Canada Communicable Disease Report
Vol. 24 (ACS-1)
1 January 1998

An Advisory Committee Statement (ACS)
Committee to Advise on Tropical Medicine and Travel (CATMAT)*

PERSISTENT DIARRHEA IN THE RETURNED TRAVELLER

Introduction

Diarrhea is the most common affliction of travellers to developing countries⁽¹⁾ occurring in 20% to 50% of those travelling to destinations in tropical and subtropical areas of Latin America, Africa, and southern Asia^(2,3).  Even within the developed world, severe or temporary sewage-system failures or flooding may contaminate water supplies, and diarrheal illness may result^(4,5).

Travellers' diarrhea (TD) is usually an acute illness characterized by at least three loose or semiformed stools per day.  It may be associated with other symptoms such as nausea, vomiting, and abdominal pain⁽⁶⁾. The onset of illness usually coincides with travel, although it may occur during the first 7 to 10 days after returning home.

The prevention and treatment of acute, usually self-limiting, TD can be found in the CATMAT statement on TD⁽⁷⁾. In general, no investigations are necessary and self-treatment can be advocated for acute TD unless the patient is very ill, has a significant underlying medical illness, is immunodeficient, or has bloody stools; if any of these apply, medical assistance should be sought for investigation and management.

Some travellers may not have onset of their symptoms until after returning from travel.  This may be acute TD with a prolonged incubation period, i.e. onset > 7 days after leaving a tropical location.  In such cases diarrhea is less likely to be due to bacterial agents.  Campylobacter may have an incubation period of up to 10 days; however, the illness which begins after return is more likely to be due to other etiologies with longer incubation periods such as giardiasis (3 to 25 days), amoebiasis (2 to 4 weeks), and schistosomiasis (2 to 6 weeks).  As well, the gastrointestinal illness may be unrelated to and only coincident with the recent travel.  These individuals should be evaluated by a health-care worker and investigated to determine the etiology as outlined for travellers with persistent diarrhea.  This subgroup of patients is less likely to respond to the standard recommendations for acute TD.

The present statement specifically addresses the returned traveller with persistent diarrhea, i.e. with symptoms lasting >=14 days as defined by the World Health Organization⁽⁸⁾.  Relevant English-language articles published between October 1990 and June 1997 were identified through MEDLINE using the terms "diarrhea" and "travel"; relevant articles cited in the bibliographies were searched manually.

Incidence and Etiologies of Persistent Travellers' Diarrhea

The true incidence of persistent diarrhea related to travel is not known, but has been estimated to occur in 1% to 3% of those experiencing acute TD^(1,6,9-11). Unfortunately, most cases of persistent diarrhea have no known etiology.  Patients presenting with acute TD often suffer from bacterial infection, with bacteria accounting for 50% to 70% of cases; those with persistant TD often have post-infectious lactose intolerance or irritable bowel syndrome.

The differential diagnosis of persistent diarrheal illness includes the following:

• missed diagnosis, which should be minimized with the use of a competent laboratory employing special stains and procedures for specific pathogens such as cryptosporidiasis, cyclosporiasis, and strongyloidiasis
• malabsorption
• inflammatory bowel disease
• irritable bowel syndrome (neuromuscular discoordination)
• bile-salt enteritis
• lactose intolerence.

Etiologic agents, if found, are more likely to be parasitic in origin (Table 1).  Certain geographic areas are notorious for specific microbes.  Giardiasis is ubiquitous, yet it is most often thought of as a consequence of travel to Russia and mountainous areas of North America.  Cyclosporasis has been geographically linked to Nepal; however, North American outbreaks underscore its potential widespead nature^(5,12,13).

Tropical sprue, a very unusual problem for travellers, is associated with prolonged travel of  >1 year to high-risk areas such as Puerto Rico, Dominican Republic, Haiti, Cuba, West Indies, India, Burma, southeast Asia, and the Phillippines.

Table 1 Etiology of persistent TD

Patient Evaluation

Evaluation of the patient should include a complete history and physical examination, with particular emphasis on the travel itinerary and potential exposure to enteric pathogens based on assessment of the sanitary quality of water and food during travel. Note should be made of the time of the symptom onset in relation to travel.  Some travellers attribute their diarrhea to their trip, when their symptoms may have antedated the trip or be only coincident with travel.  A careful history of gastrointestinal symptoms antedating travel may provide an important clue to the presence of irritable bowel syndrome or other etiologies.

If fever occurs in conjunction with diarrhea and a travel itinerary indicates travel to a malaria-endemic area, it is imperative to do blood smears to rule out malaria, as well as blood cultures. Note should be made of the stool quality and quantity; for example, watery, malabsorptive (semiformed, bulky, greasy, or malodorous), or bloody.  Are the stools small in volume and frequent, associated with tenesmus suggesting large bowel origin, or are they voluminous and watery suggesting of small bowel pathology?  Characterizing the stool quality may help to direct further investigation to the small or large bowel.  In general, bloody diarrhea requires investigation as it may be associated with persistent invasive bacterial gastroenteritis, amoebiasis, or inflammatory bowel disease.

Weight loss should be noted, with emphasis on the time of the weight loss in relation to the onset of diarrhea; significant weight loss suggests underlying pathology rather than irritable bowel syndrome or lactose intolerence. Other important questions include the following:

• Are there any other associated symptoms, such as extra intestinal manifestations of disease (inflammatory bowel disease)?
• Has there been any antimicrobial ingestion in the previous month (Clostridium difficile colitis)?
• Is there any change in symptoms related to oral intake, specifically with respect to lactose or fatty foods?
• Is there any underlying condition that might predispose to more severe or prolonged diarrhea, for example, infection with the HIV?

Management of the Patient

Figure 1 presents an approach to the management of patients with persistent diarrhea following travel. Bacterial culture of a single stool specimen⁽¹⁴⁾ as well as ova and parasite examination of three stool specimens collected on different days⁽¹⁵⁾ should be undertaken.  An assay for C. difficile cytotoxin should be done if there is a history of antimicrobial ingestion within the past month.  While awaiting the results of these initial investigations, patients should be advised to avoid all lactose in their diet or pretreat with a commercial lactase; this may alleviate the symptoms and negate the need for further intervention.  As well, they should be advised to decrease caffeine intake and increase dietary bulk.

Figure 1 Approach for the management of persistent travellers' diarrhea Prise en charge de la diarrhée persistante des voyageurs

In general, profuse diarrhea should be treated with fluids to maintain hydration.  For guidelines concerning the management of hydration in children, refer to the Canadian Paediatric Society's statement on the use of oral rehydration solution⁽¹⁶⁾.

Specific etiologic agent(s) identified in the initial investigation should be treated using appropriate published recommendations.  If, however, there is no diagnosis established after appropriate investigation and dietary restrictions, then symptomatic treatment with bulk agents (e.g. metamucil), antimotility agents (e.g. loperamide) or bile-salt therapy (cholestyramine for the control of bile-salt enteritis following TD) may be considered.  If these measures fail to control symptomatology, or stools are malabsorptive or bloody, or weight loss continues, then further investigation including bowel imaging, endoscopy, and biopsy should be undertaken.  Upper endoscopy with small bowel biopsy can diagnose or exclude tropical sprue and may contribute to the diagnosis of other conditions that have been missed by stool examination.  Sigmoidoscopy or colonoscopy may contribute to the diagnosis of such conditions as invasive amoebiasis, intestinal schistosomiasis, or inflammatory bowel disease. However, there are currently no good data to define the role of these investigations in the management of patients with persistent TD.

Some experts⁽⁹⁾ advocate trials of therapy with agents such as metronidazole or a quinolone antimicrobial if the above investigations have failed to identify an etiology for the persistent diarrhea.

Recommendations

Table 2 presents evidence-based medicine categories⁽¹⁷⁾ for the strength and quality of evidence for each of the recommendations that follow.

Table 2 Strength and quality of evidence summary sheet

1. In general, returned travellers with diarrhea of < 5 days duration require no work up and should be managed as per the CATMAT statement on TD⁽⁷⁾. Epidemiologically, in the case of an outbreak there may be a reason to investigate (B III).

2. Returned travellers with persistent diarrhea should be assessed with a complete history, including a travel history with a review of potential enteric pathogen exposure, ingestions, and recent antimicrobial use.  Evidence of disease antedating the trip should be sought and a physical examination should be carried out (B III).

3. In cases of persistent diarrhea, stool samples should be examined at a competent laboratory for ova and parasites; bacterial culture should be done, and if there has been recent antimicrobioal ingestion, evaluation for C. difficile cytotoxin should also be carried out. Appropriate diagnostic imaging and/or endoscopy should be considered particularly if diarrhea is accompanied by weight loss, hematochezia, or other systemic symptoms of illness (B III).

4. Specific therapy to eradicate microbial agents should be used, when justified, using published guidelines (A II).

5. Any febrile traveller with diarrhea who has visited a malaria-endemic area should have blood smears carried out to rule out malaria (A II).

6. Blood culture examination should be undertaken if there is fever associated with the diarrhea (A II).

References

1. Steffen R, Rickenbach M, Wilhelm U et al.  Health problems after travel to developing countries.  J Infect Dis 1987;156:84-91.

2. Steffen R. Epidemiologic studies of travelers' diarrhea, severe gastrointestinal infections and cholera.  Rev Infect Dis 1986;8:S122-S130.

3. Dupont HL, Khan FM.  Travelers' diarrhea: epidemiology, microbiology, prevention, and therapy.  J Travel Med 1994;1:84-93.

4. MacKenzie WR, Hoxie NJ, Proctor ME et al. A massive outbreak in Milwaukee of cryptosporidium infection transmitted through the public water supply.  N Engl J Med 1994;331:161-67.

5. CDC. Outbreaks of Cyclospora cayetanensis infection - United States, 1996.  MMWR 1996;45:549-51.

6. Dupont HL, Ericsson CD.  Prevention and treatment of travelers' diarrhea.  N Engl J Med 1993;328:1821-27.

7. Committee to Advise on Tropical Medicine and Travel. Statement on travellers' diarrhea.  CCDR 1994;20:149-55.

8. Health Organization Diarrhoea Disease Control Programme. Persistant diarrhoea in children in developing countries. Presented at the Meeting on Persistant Diarrhoea in Children in Developing Countries. Geneva, Switzerland, 1987.

9. Dupont HL, Capsuto EG. Persistent diarrhea in travelers. Clin Infect Dis 1996; 22:124-28.

10. Guerrant R, Rouse J, Hughes J et al.  Turista among members of the Yale Glee Club in Latin America.  Am J Trop Med Hyg 1980; 29:895-900.

11. Addiss DG, Tauxe RV, Bernard KW.  Chronic diarrhoeal illness in US Peace Corps volunteers.  Int J Epidemiol 1990; 19:217-18.

12. Himy R, Villard O, and Kremer M.  Cyclosporida: a general review. J Travel Med 1995;2:33-6.

13. CDC. Update: outbreaks of Cyclospora cayetanensis infection - United States and Canada, 1996. MMWR 1996;45:611-12.

14. Church DL, Cadrain G, Kabani A et al. Practice guidelines for ordering stool cultures in a pediatric population.  Am J Clin Pathol 1995;103:149-53.

15. Hiatt RA, Markwell EK, Ng E.  How many stool examinations are necessary to detect pathogenic intestinal protozoa?  J Trop Med Hyg 1995;53:36-9.

16. Canadian Paediatric Society. Oral rehydration therapy early refeeding in the management of childhood gastroenteritis. Can J Ped 1994;1:160-64.

17. MacPherson DW. Evidence-based medicine. CCDR 1994;20:145-47.

Members: Dr. K. Kain (Chairperson); H. Birk; Ms. M. Bodie-Collins (Secretariat);   Dr. S.E. Boraston; Dr. W. Bowie; Dr. H.O. Davies; Dr. J.S. Keystone;  Dr. D.W. MacPherson; Dr. A. McCarthy (Executive Secretary); Dr. J.R. Salzman; Dr. D. Tessier.

Ex-Officio Members: Dr. E. Callary (HC); LCdr. D. Carpenter (DND);  R. Dewart (CDC); Dr. E. Gadd (HC); Dr. C.W.L. Jeanes; Dr. H. Lobel (CDC).

[Canada Communicable Disease Report]