians had a systemic febrile illness, 222 had acute diarrhea, 170 had a dermatologic disorder, 113 had chronic diarrhea, and 77 had a respiratory disorder. Important region-specific disease occurrence data indicated that—

• Febrile illness is most likely from Africa and Southeast Asia.
• Malaria is among the top three diagnoses from every region.
• Over the past decade dengue has become the most common febrile illness from every region outside sub-Saharan Africa.
• In sub-Saharan Africa, rickettsial disease is second only to malaria as a cause of fever.
• Respiratory disease is most likely in Southeast Asia.
• Acute diarrhea is disproportionately seen in travelers from South Central Asia.

Future Challenges and Priorities for Travel Epidemiology

Issues surrounding the relative merits of different methodologic approaches to defining travel-associated disease risk have recently been reviewed at length. Some epidemiologic priorities include:

• Travel-related data for many existing and potentially vaccine-preventable diseases. Current data are sparse, and incidence in local populations is often not reflective of travelers’ risk due to different risk behaviors, previous infection, or pre-existing vaccination campaigns.
• Development of better surrogate markers for malaria exposure during travel to facilitate interventional studies for novel malaria chemoprophylaxis drugs. Such information is difficult to obtain because of the inability to perform placebo drug studies given the life-threatening nature of the infection.
• Studies of the impact of high-risk medical conditions or immunocompromising medications on travel outcome.
• Better understanding is needed of the impact of host behavior related to differing travel purposes, such as tourism, business travel, travel to visit friends and relatives, missionary travel, and volunteer travel.
• More insight is needed of exposure-related factors, such as urban vs. rural travel, long-stay vs. short-stay travel, luxury vs. rough travel, season of travel, and organized package travel vs. self-directed travel.

References

1. Steffen R, deBernardis C, Baños A. Travel epidemiology—a global perspective. Int J Antimicrob Agents. 2003;21(2):89–95.
2. Steffen R, Rickenbach M, Wilhelm U, et al. Health problems after travel to developing countries. J Infect Dis. 1987;156(1):84–91.
3. Hill DR. Health problems in a large cohort of Americans traveling to developing countries. J Travel Med. 2000;7(5):259–66.
4. Leder K, Wilson ME, Freedman DO, Torresi J. A comparative analysis of methodological approaches used for estimating risk in travel medicine. J Travel Med. 2008;15(4):263–72.
5. Caumes E, Ehya N, Nguyen J, Bricaire F. Typhoid and paratyphoid fever: A 10-year retrospective study of 41 cases in a Parisian hospital. J Travel Med. 2001;8(6):293–7.
6. Shah S, Filler S, Causer LM, et al. Malaria surveillance—United States, 2002. MMWR Surveill Summ. 2004;53(1):21–34.
7. Raoult D, Fournier PE, Fenollar F, et al. Rickettsia africae, a tick-borne pathogen in travelers to sub-Saharan Africa. N Engl J Med. 2001;344(20):1504–10.
8. Whitty CJ, Mabey DC, Armstrong M, et al. Presentation and outcome of 1107 cases of schistosomiasis from Africa diagnosed in a non-endemic country. Trans R Soc Trop Med Hyg. 2000;94(5):531–4.
9. Schwartz E, Weld LH, Wilder-Smith A, et al. GeoSentinel Surveillance Network. Seasonality, annual trends, and characteristics of dengue among ill returned travelers, 1997–2006. Emerg Infect Dis. 2008;14(7):1081–8.
10. Taylor DN, Houston R, Shlim DR, et al. Etiology of diarrhea among travelers and foreign residents in Nepal. JAMA. 1988;260(9):1245–8.
11. Liese B, Mundt KA, Dell LD, et al. Medical insurance claims associated with international business travel. Occup Environ Med. 1997;54(7):499–503.
12. Herwaldt BL, de Arroyave KR, Roberts JM, Juranek DD. A multiyear prospective study of the risk factors for and incidence of diarrheal illness in a cohort of Peace Corps volunteers in Guatemala. Ann Intern Med. 2000;132(12):982–8.
13. Patel D, Easmon CJ, Dow C, et al. Medical repatriation of British diplomats resident overseas. J Travel Med. 2000;7(2):64–9.
14. Steffen R, Amitirigala I, Mutsch M. Health risks among travelers-need for regular updates. J Travel Med. 2008;15(3):145–6.
15. Mutsch M, Spicher VM, Gut C, Steffen R. Hepatitis A virus infections in travelers, 1988–2004. Clin Infect Dis. 2006;42(4):490–7.
16. Freedman DO, Weld LH, Kozarsky PE, et al. GeoSentinel Surveillance Network. Spectrum of disease and relation to place of exposure among ill returned travelers. N Engl J Med. 2006;354(2):119–30.