Hard Facts About Loose Stool Persistent Diarrhoea in the Returned Traveller

1. Hard Facts About Loose StoolPersistent Diarrhoea in the Returned Traveller Stan Houston Dep’t of Medicine & School of Public Health, U of Alberta

2. Objectives: Persistent Diarrhoea • A subset, generally a complication, of “regular” acute travellers diarrhoea • What is it? (arbitrarily, duration > 30 days) • Who gets it? • What causes it? • What investigations are appropriate? • How should we manage it?

3. Why Talk About Persistent Diarrhoea? • It is not uncommon • It is a significant challenge when it occurs • We are getting a handle on acute, “garden variety” travellers’ diarrhoea • Very common • Mainly food borne • Usually bacterial (? Role of norovirus) • Realistic expectations • Practical strategies • We are learning more about persistent diarrhoea

4. Persistent Diarrhea Post-TravelDifferential Diagnosis • “Typical” protozoan cause (E. histolytica, G. lamblia) • Atypical presentation of “acute” pathogens, e.g. Shigella • Newer pathogens: Cyclospora, Cryptosporidia, Dientameba fragilis • ?Lactose intolerance • Clostridium difficile diarrhea (antibiotic-related) • “Unmasked” inflammatory bowel disease (IBD) or celiac disease • Tropical sprue • HIV-related • Post infectious irritable bowel • Helminths (worms or flukes) rarely cause diarrhea in travellers

5. Case 1. • 38 y.o. man returned from living in Mexico with a history of intermittent bloody, mucusy diarrhoea over a period of months. • Multiple stool exams for everything, specifically amebiasis, negative • Colonoscopy when he had been asymptomatic for some time…negative

6. The doctor has to be persistent too • Physical examination unremarkable • Stool examinations negative • Repeat colonoscopy showed ulcerative colitis (and biopsies confirmed absence of ameba) • Responded well to standard therapy

7. Case 2. 33 y.o. alternative medicine enthusiast, • Persistent diarrhoea on return from Yemen • Large volume, minimal pain, occasionally nocturnal • 20 lb. weight loss* • I was hoping for my first case of tropical sprue!

8. Case 2, cont’d • Small bowel biopsy: celiac disease (serology positive) • Responded to celiac diet

9. Unmasked disease • Inflammatory bowel disease • Celiac disease • ? Lactose intolerance, irritable bowel syndrome

10. Tropical sprue • Much discussed in the era of the British empire and the wars of the first half of the 20th century • Persistent malabsorption syndrome acquired in the tropics • Epidemiology unclear or inconsistent • Thought to be mediated by bacterial overgrowth in small intestine • Rx: antibiotics & folate • Rarely if ever seen now

11. Family Doc in her 30’s • Went to Chad as a missionary • Within 48 hrs. of arrival, her kids got very sick with febrile diarrhea, improved with cotrimoxazole • 3 wks later she got sick • Cramps “worse than labour” • In bed X 10 days • Tenesmus, some blood & mucus

12. For the next 10 months • Diarrhea persisted, waxed & waned, never resolved • Experienced severe urgency & incontinence • Lost 9 kg • Had amebiasis diagnosed in a Chadian lab, Rx with no benefit • Cultures negative in Burkino Faso & Nairobi • Never took antibiotics! • In Canada, 1 culture negative • So of course, she was scoped

13. Chadian Diarrhea

14. Endoscopic Diagnosis • Definite IBD • Given a prescription for Asacol • A report was received

15. 2nd specimen: Shigella flexneri serotype 1. • R Amp, S TMPSMX, S ciproflox

16. Course • Rx: ciprofloxacin 500 bid X 14 • Better within days, rapidly returned to normal health, stool habit and weight, fine since.

17. Common bugs behaving uncommonly • Shigella normally self limiting • Persistent shigella has been described, often in association with HIV (my colleague was HIV negative)

18. Case 3. 26 y.o. ♀ epidemiologist • Returned from a year working in Brazil, via Peru, where she had an acute diarrhoeal illness, treated with ciprofloxacin with improvement • On return, within 1-2 weeks, had recurrent diarrhoea with small volume, tenesmus, mucus in stool and lower abdominal pain

19. Case 3 cont’d • Stool C&S negative • Stool O&P negative • Stool positive for Clostridium difficile toxin • Responded to metronidazole (but had one relapse). Has done well since.

20. Clostridium difficile • Infamous as a nosocomial pathogen • Requires “2 hit” sequence, timing may be important • Alteration of normal flora by antimicrobial Rx • Exposure to C. difficile, which is common, ubiquitous in health care settings • Occasionally recognized as a TD pathogen • CID 2008:46:1060. 6 cases, all had taken abx, no hospital contact • Travellers frequently take antibiotics for various reasons • Evolving issues • Increased virulence and changing drug resistance • Relapses common; management unclear

21. Case 7: 39 y.o ♂. highly travelled hotel manager • Progressive diarrhoea  15 stools/day over 3-4 weeks after return from Hong Kong • 20 lb weight loss • Previous stool C&S & O&P negative • O/E • Thin, slightly dehydrated • Oral candidiasis • Lab: cryptosporidia in stool

22. Case 7 cont’d • Subsequently obtained history of homosexual riskHIV test + • HIV +, CD4 count 60/ • Required hospitalization, nitazoxanide, antiretroviral therapy (ART) initiation; interestingly, he had colonic involvement • Now doing well on ART, diarrhoea long since resolved, recently sent a postcard from Sri Lanka.

23. Cryptosporidia • Cryptosporidia ubiquitous in low income & industrialized countries, probably a fairly common cause of travel-related diarrhea in some settings • Self limited, albeit after +/- 2 weeks in the immunocompetent • Severe persistent disease often seen in presence of decreased cell mediated immunity

24. Misc. • Amebiasis, Entameba histolytica. • Not strictly a tropical disease • Causes persistent colonic involvement • Can cause liver abscess (with or without diarrhoea or positive stool) • The practical problem is that microscopy cannot distinguish it from E. dispar, a non-pathogenic commensal which is much more common than E. histolytica

25. What if the only positive result isBlastocystis hominis? • Controversial as a pathogen • ? Strain specificity • Treatment unclear; options include metronidazole, cotrimoxazole

26. What About “Post-Infectious Irritable Bowel Syndrome” • Largely a diagnosis of exclusion at present • Conceivably some of these patients have infection with as-yet unrecognized organisms • Several follow up studies show that after specific infections, e.g. Salmonella, verotoxin producing E. coli , Campylobacter & Shigella, a high proportion of people have altered bowel habit when surveyed many months later, even though most had not presented to a health care provider • 4-32% of people who have travellers diarrhoea met the criteria for irritable bowel syndrome months later

27. Dupont CID 2008;46:594 b Study without pathogen identification

28. A Biological Basis? • Significant increases in the number of rectal enterochromaffin cells and in lymphocyte counts have also been reported in patients with postinfectious IBS, compared with matched control subjects who recovered from their acute illness without subsequent IBS • Alterations of cytokines, serotonin levels & gut permeability have been reported in PIIBS as compared to normals • Is this really a form of irritable bowel syndrome, or are the mechanisms different?

29. Risk Factors Associated with Post Infectious IBS Dupont, CID 2008 • Psychological factors • preexisting psychological disorders have repeatedly been associated with an increased risk of postinfectious IBS • a history of anxiety or depression has been shown to be less common among patients with postinfectious IBS than among those with non-postinfectious IBS (26% vs. 54%). • Duration of the acute episode • 11-fold increase in the risk of developing postinfectious IBS in those with acute symptoms lasting >3 weeks compared with those with an acute illness duration of <1 week • ? severity • Etiologic organism? Suggestion of ↑ risk with invasive pathogens • Antibiotic use associated with development of PI-IBS in some studies (? Indicator of severity)

30. Approach to the Patient with Persistent Diarrhoea Post Travel • History • Persistent or recurrent? • Previous bowel habit • Other health problems, *medications • Severity • Blood, mucus • Small vs. large bowel features • Weight loss

31. Investigation • ? Trial of lactose elimination • Stool for O&P X ? • Stool C&S • Stool for C. difficile if any history of antibiotic exposure • ??empiric metronidazole +/or ciprofloxacin • observation

32. Further investigation? • If: • Severity • Interfering with activity • +/- patient’s perception • Weight loss • Blood/mucus in stool • Consider endoscopy + biopsy, starting at the most likely end, depending on symptoms • Role for breath test for bacterial overgrowth?

33. Post Travel IBS: treatment • Antimotility agents (loperamide, diphenoxylate) • Bulking agents • Other strategies: bismuth, bile salt binders, probiotics • ?? New irritable bowel drugs, e.g. tegaserod • *Reassure the patient regarding our understanding of the condition, that there are many other people in the same boat, that whatever we don’t know about it, we do know that people with this presentation don’t turn out later to have some awful exotic disease that does them in years later

34. Post travel IBS: ? prevention • Measures to prevent acute travellers’ diarrhoea • Risk reduction • Bismuth • ??Dukoral

35. References • Dupont. (review post infectious IBS) CID 2008:46 594 • CATMAT statement. http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/06vol32/acs-01/index.html