Incidence, risk factors and treatment of diarrhoea among Dutch travellers: reasons not to routinely prescribe antibiotics

International tourism in 2007 showed approximately 908 million tourist arrivals worldwide [1]. Among tourists from industrialized countries, about 80 million crossed the borders of tropical and subtropical countries, many of which are developing areas, each year [2]. The most common infectious health problem among travellers from industrialized regions to developing countries is travellers' diarrhoea (TD) [2–11]. Because of the continuing high rates of international travel, TD will continue to be an important problem.

The annual number of Dutch travellers to tropical and subtropical countries doubled from approximately 1 million in 1999 to about 2 million in 2007 [12]. The Netherlands has a restrictive antibiotic policy and, therefore, low microbial resistance patterns [13–15]. The Dutch national guidelines for traveller's health advice do not advise everyone to carry stand-by treatment, only those at increased risk, such as immunocompromised persons and travellers to very remote areas [16].

In this prospective study we estimated the attack rate and incidence rate and studied risk factors and characteristics of TD among a cohort of immunocompetent, short-term travellers to tropical and subtropical countries. Further, we described treatment and the severity of episodes.

Despite the pre-travel advice on personal hygiene measures to prevent travellers' diarrhoea, it still occurred in half of all travellers. Compliance with these measures and, therefore, the effectiveness of the recommendations has been found to be poor [6, 20]. The high risk of TD found in our study is comparable with earlier prospective studies, which have found attack rates to vary between 25% and 57% [4, 9, 11, 21, 22].

In our study, the IR and AR were highest in South-Central (the Indian subcontinent) and Western Asia, followed by Middle, Western and Northern Africa and Central America and the Caribbean. Most other studies have also found the Indian subcontinent to be a high-risk area, followed by African regions [2–4, 9, 11, 23, 24]. Findings of AR and IR in different regions within Latin America differ between studies [3, 4, 9, 11, 23, 24]. However, comparing risk patterns between destinations in various studies is difficult, because of differing study methods and definitions for travellers' diarrhoea and for regions. The regional variations in AR and IR may be due to differences in circulating pathogens [8] and in hygienic standards between countries [25].

Of all 781 episodes of TD in our study, only 29 (4%) were considered severe, as defined by blood and/or mucous content. Possibly these episodes were caused by one of the invasive pathogens, like Campylobacter jejuni, shigella or salmonella species. As in other studies, most TD episodes were mild. Cobelens et al. [3] found fecal blood loss and concomitant abdominal and systemic symptoms in subsequent episodes more often than in first episodes and subsequent episodes lasted longer than first. However, we found no difference in severity of TD between first and subsequent episodes and subsequent episodes had a significant shorter median duration than first episodes. Because it is unlikely that exposure to pathogens decreases, this could possibly mean that travellers acquire immunity to some pathogens, similar to people born in non-Western countries.

Baaten et al. [25] found that the incidence of other feco-orally transmitted infections like hepatitis A, shigellosis, and typhoid fever among travellers declined in the past 10 years, which seemed related to an increase in hygienic standards in the destination countries. On that basis, we would expect the incidence of TD to have declined over the last decades. Indeed, the overall incidence rate of TD in our study of 2.49 per 100 travel days (95% CI 2.30 - 2.70) was significantly lower compared to the IR of 3.14 per 100 travel days (95% CI 2.86 - 3.43) observed 10 years ago among travellers in Amsterdam [3]. However, these two studies were different in some respects. First, because the travellers in our study had different travel patterns, we defined somewhat larger regions. Second, we used the WHO definition of TD, whereas Cobelens defined TD as any episode of 3 or more unformed stools daily or any number of such bowel movements accompanied by vomiting, abdominal cramps, or subjective fever, with an onset between the beginning and end of the journey. Finally, our study was prospective, with travellers asked to record symptoms daily in a diary, whereas Cobelens' study was retrospective, and thus may be subject to recall bias. Although we cannot conclude that the IR of TD has actually decreased, the finding of a lower IR with a broader definition could indicate that it is indeed declining.

Independent risk factors for first episodes of TD in our study were female sex, a Western country of birth, tourism as the purpose of travel, and some travel destinations. Also, female sex was an independent risk factor for subsequent episodes of TD. Sex differences in travel-associated disease and diarrhoea have been reported previously [26], but it is unclear if this difference can be explained by different travel behavior or by women being more susceptible to diarrhoea or more likely to report diarrhoea. Birth in a non-Western country may confer immunity to TD because of increased exposure to infections endemic in those countries [2, 27]. Several studies have shown an increased risk of TD in younger age groups [5, 6, 9]; we also found an association between younger age and the risk of TD, although not significant.

To our knowledge, our study is the first to calculate IR for subsequent episodes. Incidence rates did not differ between the development of a first episode of TD and a later episode, and neither did we find differences in severity between the first and subsequent episodes. Apparently, having had an episode of diarrhoea is not protective for a subsequent episode. Although antibiotic stand-by treatment was not prescribed before travel, only 5% of travellers with TD resorted to antibiotics purchased locally. Prescribing them to all would leave millions of courses of unused antibiotics in circulation. Aside from the unnecessary cost to travellers, public health services, and/or insurers, improper use can contribute to increased antimicrobial resistance.

Some people might argue that the use of antibiotics would result in a shorter duration of diarrhoea, as was found in a recent Cochrane meta-analysis [28]. The end-point of this placebo controlled analysis was duration of diarrhoea less than 72 hours, and severity. As our study showed an overall mild course of TD, and a short median duration of TD of 48 hours, it remains questionable whether antibiotics would have benefited our group of travellers, especially since the occurrence of side effects of antibiotics as shown by the same analysis.

The strength of our study is that it is prospective, which is the best approach for estimating attack rates and incidence rates of travellers' diarrhoea. Another strength is the daily diary entries, which minimizes recall bias. Our study also had some possible limitations. We used the WHO definition of TD (any number of more frequent passage of loose or liquid stools per day than is normal for the individual), and asked for accompanying symptoms to define the severity of diarrhoea. We did not ask participants to record the frequency of stools per 24 hr nor the degree of disability that travellers experienced, which would have possibly allowed us to make more detailed analyses and compare our results with more studies. On the other hand, asking holiday makers to fill out too many details could lead to less compliance with our study.

Diarrhoea is still a very frequently contracted infectious disease by travellers, but the overall course of TD appears to be mild, not requiring treatment. Prescriptions for stand-by antibiotics should be limited to travellers at high risk, such as those who are immunocompromised or are visiting very remote areas.