Hard Facts About Loose Stool Persistent Diarrhoea in the Returned Traveller

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Hard Facts About Loose StoolPersistent Diarrhoea
in the Returned Traveller

• Stan Houston
• Dept of Medicine School of Public Health, U of
  Alberta

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Objectives Persistent Diarrhoea

• A subset, generally a complication, of regular
  acute travellers diarrhoea
• What is it? (arbitrarily, duration gt 30 days)
• Who gets it?
• What causes it?
• What investigations are appropriate?
• How should we manage it?

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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

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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

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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 timenegative

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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

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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!

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Case 2, contd

• Small bowel biopsy celiac disease (serology
  positive)
• Responded to celiac diet

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Unmasked disease

• Inflammatory bowel disease
• Celiac disease
• ? Lactose intolerance, irritable bowel syndrome

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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

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Family Doc in her 30s

• 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

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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

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Chadian Diarrhea
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Endoscopic Diagnosis

• Definite IBD
• Given a prescription for Asacol
• A report was received

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

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Course

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

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Common bugs behaving uncommonly

• Shigella normally self limiting
• Persistent shigella has been described, often in
  association with HIV (my colleague was HIV
  negative)

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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

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Case 3 contd

• Stool CS negative
• Stool OP negative
• Stool positive for Clostridium difficile toxin
• Responded to metronidazole (but had one relapse).
  Has done well since.

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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 2008461060. 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

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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 CS OP negative
• O/E
• Thin, slightly dehydrated
• Oral candidiasis
• Lab cryptosporidia in stool

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Case 7 contd

• 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.

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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

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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

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What if the only positive result isBlastocystis
hominis?

• Controversial as a pathogen
• ? Strain specificity
• Treatment unclear options include metronidazole,
  cotrimoxazole

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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

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Dupont CID 200846594
b Study without pathogen identification
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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?

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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 gt3 weeks compared with those with an
  acute illness duration of lt1 week
• ? severity
• Etiologic organism? Suggestion of ? risk with
  invasive pathogens
• Antibiotic use associated with development of
  PI-IBS in some studies (? Indicator of severity)

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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

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Investigation

• ? Trial of lactose elimination
• Stool for OP X ?
• Stool CS
• Stool for C. difficile if any history of
  antibiotic exposure
• ??empiric metronidazole /or ciprofloxacin
• observation

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Further investigation?

• If
• Severity
• Interfering with activity
• /- patients 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?

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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 dont
  know about it, we do know that people with this
  presentation dont turn out later to have some
  awful exotic disease that does them in years later

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Post travel IBS ? prevention

• Measures to prevent acute travellers diarrhoea
• Risk reduction
• Bismuth
• ??Dukoral

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References

• Dupont. (review post infectious IBS) CID 200846
  594
• CATMAT statement. http//www.phac-aspc.gc.ca/publi
  cat/ccdr-rmtc/06vol32/acs-01/index.html