Of the several million people who travel from temperate industrialized countries to tropical regions of Asia, Africa, and Central and South America each year, 20–50% experience a sudden onset of abdominal cramps, anorexia, and watery diarrhea; thus traveler’s diarrhea is the most common travel-related infectious illness (Chap. 119). The time of onset is usually 3 days to 2 weeks after the traveler’s arrival in a resource-poor area; most cases begin within the first 3–5 days. The illness is generally self-limited, lasting 1–5 days. The high rate of diarrhea among travelers to underdeveloped areas is related to the ingestion of contaminated food or water.
The organisms that cause traveler’s diarrhea vary considerably with location (Table 128-3), as does the pattern of antimicrobial resistance. In all areas, enterotoxigenic and enteroaggregative strains of E. coli are the most common isolates from persons with the classic secretory traveler’s diarrhea syndrome. Infection with Campylobacter jejuni is especially common in areas of Asia.
TABLE 128-3Causes of Traveler’s Diarrhea ||Download (.pdf) TABLE 128-3 Causes of Traveler’s Diarrhea
|Etiologic Agent ||Approximate Percentage of Cases ||Comments |
|Bacteria ||50–75 || |
|Enterotoxigenic Escherichia coli ||10–45 ||Single most important agent |
|Enteroaggregative E. coli ||5–35 ||Emerging enteric pathogen with worldwide distribution |
|Campylobacter jejuni ||5–25 ||More common in Asia |
|Shigella ||0–15 ||Major cause of dysentery |
|Salmonella ||0–15 ||— |
|Others ||0–5 ||Including Aeromonas, Plesiomonas, and Vibrio cholerae |
|Viruses ||0–20 || |
|Norovirus ||0–10 ||Associated with cruise ships |
|Rotavirus ||0–5 ||Particularly common among children |
|Parasites ||0–10 || |
|Giardia lamblia ||0–5 ||Affects hikers and campers who drink from freshwater streams |
|Cryptosporidium ||0–5 ||Resistant to chlorine treatment of water sources |
|Entamoeba histolytica ||<1 ||— |
|Cyclospora ||<1 ||— |
|Other ||0–10 || |
|Acute food poisoninga ||0–5 ||— |
|No pathogen identified ||10–50 ||— |
Closed and semi-closed communities, including day-care centers, schools, residential facilities, and cruise ships, are important settings for outbreaks of enteric infections. Norovirus, which is highly contagious and robust in surviving on surfaces, is the most common etiologic agent associated with outbreaks of acute gastroenteritis. Other common organisms, often spread by fecal–oral contact in such communities, are Shigella, C. jejuni, and Cryptosporidium. Rotavirus is rarely a cause of pediatric diarrheal outbreaks in the United States since rotavirus vaccination was broadly recommended in 2006. Similarly, hospitals are sites in which enteric infections are concentrated. Diarrhea is one of the most common manifestations of nosocomial infections. C. difficile is the predominant cause of nosocomial diarrhea among adults in the United States, and outbreaks of norovirus infection are common in health care settings. Klebsiella oxytoca has been identified as a cause of antibiotic-associated hemorrhagic colitis. Enteropathogenic E. coli has been associated with outbreaks of diarrhea in nurseries for newborns. One-third of elderly patients in chronic-care institutions develop a significant diarrheal illness each year; more than one-half of these cases are caused by cytotoxin-producing C. difficile. Antimicrobial therapy can predispose to pseudomembranous colitis by altering the normal colonic flora and allowing the multiplication of C. difficile (Chap. 129).
Globally, most morbidity and mortality from enteric pathogens involves children <5 years of age. Breast-fed infants are protected from pathogens in contaminated food and water and derive some protection from maternal antibodies, but their risk of infection rises dramatically when they begin to eat solid foods. Exposure to rotavirus is universal, with most children experiencing their first infection in the first or second year of life if not vaccinated. Older children and adults are more commonly infected with norovirus. Other organisms with higher attack rates among children than among adults include enterotoxigenic, enteropathogenic, and enterohemorrhagic E. coli; Shigella; C. jejuni; and G. lamblia.
Immunocompromised hosts are at elevated risk of acute and chronic infectious diarrhea. Individuals with defects in cell-mediated immunity (including those with AIDS) are at particularly high risk of invasive enteropathies, including salmonellosis, listeriosis, and cryptosporidiosis. Individuals with hypogammaglobulinemia are at particular risk of C. difficile colitis and giardiasis. Patients with cancer are more likely to develop C. difficile infection as a result of chemotherapy and frequent hospitalizations. Infectious diarrhea can be life-threatening in immunocompromised hosts, with complications including bacteremia and metastatic seeding of infection. Furthermore, dehydration may compromise renal function and increase the toxicity of immunosuppressive drugs.
If the history and the stool examination indicate a noninflammatory etiology of diarrhea and there is evidence of a common-source outbreak, questions concerning the ingestion of specific foods and the time of onset of diarrhea after a meal can provide clues to the bacterial cause of the illness. Potential causes of bacterial food poisoning are shown in Table 128-4.
TABLE 128-4Bacterial Food Poisoning ||Download (.pdf) TABLE 128-4 Bacterial Food Poisoning
|Incubation Period, Organism ||Symptoms ||Common Food Sources |
|1–6 h || || |
|Staphylococcus aureus ||Nausea, vomiting, diarrhea ||Ham, poultry, potato or egg salad, mayonnaise, cream pastries |
|Bacillus cereus ||Nausea, vomiting, diarrhea ||Fried rice |
|8–16 h || || |
|Clostridium perfringens ||Abdominal cramps, diarrhea (vomiting rare) ||Beef, poultry, legumes, gravies |
|B. cereus ||Abdominal cramps, diarrhea (vomiting rare) ||Meats, vegetables, dried beans, cereals |
|>16 h || || |
|Vibrio cholerae ||Watery diarrhea ||Shellfish, water |
|Enterotoxigenic Escherichia coli ||Watery diarrhea ||Salads, cheese, meats, water |
|Enterohemorrhagic E. coli ||Bloody diarrhea ||Ground beef, roast beef, salami, raw milk, raw vegetables, apple juice |
|Salmonella spp. ||Inflammatory diarrhea ||Beef, poultry, eggs, dairy products |
|Campylobacter jejuni ||Inflammatory diarrhea ||Poultry, raw milk |
|Shigella spp. ||Dysentery ||Potato or egg salad, lettuce, raw vegetables |
|Vibrio parahaemolyticus ||Dysentery ||Mollusks, crustaceans |
Bacterial disease caused by an enterotoxin elaborated outside the host, such as that due to Staphylococcus aureus or B. cereus, has the shortest incubation period (1–6 h) and generally lasts <12 h. Most cases of staphylococcal food poisoning are caused by contamination from infected human carriers. Staphylococci can multiply at a wide range of temperatures; thus, if food is left to cool slowly and remains at room temperature after cooking, the organisms will have the opportunity to form enterotoxin. Outbreaks following picnics where potato salad, mayonnaise, and cream pastries have been served offer classic examples of staphylococcal food poisoning. Diarrhea, nausea, vomiting, and abdominal cramping are common, while fever is less so.
B. cereus can produce either a syndrome with a short incubation period—the emetic form, mediated by a staphylococcal type of enterotoxin—or one with a longer incubation period (8–16 h)—the diarrheal form, caused by an enterotoxin resembling E. coli LT, in which diarrhea and abdominal cramps are characteristic but vomiting is uncommon. The emetic form of B. cereus food poisoning is associated with contaminated fried rice; the organism is common in uncooked rice, and its heat-resistant spores survive boiling. If cooked rice is not refrigerated, the spores can germinate and produce toxin. Frying before serving may not destroy the preformed, heat-stable toxin.
Food poisoning due to Clostridium perfringens also has a slightly longer incubation period (8–14 h) and results from the survival of heat-resistant spores in inadequately cooked meat, poultry, or legumes. After ingestion, toxin is produced in the intestinal tract, causing moderately severe abdominal cramps and diarrhea; vomiting is rare, as is fever. The illness is self-limited, rarely lasting >24 h.
Not all food poisoning has a bacterial cause. Nonbacterial agents of short-incubation food poisoning include capsaicin, which is found in hot peppers, and a variety of toxins found in fish and shellfish (Chap. 451).
Many cases of noninflammatory diarrhea are self-limited or can be treated empirically, and in these instances, the clinician may not need to determine a specific etiology. Potentially pathogenic E. coli cannot be distinguished from normal fecal flora by routine culture, and tests to detect enterotoxins are not available in most clinical laboratories. In situations in which cholera is a concern, stool should be cultured on selective media such as thiosulfate–citrate–bile salts–sucrose (TCBS) or tellurite–taurocholate–gelatin (TTG) agar. A latex agglutination test has made the rapid detection of rotavirus in stool practical for many laboratories, while reverse-transcriptase polymerase chain reaction (PCR) and specific antigen enzyme immunoassays have been developed for the identification of norovirus. Stool specimens should be examined by immunofluorescence-based rapid assays or (less sensitive) standard microscopy for Giardia cysts or Cryptosporidium if the level of clinical suspicion regarding the involvement of these organisms is high.
All patients with fever and evidence of inflammatory disease acquired outside the hospital should have stool evaluated for Salmonella, Shigella, and Campylobacter. Salmonella and Shigella can be selected on MacConkey agar as non-lactose-fermenting (colorless) colonies or can be grown on Salmonella–Shigella agar or in selenite enrichment broth, both of which inhibit most organisms except these pathogens. Evaluation of nosocomial diarrhea should initially focus on C. difficile; stool culture for other pathogens in this setting has an extremely low yield and is not cost-effective. Toxins A and B produced by pathogenic strains of C. difficile can be detected by rapid enzyme immunoassays, latex agglutination tests, or PCR (Chap. 129). Isolation of C. jejuni requires inoculation of fresh stool onto selective growth medium and incubation at 42°C in a microaerophilic atmosphere. In many laboratories in the United States, E. coli O157:H7 is among the most common pathogens isolated from visibly bloody stools. Strains of this enterohemorrhagic serotype can be identified in specialized laboratories by serotyping but also can be identified presumptively in hospital laboratories as lactose-fermenting, indole-positive colonies of sorbitol nonfermenters (white colonies) on sorbitol MacConkey plates. If the clinical presentation suggests the possibility of intestinal amebiasis, stool should be examined by a rapid antigen detection assay or by (less sensitive and less specific) microscopy. Multiplex nucleic acid amplification methods for detection of many stool pathogens (viral, bacterial, and parasitic) are increasingly being used in clinical microbiology laboratories to decrease the time to detection of a pathogen. Although these tests may be more sensitive and rapid than standard culture methods, the lack of a microbial isolate prevents determination of antimicrobial susceptibility and typing of strains by public health authorities in order to detect and respond to common-source outbreaks. For this reason, the Centers for Disease Control and Prevention suggests that diagnosis of an enteric bacterial infection by a nucleic acid amplification method should be followed by attempted isolation of the pathogen by culture.
TREATMENT Infectious Diarrhea or Bacterial Food Poisoning
In many cases, a specific diagnosis is not necessary or not available to guide treatment. The clinician can proceed with the information obtained from the history, stool examination, and evaluation of dehydration severity. Empirical regimens for the treatment of traveler’s diarrhea are listed in Table 128-5.
The mainstay of treatment is adequate rehydration. The treatment of cholera and other dehydrating diarrheal diseases was revolutionized by the promotion of oral rehydration solution (ORS), the efficacy of which depends on the fact that glucose-facilitated absorption of sodium and water in the small intestine remains intact in the presence of cholera toxin. The use of ORS has reduced cholera mortality rates from >50% (in untreated cases) to <1%. A number of ORS formulas have been used. Initial preparations were based on the treatment of patients with cholera and included a solution containing 3.5 g of sodium chloride, 2.5 g of sodium bicarbonate (or 2.9 g of sodium citrate), 1.5 g of potassium chloride, and 20 g of glucose (or 40 g of sucrose) per liter of water. Such a preparation can still be used for the treatment of severe cholera. Many causes of secretory diarrhea, however, are associated with less electrolyte loss than occurs in cholera. Beginning in 2002, the World Health Organization recommended a “reduced-osmolarity/reduced-salt” ORS that is better tolerated and more effective than classic ORS. This preparation contains 2.6 g of sodium chloride, 2.9 g of trisodium citrate, 1.5 g of potassium chloride, and 13.5 g of glucose (or 27 g of sucrose) per liter of water. ORS formulations containing rice or cereal as the carbohydrate source may be even more effective than glucose-based solutions. Patients who are severely dehydrated or in whom vomiting precludes oral therapy should receive IV solutions such as Ringer’s lactate.
Most secretory forms of traveler’s diarrhea (usually due to enterotoxigenic or enteroaggregative E. coli or to Campylobacter) can be treated effectively with rehydration, bismuth subsalicylate, or antiperistaltic agents. Antimicrobial agents can shorten the duration of illness from 3–4 days to 24–36 h but may be associated with the acquisition of multidrug-resistant organisms. Changes in diet have not been shown to have an impact on the duration of illness, while the efficacy of probiotics continues to be debated. Most individuals who present with dysentery (bloody diarrhea and fever) should be treated empirically with an antimicrobial agent (e.g., a fluoroquinolone or a macrolide) pending microbiologic analysis of stool. Individuals with shigellosis should receive a 3- to 7-day course. Individuals with more severe or prolonged Campylobacter infection often benefit from antimicrobial treatment as well. Because of widespread resistance of Campylobacter to fluoroquinolones, especially in parts of Asia, a macrolide antibiotic such as erythromycin or azithromycin may be preferred for this infection.
Treatment of salmonellosis must be tailored to the individual patient. Since administration of antimicrobial agents often prolongs intestinal colonization with Salmonella, these drugs are usually reserved for individuals at high risk of complications from disseminated salmonellosis, such as infants, patients with prosthetic devices, patients over age 50, and immunocompromised persons. Antimicrobial agents should not be administered to individuals (especially children) in whom enterohemorrhagic E. coli infection is suspected. Laboratory studies of enterohemorrhagic E. coli strains have demonstrated that a number of antibiotics induce replication of Shiga toxin–producing lambdoid bacteriophages, thereby significantly increasing toxin production by these strains. Clinical studies have supported these laboratory results, and antibiotics may increase by twentyfold the risk of hemolytic-uremic syndrome and renal failure during enterohemorrhagic E. coli infection. A clinical clue in the diagnosis of the latter infection is bloody diarrhea with low fever or none at all.
TABLE 128-5Treatment of Traveler’s Diarrhea on the Basis of Clinical Featuresa ||Download (.pdf) TABLE 128-5 Treatment of Traveler’s Diarrhea on the Basis of Clinical Featuresa
|Clinical Syndrome ||Suggested Therapy |
|Watery diarrhea (no blood in stool, no fever), 1 or 2 unformed stools per day without distressing enteric symptoms ||Oral fluids (oral rehydration solution, Pedialyte, Lytren, or flavored mineral water) and saltine crackers |
|Watery diarrhea (no blood in stool, no fever), 1 or 2 unformed stools per day with distressing enteric symptoms ||Bismuth subsalicylate (for adults): 30 mL or 2 tablets (262 mg/tablet) every 30 min for 8 doses; or loperamideb: 4 mg initially followed by 2 mg after passage of each unformed stool, not to exceed 8 tablets (16 mg) per day (prescription dose) or 4 caplets (8 mg) per day (over-the-counter dose); drugs can be taken for 2 days. Antibacterial drugc can be considered in selected circumstances. |
|Dysentery (passage of bloody stools) or fever (>37.8°C) ||Antibacterial drugc |
|Vomiting, minimal diarrhea ||Bismuth subsalicylate (for adults; see dose above) |
|Diarrhea in infants (<2 years old) ||Fluids and electrolytes (oral rehydration solution, Pedialyte, Lytren); continue feeding, especially with breast milk; seek medical attention for moderate dehydration, fever lasting >24 h, bloody stools, or diarrhea lasting more than several days |