Children present with acute infection more often than adults, but they receive less advice before a trip.

An estimated 2 million children travel overseas annually, either as tourists or to visit friends and families, yet they often do so without having strategies in place to protect themselves from ailments most likely to affect them.

“Ill children were less likely than adults to have received pre-travel medical advice but were more likely to present for care within 7 days after return and to require hospitalization,” researchers wrote in a study published in a 2010 issue of Pediatrics.

They said pediatric travelers who were visiting friends and relatives abroad were especially less likely to receive pre-travel medical advice than those who were traveling as tourists.

Travelers’ diarrhea most common in developing nations

“When traveling in the US, the risk for contracting bacterial-related diarrhea is 4%,” Herbert L. DuPont, MD, vice chair in the department of medicine at Baylor College of Medicine and chief of medicine at St. Luke’s Episcopal Hospital, Houston, told Infectious Diseases in Children. “When people travel from more industrialized regions of the world to less developed ones, the rates of infection from bacterial-related diarrhea average 40%.”

According to the CDC’s website, the most important determinant of risk is destination; the most high-risk locations are developing countries in Latin America, Africa, the Middle East and Asia. DuPont said cruise ships, which occasionally experience norovirus outbreaks, “are actually quite safe, considering the number of people carried per year (10 million). It is just a few ships that have trouble getting rid of this hardy virus that infects with a very low dose.”

Causes of infection in pediatric population

According to the CDC website, “The primary source of (travelers’ diarrhea) infection is ingestion of fecally contaminated food or water.” The most common causative agent is Escherichia coli; other viral and parasitic enteric pathogens also cause the infection.

“Diarrhea in the US is caused by bacterial agents in up to 15% of reported cases. In nations where travelers’ diarrhea is common, bacteria, especially E. coli, cause 85% of the illness,” DuPont said, adding that viral agents, such as norovirus, cause between 5% and 15% of the illness.

Protozoal parasites account for a fractional amount of reported cases. The CDC said most infections are transmitted by contaminated food, although tainted water can also cause illness.

“The highest rate of incidence of travelers’ diarrhea is seen in toddlers and adolescents: Toddlers put everything in their mouths and adolescents have big appetites; all infections are dose-related,” DuPont said.

The infection is not fatal, he said, although it can lead to irritable bowel syndrome in up to 5% of those who contract it.

“Children develop chronic abdominal pain when they have irritable bowel syndrome, but we don’t know how often travelers’ diarrhea leads to this in kids. The studies have been done with adults,” DuPont said.

Tainted comestibles

“The evidence implicating food as the source of most cases of travelers’ diarrhea is strong,” DuPont wrote in a 2010 issue of Clinical Gastroenterology and Hepatology. The CDC advises avoidance of foods and beverages purchased from street vendors or other places where hygiene is dubious; avoiding raw or undercooked meat and seafood; and avoiding eating raw fruits and vegetables unless they have been peeled by the traveler. “Tap water, ice, unpasteurized milk and dairy products are associated with increased risk for travelers’ diarrhea,” according to the CDC.

To minimize risk of infection, DuPont also recommended steaming food or consuming beverages that have been boiled, such as tea or coffee.

“Bacterial pathogens can survive in or on food if not heated to 60·C before consumption,” said DuPont, who indicated in the study that foods with a high sugar content, which inhibits the growth of bacteria, such as syrups, jellies, jams and honey, are generally safe to eat. Also noted in the study as safe to consume are bottled beverages with an intact seal, including carbonated ones.

Symptoms of travelers’ diarrhea

In a 2009 issue of Alimentary Pharmacology & Therapeutics, DuPont wrote that the most common presentation of travelers’ diarrhea is acute, watery stools accompanied by abdominal pain and cramps.

“Approximately 10% of subjects with enteric disease during international travel present with vomiting as the primary feature of the disease. Diarrhea may complicate the illness, but vomiting predominates,” DuPont said in the study. Bloody stools and fever are seen in up to 3% of reported cases.

According to the CDC, most cases are benign and resolved within 48 hours; 90% of cases resolve within 1 week and 98% resolve within 1 month. However, some cases are more complex.

The Pediatrics study said, “Children presented earlier than adults required hospitalization more often, had shorter duration of travel, and were less likely to have received pre-travel medical advice. … Younger children were more likely than older children to present sooner after return and to have had longer travel duration.”

Antibacterial treatment of travelers’ diarrhea

DuPont recommended in the Alimentary Pharmacology & Therapeutics study that traveling patients have with them a supply of one of three antibacterial drugs — rifaximin (Xifaxan, Salix Pharmaceuticals), ciprofloxacin or azithromycin — to use for self-therapy if travelers’ diarrhea occurs.

Because it has the least number of known adverse effects and because it has not demonstrated antibacterial resistance outside of the gut, rifaximin is the preferred antibacterial, DuPont said.

“Although a single daily dose of rifaximin is effective in preventing travelers’ diarrhea, the recommended dose is one 200-mg tablet twice a day with major meals while in areas of high risk. Two doses are recommended for enhanced protection and to assure that at least one daily dose is taken by the poorly compliant traveler,” he said.

Of the three drugs, DuPont told Infectious Diseases in Children that rifaximin is safe to dispense to patients 12 years of age and older; azithromycin can be used in younger patients.

In 2008, the FDA issued a black box warning for fluoroquinolones, including ciprofloxacin, because of its link to tendonitis and ruptured Achilles’ tendon, the suspicion that it might deplete colonic flora, and because it may predispose patients to Clostridium difficile colitis. Azithromycin is the preferred treatment for travelers’ diarrhea accompanied by fever and bloody stools, DuPont said.

“All travelers should be armed with at least one of the effective drugs for trips to high-risk regions and advised to employ self-treatment at disease onset,” he wrote in the study.

“Some groups of adults can be encouraged to use rifaximin prophylactically while traveling internationally, but this approach is not recommended for children,” DuPont told Infectious Diseases in Children.

Other treatment measures

According to the CDC, antimicrobial prophylaxis may increase a patient’s susceptibility to resistant bacterial pathogens while providing no protection against either viral or parasitic pathogens.

“As a result, strict adherence to preventive measures is encouraged, and bismuth subsalicylate (Kaopectate, Chattem; Pepto-Bismol, Procter & Gamble) should be used as an adjunct if prophylaxis is needed,” the CDC said on its website.

DuPont said bismuth subsalicylate has a 65% protection rate vs. 60% to 70% for rifaximin, “but it is a less convenient approach.” Bismuth subsalicylate’s adverse effects include blackening of tongue and stools, and mild tinnitus. Contraindications for bismuth subsalicylate include patients with aspirin allergies and those taking anticoagulants, probenecid or methotrexate. Bismuth subsalicylate should not be used for more than 3 weeks, according to the CDC.

Edward A. Bell, PharmD, BCPS, Infectious Diseases in Children’s contributing columnist for the Pharmacology Consult section, told Infectious Disease in Children that physicians should be aware that Children’s Pepto (Procter & Gamble), now on the market, is “somewhat misleading because its active ingredient is an antacid (calcium carbonate). The product has none of the antidiarrheal effects of Pepto-Bismol.”

Bell said pediatricians “must underscore the fact that replacing bodily fluids is one of the main goals of treating diarrhea.” He recommends that pediatricians advise their patients’ parents to pack oral rehydration solutions such as Pedialyte (Abbott Laboratories) because it contains electrolytes commonly lost during bouts of dysentery.

“Patients and their families might want only to focus on stopping the diarrhea rather than on staying hydrated, but if the bodily fluids are not replaced, patients could end up significantly sicker than when the diarrhea first occurred,” Bell said.

Currently, there is no vaccine for travelers’ diarrhea, although several studies are under way to determine their value, DuPont told Infectious Diseases in Children. These studies are based on observations of immunity to travelers’ diarrhea in people who remain in areas of high risk for travelers’ diarrhea. The vaccines are primarily directed at enterotoxigenic E. coli, particularly heat-labile enterotoxin-producing enterotoxigenic E. coli.

For more information:

• CDC. Travelers’ Diarrhea: General Information. Available at: www.cdc.gov/nczved/divisions/dfbmd/diseases/travelers_diarrhea/. Accessed Feb. 24, 2011.
• CDC. Travelers’ Health - Yellow Book: Chapter 2. Available at: wwwnc.cdc.gov/travel/yellowbook/2010/chapter-2/travelers-diarrhea.aspx. Accessed Febrary 24, 2011.
• DuPont HL. Aliment Pharmacol Ther. 2009;30:187-196.
• DuPont HL. Clin Gastroenterol Hepatol. 2010;8:490-493.
• Hagmann S. Pediatrics. 2010;125:e1072-e1080.
• Maloney SA. Semin Pediatr Infect Dis. 2004;15:137-149.

Disclosures: Dr. DuPont has consulted with, received honoraria for speaking and has received research grants administered through his university from Salix Pharmaceutical Company; has received research grants administered through his university from IOMAI Corporation (now Intercell Corporation); has received research grants administered through his university from Santarus Corporation; and has received research grants administered through his university from Osel Corporation.

Bell reports no relevant financial disclosures.