For the full versions of these articles see bmj.com CLINICAL REVIEW Management of travellers’ diarrhoea DavidRHill,1 Edward T Ryan2 1National Travel Health Network Travellers’ diarrhoea is one of the most common Enterohaemorrhagic E coli (producing shiga toxin or and Centre, and London School of illnesses in people who travel internationally, and vero cytotoxin) are not typically described in travellers. Hygiene and Tropical Medicine, Hospital for Tropical Diseases, depending on destination affects 20-60% of the more Enterotoxigenic E coli predominates in travellers to London WC1E 6JB than 800 million travellers each year. In most cases the Latin America but is also seen globally. Rates of 2Travelers’ Advice and diarrhoea occurs in people who travel to areas with Campylobacter infection per traveller are highest in those Immunization Center, and Tropical poor food and water hygiene.1 This review examines visiting South Asia and South East Asia, 6 exceeding and Geographic Medicine Center, Massachusetts General Hospital, the approach to the prevention and treatment of those of enterotoxigenic E coli in some studies. Boston, USA diarrhoea in travellers. Much of the evidence base for Norovirus and rotavirus are the most commonly Correspondence to: D R Hill travellers’ diarrhoea has been established over the past identified viral causes of travellers’ diarrhoea, although [email protected] 30 years, with a strong body of randomised trials and these agents have not been uniformly examined.7 Cite this as: BMJ 2008;337:a1746 consensus opinion in support of recommendations. Norovirus is often associated with outbreaks of doi:10.1136/bmj.a1746 The use of antibiotics for self treatment or chemopro- diarrhoea in holiday resorts or on cruise ships. Parasites phylaxis, however, remains debatable. are less common causes of travellers’ diarrhoea; of these, the protozoa Giardia intestinalis and Cryptospor- ’ What is travellers diarrhoea? idium are most commonly identified.8Cyclospora and Classic travellers’ diarrhoea is defined as at least three Entamoeba histolytica are less common causes, and loose to watery stools in 24 hours with or without one or typically associated with long term travel. In 10-15% of more symptoms of abdominal cramps, fever, nausea, cases more than one pathogen is identified, and in up to vomiting, or blood in the stool. Mild to moderate 50% of studies no pathogen is described.49 Acute food diarrhoea is one or two loose stools in 24 hours with or poisoning—the sudden onset of nausea, vomiting, and without another enteric symptom. The median time to diarrhoea after ingestion of a toxin (usually produced onset is six or seven days after arrival. Although the by Staphylococcus aureus, Bacillus cereus,orClostridium diarrhoea often resolves spontaneously over three or perfringens) in food that has not been properly cooked or four days, up to a quarter of affected travellers need to stored, accounts for up to 5% of cases. alter their plans, interrupting their holiday or business activities.2 What are the consequences of having travellers’ diarrhoea? ’ What causes travellers diarrhoea? As the causes of travellers’ diarrhoea are multiple the ’ The causes of travellers diarrhoea depend on the clinical features vary: from the typical watery stools destination, setting, and season, although studies have with cramping and nausea associated with enterotoxi- been done in only a limited number of countries genic E coli, to dysentery with Shigella, to short lived 34 (table 1). Enteric bacteria are documented as the nausea, vomiting, and diarrhoea associated with acute most common causes: several types of Escherichia coli food poisoning or norovirus. Although most cases and Campylobacter, Salmonella, and Shigella spp; Vibrio resolve without treatment over several days, in about cholerae is rare in travellers. Enterotoxigenic E coli 10% the symptoms persist for more than a week, and in that produce a heat labile or heat stable toxin are the about 2% for more than a month.2 About one quarter of most common species of Ecoliimplicated, with travellers alter their plans because of diarrhoea, and 5 enteroaggregative Ecoliincreasingly recognised. about 5% seek medical care.2 Illness tends to be more severe in infants and young children, and precautions should be taken to deal with a potentially dehydrating Sources and selection criteria diarrhoeal illness in children when travelling. Serious We identified articles through an electronic search of PubMed and the Cochrane library complications include haemolytic uraemic syndrome “ ’ ” “ ” “ ” using the term travelers diarrhea alone and in combination with treatment , etiology , with bacteria that produce shiga toxin, Guillain Barré and “prevention”. Additional studies were sourced from the retrieved articles. We also syndrome with Campylobacter, and post-infectious reviewed our extensive collection of articles on the subject, as well as current national arthropathies with any invasive bacteria. Prolonged guidelines in travel medicine. illness (>10 days), illness that begins after return, and BMJ | 11 OCTOBER 2008 | VOLUME 337 863 CLINICAL REVIEW Table 1 | Causes of travellers’ diarrhoea diarrhoea increasingly seems related to the sanitation level at the destination rather than the ability to adhere Agent* Frequency (%)† to avoidance measures.12-15 Bacteria 50-75 Escherichia coli (enterotoxigenic) 10-45 Vaccines Ecoli(enteroaggregative) 5-35 No single vaccine prevents travellers’ diarrhoea, Campylobacter 5-25 because of the multiple potential causes. Enteric Salmonella 0-15 vaccines prevent rotavirus (being introduced into Shigella 0-15 childhood immunisation programmes), hepatitis A, Others 0-5 typhoid, and cholera and such vaccines can be given Viruses 0-20 when indicated after a careful risk assessment based on Noroviruses 0-10 destination and itinerary. Rotavirus 0-5 Some enterotoxigenic Ecolistrains express a heat Parasites 0-10 labile enterotoxin that is similar to cholera toxin Giardia intestinalis 0-5 produced by V cholerae. Consideration has therefore Cryptosporidium spp 0-5 been given to using the oral killed cholera vaccine Cyclospora cayetanensis <1 (Dukoral; Crucell, Leiden), which contains a non-toxic Entamoeba histolytica <1 portion of cholera vaccine, to induce cross protective Acute food poisoning 0-5 immunity against enterotoxigenic Ecoli.Upto50%of No pathogen identified 10-50 enterotoxigenic Ecolistrains do not, however, express *Coinfection with multiple pathogens occurs in 10-15% of cases. heat labile enterotoxin, and an analysis of studies †Frequency varies between travel destination, setting, and season. suggests that using oral killed cholera vaccine would prevent only 1-7% of people from developing travellers’ illness associated with weight loss are more likely to be diarrhoea, depending on destination and frequency of 16 caused by protozoan parasites such as Giardia. heat labile producing entertoxigenic Ecoli. In a phase Irritable bowel syndrome can occur after travellers’ II trial, vaccination of travellers with heat labile diarrhoea. In two prospective observational studies, enterotoxin using a transcutaneous delivery system travellers who had diarrhoea were more likely to have a showed 75% protective efficacy against all cause moderate to severe diarrhoea (defined as ≥4 stools in 24 new diagnosis of irritable bowel syndrome at six hours).17 Although no difference was found in the months after return.10 11 overall incidence of diarrhoea between the recipients of How can travellers’ diarrhoea be prevented? the vaccine and those of placebo, vaccine recipients had Food, water, and personal hygiene fewer stools and a shorter duration of illness. Travellers’ diarrhoea is acquired through the ingestion Chemoprophylaxis of contaminated food and water, therefore strict food, Chemoprophylaxis comprises two approaches: the use of water, and personal hygiene precautions should non-antibiotic products (bismuth subsalicylate and pro- decrease the risk (see box). Despite an increased biotics) and the use of antibiotics. Bismuth subsalicylate understanding of the causes and pathogenesis of (preferably in tablet form) provides about 60% protection travellers’ diarrhoea, its incidence has not substantially against travellers’ diarrhoea; however, adverse events decreased over the past few decades, and travellers who may be common at the most effective doses.18 A meta- practise preventive measures do not always have a analysis suggests that probiotics can lessen the likelihood lower incidence of the condition. The risk of travellers’ of travellers’ diarrhoea by about 15%.19 Although several randomised placebo controlled studies in the 1970s and ‘80s showed antibiotic Diet and personal hygiene measures to prevent travellers’ diarrhoea prophylaxis to be effective in preventing travellers’ Foods and beverages to be avoided diarrhoea, it is not currently recommended for most Raw or undercooked meats, fish, and seafood travellers for several reasons: the potential adverse events Unpasteurised milk, cheese, ice cream, and other dairy products associated with prophylactic antibiotics, predisposition to Tap water and ice cubes otherinfectionssuchasvaginalcandidiasisorClostridium difficile associated disease, development of bacterial Cold sauces and toppings resistance, cost, and lack of data on the safety and efficacy Ground grown leafy greens, vegetables, and fruit of antibiotics given for more than two or three weeks.20 In Cooked foods that have stood at room temperature in warm environments