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Travelers' Diarrhea (TD) 2000

Course Authors

Gary M. Gray, M.D.

Dr. Gray reports no commercial conflict of interest.

This activity is made possible by an unrestricted educational grant from the Novartis Foundation for Gerontology.

Estimated course time: 1 hour(s).

Albert Einstein College of Medicine – Montefiore Medical Center designates this enduring material activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

In support of improving patient care, this activity has been planned and implemented by Albert Einstein College of Medicine-Montefiore Medical Center and InterMDnet. Albert Einstein College of Medicine – Montefiore Medical Center is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

 
Learning Objectives

Upon completion of this Cyberounds®, you should be able to:

  • Recognize the syndrome of Travelers' Diarrhea

  • Institute the appropriate therapy for Traveler's Diarrhea

  • Evaluate patients for unusual causes of diarrhea when the expected positive response is not achieved with conventional therapy.

 

The development of diarrhea in those traveling to foreign lands continues to be a problem that produces considerable morbidity and loss of function for at least two days in a relatively high proportion of those who venture from North America or Western Europe to countries closer to the equator. A relatively high proportion of those who travel to other countries such as Mexico, Central America, Morocco, Jamaica, Thailand, Micronesia, Nepal and the Philippines contract the syndrome of Travelers' Diarrhea (TD). The rate of diarrheal development in travelers varies somewhat with the year and season, but, on average, nearly 25 percent of those from the United States or Western Europe who visit these regions develop a diarrheal illness.(1)

The Presentation

Acute onset of abdominal cramping pains quickly progresses to daily multiple watery stools and is often accompanied by nausea and, not infrequently, emesis. Fever may be present but is often absent. Symptoms usually continue for more than two days and, then, gradually subside. Patients often become incapacitated with anorexia, thirst and fatigue, and requirement for bed rest is common. Dehydration may become severe, and intravenous replacement is sometimes necessary.

The Culprits

Many studies have documented that a bacterial infection accounts for the vast majority of cases of Travelers' Diarrhea, the most common source being contamination of food and water with fecal organisms. Enterotoxigenic or enteroaggregative E. coli have been the most thoroughly studied -- evidence of infestation with these organisms having been found in one-quarter to one-half the cases of TD in Jamaica and Mexico.(2),(3) Other bacteria are also important pathogens in TD, particularly Campylobacter species that has been shown to be even more common than E. coli in traveling United States military personnel.(4)

Salmonella and shigella are also commonly responsible bacterial species; rotavirus has also proved to be the most likely culprit in some cases. Epidemics of severe secretory diarrhea caused by Vibrio cholera, often from contaminated shellfish, appear from time to time. In protracted diarrheal illness, especially in the immunocompromised host, cyclospora(5) and microsporidium(6) have been isolated.

Are Diagnostic Tests Required?

Recent applications of newer molecular probes for bacteria, particularly utilizing the polymerase chain reaction (PCR) to amplify the bacterial gene product in stool, have improved the sensitivity of detection.(7) However, because bacteria that are susceptible to quinolone antibiotic therapy cause the majority of TD cases, a clinical diagnosis of the disease is sufficient to warrant therapy.

Is Therapy Worthwhile?

When it became appreciated many years ago that bacteria were present in the liquid stools of many sufferers of TD, prophylaxis with trimethiprim-sulfamethoxazole (TMP-SMX) was demonstrated to markedly reduce the development of TD. However, the large fraction (75%) of travelers who escape the disease must be subjected needlessly to the drug, and this might also lead to the development of antibiotic resistance. After the initial enthusiasm for the prophylactic treatment of all travelers to the endemic areas, therapy at the first symptom of TD was found to be effective. Subsequent clinical trials revealed that institution of antibiotic coverage at the outset of symptoms is very effective in aborting the acute diarrheal disease. Also, the addition of loperamide (Immodium®) to the therapeutic regimen to control the cramps and frequent loose stools has proved to be a useful supplement to the antibacterial therapy.

As some resistance to TMP-SMX began to develop, the quinolone antibiotics, especially ciprofloxacin, became the most commonly chosen antibacterial drugs. An effective combination is ciprofloxacin 500 mg b.i.d. for 3-5 days and loperamide, initially at a 4 mg loading dose and, then, 2 mg after each passage of any unformed stool.(8) Such combined therapy of a quinolone antibiotic with the anti-diarrheal agent shortens the course of the symptomatic illness from greater than two days to a single day.(9) A clinical cure with complete disappearance of symptoms is achieved in 95 percent of patients with three days of quinolone antibiotic therapy, whereas symptoms resolve in only 25 percent of patients within this time if no antibiotic is taken. Notably, although a definitive diagnosis of a precise bacterial cause is not routinely made, antibiotic therapy shortens the average course of the illness from 69 hours (placebo) to 28 hours (control),(10) and there are no significant complications or side-effects. Certainly, quinolone antibiotic therapy is effective in shortening the course of TD.

The periodic attacks of cholera caused by the secretory toxin of Vibrio cholera can exhaust the capacity of local health care facilities to provide the major oral fluid replacement that is required. Fortunately, a live, attenuated, oral V. cholera vaccine, designed by deletion of most of the gene for the active subunit, has been recently demonstrated to protect human volunteers from V. cholera infections.(11) This vaccine may prove to be useful in special groups, such as those on military expeditions who travel to areas of high risk for cholera.

Well Established Beliefs and Practices Have Been Set Aside in the Therapy of TD

For many years, there had been several accepted dicta that have led to a reluctance to use antibiotics in an apparent infectious process of the hollow gut, unless a pathogen could be identified. But frequency of TD has provided the broad experience with these groups of illnesses and has resulted in rejection of long-held beliefs of the past.

The concept that antibiotic therapy of a relatively routine bacterial enteric infection, such as that caused by Salmonella sp., may predispose to a relapsing infection, perhaps with resistant organisms, has not been supported by the clinical trials in TD. With the exception of the occasional case of recurrent Campylobacter sp. when quinolone antibiotic therapy is used.(4) antibiotic therapy with the commonly used ciprofloxacin, has been highly effective in aborting the TD attack in recent years.

The espoused advice to avoid anti-diarrheal agents, because reduction of stool flow may lead to delay in the clearance of the bacterial pathogen, has not been substantiated in the TD clinical trials. Instead, a drug such as loperamide plays a role in reducing the number and increasing the consistency of stools, thereby shortening the clinical course.

Oral Rehydration Therapy (ORT), known to be highly effective in the devastating secretory diarrheas and particularly popularized in World Health Organization trials in the "rice water" diarrhea induced by Vibrio cholera, does not shorten the course in TD over and above that provided by loperamide alone.(*)

A Practical Approach of the Physician for the Traveler to Endemic Areas

It has been well established that those traveling to endemic areas of TD find it very difficult to avoid contaminated food and water, so avoidance of the ingestion of contaminated food and water is not a reasonable expectation. Because about 25 percent of such travelers will develop symptoms of abdominal cramps and diarrhea that will interfere with their ability to function normally, antibiotic therapy at the outset of the disease is the first line of defense. For those traveling to developing countries having more temperate climates, where bacterial contamination of food and water is known to be endemic, therapy should be instituted with the first sign of abdominal cramping pain and watery stools. It is reasonable for individuals traveling to the endemic locales to be given a three-day supply (six 500 mg capsules) of ciprofloxacin or other quinolone antibiotic and sufficient loperamide capsules to allow for the loading dose and several subsequent doses (a total of ~20 tablets). For the few patients who do not respond with a rapid return to normal bowel function, the physician should then examine the patient, obtain routine laboratory blood tests (complete blood count, other appropriate tests depending upon the physical exam), stool analysis for bacterial culture and ova and parasite examination.


Footnotes

*
1Steffen R, Collard F, Tornieporth N, Campbell-Forrester S, Ashley D, Thompson S, Mathewson JJ, Maes E, Stephenson B, DuPont HL, von Sonnenburg F. Epidemiology, etiology, and impact of traveler\'s diarrhea in Jamaica. JAMA 281:811-817, 1999.
2Glandt M, Adachi JA, Mathewson JJ, Jiang ZD, DiCesare D, Ashley D, Ericsson CD, DuPont HL.: Enteroaggregative Escherichia coli as a cause of traveler\'s diarrhea: clinical response to ciprofloxacin Clin Infect Dis 29:335-338, 1999.
3Jiang ZD, Mathewson JJ, Ericsson CD, Svennerholm AM, Pulido C, DuPont HL: Characterization of enterotoxigenic Escherichia coli strains in patients with travelers\' diarrhea acquired in Guadalajara, Mexico, 1992-1997. J Infect Dis 181:779-782, 2000.
4Petruccelli BP, Murphy GS, Sanchez JL, Walz S, DeFraites R, Gelnett J, Haberberger RL, Echeverria P, Taylor DN: Treatment of traveler\'s diarrhea with ciprofloxacin and loperamide. J Infect Dis 165:557-560, 1992.
5Lopez-Velez R, Turrientes MC, Garron C, Montilla P, Navajas R, Fenoy S, delAguila C: Microsporidiosis in travelers with diarrhea from the tropics. J Travel Med 6:223-227, 1999.
6Caeiro JP, Estrada-Garcia MT, Jiang ZD, Mathewson JJ, Adachi JA, Steffen R, DuPont HL: Improved detection of enterotoxigenic Escherichia coli among patients with travelers\' diarrhea, by use of the polymerase chain reaction technique J Infect Dis 180:2053-2055, 1999.
7Okhuysen PC, DuPont HL, Ericsson CD, Marani S, Martinez-Sandoval FG, Olesen MA, Ravelli GP: Zaldaride maleate (a new calmodulin antagonist) versus loperamide in the treatment of traveler\'s diarrhea: randomized, placebo-controlled trial. Clin Infect Dis 21:341-344, 1995.
8Mattila L, Peltola H, Siitonen A, Kyronseppa H, Simula I, Kataja M : Short-term treatment of traveler\'s diarrhea with norfloxacin: a double-blind, placebo-controlled study during two seasons. Clin Infect Dis 17:779-782, 1993.
9DuPont HL, Ericsson CD, Mathewson JJ, DuPont MW: Five versus three days of norfloxacin therapy for traveler\'s diarrhea: a placebo-controlled study. Antimicrob Agents Chemother 36:87-91, 1992.
10Tacket CO, Cohen MB, Wasserman SS, Losonsky G, Livio S, Kotloff K, Edelman R, Kaper JB, Cryz SJ, Giannella RA, Schiff G, Levine MM: Randomized, double-blind, placebo-controlled, multicentered trial of the efficacy of a single dose of live oral cholera vaccine CVD 103-HgR in preventing cholera following challenge with Vibrio cholerae O1 El tor inaba three months after vaccination. Infect Immun 67:6341-6345, 1999.
11Caeiro JP, DuPont HL, Albrecht H, Ericsson CD: Oral rehydration therapy plus loperamide versus loperamide alone in the treatment of traveler\'s diarrhea Clin Infect Dis 28:1286-1289, 1999.