February 2, 2012 — Patients with inflammatory bowel disease (IBD) who traveled to developed countries had a higher rate of illness compared with other travelers, but the rate of illness was the same for travel to developing or tropical regions. Most travel-related illnesses among the patients with IBD arose from sporadic flares of their disease, rather than increased susceptibility to enteric infections, suggested study authors Shomron Ben-Horin, MD, director of the IBD service, and coauthors from the Sheba Medical Center and Sackler School of Medicine of Tel-Aviv University in Tel Hashomer, Israel.
The research was published online November 3 and in the February print issue of Clinical Gastroenterology and Hepatology.
Compared with healthy control patients, the absolute increased risk for patients with IBD was small, and most episodes of illness that they experienced were mild, providing reassurance for many patients who want to travel.
Patients with IBD have often been advised to avoid travel, especially to developing countries, for fear of contracting infections or experiencing disease flares in regions with poor hygiene or potentially inadequate medical facilities. Self-imposed or physician-advised restrictions on travel can severely limit patients' quality of life or opportunities to do business abroad.
Because little data exist on the risk of travel for patients with IBD, the investigators performed a retrospective, case–control study comparing illnesses among patients with IBD (n = 222; 523 trips) and healthy control individuals (n = 224; 576 trips), using validated, structured questionnaires, interviews, and chart reviews. The questionnaires included items related to demographics, medical history (eg, travel clinic attendance, immunizations, and prophylactic and regular medications), details of all travel going back 5 years, and any illness during or within 3 months after any trips. The authors used the United Nations Human Developmental Index classification to identify developing and developed countries.
Individuals in the case group included individuals attending outpatient gastroenterology (GI) clinics at the medical center. Individuals in the control group included volunteers without known IBD who were drawn from hospital staff, their family members, and people escorting relatives undergoing endoscopies. The mean age of both groups was 37 years. Individuals in the control group received the same questionnaire as patients with IBD, but without IBD-specific items. The authors defined illness as any GI or non-GI episode.
Patients with IBD experienced illness in 15.1% of their trips compared with 10.9% of trips made by control patients (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.01 - 2.0; P = .04). For both patients with IBD and control participants, enteric disease accounted for 92% of the episodes, most of which were mild to moderate and resolved within a few days, the authors report. Only 5 patients with IBD and 4 control participants required hospital admission for any reason while traveling.
Travel to developed countries accounted for most of the difference in illness between patients with IBD and control participants. For the 2 groups, the rates of illness were the same when they went to developing regions (17% vs 21% of trips, respectively; P = .24).
Their rates of illness when traveling to developing countries (17% of trips) was not statistically different from when they went to developed countries (13.9% of trips; P = .32). They did, however, experience an almost 2-fold increased risk when traveling to the tropics compared with developed countries (OR, 1.9; 95% CI, 1.1 - 3.3; P = .02).
Control individuals experienced much less illness in developed countries (3.3% of trips) compared with travel in developing regions (21.4% of trips; OR, 6.6; 95% CI, 3.2 - 12.2; P < .001). When they went to the tropics, however, their rates of illness increased 10-fold compared with travel in developed countries (33.3% vs 3%, respectively; OR, 13.6%; 95% CI, 6.7 - 27.6; P < .001) and were not statistically different from the rate of illness for patients with IBD (P = .18).
Factors Influencing Travel-Related Risk
It appeared that underlying IBD activity was an important determinant of travel-related disease activity. Multivariate analysis showed that risk increased if patients experienced frequent flares (OR, 1.9; 95% CI, 1.1 - 3.4; P = .02) or had prior IBD-related hospitalizations (OR, 3.5; 95% CI, 1.3 - 9.3; P = .01). Among patients with IBD, disease remission for at least 3 months before traveling reduced the risk for travel-related illness by 70% (OR, 0.3; 95% CI, 0.16 - 0.5; P < .001). Patients in remission had the same risk for illness during travel as did individuals in the control group (12% vs 10.9%; P = .5).
In the multivariate analysis, there was no independent effect of the use of immunomodulatory drugs during the trip on the risk for illness during travel (P = .5).
Because the length of the trip may affect the likelihood of illness, the investigators normalized the results per 10 days of travel and found a 7% risk per 10 days for individuals in the case group vs 5% per 10 days for individuals in the control group (OR, 1.4; 95% CI, 1.01 - 1.96; P = .04). When stratified by trip duration, there was no increased risk for patients with IBD traveling to developing or tropic areas, in line with the nonnormalized analyses.
Travelers with IBD experienced disease flares within 3 months of returning to Israel after 16% of their trips. The incidence of flares was higher if travelers had experienced an episode of illness during the trip than for uneventful trips (43% vs 11.6%, respectively; OR, 7.4; 95% CI, 4.2 - 12.9; P < .001). The authors note that almost half of the patients with illness during the trip and flares afterward felt that the flare was a direct continuation of the episode during the trip.
The authors caution that the retrospective nature of the study makes it susceptible to recall bias, and they emphasize that it was not sufficiently powered to detect differences in rare opportunistic infections that may affect immunocompromised patients. They also warned that live attenuated vaccines such as those against yellow fever are contraindicated in such patients. Another limitation of the study is that it involved travelers from a single, developed country, and therefore the results may not be generalizable to travelers with IBD from other developed or developing countries.
Charles Ericsson, MD, professor of medicine, head of clinical infectious diseases, and director of the travel medicine clinic at the University of Texas Medical School at Houston; founding editor-in-chief of the Journal of Travel Medicine; and past-president of the International Society of Travel Medicine, told Medscape Medical News that the study is retrospective, albeit case-controlled, "so that immediately calls into question recall bias when you're asking people to remember trips up to 5 years later. I'm taking any of the data with a bit of a grain of salt." He said most of the illnesses were reportedly mild, but people tend especially to remember more severe illnesses.
"The data are OK as far as they go, but I think you're left with enough uncertainties that I will refuse to use data like this to say that I'm not going to worry about somebody with IBD when they travel to a developing country" and not offer them chemoprophylaxis against travelers' diarrhea, Dr. Ericsson said. Even if the incidence is not different from control participants, "when they do get travelers' diarrhea, I think the impact on the subject is profound because they don't know whether it's a flare of their IBD" that requires treatment or not, "and I'd rather prevent that conundrum to begin with." He admits he's "a fan of chemoprophylaxis" in general, offering rifaximin to his high-risk travelers, which is active in the upper GI tract, and therefore a good prophylactic agent.
Another issue "that does bug me a little bit is the outcome measurement [of] any illness," he said. He would have preferred the authors to distinguish enteric conditions from other types of illness. "They allude to the fact that...92% of the outcomes were enteric disease," he noted. "Then why not just study that 92%, to keep it clean? You would have a study that would have focused on the most important issue."
Dr. Ericsson also wondered about the meaning of the finding that the patients with IBD experienced more illness when they went to developed countries compared with control patients (P < .001), but not when they visited developing ones (P = .2). "What they didn't control for is the likelihood, I would think, that anybody traveling from a developed to another developed country may well not have been on a vacation but, rather, traveling for business, and was stressed out, and that's a known precipitator for a flare of your IBD," he noted. And he speculated that "the IBD people in fact are concerned about going to a developing country and take extra precautions," such as chemoprophylaxis or watching out for food and beverages.
The finding that people with IBD had such a high level of problems in developed countries, but not in developing ones, implies that they experienced only a very small level of travelers' diarrhea in developing countries. "It doesn't sit well with me," Dr. Ericsson said. "I'm not quite sure how to interpret it. I'm worried that there's confounding issues going on of behavioral differences that were not assessed."
Also, with a reported mean trip length of 22 days for both patients with IBD and control participants, he found the incidence of illness quite low compared with previous reports of travelers' diarrhea, depending on trip length. The specific countries, areas of the countries, and purposes of the trips may have affected the outcomes.
In summary, Dr. Ericsson said the study is valid as it is presented, but "it's the interpretation of it that has to be taken with a bit of a grain of salt." He said the findings may lead him to advise a patient with IBD who has had many flares to find out where to get treatment while traveling, as their risk for illness is increased.
He said that going forward, he would like to see a properly designed prospective case–control study implemented that looks at a sufficient number of patients with IBD as they travel, which may avoid some of the problems of recall bias during such a long period of a retrospective study as this one.
Dr. Ben-Horin has received consultancy fees from Schering-Plough and Abbott Laboratories. The other authors and Dr. Ericsson have disclosed no relevant financial relationships.
Clin Gastroenterol Hepatol. 2012;10:160-165. Abstract
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Cite this: Patients With IBD Fare Well on Their Travels - Medscape - Feb 02, 2012.