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Background. Traveling the world may result in infection with tropical or other travel-associated diseases. This applies increasingly also to people with immune-compromising and other medical conditions, as well as to elderly individuals. To reduce exposure and susceptibility to health risks, there is a need for appropriate pre-travel advice for these particular groups of travelers.
Methods. In this observational study, we analyzed the overall risk of health problems among travelers with underlying medical conditions who attended the University of Amsterdam's Academic Medical Center's (AMC) travel clinic from January to October 2010. Telephone questionnaires were administered to 345 travelers with underlying conditions and 100 healthy travelers.
Results. The most common underlying medical conditions studied included: (1) diabetes mellitus; (2) impaired immunity due to use of immune-suppressing medication; (3) reduced gastric barrier; and (4) HIV infection. The overall incidence of travel-related diseases (TRDs) was higher among those patients with underlying medical conditions compared to healthy travelers [incidence rate ratio (IRR) 2.26, 95% CI (1.29–3.98)]. Of all diseases reported, gastrointestinal disease, fever, and respiratory problems were reported most frequently. Travel to Central America, South Central Asia, Northeast Asia, and North Africa was associated with increased risk of contracting TRD. Hepatitis B protection was absent or unknown in 75% of these travelers.
Conclusions. Travelers with medical conditions had a higher risk of obtaining TRD, predominantly gastrointestinal in nature.
People travel the world extensively, and increasingly so. Between 20 and 70% of the 50 million people from the industrialized world visiting the developing world report illness associated with their travel. Although most illnesses are mild, 1 to 5% of returned travelers become ill enough to seek medical attention, and 1 in 100, 000 succumbs to travel-related disease (TRD).1
Among patients with underlying medical conditions, diseases acquired during travel may lead to more severe consequences compared to healthy travelers.2–5 Also, depending on the underlying condition there may be diminished immunogenicity and clinical efficacy of vaccinations. Live attenuated vaccines, such as that for yellow fever, may elicit disease.
As the overall mobility of this group of travelers increases, so does their motivation to travel to destinations outside Europe and Northern America. Tailor-made pre-travel advice relates to the type and severity of the immune disorder.
The immune-deficiencies that influence travel can be divided in several groups:
humoral immune-deficiency with primary or secondary hypo- or agammaglobulinaemia, eg, due to the use of rituximab, chronic lymphatic leukemia, multiple myeloma, or nephrotic syndrome;
cellular immune-deficiency, eg, due to HIV infection or immune-suppressive therapy;
nonspecific immune disturbance due to defective barriers such as skin or mucosal disorders, or a reduced gastrointestinal acid barrier;
other conditions that cause a higher risk of infection such as diabetes, malignancies, pregnancy, functional asplenia/splenectomy, hematologic stem cell transplantations, complement disorders, cardiovascular prostheses, and older age (>60 years).
Because the different components of the immune system are intertwined, immune-deficiency is often of a combined type.6
Literature and many recommendations exist on the HIV-infected traveler in whom the degree of immune-compromise can be quantified by measuring CD4+ lymphocytes.4,7,8 Little evidence and fewer recommendations are available with respect to transplant patients, and even less with respect to other forms of immune-suppression. In addition, no well-validated laboratory measures are available that quantify the degree of immune-suppression in these patients.
This analysis focuses on travel-related health risks for different groups of travelers with underlying medical conditions who visited the Academic Medical Center travel clinic in Amsterdam. In the Netherlands, national guidelines for pre-travel advice have been issued by the LCR (Landelijk Coördinatiecentrum Reizigersadvisering).9 These serve as guidance for all travelers, including immune-compromised travelers. By assessing which groups of travelers with medical conditions have high risks of relevant TRD compared to healthy travelers, we aim at identifying areas in which future research might contribute to optimizing those guidelines.
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We presented an overview of various groups of travelers with underlying medical conditions, their travel destinations, and risk of obtaining TRD. Although results are based on small numbers of individuals, interesting observations on specific health problems were made.
We found that (1) travelers with underlying conditions are at increased risk for health problems, specifically those using immune-suppressive medication, HIV positives with CD4 counts <500/µL, and those with a reduced gastric barrier; (2) traveling to Central America, South Central Asia, Northeast Asia, and North Africa was associated with an increased risk of TRD; (3) gastrointestinal symptoms were reported most frequently; (4) we found a low protection rate against hepatitis B in travelers with underlying conditions.
The fact that we found most groups of travelers with underlying medical conditions to be at increased risk for health problems is an important finding. However, as not all recent studies point to the same conclusion,11 further prospective research on this topic is definitely useful.
An impaired cellular response among patients using immune-suppressive medication probably accounts for the high rate of TRDs.3 Risk of infection for HIV positive patients depends on CD4 counts. With higher and stable CD4 counts, travel risks are considerably lower.2,9,12 This is illustrated by the difference in IRR we found among those with CD4 counts >500/µL [IRR 1.33, 95% CI (0.43–4.10)] and <500/µL [3.40, (1.40–8.20)]. Reduced mucosal and gastric barriers are known causes of increased risk of contracting gastroenteritis.12,13
In the group with underlying conditions, travelers aged >60 were not found to have an increased risk of contracting TRD compared to travelers aged <60. This is in accordance with previous studies14,15 and despite waning immunity, as described elsewhere.5,16
For diabetics, an increased risk for TRD was found, specifically for those with insulin-dependent diabetes mellitus (IDDM). Although it is widely accepted that hyperglycemia causes a higher propensity for infections17,18 and that metabolic dysregulation in IDDM patients is a frequent problem,19 there is controversy about the susceptibility to infections in diabetics. A study by Baaten and colleagues, for example, showed that diabetic travelers have a low risk of infection compared to healthy controls.20
The types of health problems (gastrointestinal problems, fever, dermatological, and respiratory complaints) were similar to those described previously in healthy populations.10
Gastrointestinal complaints were most frequently reported (66.7% of all TRDs, 19.1% overall attack rate). Previously, travelers' diarrhea has been described with attack rates ranging from 34.4%21 to 52%12 in general populations. An explanation for our lower percentage might be our more narrow definition of travelers' diarrhea.
In a study by Freedman and colleagues, 33.5% of 17,353 ill-returned travelers reported gastrointestinal disease.10 We can therefore conclude that our overall attack rate is low (18.5%), but the relative percentage of gastrointestinal disease (66.7%) is high compared to other studies. This high percentage could be explained by our exclusion of noninfectious diseases.
Only 18.6% of the population with a medical history had a known protective hepatitis B titer. Importantly, in this population, 2.6% were admitted in a foreign health-care facility. The WHO has advised all countries to integrate universal hepatitis B vaccination into their national immunization programs by 1997.22 Until recently, such a program was not implemented in the Netherlands, because there is a low carrier rate of hepatitis B in the Dutch population.23 In developing countries, however, prevalence is high compared to Europe and North America24 and unsafe needle practices are still common.25 Moreover, the disease may follow a more severe course in patients with an impaired immune system.26 Possibly, vaccination against this virus could more often be considered in this group of travelers.
This study has several strengths, as well as weaknesses. Regarding strengths, due to the broad inclusion criteria, all groups that visited the travel clinic and all frequently visited destinations could be described. Additionally, specific groups could be assessed in detail and an indication of the risks for various regions could be assessed.
However, because of the retrospective nature of this study, details on the timing and exact symptoms of health problems may not be reliable. Also, not much detail on the etiology of reported diseases could be acquired. Because our control group was relatively small, low statistical power could have obscured and influential observations (eg, on travel habits) could have exaggerated observed associations.
In conclusion, we found that travelers with underlying conditions were at increased risk for TRD compared to healthy travelers. Prospective studies are needed to assess whether broader indications for (emergency) self-treatment antibiotics and hepatitis B vaccination might reduce morbidity. Also, prospective research should assess the pathogenic causes of travel-related health risks of at least the largest groups of travelers with underlying medical conditions.