ID Symptoms in Immune Suppressed Travelers
Abstract and Commentary
By Lin H. Chen, MD
Dr. Chen is Assistant Clinical Professor, Harvard Medical School; Director, Travel Medicine Center, Mt. Auburn Hospital, Cambridge, MA
Dr. Chen has received research grants from the Centers for Disease Control and Prevention and Xcellerex.
Source: Baaten GG, Geskus RB, Kint JA, et al. Symptoms of infectious diseases in immunocompromised travelers: a prospective study with matched controls. J Travel Med 2011;18(5):318-326.
Investigators from The Netherlands conducted a prospective study to assess whether short-term travelers on immunosuppressive agents (ISA) or those with inflammatory bowel disease (IBD) had increased risk of infectious diseases compared to matched controls. The study enrolled travelers seen at the travel clinics of the Public Health Service Amsterdam and the University Medical Centre Leiden from October 2003 to May 2010, and obtained data using a structured diary. Immunosuppressive agents included in the ISA group were those based on World Health Organization guidelines.1 A total of 75 ISA and their 75 matched controls (non-immunosuppressed travel companions within 10 years of age) completed the study, as well as 71 IBD patients and their 71 matched controls. The median trip duration for all groups was 16 days. The ISA travelers were using systemic corticosteroids, methotrexate, a TNF-alpha inhibitor, or other immunosuppressives for various diagnoses including rheumatic disease, psoriasis/psoriatic arthritis, renal transplant and others. They were 64% female with a median age of 48 years. Their controls were 41% female with a median age of 46 years. The IBD travelers were 72% female whereas their controls were 45% female, and their median ages were 35 and 34 years, respectively.
Compared to the control group, the ISA travelers had higher incidence rate and number of days with skin infection (0.11 days versus 1.34 days, respectively). ISA also had more fatigue and arthralgia compared to their controls. Travel-associated diarrhea was reported by 47% of ISA and 40% of their controls, occurring at 1.32 days per month for both groups. There was no statistically significant difference for vomiting, fever, cough, and rhinitis.
Commentary
Little data exist regarding travelers with autoimmune disorders such as IBD, rheumatoid arthritis, and psoriasis. Many treatments for autoimmune disorders have long been recognized to be immunosuppressive, including prednisone, methotrexate, azathioprine, 6-mercaptopurine, and cyclosporine. The use of biologic immunomodulating agents (such as the tumor necrosis factor inhibitors infliximab, etanercept, and adalimumab) has vastly improved the courses of illness for many patients with autoimmune disorders, and more patients on these agents will likely be traveling frequently and widely in the future. Therefore, travel-related morbidity data on travelers with autoimmune disorders or receiving immunomodulating therapy will benefit travel medicine specialists in guiding their advice to these travelers.
Solid organ transplant (SOT) recipients are a group of travelers that have received more attention regarding travel health concerns and exposure risks, probably because of their obvious immunosuppressed status.2,3,4 Yet travel health preparations were suboptimal among these patients. Boggild et al from Toronto found that 36% of 267 SOT recipients traveled outside of Canada and the US, about 2/3 to countries at risk for hepatitis A; only 5% of the travelers to hepatitis A-endemic countries received hepatitis A immunization.2 Less than 25% of those visiting areas endemic for dengue and malaria followed mosquito avoidance recommendations, and 10% had potential blood or body fluid exposure.2 Another center found that 16% of their SOT patients (n = 1,130) traveled to developing countries, where only 4% sought pre-travel evaluation,3 and most of the SOT travelers sought pre-travel evaluation from their transplant surgeons.2,4 Because some patients with autoimmune disorders may not realize that their treatments may be immunosuppressive, travel medicine specialists need to collaborate with specialists on autoimmune disorders to raise awareness of travel health issues facing these patients.
Baaten et al report that the prevalence of ISA and IBD among travelers seen in 2008 in the travel clinic of the Public Health Service Amsterdam was 0.5 and 0.4%, respectively. These estimates are important for travel medicine experts in considering the size of the population that may need special attention. Although the sample size is small, the Baaten study compared targeted study groups with their travel companions who probably had similar exposures.
It is interesting that the only significantly increased risk among ISA travelers compared to their control group is skin infections, which is also associated with increased number of symptomatic days per month. Similarly, IBD travelers had more symptomatic days for skin infection although their incidence rate was not statistically different from their control group. The diarrhea incidence rates in the ISA and IBD travelers did not differ significantly from their controls, but the survey may not have captured any differences in diarrhea severity. The higher proportion of antibiotic usage in the ISA travelers hints at a possibility of more severe symptoms. An alternative explanation is that ISA travelers had a lower threshold for antibiotic treatment than IBD travelers.
It is reassuring that the frequency of seeking medical evaluation appears to be comparable to the general traveler population, 11-12% in ISA and IBD travelers and 10-11% in their controls. Finally, the study did not report hospitalizations during travel, which may also be useful to determine the severity of illness.
Given the findings of this study, ISA travelers should be advised on the prevention and recognition of skin infections, as well as initial management. IBD travelers should be better prepared to manage vomiting. More data are needed to better understand the travel-related disease risks in travelers on immunosuppressive or immunomodulating agents. The use of immunomodulators, especially the biologic agents, will continue to increase, and travel medicine practitioners need to know these agents, understand special risks facing the immunosuppressed travelers, and highlight advice regarding these risks.
References
- WHO Collaborating Centre for Drug Statistics Methodology. Guidelines for ATC classification and DDD assignment, 2010. Oslo, Norway: WHO Collaborating Centre for Drug Statistics Methodology, 2009. Available at http://bit.ly/AabBaa
- Boggild AK, et al. Travel patterns and risk behavior in solid organ transplant recipients. J Travel Med 2004; 11:37-43.
- Uslan DZ, et al. International travel and exposure risks in solid-organ transplant recipients. Transplantation 2008;86(3):407-412.
- Roukens AHE, et al. Health preparations and travel-related morbidity of kidney transplant recipients traveling to developing countries. Clin Transplant 2007;21:567-570.
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