Introduction

Recently, much attention has been drawn to viral infections affecting cruise ship passengers (e.g. the Norwalk virus). Information on such epidemics can be obtained from the US Centers for Disease control & prevention (CDC) at: "Viral Gastroenterology" http://www.cdc.gov/ncidod/dvrd/gastro.htm. (Robert Griffith, Editor)

A relatively high proportion of travelers from North America or Western Europe to other world countries closer to the equator, such as Mexico, Central America, Morocco, Jamaica, Thailand, Micronesia, Nepal and the Philippines, contract the syndrome of Travelers' Diarrhea (TD). Considerable morbidity and loss of bowel function for at least two days characterize TD. The rate of TD varies somewhat with the year and season, but, on average, nearly 25 % of those from the United States or Western Europe who visit these regions develop a diarrheal illness.

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. Symptoms usually continue for more than two days and, then, gradually subside. Patients often become incapacitated with anorexia, thirst and fatigue; dehydration may become severe and intravenous replacement is sometimes necessary.

The Culprits

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 found in one-quarter to one-half the cases of TD in Jamaica and Mexico. 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, as well as salmonella and shigella. Epidemics of severe secretory diarrhea caused by Vibrio cholera, most often from contaminated shellfish, appear from time to time. In protracted diarrheal illness, especially in the immunocompromised host, cyclospora and microsporidium 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. 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?

Many years ago, 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. Instead of prophylactic treatment of all travelers to the endemic areas, therapy at the first symptom of TD was been found to be very effective in aborting the acute diarrheal disease. Also, the addition of loperamide 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. 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. A clinical cure with complete disappearance of symptoms is achieved in 95 % of patients with three days of quinolone antibiotic therapy, whereas symptoms resolve in only 25 % of patients within this time if no antibiotic is taken.

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 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.

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, 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.

Practical Approach by the Physician

It is impractical for the traveler to avoid ingestion of contaminated food and water. Instead, antibiotic therapy at the outset of the disease is the first line of defense. For those traveling to developing countries located in 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. Providers should give travelers to these endemic locales 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.

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