First published in ITIJ 107, December 2009
Robert Steffen of the University of Zurich details the incidence and increasing costs associated with treating one of the most common travelling ailments
It’s no secret that diarrhoea is a frequent health problem in developing countries. Most importantly, it still is a very relevant cause of death mainly among infants and children - inthe year 2000 alone, 2.1 million people died from diarrhoeal diseases. Similarly to these children, travellers visiting third-world destinations are non-immunes with respect to the many gastrointestinal pathogens occurring there, since they have never or not recently been exposed to them and they have thus been unable to gradually develop immunity or to remain immune.
Travellers’ diarrhoea (TD) is usually defined as three or more unformed stools per 24 hours with at least one accompanying symptom, such as fecal urgency, abdominal cramps, nausea, vomiting or a fever. However, milder forms of TD may also result in incapacitation, as the patients cannot predict how the illness will evolve. Dysentery is usually pragmatically defined in travellers as TD that has invaded the intestinal mucosa, resulting in systemic disease with fever and/or blood admixed to the stools.
TD mainly results in great frustration at times of highest expectations – both for tourists or people travelling on business. TD is hardly ever life threatening, on average the symptoms spontaneously disappear after four days; however in 1 per cent of patients they persist for over one month. In more than 10 per cent, TD may be followed by an Irritable Bowel Syndrome (IBS).
The risk of infection depends strongly on the destination, the type of travel (accommodation), and other individual host factors. Travellers from industrialised countries journeying to developing countries are at the highest risk (between 20 and 66 per cent) during the first two weeks of their stay (Figure 1), thus TD still is the most frequent illness in this population. If we conservatively estimate that 50 million travellers visit a developing country every year [World Tourism Organization, unpublished data], and that overall 30 to 40 per cent of these travellers will develop TD, we can conclude that 15 to 20 million people annually will confront TD problems - that is 40,000 travellers per day.
Due to acquired immunity, the risk of illness is much less in those living in areas with high endemicity. In contrast, those groups who are at particularly high risk of illness include infants, young adults and persons with an impaired gastric acid barrier. Recently, it has been demonstrated that there is also a genetic susceptibility to TD. It has also been noted by researchers that TD often has a particularly severe and long‑lasting course in small children.
The risk of TD also depends of the selection of hotel. In Jamaica for instance, TD incidence rates in 18 hotels visited by at least 40 clients for one week varied between 0 and 33 per cent, a highly significant difference. When visiting these places, food hygiene experts realised that this statistic mirrors the hygienic conditions. Already in previous studies, it had been demonstrated that five-star hotels tend to have a slightly higher TD incidence rate as compared to many three or four star hotels. This is plausible, considering that food items are more frequently prepared with the assistance of fingers in the more refined places.
However, milder forms of TD may also result in incapacitation, as the patient cannot predict how the illness will evolve
TD is usually caused by fecal contamination of food and beverages. The pathogens responsible for TD are primarily bacteria, such as enterotoxigenic and other types of E. coli, Salmonella, Shigella, Campylobacter. Viruses are infrequently detected in adults; parasites, such as Entamoeba histolytica or Giardia lamblia are the cause of TD in less than five per cent of sufferers, but they may persist for a longer period upon return home.
Is prevention possible?
Avoidance of potentially contaminated food and beverages along the rule ‘boil it, cook it, peel it — or forget it’ has been shown to drastically reduce the risk of TD in one prospective study. However, less than five per cent of tourists strictly adhere to these recommendations, and the majority of travellers select, for instance, salads from attractive buffets or accept ice cubes in their drinks. Organisms in contaminated ice will survive concentrations of alcohol found in drinks mixed with tequila and whisky. On the other hand, almost all enteropathogens are killed at 100 oC and most food items served at 60oC are safe.
A variety of drugs have been considered for prevention of TD. These include probiotics, bismuth subsalicylate (the active ingredient found in Pepto-Bismol, which is only available in certain coutries, including the United States) and antibiotics. Only the latter group offers a satisfactory protection, reducing the incidence of TD by 80 per cent or more. Quinolones (mainly ciprofloxacine) and rifaximine (a non-absorbed antibiotic that therefore has a profile of adverse events similar to placebo) are those most often considered. This is controversial: While in North America such prophylaxis is frequently prescribed, European doctors are more restrictive and would, for the most part, consider it only for high-risk groups, such as for patients with pre-existing illnesses in whom dehydration subsequent to TD may be dangerous (e.g., those with a history of stroke or transient ischemic attacks, inflammatory bowel disease, insulin-dependent diabetes mellitus, chronic renal failure, or AIDS), or persons who are particularly prone to suffer of TD, be that for genetic reasons (rare) or due to a lack of the gastric acid barrier. Such prophylaxis may also be considered for VIPs during short trips.
Currently, no vaccine offers satisfactory protection against TD. Typhoid vaccines are specific against typhoid, which is not characterised by diarrhoea. The only cholera vaccine available in a limited number of countries (not in the United States) offers some limited cross-protection against enterotoxigenic E. coli (ETEC), but the estimated efficacy against TD of all causes is limited to between 5 and 23 per cent. A skin-patch vaccine against ETEC is currently being tested.
As described above, it is nearly impossible to avoid TD by clever behavior, medication or vaccines. Therefore, therapy plays a dominating role and for reasons explained below, self-treatment is important.
The leading principle in the management of TD is to avoid dehydration. In healthy adults, an adequate fluid and electrolyte balance can be maintained with tea with sugar (fluids without sugar are not well absorbed by the infected gastrointestinal tract), bottled soft drinks (no cola, as that contains caffeine, which increases intestinal motility and thus diarrhoea), juices, soups and crackers etc., to replace electrolytes. Electrolyte-containing oral rehydration solutions, such as those formulated by WHO, will neither diminish the amount nor duration of diarrhoea, but they are paramount in infants, children or senior TD patients in whom dehydration may much more rapidly have devastating effects. Because of damage to the intestinal lactase-producing cells by enteric pathogens, dairy products should be avoided during illness, otherwise no diet is indicated.
Most experts agree that travellers to TD risk destinations should carry an antimotility agent (usually loperamide) and an antibiotic for self-treatment. Many studies have shown that both types of medication lead to rapid symptomatic improvement; the most dramatic reduction in the duration of illness is achieved by a combination therapy: two thirds of patients are free of symptoms within four hours.
In adult TD patients, loperamide (up to 16 mg every 24 hours) may be used, but such high doses often subsequently result in constipation; also loperamide should really be avoided during bouts of dysentery, unless used in combination with an antibiotic.
Quinolones, and in Southeast Asia azithromycin, have become the antibiotics of choice for self-treatment. Studies have shown single-dose therapy and three- to five-day courses to be equally effective in most situations. Therapy with lactobacilli or other probiotics has not been shown to be effective in modifying the course of travellers’ diarrhoea, although it appears that early therapy is slightly more effective.
Avoidance of potentially contaminated food and beverages along the rule 'boil it, cook it, peel it - or forget it' has been shown to drastically reduce the risk of TD
Some with concerns about self-therapy have recommended that TD patients should consult a local doctor. A recent study conducted in Phuket (Thailand), Goa (India) and Mombasa (Kenya) illustrated that some physicians caring for patients at tourist hotels use obsolete antimicrobials or combinations, which are not recommended in industrialised nations. Additionally, many have now set up their private clinics in the vicinity of the hotels and increasingly hospitalise TD patients (some 80 per cent of the TD consultations) there overnight for antimicrobial infusion therapy — that results in costs amounting to several hundred US dollars, which the patients must then try to get reimbursed from their insurances upon return. Lastly, in some more remote areas there is concern about nosocomial transmission, mainly of the hepatitis B virus, and occasionally also of other pathogens.
Travellers’ diarrhoea persisting upon return
While at most destinations in developing countries, no state-of-the-art laboratory investigation on the origin of TD is feasible, this may become a necessity upon return. In the initial phase, priority will often be given to stool analysis for parasites, particularly considering that most patients already had received antibiotics. However, ultimately a colonoscopy may be indicated, as rarely, TD symptoms may be the expression of a yet undetected malignancy in the gastrointestinal tract.