Traveller's Diarrhoea

CME With theexceptionofsymptomatic amoebiccolitis, Most travellers fallillandrecover visited. in thecountry diarrhoea whereas southernEurope hasariskof8–20%. and Asia have a20–50%incidence of Haiti, Republic, theDominican someoftheMiddle East, Africa, America, Travellers toLatin hygiene isnotrigorously supervised. orwhere kitchen not guaranteeduncontaminated, where watersuppliesare sewage disposalmay besuspect, ofacquisition where The mainriskfactorisacountry OVERVIEW andantibioticsinselectedpatients. occupations, from work for certain rest ifthere ismuch colic,exclusion bed Treatment rests uponadequatefluid replacement, and they may alsocausediarrhoea. but widespread usemay becounterproductive diarrhoea, Antibioticscanbeusedtoprevent andtreat practice. advice aimedatavoiding exposure may bedifficultin and of antibioticsfor prevention would beill-advised, butwidespread use Prevention may bebetterthancure, infection from abroad spectrumofpathogens. andare thusatriskof contaminated) waterandfood, travellers may beexposedtoimpure (meaningfaecally andinsomedeveloped countries, In developing countries, travellers develop diarrhoea. andabout40%of significant riskofgastroenteritis, about5%ofjourneys are to countrieswith are airborne, Atany onetimeabout300,000people foreign holidays. Diarrhoea isrecognised asafrequent accompanimentto SUMMARY DECLARATION OFINTERESTS rehydration solution(ORS) LIST OF ABBREVIATIONS KEYWORDS situations. andantibioticsincertain from infections, work incertain exclusion Treatment bedrest ifthere ismuch colic, isessentially fluidreplacement, daignosis andmanagementofdirrahoea inreturned travellers totheUK. ABSTRACT ‘Travel broadens themindbutopensbowels’ Traveller’s diarrhoea I 40 England Edinburgh, Hospital, General Western Unit, Diseases Infectious WelsbyPD Gastr Gastr n t r o d u c t i o n Traveller’s diarrhoea is a common problem. This article features Thisarticle the Traveller’s diarrhoea isacommonproblem. oenter oenter rvl irhe,ifcin netgto,tetet screening treatment, investigation, infection, diarrhoea, Travel, olog olog Enterotoxigenic (ETEC), No conflictofinterest declared. y y Escherichia coli Escherichia implies largeintestinalproblems. orincontinenceusually faecal urgency, or onthestool, Bloodin mucus orpus. stool whichmay containblood, usually comprisesfrequent passageof solargeintestinaldiarrhoea large intestinaldisease, smallintestinal functionisunaffected by Often, absorbed. reservoir from whichwaterandelectrolytes are large intestinecannotfulfilitsnormalfunctionasa that invade orirritate thelargeintestinalwallandthus Large intestinaldiarrhoea isoftencausedby processes mechanisms. currently unknown, must dependonother,organisms andthatthepathology known thatthesyndrome canbeproduced by only afew lining thebowel causedmalabsorptionbutnow itis Withgiardia itwasthoughtthatthetrophozoites sprue. diarrhoea canoccuringiardiasis‘porridgy’ andtropical malabsorptive-type smallintestinal Alternatively, invasion. the smallbowel lumenwithoutsignificant bowel wall cholera inwhichthere may beanetsecretion offluidinto Thisisthemechanismof induce thecellstosecrete. adenine monophosphate(the ‘second messenger’)to toxins oftenactby stimulating production ofcyclic Direct invasion ofthesmallbowel wallisonemechanism but orpus. mucus, which rarely containsblood, diarrhoea comprises Smallintestinal organ responsible for fluidbalance. The smallintestineissecondonly tothekidney asthe detailed in Table 2. listed in Table 1andsomerelevant characteristicsare Themajorcausesofdiarrhoea are have notrecovered. Thisoverview dealsmostly withthosewho two weeks. tend tobeofrapid onsetandrarely persistfor more than mostinfective diarrhoeas giardiasis andtropical sprue, C l i n i c a l

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Published online Published d Correspondence to to Correspondence i amounts of watery diarrhoea, amounts ofwatery Infectious Diseases Unit, Western Unit, Diseases Infectious a General Hospital, Crewe Road Crewe Hospital, General South, Edinburgh, EH4 2XU EH4 Edinburgh, South, r e-mail e-mail J RCollPhysicians Edinb r h o e a [email protected] small November 2004 November P Welsby, P amounts of 2005; 35: 40–44 Traveller’s diarrhoea

TABLE 1 Microbial causes of diarrhoea in returning travellers Microbiology Brief duration diarrhoeas Staphylococcal and Bacillus cereus food poisoning Shigella and amoebae are almost exclusively large bowel Campylobacter pathogens whereas Giardia lamblia and Vibrio cholerae are Salmonella exclusively small bowel pathogens. Some pathogens, Cholera including Campylobacter jejuni and Salmonella, may produce Enterotoxin-producing E. coli a sequential mixed picture, with small bowel diarrhoea Enteroinvasive E. coli initially, followed by large bowel diarrhoea. Invasive Shigella pathogens often produce fever, whereas toxin-mediated Antibiotic-related (including Clostriduim difficile infection) illness usually does not produce a febrile response. Dysentry is diarrhoea with blood and usually implies an Persisting diarrhoeas invasive pathogen rather than a purely toxin-mediated Giardia lamblia illness. Entamoeba histolytica Schistosomiasis Bacteriological diagnosis may be suspected from Tropical sprue symptomatology. A standard ‘stool for culture’ will not reveal non-bacterial pathogens; examination for ova, cysts, and parasites has to be requested specifically. Clinical features Suspected amoebiasis is the only indication for hot stools (meaning either ‘instant microscopy’ or very rapid Traveller’s diarrhoea is defined by the passage of transport of the stool sample to the laboratory in a unformed stool twice as frequently as the normal bowel thermos flask). Occasionally viral examination is habit. Most pass 4–5 stools daily. Recovery occurs within required. Viral examination would rarely be necessary a week in 90% of cases, and <1% have symptoms at 3 for isolated instances of bacteriologically culture- months. Usually there is an abrupt onset with diarrhoea negative diarrhoea, but may be important if there is an and cramps, malaise, nausea, and possibly fever. Abdominal outbreak of bacteriologically negative diarrhoea – on pain is occasionally severe (Table 2). Signs of dehydration cruise ships for example. can occur in more severe cases. CME

TABLE 2 Infections in which diarrhoea is a predominant feature

Organism Nature of illness Usual incubations Blood in stool Abdominal pain Amoebic colitis Invasion of bowel wall Variable 5–7 days Usually (with Possible: large mucus) bowel type

Campylobacter Penetration of bowel wall 5–7 days (3–10 In about 40% Possibly very days possible) severe

Non-typhoidal Salmonellae Invasion of bowel wall some toxins 12–48 About 30% Possible hrs 6–72 hrs

Clostridium perfringens Toxin mediated 8–16 hrs No Mild Type A

Enterotoxin-producing E. Enterotoxin A few days No Possible: usually coli mild

Giardia lamblia Upper small bowel Variable: large No Possible: small dysfunction range intestinal

Rotavirus Infection of bowel wall 1–2 days usually Not usually Possible: mild

Shigella sonnei, flexneri, Invasion of large bowel 3–4 days (1–7 Very common Large bowel boydii, dysenteriae wall days possible) (with mucus) type colic

Vibrio cholerae Toxin- mediated 6–72 hrs No Colicky

Brief duration, infection-related diarrhoeas E. coli Is a normal resident of the large gut but certain strains are Staphylococcal and Bacillus cereus associated with diarrhoeal illnesses: These causes of food poisoning have such short • Enterotoxigenic strains are the most common cause incubation periods, 3–8 hours and 6–24 hours, of self-limiting traveller’s diarrhoea; respectively, that they are almost always acquired during • Enteroinvasive strains produce a shigella-like illness the return journey. Both produce vomiting and diarrhoea (indeed Shigella and E. coli are close bacterial relatives); of less than 24 hours duration, and are toxin-mediated. • Verocytotoxin-producing strains of E. coli O157, in particular, produce a toxin that can damage red blood Campylobacter corpuscles and cause kidney failure (haemolytic Fever and severe abdominal pain often accompany this uraemic syndrome) or a predominantly nervous cause of diarrhoeal illness. Occasionally abdominal pain is system illness (thrombotic thrombocytopenic so severe that peritonitis or perforation is wrongly purpura). Both these syndromes tend to appear as diagnosed. A significant clue to the correct diagnosis is the diarrhoea is improving. Often patients look that patients with peritonitis or perforation usually have systemically unwell and often have dysentery. The role absent bowel sounds whereas patients with invasive of antibiotics is uncertain. Campylobacter (or Salmonella) often have increased bowel • Enteropathogenic strains mostly cause watery sounds. Infection is usually from animal sources. diarrhoea in children by causing dysfunction of the Antibiotics (usually an erythromycin) are only indicated if intestinal brush border and microvilli. the illness is severe or if symptoms are not improving once the diagnosis is confirmed. Shigella These organisms invade the large intestine only and cause Salmonella classical large intestinal diarrhoea (‘bacillary dysentery’). There are three main clinical syndromes but there may be Patients often look toxic and ill whereas those with some overlap. amoebic dysentery often look relatively well. Antibiotics may have a role if patients are unwell. • The first, and most common type of illness (‘gastroenteritis’, ‘food poisoning’) is produced by Antibiotic-related diarrhoea infection which usually remains confined to the gut This is usually caused by infection with Clostridium difficile and causes diarrhoea and vomiting, abdominal pain, and has a wide spectrum of severity, ranging from mild or CME and flu-like symptoms. Infection is usually acquired no symptoms through to fulminant pseudomembranous from undercooked animal carcasses. Antibiotic enterocolitis. therapy is not indicated unless patients have additional risk factors such as cardiovascular disease Infections that can produce persisting diarrhoea and immunodeficiency. • The second type of illness is caused by bloodstream Giardia lamblia invasion with possible focal sepsis in which This infection is the most common cause of persistent gastrointestinal symptoms and signs may be traveller’s diarrhoea. It produces a malabsorption-type prominent, minimal, or absent. Fever may be high and diarrhoea with giardia trophozoites present in the upper constitutional symptoms may be marked with rigors. small bowel. The trophozoites are not invasive and Antibiotic therapy is indicated, largely in an attempt essentially provoke a malabsorptive reaction (a to prevent seeding of infection, particularly into suggestive feature) with bloating after food because bones, joints, or pre-existing cardiovascular lesions undigested food passes through the upper small bowel • The third type of illness is caused by strains that are producing osmotically mediated distention. Anorexia strict human pathogens which usually invade the and nausea are associated features. Giardia stools are bloodstream to produce typhoid or paratyphoid often foul, both in smell and appearance. The diagnosis fever. Initial symptoms, other than feverishness, may can be made by finding cysts in the stool – a stool need be vague but abdominal discomfort, splenomegaly, not be freshly passed if searching for cysts. constipation (not diarrhoea), and dry cough are Metronidazole or tinidazole is effective treatment and suggestive. Later in the illness, which may last for patients should be made aware that interaction of the four weeks or so,‘pea soup’ diarrhoea occurs when treatment with alcohol causes vomiting. If stools are the organism relocalises to the terminal ileum. negative for cysts a therapeutic trial may be given; duodenal aspiration should be reserved for those who Cholera do not respond to treatment. Other protozoa that may This has such a short incubation period (6–72 hours) and cause persistent diarrhoea include cryptosporidium and such a brief, although possibly fatal, course that it usually cyclospora, both of which may affect patients with begins and ends in the country of acquisition. normal immunity to give a self-limiting, if protracted, illness. In the immunocompromised, especially those

with AIDS, symptoms may last for months and weight The vulnerable traveller loss may be severe. Patients with pre-existing bowel disease may be at Entamoeba histolytica increased risk of infection. Those with inflammatory This is an infection usually acquired in the tropics. The bowel disease may also suffer relapses after minor organisms invade the large gut to cause typical large traveller’s diarrhoea (see also S Ghosh. Recognition and bowel-type diarrhoea (‘amoebic dysentery’). Amoebae management of inflammatory bowel disease. J R Coll may produce acute dysentery, but infection often Physicians Edinb 2005; 35:50–54). Those with presents as insidious onset chronic diarrhoea, which may hypochlorhydria or those receiving acid-reduction be confused with ulcerative colitis. Diagnosis is by finding therapies lose the protection of gastric acid, which cysts in the stool or by finding actively motile reduces the number of most ingested pathogens (but trophozoites on stool or rectal mucus examination. notably not Shigella) that pass onward into the small Suspected amoebiasis is the only indication for a hot bowel. Immunosuppressed patients may be at increased stool examination (see Microbiology above). risk of acquiring infection in at-risk countries, as they may Metronidazole followed by furamide (to eradicate have more severe and/or protracted gastroenteritis, and intraluminal parasites) is required. may excrete the organism(s) for longer.

Schistosomiasis (Bilharzia) Prophylaxis This is caused by three main nematodes: Schistosoma mansoni and Schistosoma japonicum both have an affinity In at-risk countries, the most important measures for for the human gut and other viscera whereas Schistosoma prevention are self-protection against enteric infection. haematobium mostly affects the human bladder. The The main steps are to avoid tap water, ice, undercooked distribution depends on that of the snails in which the meat, seafood, fruit not needing to be peeled, salads, schistosomal life cycle occurs. Schistosoma mansoni is uncooked vegetables, fresh cheeses, unpasteurised milk or found in Africa, Central and South America and in the butter, and buffet food at room temperature. Above all, Caribbean whereas S. japonicum is found in the Far East. avoid street vendors. Fruits requiring to be peeled, piping Larvae penetrate the skin in still-water bathers, the larvae hot foods, cooked vegetables, carbonated or boiled water, mature, and the adults mate and lay eggs in the gut (and and hot teas or coffee are generally safe. Drug elsewhere) which may cause acute or chronic fibrosing prophylaxis, apart for antibiotics (see below), with agents inflammation possibly leading to intestinal ulceration and such as bismuth subsalicylate or antimotility agents is of narrowing. Chronic diarrhoea can occur in patients who no value and may be dangerous. CME have repeated long-term infections. Short-term bathers in a schistosomiasis endemic area may acquire infection Antibiotic prophylaxis can be effective but is limited by the but chronic diarrhoea is unlikely. resistance patterns of the organisms in countries visited. These are seldom known before travel. Prohylaxis for all Tropical sprue travellers would inevitably increase resistance rates and This produces chronic malabsorption, weight loss, and limit the use of those antibiotics. The cost in the UK, if all multiple deficiencies particularly of iron and folate. Sprue visitors to higher risk areas were prescribed antibiotics, is often associated with small bowel colonisation with would be about £24 million a year! Antibiotic prophylaxis Gram-negative bacteria. Sprue is found in those who stay is best reserved for those visiting high-risk areas for brief in certain geographically well-defined tropical areas for periods during which they will be performing important longer than one month and is presumed to have an tasks. They can also be given to immunocompromised or infection-related pathology causing malabsorption, immunodeficient individuals. Antibiotics used included steatorrhoea, and folate and vitamin B12 deficiency. There ciprofloxacin, trimethoprim, co-trimoxazole, norfloxacin, are highly endemic areas in India and the Far East and and doxycycline (now often given for malaria prophylaxis) areas of low endemicity in South and Central America, and it will be interesting to see if bacterial resistance in and Africa. Treatment is with antibiotics (usually Gram-negative bacilli increases. Various dosages have tetracyclines) and folic acid. been used but one tablet daily seems to be effective. Ciprofloxacin produces a protection rate of up to 95%. Lactase deficiency Antibiotics are of no value in preventing viral or parasitic This may take months to recover from and may occur in diarrhoea. those who have had severe gastroenteritis. A trial of a lactose-free diet may be helpful. Specific treatments

Irritable bowel syndrome Rehydration This occurs frequently after bacterial gastroenteritis Treatment depends on adequate fluid replacement (ORS), and may last for several months. Antispasmodics should colic relief, sometimes anti-diarrhoeal agents, and be tried. sometimes antibiotics. Oral rehydration solution does not

relieve diarrhoea – its purpose is to replace fluid and Antibiotics electrolyte losses rather than relieve diarrhoea. It Antibiotics, notably quinolones, shorten diarrhoea by contains water, sodium, glucose (sodium absorption about 1–2 days and reduce the severity to some extent. requires glucose), potassium, and an alkali to combat the Not all gut pathogens, however, are sensitive to acidosis resulting from an alkaline diarrhoea. Glucose is quinolones, and, indeed, the therapeutic use of antibiotics necessary to promote sodium absorption but the amount after diarrhoea develops is controversial. If diarrhoea is present is small and of little nutritional value. However, mild then ORS should suffice, if diarrhoea is moderate an lack of nutrition in a previously well patient with antibiotic plus loperamide should be used, and if diarrhoea diarrhoea of short duration is not critical. The aim should is severe (especially with fever,dysentery, or incapacitating be to replace fluid losses over about 3–4 hours followed symptoms) then an antibiotic for 3–5 days would be by sufficient fluid to replace continuing losses, usually reasonable without an antimotility agent, which may given on an empirical basis. Severe continuing diarrhoea, worsen the situation. The role of probiotics in prevention particularly in children, should lead to hospital admission. and treatment is under investigation. Malnourished children require continued feeding during treatment and also need hospital admission. Bed rest is a HIGHLIGHTS much neglected intervention for relieving colic and settling diarrhoea. • Rehydration therapy is advised for all patients • Travel destination(s) should be chosen with care, Antimotility drugs particularly for those with pre-existing bowel disease Antimotility drugs such as loperamide are useful in and immunosuppressed patients. controlling acute symptoms in adults. The • Increased bowel sounds in a diarrhoeal illness with manufacturer’s instructions should be followed and the severe abdominal pain speak against a diagnosis of maximum dose not exceeded. Antimotility drugs should perforation or peritonitis. be avoided if there is a possibility of dysentery or • Giardia is the most common cause of persistent inflammatory bowel disease. traveller's diarrhoea. • Antibiotic prophylaxis is best used only for those visiting high-risk areas to perform important tasks.

FURTHER READING travellers’ diarrhoea (Cochrane review). From The Cochrane Library, CME Issue 3, 2004. Chichester, UK: John Wiley & Sons, Ltd. • • Caeiro J-P,DuPont HL. Management of travellers’ diarrhoea. Drugs Rodriguez LA, Ruigomez A. Increased risk of irritable bowel 1998; 56(1):73–80. syndrome after bacterial gastoenteritis: cohort study. BMJ 1999; • Casburn-Jones AC, Farthing MJ. Traveler’s diarrhea. J Gastroenterol 318(7183):565–6. • The Travel Doctor. Travellers' Diarrhoea. Hepatol 2004; 19(6):610–18. • • Centers for Disease Control and Prevention. Travelers’ Health. Thielman NM, Guerrant RL. Clinical practice. Acute infectious • De Bruyn G, Hahn S, Borwick A. Antibiotic treatment for diarrhoea. N Engl J Med 2004; 350(1):38–47.

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