Chapter 2 The Pre-Travel Consultation Self-Treatable Conditions
For the Record: A History of the Definition & Management of Travelers’ Diarrhea
Travelers’ diarrhea (TD) is defined as the passage of ≥3 unformed stools per day plus ≥1 associated enteric symptoms, such as abdominal pain or cramps, occurring in a traveler after arrival, usually in a resource-limited destination. Many colorful terms have been used for the condition according to the places where diarrhea commonly occurred, such as Aztec Two-Step, Delhi Belly, Hong Kong Dog, Montezuma’s Revenge, and the Pharaoh’s Curse.
While it was known for centuries that diarrhea and dysentery complicated armed conflicts in international settings, it wasn’t until the 1940s that diarrhea was closely correlated with international travel and relocation in tropical regions. In the 1950s, B. H. Kean from Cornell University increased awareness of the problem by studying travelers and students from the United States in Mexico. The field mushroomed in later years, when groups studied international students and travelers, expatriates, and military populations. The history of TD can be viewed in 3 time blocks based on the nature of the research conducted, focusing first on the magnitude of the problem, then with studies of etiology and specific therapy and prevention, followed by a better understanding of the consequences of the illness.
THE 1950s THROUGH THE 1960s—IDENTIFICATION OF THE PROBLEM AND SUCCESSFUL CHEMOPROPHYLAXIS
Kean and Waters studied the risk of TD among students and travelers to Mexico, finding rates of illness in international travelers of 40%—a rate that persists in many areas of the developing world. They described low rates of TD when international visitors from one developing region visited another suggesting that immunity developed secondary to exposure to common etiologic agents. This group also demonstrated successful disease prevention with antibiotic chemoprophylaxis, which provided the first evidence, albeit indirect, that bacterial pathogens were responsible for most TD. Chemoprophylaxis was used in a little more than one-third of US visitors to Mexico in the 1950s and 1960s and was used by the US, Australian, and British athletes competing in the Olympics in Mexico City in 1968.
THE 1970s THROUGHT THE 1990s—EPIDEMIOLOGY, ETIOLOGY, AND THERAPY
Clinical and epidemiologic features of TD were described. Microbiologic studies were carried out to determine the etiology of the illness, beginning with a study published in 1970 describing a single strain of Escherichia coli as the cause of TD in British troops stationed in Aden on the Red Sea. The next year, 2 strains of E. coli isolated from American soldiers with diarrhea acquired in Vietnam were shown to be enterotoxigenic in animals and adult volunteers, and 4 years later enterotoxigenic E. coli (ETEC) was found in most cases of TD among US students studying in a language school in Mexico.
The first clear evidence that antibiotics were effective in treating TD was in 1981 when trimethoprim-sulfamethoxazole was shown to reduce the duration of the illness in a group of travelers with TD caused by different etiologies. Placebo-controlled clinical trials then demonstrated the value of fluoroquinolones in treating TD. Regions of the tropical and semitropical world were studied, allowing scientists to categorize areas according to risk that international visitors would face of acquiring TD.
Although oral fluid electrolyte therapy had been shown to prevent dehydration-associated deaths in children, otherwise healthy travelers were able to keep up with fluids and salt requirements through diet and available drinks.
Although prophylactic antibiotics were used by international travelers at the time, in 1985 chemoprophylaxis with systemic antibiotics was strongly discouraged because of concerns about adverse drug events and development of drug resistance. The Consensus Development Panel favored self-treatment with short-course (single-dose or 3 days) antibiotics. Bismuth subsalicylate, a commonly used over-the-counter drug, was shown during this time period to prevent TD, giving hope that prevention strategies without stimulation of resistance might be achievable.
2000 AND BEYOND—ANTIOBIOTIC RESISTANCE AND CHRONIC COMPLICATIONS
During this phase, the fluoroquinolones, particularly ciprofloxacin, became the mainstay of therapy for TD. The poorly absorbed (<0.4%) rifamycin antibiotic, rifaximin, was found to be as effective as ciprofloxacin for the most common TD syndrome, watery diarrhea. After more than a decade of use of fluoroquinolones for a variety of infectious disease conditions, resistance to this class of drugs has become more common among some bacterial causes of TD, particularly Campylobacter jejuni. The emergence of resistance encouraged the wider use of azithromycin, either single-dose or 3-day courses, to treat TD, particularly that associated with fever or bloody stools.
Chemoprophylaxis was once more examined with rifaximin, having a more acceptable safety profile and fewer concerns about resistance compared with the absorbed antibiotics. Currently, there are no general recommendations for this approach.
With the knowledge that bacterial diarrhea may be associated with the development of postinfectious irritable bowel syndrome and that bacterial enteropathogens caused most cases of TD, studies of travelers were undertaken. These small studies found that 5%–10% of people developed new-onset irritable bowel syndrome after experiencing TD in Mexico or Asia, although in most of these people no bacterial pathogen was identified. Studies are needed to further analyze this possible association and to develop and analyze methods of prevention, which could include early therapy (with passage of the first unformed stool), antibiotic chemoprophylaxis, or a vaccine. Studies are also needed to assess the effect of TD and its chemoprophylaxis and treatment on the intestinal microbiome. Rates of TD seem to be decreasing in many regions, and some areas that were previously considered high risk (such as Thailand) appear to currently have lower rates of the disease.
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