Canada Communicable Disease
Report
Volume 32 • ACS-1
15 February 2006
An Advisory Committee Statement (ACS)
PDF Version
16 Pages - 1.26 MB
The Committee to Advise on Tropical Medicine and Travel (CATMAT) provides the Public Health Agency of Canada (PHAC) with ongoing and timely medical, scientific, and public health advice relating to tropical infectious disease and health risks associated with international travel. PHAC acknowledges that the advice and recommendations set out in this statement are based upon the best current available scientific knowledge and medical practices, and is disseminating this document for information purposes to both travellers and the medical community caring for travellers.
Persons administering or using drugs, vaccines, or other products should also be aware of the contents of the product monograph(s) or other similarly approved standards or instructions for use. Recommendations for use and other information set out herein may differ from that set out in the product monograph(s) or other similarly approved standards or instructions for use by the licensed manufacturer(s). Manufacturers have sought approval and provided evidence as to the safety and efficacy of their products only when used in accordance with the product monographs or other similarly approved standards or instructions for use.
Diarrhea is the most common medical problem among travellers to low-income countries. A large number of enteric pathogens are much more prevalent in resource-poor countries, and the standards of water quality, sanitation, and food preparation result in an increased risk of transmission. Although travellers are advised to take food, water, and hygiene precautions to minimize their risk of enteric infection1, the effectiveness of these measures is limited in practice. Acute diarrhea may have many causes, but bacterial pathogens predominate. In general, no investigations are necessary, and self-treatment can be advocated for acute traveller's diarrhea (TD). However, even when empiric therapy is initiated, medical assistance should be sought for investigation and management as soon as possible when the patient is very ill (e.g., high fever, prostration, severe abdominal pain), has a significant underlying medical illness, is immunodeficient, or has bloody stools. In practice, the majority of diarrheal episodes resolve, even without treatment, after a period of between hours and weeks. However, noticeable changes in bowel habit often persist for considerably longer after documented bacterial gastroenteritis2,3.
The present statement specifically addresses the returned traveller with persistent diarrhea, lasting ≥30 days, which began during travel or within 30 days after return from travel, usually to a low- or middle-income country. Relevant English, French, and Spanish language articles published between October 1990 and August 2005 were identified through MEDLINE using the terms "diarrhea" and "travel"; relevant articles cited in the bibliographies and personal files of the authors were searched manually.
The incidence of persistent diarrhea of ≥ 30 days in travellers has been estimated at 1% to 3% in several reports4,5. The condition has been described in children as well as adults(6) and, indeed, such diarrhea may be more severe in children7. Recent immigrants (adults and children) may also be at elevated risk of persistent diarrhea, although this group has not been well studied. Although the risk of persistent diarrhea is likely to be related to the style and duration of travel, there is no specific geographic association with persistent TD; the problem has been reported following travel to a wide range of low-income countries.
In a high proportion of cases, no specific etiology has been identified in spite of extensive investigation. It has been postulated that there are intestinal pathogens that remain unidentified or unrecognized at the present time8,9; however, other mechanisms, including post-infectious functional disorders of intestinal secretion and motility, appear to be a more likely cause for persistent gastrointestinal (GI) symptoms. The management of some travellers with prolonged diarrhea may be complicated by their conviction, and that of their health care provider, that a parasite or other microbial agent persists, despite all evidence to the contrary.
Table 1. Etiology of persistent TD (no specific order)
Non-infectious |
Lactose intolerance, irritable bowel syndrome, post-infectious disturbance of bowel function, bile-salt enteritis, “unmasked” inflammatory bowel disease or celiac disease |
Other infections |
Small-bowel overgrowth, tropical sprue, HIV |
Parasites |
Giardia lamblia, Cryptosporidium spp.†, Cyclospora cayetanensis†, Isospora belli, Entamoeba histolytica, Strongyloides spp., Dientamoeba fragilis, Blastocystis hominis‡ |
Bacteria |
Various Escherichia coli, Shigella spp., Campylobacter spp., Aeromonas, Clostridium difficile toxin, Salmonella spp. |
Minor or nomedicalimportance (probable commensals; at most, causing only minor symptoms that do not require specific therapy) |
Endolimax nana, Entamoeba coli, Entamoeba dispar, Entamoeba hartmani, Entameoba polecki , Iodamoeba buetschlii, Chilomastix mesnili |
† Requires special diagnostic
techniques. |
Shigella, Salmonella, Campylobacter, various E. coli species, including enteroaggregative types, and other organisms more commonly associated with acute illness can, rarely, cause persistent diarrhea10 and respond to appropriate antimicrobial therapy11,12.
Clostridium difficile enters the differential diagnosis in a substantial proportion of travellers who have received antimicrobial treatment for any reason, including the use of doxycycline for malaria prophylaxis. It usually responds to standard therapy with metronidazole or vancomycin given orally, but relapse occurs relatively frequently.
Tropical sprue is an uncommon, acquired malabsorption syndrome believed to involve bacterial overgrowth13,14. Prolonged antimicrobial therapy combined with supplementation of micronutrients, especially folate, is usually effective.
Giardia lamblia is a very widely distributed parasite, which can cause a subacute to chronic small bowel infection that may be asymptomatic or associated with diarrhea or even malabsorption. Metronidazole or any of several other agents is usually effective, but metronidazole resistance is increasingly recognized.
Entamoeba histolytica can cause subacute to chronic large-bowel infection. This organism is widely distributed, largely in the tropics and subtropics. It is often over-diagnosed in developing countries, where access to bacterial culture is not available. E. histolytica can also cause liver abscess. It is morphologically identical to non-pathogenic E. dispar, which complicates decisions about causation and therapy. Most cases of symptomatic E. histolytica are associated with positive serologic tests; molecular techniques to distinguish between E. histolytica and E. dispar are becoming available. Cryptosporidium parvum infection commonly results in a small-bowel infection, which is self-limiting after an average duration of approximately 2 weeks in the normal host but is often chronic in the immune suppressed. Its distribution is cosmopolitan and includes industrialized countries. Recent studies show benefit from treatment with nitazoxanide15. Cyclospora cayetanensis is a cause of small-bowel diarrhea, often associated with fatigue and weight loss and lasting an average of 6 weeks without treatment. Treatment with cotrimoxazole is effective. Dientamoeba fragilis, which has been associated with enterobiasis (pinworm), is a non-invasive large-bowel organism occasionally associated with symptoms. A thorough search for the previously described, well-established enteric pathogenic organisms should be carried out before attributing symptoms to D. fragilis. Several agents have activity against this organism when treatment is felt to be indicated. Blastocystis hominis is a non-invasive organism of controversial pathogenicity, for which reliably effective therapy has not been established16. Other: microsporidia have rarely been reported as causes of travel-related diarrhea17.
Helminths are uncommon causes of persistent diarrhea. The evidence for an association with diarrhea is strongest for Strongyloides stercoralis, Capillaria philippinensis, Trichuris trichiura, and Schistosoma sp.18. Other intestinal flukes (e.g., Fasciolopsis buski) may also be associated with diarrhea.
Persistent diarrhea is a relatively common manifestation of advanced immunosuppression with HIV, and cytomegalovirus may cause colitis in this setting. Viruses are otherwise not recognized as causes of chronic diarrhea.
A change in bowel function following infectious enteritis may be much more common and last longer than generally recognized 2,3. "Post-travel irritable bowel syndrome" is for the most part a diagnosis of exclusion and likely reflects a spectrum of disturbance of bowel function following travel-related infection. Whether it is similar in its pathophysiology to irritable bowel syndrome not related to travel is not known.
Lactose intolerance precipitated by infectious injury to the brush border of the small bowel mucosa may contribute to persistent travel-related diarrhea.
Any cause of chronic diarrhea may be coincidentally related to travel.
“Unmasked” or coincidental inflammatory bowel disease, celiac disease, etc., and a number of small and large intestinal neoplasias and endocrine abnormalities may enter the differential diagnosis of persistent diarrhea.
Similarly, various drugs, including laxatives, Mg++-containing agents, thyroid replacements, herbal medications, and some antiretroviral agents, can cause or complicate persistent diarrhea.
In the evaluation, the following specific elements of the history may be helpful:
Clarify whether there have been asymptomatic intervals. If so, this may suggest that repeated acute infections, not uncommon in the traveller, rather than one persistent illness explain the patient's course, which in turn would indicate a very different diagnostic and therapeutic approach.
Ascertain any relevant past medical history, specifically including baseline bowel habit and history of past GI symptoms, stress-induced symptoms, or irritable bowel syndrome-like symptoms antedating travel. If this history is present, if current symptoms are consistent with irritable bowel syndrome and if stool examination for common pathogens is negative, it may be appropriate to direct the focus to symptomatic management of the irritable bowel symptoms. A strong family history of inflammatory bowel disease could be a useful clue.
Determine comorbidity, such as with diabetes or HIV (or risk of HIV infection).
Enquire about medications taken, specifically including antimicrobials, either before or after diarrhea onset, and the effect of any therapy. A history of improvement following antimicrobial therapy is of limited diagnostic value. Recent antimicrobial use, usually within the previous 2 months, should prompt consideration of Clostridium difficile disease.
Ascertain travel history – destinations, duration, and conditions. Although many diarrheal pathogens are cosmopolitan, some, such as Schistosoma mansoni, have specific geographic distributions. A diagnosis of a similar illness in travelling companions may be useful.
Behavioural history, particularly food and water “precautions”, and the circumstances under which the diarrhea was likely to have been acquired may occasionally contribute to the assessment of diarrhea.
The following characteristics are associated with invasive, predominantly ileal, or large-bowel involvement: small-volume stools, lower abdominal cramps, blood and/or mucus or leukocytes in the stool, tenesmus and high/persistent fever.
Large-volume stools, without significant cramping or with mid-upper abdominal localization of pain and weight loss in the face of adequate caloric intake, are characteristic of small-bowel disorders. Most of the causes of persistent diarrhea involve either small or large bowel, so that localization can assist in predicting the likely etiology and can also guide investigations, both microbiological and endoscopic, when indicated. In many patients, the clinical picture does not fall clearly into either category or may even evolve.
Of particular practical importance in determining the extent and logical order of investigations are the following two issues: degree of interference with well-being and normal life activities, and trend in symptoms since onset, i.e. are they getting better or worse? Limited investigation may be appropriate in patients whose symptoms are mild or improving.
Acute diarrhea In general, returned travellers with diarrhea of < 5 days' duration require no investigation and should be managed as per the CATMAT statement on TD1. Etiologic investigations may be appropriate for epidemiologic reasons in the case of an outbreak in a travelling group (e.g., cruise ship, organized tour). |
B III |
Associated fever and other symptoms
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A II |
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B III |
Initial investigation of persistent diarrhea The following elements should be included in the approach to the returned traveller with persistent diarrhea:
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B II |
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A II |
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A II |
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A II |
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A II |
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A II |
Indications for GI endoscopy Among patients with persistent and substantial symptoms, GI endoscopy may contribute to management in the following circumstances. If sustained or progressive weight loss is a prominent feature, upper GI endoscopy with small-bowel biopsy should be performed. Alternatively, a 72-hour stool collection for fecal fat will confirm malabsorption, but not the cause. If the fecal fat excretion is elevated, upper GI endoscopy and biopsy would be clearly indicated. |
B III |
If features of large-bowel diarrhea or rectal bleeding are present, lower GI endoscopy with biopsies should be considered first. |
B III |
Endoscopic examination and biopsies may be considered for patients with persistence of significant diarrhea, even in the absence of the specific features mentioned, particularly if the empiric therapy and symptomatic measures outlined in the next paragraph have been unsuccessful. |
C III |
Empiric therapy Some authors have suggested a trial of an antibacterial agent such as a quinolone and/or an antiprotozoal agent such as metronidazole; indeed, some have advised this as an early step in the approach to the patient21,22. |
C III |
If major symptoms persist, or if symptoms such as weight loss progress, the full spectrum of non-travelrelated causes of diarrhea23,24 may enter the differential diagnosis. Other investigations, such as measurement of serum anti-transglutaminase antibodies (for celiac disease), should be carried out, and consultation with a gastroenterologist should be considered. |
C III |
In the absence of a specific etiologic diagnosis, the following therapeutic modalities have been suggested: Discontinue medications that cause diarrhea (e.g., laxatives, antacids containing magnesium, antibiotics, diuretics, theophylline, cholinergic drugs, promotility agents, prostaglandins). |
B II |
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B II |
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C III |
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B II |
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C III |
Patients who have no diagnosis after thorough investigation are thought to have “post-infectious” symptoms. Follow-up of these patients has demonstrated a tendency to improve over subsequent months to years. Unless new symptoms or findings appear, these patients can be reassured that life- or health-threatening disease is highly unlikely38. However, it is important to recognize that the patient's symptoms may have a substantial impact on his or her quality of life and to demonstrate an empathetic and supportive approach. Rigorous efforts should be made, with the patient, to explore measures that may provide symptom relief. An algorithm for the management of persistent travel-associated diarrhea is presented in Figure 1.
Figure 1. Approach to the management of persistent travel-associated diarrhea
At any point in the algorithm, if the patient is other wise well and symptoms are improving or mild, consider postponing the next investigate step and trial of symptomatic treatment. C & S, culture and sensitivity; O& S and parasites.
Thanks go to Dr. Richard Fedorak, Division of Gastroenterology, University of Alberta, and to Dr. Jay Keystone, Toronto Hospital Tropical Disease Unit, for reviewing the manuscript and providing expert comments.
Committee to Advice on Tropical Medicine and Travel. Statement on travellers' diarrhea. CCDR 2001;27(ACS-3):1-12.
Neal KR, Hendon J, Spiller R. Prevalence of gastrointestinal symptoms six months after bacterial gastroenteritis and risk factors for development of the irritable bowel syndrome: postal survey of patients. Br Med J 1997;314:779-82.
Okhuysen PC, Jiang ZD, Carlin L et al. Post-diarrhea chronic intestinal symptoms and irritable bowel syndrome in North American travelers to Mexico. Am J Gastroenterol 2004;99(9):1774-8.
Steffen R, Rickenbach M,Wilhelm U et al. Health problems after travel to developing countries. J Infect Dis 1987;156:84-91.
Addiss DG, Tauxe RV, Bernard KW. Chronic diarrhoeal illness in US Peace Corps volunteers. Int J Epidemiol 1990;19:217-8.
Msengi AE, Phillips AD, Risdon RA et al. Travellers' diarrhoea among children returning to the United Kingdom from visits abroad. Ann Trop Paediatr 1998;8:173-80.
Pitzinger B, Steffen R, Tschopp A. Incidence and clinical features of traveler's diarrhea in infants and children. Pediatr Infect Dis J 1991;10(10):719-23.
Osterholm MT, MacDonald KL,White KE et al. An outbreak of a newly recognized chronic diarrhea syndrome associated with raw milk consumption. JAMA 1986;256:484-90.
Mintz ED,Weber JT, Guris D et al. An outbreak of Brainerd diarrhea among travelers to the Galapagos Islands. J Infect Dis 1998;177:1041-5.
El Ghaffar YA, El Ghaffar MA. Atypical chronic intestinal shigellosis. Am J Trop Med Hyg 1955;4:301-9.
Bhan MK, Raj P, Levine MM et al. Enteroaggregative Escherichia coli associated with persistent diarrhea in cohort of rural children in India. J Infect Dis 1989;159:1061-4.
Lima AA, Fang G, Schorling JB et al. Persistent diarrhea in northeast Brazil: Etiologies and interactions with malnutrition. Acta Paediatr 1992(suppl)381:39-44.
Walker MM. What is tropical sprue? J Gastroenterol Hepatol 2003;18:887-90.
Ghoshal UC, Ghoshal U, Ayyagari A et al. Tropical sprue is associated with contamination of small bowel with aerobic bacteria and reversible prolongation of orocecal transit time. J Gastroenterol Hepatol 2003;18:540-7.
Rossignol J-FA, Ayoub A, Ayers MS. Treatment of diarrhea caused by Cryptosporidium parvum: a prospective randomized, double-blind, placebo-controlled study of nitazoxanide. J Infect Dis 2001;284:103-6.
Leder K, Hellard ME, Sinclair MI et al. No correlation between clinical symptoms and Blastocystis hominis in immunocompetent individuals. J Gastroenterol Hepatol 2005;20(9):1390-4.
Lopez-Velez R, Turrientes MC, Garron C et al. Microsporidiosis in travelers with diarrhea from the tropics. J Travel Med 1999;6(4):223-7.
Genta RM. Diarrhea in helminthic infections. Clin Infect Dis 1993;16(suppl 2):S122-S129.
Gill CJ, Lau J, Gorback SL et al. Diagnostic accuracy of stool assays for inflammatory bacterial gastroenteritis in developed and resource-poor countries. Clin Infect Dis 2003;37:367-75.
McNeelyWS, Dupont HL, Mathewson JJ et al. Occult blood versus fecal leukocytes in the diagnosis of bacterial diarrhea: a study of US travelers to Mexico and Mexican children. Am J Trop Med Hyg 1996;55:430-3.
Bauer TM. Chronic diarrhea: therapy with antibiotics. Schweiz Rundsch Med Prax 2000;89(41):1643-6.
Taylor DN, Connor BA, Shlim DR. Chronic diarrhea in the returned traveller. Med Clin North Am 1999;83(4):1033-52.
Schiller LR, Sellin JH. In: Feldman M (ed). Sleisenger and Fordtran's gastrointestinal and liver disease, 7th ed. Philadelphia: Saunders, 2002:131-50.
Camilleri M. Chronic diarrhea: a review on pathophysiology and management for the clinical gastroenterologist. Clin Gastroenterol Hepatol 2004;2:198-206.
Schiller LR. Review article: anti-diarrhoeal pharmacology and therapeutics. Aliment Pharmacol Ther 1995;9:87-106.
Tagkalidis P, Bhathal P, Gibson P. Microscopic colitis. J Gastroenterol Hepatol. 2002;17(3):236-48.
Allen S, Okoko B, Martinez E et al. Probiotics for treating infectious diarrhoea. Cochrane Database Syst Rev. 2004;2:CD003048.
Rosenfeldt V, Michaelsen KF, Jakobsen M et al. Effect of probiotic Lactobacillus strains in young children hospitalized with acute diarrhea. Pediatr Infect Dis J 2002;21(5):411-6.
D'Souza AL ll, Rajkumar C, Cooke J et al. Probiotics in prevention of antibiotic associated diarrhoea: meta-analysis. Br Med J 2002;324:1361-6.
McFarland LV, Surawicz CM, Greenberg RN et al. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA 1994;271:1913-8.
Gaon D, Garcia H, Winter L et al. Effect of Lactobacillus strains and Saccharomyces boulardii on persistent diarrhea in children. Medicina (B Aires) 2003;63(4)293-8.
Kirchhella A, Fruhwein N, Toburen D. Treatment of persistent diarrhea with S. boulardii in returning travelers. Results of a prospective study. Fortschr Med 1996;114(11):136-40.
Huang DB, Awashti M, Le BM et al. The role of diet in the treatment of travelers' diarrhea: a pilot study. Clin Infect Dis 2004;468-71.
Steffen R, Gyr K. Diet in the treatment of diarrhea: from tradition to evidence. Clin Infect Dis 2004;39:472-3.
Niaz SK, Sandrasegaran K, Renny FH et al. Postinfective diarrhoea and bile acid malabsorption. J R Coll Physicians Lond 1997;31(1):53-6.
Eherer AJ, Santa Ana CA, Porter J et al. Effect of psyllium, calcium polycarbophil, and wheat bran on secretory diarrhea induced by phenolphthalein. Gastroenterology 1993;104:1007-12.
Talley NJ. Pharmacologic therapy for the irritable bowel syndrome. Am J Gastroenterol 2003;98(4):750-8.
Afzalpurkar RG, Schiller LR, Little KH et al. The self-limited nature of chronic idiopathic diarrhea. N Engl J Med 1992;327:1849-52.
Taylor DN, Connor BA, Shlim DR. Chronic diarrhea in the returned traveller. Med Clin North Am 1999;83(4):1033-52.
Dupont HL, Capsuto EG. Persistent diarrhea in travelers. Clin Infect Dis 1996;22:124-28.
Giannella RA. Chronic diarrhea in travelers: diagnostic and therapeutic considerations. Rev Infect Dis 1986;8(suppl 2):S223-S226.
*Members: Dr. B.Ward (Chair); Dr. C. Beallor; M. Bodie-Collins (Executive Secretary); Dr. K. Gamble; Ms. A. Henteleff; Dr. S. Houston; Dr. S. Kuhn; Dr. A. McCarthy; Dr. K.L. McClean; Dr. P.J. Plourde; Dr. J.R. Salzman.
Liaison Representatives: Dr. R.J. Birnbaum; Dr. C. Greenaway; Dr. C. Hui; Dr. R. Saginur; Dr. P. Teitelbaum; Dr. M.Woo.
Ex-Officio Representatives: Dr. N. Gibson; Dr. J. Given; Dr. F. Hindieh; Dr. J.P. Legault; Dr. P. McDonald; Dr. R. Paradis; Dr. C. Reed; Dr. M. Smith; Dr. M. Tepper.
Member Emeritus: Dr. C.W.L. Jeanes.
†This statement was prepared by Dr. S. Houston and approved by CATMAT.