Dr. Rose Recommends for Healthy & Safe Travel
Health Guide Chapter 6
- Travelers’ diarrhea is the most frequent cause of illness among travelers.
- Travelers’ diarrhea is primarily non-bloody diarrhea with minimal or no fever. It is usually a watery diarrhea, but can be frequent and explosive.
- Bacteria cause 80—85% of travelers’ diarrhea, parasites about 10%, and viruses 5%.
- Enterotoxigenic E. coli (ETEC) is the most common bacterium causing travelers’ diarrhea. The diarrhea is caused by a toxin secreted by ETEC bacteria.
- Dysentery is a more serious form of travelers’ diarrhea and is associated with higher fever, bloody stools and abdominal pain. E.coli does not cause dysentery.
- Most cases of diarrhea in which no pathogen is identified respond to antibiotics, suggesting that most of these are bacterial in origin.
- Travelers to lesser-developed countries should carry stand-by antibiotics for self-treatment of diarrhea.
- There are very few indications for taking prophylactic antibiotics to prevent travelers’ diarrhea. Rifaximin, a non-absorbable antibiotic, is the best choice.
- Food and water precautions may help prevent travelers’ diarrhea but are often ineffective because of lack of compliance on the part of the traveler.
- Hand washing and hand sanitizer gels reduce the incidence of diarrhea (as well as respiratory illness).
- The oral cholera vaccine (Dukoral) provides up to 30% crossover protection against ETEC-caused diarrhea.
- A single 1-g dose of azithromycin is as effective as a 3-day course of levofloxacin for travelers’ diarrhea in Thailand, where campylobacter jejuni is common.
- Backpacking in wilderness areas in the U.S. What is the risk of acquiring infectious diarrhea? A recent study showed that alpine wilderness water below cattle areas used by pack animals is at risk for containing coliform organisms. Water from wild, day hike, or backpack areas showed far less risk for coliforms (diarreha-causing bacteria). Hikers to areas where water can be fecally contaminated by cattle should filter all drinking water.
Overview of Travelers’ Diarrhea
Diarrhea is by far the most common medical problem among people traveling to less developed tropical and subtropical countries. Travelers’ diarrhea, however, is not a specific disease. The term describes the symptoms of an intestinal infection caused by certain bacteria, parasites, or viruses that are transmitted by the consumption of contaminated food or water, get ingested after touching contaminated surfaces, or through intimate contact with people carrying the microorganism. The severity and duration of symptoms depend on which microorganism is causing the illness.
Your Risk of Getting Travelers’ Diarrhea
Your risk is related to which countries you visit, the month or season of your visit, the duration of your visit, how often you eat in restaurants, and whether or not you eat in local homes or from food vendors. Some studies show that poor restaurant hygiene may be the source of most cases of travelers’ diarrhea.
There is little risk (attack rate of about 4%) when visiting North America, northern and central Europe, Australia, and New Zealand. Intermediate attack rates (8% to 20%) are found in travelers to most destinations in the Caribbean, southern Europe, Israel, Japan, and South Africa. High-risk destinations (attack rates of up to 60% during the first 2 weeks) include Mexico, the Dominican Republic and Haiti, and the developing countries of Africa, South and Central America, the Middle East, and Asia. One attack of travelers’ diarrhea won’t “immunize” you against further episodes. In fact, the attack rate in long-term travelers and expatriates remains unchanged for several years after arrival.
Causes of Travelers’ Diarrhea (TD)
Bacteria cause 80–85% of cases; parasites cause 10%; viruses cause about 5%. In general, travelers’ diarrhea manifests in one of three ways: (1) as an acute, mostly watery diarrhea; (2) as dysentery, a more serious illness with bloody diarrhea and fever; or (3) as a less acute, but persistent (chronic) diarrhea.
Diarrhea from Bacteria
Enterotoxigenic Escherichia coli (ETEC)
The most common cause of TD worldwide is ETEC. Ingestion of a large inoculum (amount) of this organism is necessary to produce disease. These high inoculums occur when there is a breakdown in sanitation, which is often the case in developing countries where ETEC infections are common. ETEC typically produces a watery diarrhea associated with cramps. Fever may be low or absent. Another strain of E. coli, enteroaggregative E. coli (EAEC), is also a common culprit, especially in children. Other E. coli bacteria can cause more serious illness, with bloody diarrhea and fever. These include:
- Enterinvasive E. coli (EIEC) causes diarrhea with mucous and blood, severe bowel inflammation, and fever.
- Enterohemorrhagic E. coli (EHEC): This pathogen causes mainly pediatric diarrhea with copious bloody discharge (hemorrhagic colitis). EHEC is significant because it can cause the hemolytic-uremic syndrome (HUS) and renal failure. Bloody stools usually occur after several days of nonbloody diarrhea. Fever is usually absent. Treatment with antibiotics may actually be harmful by releasing more toxin and predisposing to HUS. Enterohemorrhagic E. coli (EHEC) is sometimes a contaminant of ground hamburger meat and is common in the United States, Europe, and Japan; it is rarely acquired in tropical destinations and is not a main concern for travelers.
Other Bacteria Causing Travelers’ Diarrhea
Campylobacter, Shigella Salmonella, and Vibrios (cholera organisms) make up the majority of other bacterial causes of travelers’ diarrhea.
Campylobacter jejuni (C. Jejuni) is a common cause of diarrhea in developed countries but is many times more prevalent in developing countries. The risk of acquiring infection with Campylobacter appears to vary by destination, with travel to Asia posing a higher risk. Campylobacter infections may be associated with bloody diarrhea as well as fever.
The low infectious dose of this organism makes it one of the more commonly reported bacteria associated with diarrhea. Shigella is the most frequent cause of bacterial dysentery i.e., bloody diarrhea with fever.
Although nontyphoidal Salmonella infections are frequently associated with food-borne outbreaks in industrialized countries, they are an infrequent cause of TD worldwide.
Diarrhea caused by Vibrio parahaemolyticus and Vibrio cholerae are associated with eating raw or partially cooked seafood, such as oysters. Vibrio cholerae is responsible for outbreaks of cholera, but this organism poses little threat to tourists.
Other organisms that have been isolated from patients with TD include Aeromonas hydrophila, Plesiomonas shigelloides, and Yersinia enterocolitica.
Diarrhea from Parasites and Viruses
Parasites: Parasites (protozoa) account for about 10% of cases of travelers’ diarrhea. The most common parasites are Giardia, Cryptosporidium, Cyclospora and E. histolytica (the cause of amebic dysentery and liver abscess).
Viruses: Viruses account for about 5% of travelers’ diarrhea. Norovirus, the cause of “cruiseship diarrhea,” and rotavirus predominate.
Symptoms of Travelers’ Diarrhea
Watery Diarrhea: Most of these cases are caused by ETEC. Symptoms range from several loose or watery stools per day to a more explosive cholera-like illness with profuse, but usually nonbloody, diarrhea. Other symptoms often include nausea, vomiting, and abdominal cramps. Fever is usually absent in cases of ETEC or EAEC diarrhea. The typical case of diarrhea, if not treated with antibiotics, usually last 3 to 5 days. The main danger of watery diarrhea is dehydration, with children and the elderly most at risk, but all travelers will suffer in some degree from discomfort and disruption of their trip. Early treatment (as outline below) with loperamide (Imodium) and 1-2 doses of antibiotics is usually successful in terminating symptoms.
Bloody Diarrhea (Dysentery): Up to 15% of those with travelers’ diarrhea have bloody diarrhea, or stools with mucus and blood. Bloody diarrhea with fever indicates a condition called dysentery, and implies an intestinal infection with microoganisms other than ETEC. Historically, the term “dysentery” was applied only to two diseases: shigellosis, caused by Shigella bacteria (sometimes called bacillary dysentery), and amebic dysentery, caused by E. histolytica parasites. Because other microoganisms can cause bloody diarrhea and fever, the term “dysentery” no longer applies exactly as originated and is often used to denote any patient with bloody diarrhea with fever, regardless of the etiology (cause).
Note: the term “dysentery” is not listed in the indexes of the most recent North American travel medicine textbooks.
Bloody diarrhea results when certain pathogenic bacteria or parasites invade and damage the intestinal wall, causing inflammation and bloody stools or stools with bloody mucus. (Sometimes the blood is only detected microscopically). These infections can break out into the bloodstream and are potentially much more serious than those caused by the noninvasive E. coli bacteria. Common bacterial causes of bloody diarrhea include Shigella, Campylobacter, Salmonella, and Yersinia, plus two invasive strains of E. coli: Enterinvasive E. coli (EIEC) and Enterohemorrhagic E. coli (EHEC) as described above.
Dysentery is characterized by the sudden onset of bloody diarrhea (or bloody, small-volume stools mixed with mucus), fever, abdominal pain and tenderness, prostration, and the feeling of incomplete evacuation. Blood may be visible in only 50% of cases.
Treating Bloody Diarrhea
If you have the symptoms bloody diarrhea, start antibiotics and drink sufficient fluids to prevent dehydration. If you don’t improve within 24 hours, seek medical attention; you may need a longer course of antibiotics or be hospitalized if your symptoms are severe, or not improving. See below for more information on which antibiotics to use for diarrhea.
Chronic (Persistent) Diarrhea
Three to 5% of travelers develop persistent diarrhea, defined as diarrhea lasting more than 1 month. Persistent diarrhea may be accompanied by vague abdominal pain, bloating, nausea, loss of appetite, fatigue, weight loss, and low-grade fever. If you develop persistent diarrhea, consult your physician or an infectious disease specialist.
Giardiasis (see Chapter 10) and campylobacter (C. jejuni) are the most common infectious causes of persistent travelers’ diarrhea. Other infections causing of chronic diarrhea include amebiasis, cryptosporidiosis, cyclosporiasis, and dientamebiasis.
Infections, however, account for a minority of cases of persistent travelers’ diarrhea. Postinfectious lactose intolerance and irritable bowel syndrome appear to be the most common causes of chronic bowel symptoms in returned travelers. The former results from damage to the cells lining the intestine that contain the enzyme (lactase) that digests milk, the latter from damage to bowel motility.
Testing should be done to establish a precise diagnosis, but in many cases the tests are negative, and no definite diagnosis can be pinpointed. If medical consultation is not available, assume that you may have giardiasis and self-treat with metronidazole (Flagyl), tinidazole (Fasigyn). or nitazoxanide (Alinia). Furazolidone (Furoxone) is effective against both bacterial and parasitic causes of diarrhea. Note: Giardiasis, unlike amebiasis, does not cause bloody diarrhea or fever.
Causes and Geographic Variations of Travelers’ Diarrhea
The four principal bacterial microorganisms causing travelers’ diarrhea in most high-risk areas are E. coli, Shigella species, Salmonella species, and Campylobacter.
Temperature; annual rainfall; presence or absence of rivers, lakes, or seacoasts; dry and rainy seasons (or monsoons); and other geographic and climatic factors—as well as agricultural, eating, personal hygiene and sanitary practices—will determine which diarrhea-causing bacteria are most common in any particular country, or part of a country. For example, in Thailand, after E. coli, campylobacter is most prevalent; in Nepal, after E. coli, shigella, and campylobacter are the most common diarrhea-causing bacteria. In Mexico, E. coli, salmonella, and shigella predominate in the rainy summer season, whereas campylobacter is more common in the drier winter season. These studies show that globally, the causes of infectious diarrhea are not fixed and that each region has a unique pattern of disease.
Preventing Travelers’ Diarrhea
Food and Drink Precautions—Are They Effective?
It is commonly believed that your chances of developing a gastrointestinal illness will be reduced considerably by being counseled to “boil it, cook it, peel it, or forget it.” Surveys of returning travelers, however, have shown that receiving advice about food and drink safety appears to have no significant effect on rates of diarrhea. In fact, the overwhelming majority of travelers will commit a food and beverage indiscretion within 72 hours after arrival in a developing country, despite pre-departure counseling. Why is this? In some cases, the choice of food may not be under the travelers’ control, but it may also be that many people just can’t overcome the temptation to sample delicacies in exotic locations. Most travelers find it difficult, impractical, or impossible to resist well-presented, mouth-watering and often prepaid buffets, or to eat only piping-hot foods. Perhaps then, to the adage quoted above, should be added the words “easy to remember . . . impossible to do!”
Does this mean that travelers should throw caution to the wind and simply forget about prudent dietary habits? No. The medical literature shows a definite correlation between dietary indiscretions and the frequency of travelers’ diarrhea. If you can overcome temptation, and stick to safe eating habits, you can reduce your chance of illness. For many, though, this can be a difficult task.
Note: An important benefit of prudent eating habits is the prevention of diseases other than travelers’ diarrhea. Depending on your itinerary, you could be at risk for acquiring food- and drink-transmitted diseases such as hepatitis A or hepatitis E, typhoid fever, trichinosis, tapeworm and roundworm infestations, and diseases from intestinal, liver, and lung flukes. These are souvenirs you don’t want to bring home! The impracticality of following rigid dietary precautions during international travel is a compelling argument for all travelers to carry standby anti-motility drugs (e.g., Imodium) and antibiotics for self-treatment of diarrhea, and for a minority of high-risk travelers, to take prophylactic antibiotics.
Thirty seconds of washing reduces by 95% the number of bacteria, parasites, and viruses acquired through human contact, or from contaminated surfaces or objects.* Antiseptic towelettes and hand sanitizer gels (e.g., Purell) also do an effective job and are convenient to carry. Be sure the sanitizer contains at least 60% alcohol. Hand washing and hand sanitizer gels have also been shown to reduce the spread of colds and respiratory illnesses, including SARS.
*In nearly all instances, transmission of acute gastrointestinal illness is caused by organisms that are present transiently on the hands. These organisms are easy to remove by washing. Bacteria that normally live on the hands (“resident flora”) are more difficult to remove, but they are not responsible for disease transmission.
Drug Prophylaxis for Travelers’ Diarrhea
Self-treatment for travelers’ diarrhea has become so predictably effective that most physicians no longer recommend drug prophylaxis against diarrhea except for certain high-risk travelers or when the trip is deemed critical. You might consider prophylaxis with either Pepto-Bismol or antibiotics if you will be traveling short-term (less than 3 weeks) and cannot afford to have your trip interrupted, or travel plans altered, because of illness. You might be, for example, a business person, diplomat, musician, or athlete who can’t afford to miss even 1 hour of an important meeting or event.
Or, you might have a medical condition that would be adversely affected by any additional illness. Medical conditions warranting consideration of prophylaxis would include cancer, AIDS, severe inflammatory bowel disease (colitis), kidney failure, and poorly controlled insulin-dependent diabetes. Also, if you have peptic ulcer disease and take a stomach acid-reducing drug (e.g., Zantac, Pepcid, Prilosec, Nexium, or Protonix), your risk of travelers’ diarrhea is increased. Consider taking the anti-ulcer, stomach-coating drug Carafate (sucralfate). This may reduce your risk of diarrhea because Carafate has antibacterial properties.
Pepto-Bismol Taking Pepto-Bismol (bismuth subsalicylate) will reduce your chances of getting travelers’ diarrhea by about 65% (compared with 90% efficacy for antibiotics).
How does it work? Medical studies show that Pepto-Bismol actually eliminates harmful bacteria from the stomach. This antibacterial action is due to the bismuth component of the medication. The salicylate in Pepto-Bismol has antisecretory and anti- inflammatory effects on the bowel wall, reducing the output of diarrheal fluid.
Dosage: Two tablets (or 2 tablespoons of the liquid), 4 times daily. Take with meals and at bedtime. The tablet form of Pepto-Bismol is as effective as the liquid preparation, and the tablets are easier to carry. The downside: taking medication four times a day is very inconvenient for most travelers. Children’s dosage: Pepto-Bismol may be used by children older than 3 years. They should use one half the adult dose. For using Pepto-Bismol in a child under age 3, consult your pediatrician.
Note: 2 tablespoons or tablets of Pepto-Bismol have the salicylate content of about one adult aspirin tablet. Pepto-Bismol is most effective when taken with meals to allow the drug to come into immediate contact with the microorganisms in food.
Contraindications: Pepto-Bismol should be avoided by people who (1) are allergic to, or intolerant of, aspirin; (2) have any type of bleeding disorder; (3) are taking an anticoagulant (warfarin, [Coumadin]); or (4) have a history of peptic ulcer disease or gastrointestinal bleeding.
Side Effects: Pepto-Bismol causes blackening of the tongue and stool, but this is not harmful. Overdosage can cause ringing in the ears (tinnitus) due to salicylate toxicity. Don’t take aspirin and Pepto-Bismol simultaneously—the risk of salicylate toxicity (tinnitus, easy bruising) will be increased. If you are on a warfarin anticoagulant (e.g., Coumadin), you should not take Pepto-Bismol because the risk of bleeding will be increased.
Check with your doctor about the safety of Pepto-Bismol if you have any underlying condition for which you are taking medication. Pepto-Bismol should not be taken with doxycycline because it can prevent the absorption of the latter. Pepto-Bismol may also inhibit the absorption of other antibiotics but the extent of this interaction has not been well studied.
Prophylactic Antibiotics Taking an antibiotic (especially one of the quinolones) can significantly reduce your risk of travelers’ diarrhea. However, because all antibiotics have potential side effects, physicians are hesitant to prescribe them routinely to healthy travelers. Also, if diarrhea occurs while taking the antibiotic, then what should you do? Some argue that an antibiotic, such as a quinolone, should not be used for prophylaxis when it is also the treatment of choice, and therefore, should be reserved for the latter. Prophylactic antibiotics are not generally recommended for children, except under rare circumstances.
Rifaximin (Xifaxan): This is a new, nonabsorbed antibiotic that is effective against noninvasive E. coli, the most common cause of travelers’ diarrhea. In November 2004, the company announced the results of studies that also showed effectiveness in preventing shigellosis (dysentery caused by Shigella bacteria).
Prophylactic dose: 200 mg (1 table) twice daily
Vaccination against Travelers’ Diarrhea
An oral, inactivated cholera vaccine, Dukoral™, is approved for use in Canada and European Union countries, for children aged ≥ 2 years and for adults. This vaccine comprises killed whole cell Vibrio cholerae (WC) and the non-toxic, recombinant cholera toxin B-subunit (BS). Through the BS component, the oral cholera vaccine, Dukoral™ (BS-WC), has been shown to provide moderate, short-term protection against diarrhea caused by enterotoxigenic E. coli ( ETEC).
In an oral cholera vaccine field trial in Bangladesh, the BS-WC vaccine demonstrated 67% protection against ETEC diarrhea for 3 months. Another field trial, in Mexico, demonstrated a protective efficacy of approximately 50%. Given the proportion (about 50%) of travelers’ diarrhea caused by ETEC, the overall protection against travelers’ diarrhea is estimated at no more than about 30%.
Indications for the oral BS-WC vaccine are limited because of the following: 1) most episodes of travelers’ diarrhea are usually mild and self-limited; 2) therapeutic options (oral rehydration, dietary management, and especially anti-motility drugs combined with antibiotics) are available if prevention fails; 3) < 50% (range 25% to 50%) of travelers’ diarrhea cases are caused by ETEC bacteria; 4) the protection by the vaccine against ETEC diarrhea is approximately 50%; and 5) vaccinated travelers may gain a false sense of security and possibly avoid being as strict in observing food and water precautions. There is also the consideration of vaccine cost and the short duration of protection (3 months).
The bottom line: Vaccination with the BS-WC vaccine (Dukoral) as a prevention strategy for travelers’ diarrhea is of limited value and is not routinely recommended for the majority of travelers.
Dukoral vaccine may be considered for the following selected high-risk, short-term travelers who are aged > 2 years:
- With chronic illnesses for whom there is an increased risk of serious consequences from travelers’ diarrhea (e.g., chronic renal failure, congestive heart failure, insulin-dependent diabetes mellitus, inflammatory bowel disease, the very elderly)
- With an increased risk of acquiring travelers’ diarrhea (e.g,. those with deficient gastric acid, young children aged > 2 years)
- Who are immuno-suppressed due to HIV infection or other immunodeficiency states
- With a history of repeated severe travelers’ diarrhea
- For whom a brief illness cannot be tolerated (e.g., elite athletes, performance artists, or business or political travelers)
The BS-WC vaccine provides short-term protection only (approximately 3 months) against ETEC diarrhea, so the traveler at ongoing risk who has had the vaccine administered must consider the need (and expense) for booster doses.
Vaccine Schedule and Dosage: See Ch. 3
The treatment of travelers’ diarrhea (depending on the severity) consists of one or more of the following:
- Adequate fluid intake
- Loperamide (Imodium)
- Hospitalization in some cases for treatment of dehydration and toxicity
If you are having frequent, copious diarrhea, dehydration is a potential threat and you may need treatment with an oral rehydration solution, as described in the special section, “Oral Rehydration Therapy,” starting on page 99. If your diarrhea is not particularly severe, then follow these guidelines:
Mild/moderate diarrhea: Adults—Continue with your regular diet (soup and salted crackers are good additions) and drink at least 2 to 3 liters of fluid (mostly water) daily, or more if you are in a hot climate. Water alone, however, is not sufficient to rehydrate; it must be accompanied by salt and a source of glucose for absorption by your intestine. Avoid dairy products (milk and cheese) during the acute phase of diarrhea.
Mild diarrhea: Infants—They should continue to receive their regular formula or food and full amounts of whatever liquids they normally consume.
Bismuth subsalicylate (Pepto-Bismol)
In addition to its role in prophylaxis, Pepto-Bismol, in conjunction with diet, can also be used for the treatment of travelers’ diarrhea. Pepto-Bismol reduces the number of unformed stools by 50% through its antimicrobial, antisecretory, and anti-inflammatory actions. Bloody diarrhea (dysentery) is not a contraindication to the use of Pepto-Bismol. Pepto-Bismol is more effective in relieving nausea than it is in reducing diarrhea. Pepto-Bismol is not frequently recommended because of its inconvenient dosing and efficacy, which is lower than antibiotics.
Adult Dosage Two tablets or 2 tablespoonfuls (1 dose cup, 30 mL), repeated half hourly, as needed. Do not exceed a total dose of 16 tablets, or 8 oz. of the liquid, in any 24-hour period. Don’t take aspirin at the same time you are taking Pepto-Bismol because salicylate toxicity could occur. Use acetaminophen (Tylenol) if you need medication for pain or fever while taking Pepto-Bismol. If your diarrhea is not adequately controlled with Pepto-Bismol in 6 to 8 hours, discontinue the medication and start antibiotics.
Loperamide (Imodium) reduces diarrhea (both the frequency of passage of stools and the duration of illness) by up to 80%. Its action is due to its anti-motility effect (reducing peristalsis) as well as its antisecretory effect (blocking the bowel’s output of salt and water).
Adult Dosage: Two capsules (4 mg) immediately, then 1 capsule after each loose or watery stool. Don’t take more than 8 capsules over any 24-hour period. Don’t take loperamide if you have a high fever or are severely ill. Be aware that excessive use of loperamide can cause constipation.
Child Dosage: Young infants and children appear to be more susceptible to side effects such as paralytic ileus (distended intestine), vomiting, and drowsiness. If loperamide is used in older children follow label directions carefully. Do not give loperamide to infants and children younger than 2 years old unless you have consulted your pediatrician.
Note: A theoretical concern about anti-motility drugs is that they may prolong illness by interfering with the body’s natural “flushing” mechanism. In reality, when travelers have used loperamide to treat watery diarrhea, no prolongation of illness has been observed, even when stool cultures have later shown the presence of an invasive microorganism (e.g., Shigella). Nevertheless, some medical experts still advise you not to take loperamide if you have bloody diarrhea and/or a fever greater than 101°F. However, the Health Guide believes that when a quinolone antibiotic is administered with loperamide, the benefits of combined treatment outweigh any theoretical risk of adverse effects.
Loperamide Plus Antibiotics
The problem with loperamide, used alone, is that it does not treat the cause of the diarrhea—only the symptoms. Recent studies indicate that combining loperamide with an antibiotic is better therapy for diarrhea because it combines the anti-motility action of the former with the curative effects of the latter. Studies in Mexico, for example, showed that a combination of loperamide and a quinolone antibiotic was more effective than loperamide alone.
When to add an antibiotic? If the diarrhea is mild, i.e., does not force a change in your activity, loperamide (and/or Pepto-Bismol) alone is often sufficient. An antibiotic should be added when the diarrheal illness is abrupt, with frequent and/or copious stools, or the diarrhea is bloody or accompanied by fever.
The quinolone (fluoroquinolone) antibiotics revolutionized the treatment of travelers’ diarrhea. These antibiotics achieve very high fecal drug concentrations, and just one or two doses are often curative. There is, however, increasing evidence that antimicrobial resistance is on the rise as evidenced by a 90% resistance of campylobacter to ciprofloxacin in Thailand (50% in Nepal and 40% in Egypt). Azithromycin has now become a commonly recommended alternative drug. Other alternative drugs are listed below.
Quinolones and Other Antibiotics
Single doses are often effective for watery diarrhea, but a full 3-day course is recommended for individuals who are not well after the first day of illness and in patients with bloody diarrhea and fever. Ciprofloxacin is available in liquid form for children. Ciprofloxacin or levofloxacin can be given intravenously if vomiting prevents oral administration.
Dosage: 750 mg once daily or 500 mg twice daily for 1 to 3 days
Dosage using liquid preparation: 20 to 30 mg/kg/day, divided into two doses per day, for 3 days, if necessary
Dosage: 500 mg once daily for 1 to 3 days
Note: “The U.S. Food and Drug Administration is advising that the serious side effects associated with fluoroquinolone antibacterial drugs (ciprofloxacin, levofloxacin and moxifloxacin) generally outweigh the benefits for patients with sinusitis, bronchitis and uncomplicated urinary tract infections who have other treatment options,” the FDA said in a Drug Safety Communication. “For patients with these conditions, fluoroquinolones should be reserved for those who do not have alternative treatment options.”
The FDA has not made a statement about the use of fluoroquinolones for the treatment of travelers’ diarrhea. In general, ciprofloxacin or levafloxacin are given only as short courses (1-3 days) of treatment. If there are concerns about the use of fluoroquinolone, then azithromycin can be used instead.
Azithromycin (Zithromax) Azithromycin shows a high degree of activity against diarrhea due to enterotoxigenic E. coli enteroaggregative E. coli, multiresistant Shigella species, and ciprofloxacin-resistant Campylobacter species. Azithromycin is the drug with the broadest activity against the bacterial pathogens causing travelers’ diarrhea. Also, this drug has favorable pharmacokinetics for single-dose therapy, showing an 11–14-h half-life, with nearly 50% of active drug excreted in feces and resulting in high levels in the gut. Azithromycin concentrates in tissues, including human neutrophils and other cells, and is biologically active in the presence of neutrophils. Azithromycin appears to be the drug of choice for treatment of febrile dysentery in the international traveler, for whom the expected cause of illness is Campylobacter or Shigella species.
In Thailand, azithromycin has shown more effectiveness against Campylobacter than ciprofloxacin. In Bangladesh, a single 1-Gm dose of azithromycin has been found to be more effective against severe cholera in adults than ciprofloxacin. Azithromycn is available in both 250-mg and 500-mg tablets and in liquid form in strengths of 100 mg/5ml and 200 mg/5ml.
Adult dosage: 1,000 mg (1 Gm) once as a single dose or 500 mg daily for 3-7 days if symptoms persist or are associated with dysentery. The 7-day dosage period will cover shigellosis, non typhoid salmonellosis, uncomplicated typhoid fever and enteroinvasive E. coli.
Child dosage: 10 mg/kg/day for 3-7days
Alternative Drugs Used to Treat Travelers’ Diarrhea
Rifaximin (Xifaxin): This is a new, minimally absorbed antibiotic effective against noninvasive strains of E. coli (ETEC), the most frequent cause of travelers’ diarrhea in most countries. It may be effective for treating dysentery caused by Shigella, Salmonella, or Campylobacter but further studies are required. Rifaximin should be reserved for areas of the world where ETEC is most common, e.g., Latin America. Dosage: 200 mg 3 times daily for 3 days
Cefixime (Suprax) This is a cephalosporin antibiotic that is effective against most bacteria causing infectious diarrhea, but there have been reports of Shigella resistance. Cefixime is also a useful drug for treating ear infections (otitis media), pharyngitis and tonsillitis, acute bacterial bronchitis, urinary tract infections, and gonorrhea. It is available in tablet and liquid form.
Adult dosage: 400 mg once daily for 3 to 5 days
Child dosage: 8 mg/kg once daily for 3 to 5 days
Furazolidone (Furoxone) This drug is active against most bacterial causes of travelers’ diarrhea, as well as Giardia, making furazolidone useful as a broad-spectrum treatment when the cause of the diarrhea is not known. Furazolidone is also available in a liquid preparation.
Adult dosage: 100 mg (1 tablet) 4 times daily for 3 days; for giardiasis, treatment is for 7 to 10 days
Child dosage: 5 years and older—25 to 50 mg (1/4 to 1/2 tablet) 4 times daily
Liquid Furazolidone contains 50 mg per tablespoon (15 mL)
5 years and older—1/2 to 1 tablespoon (7.5 mL to 15 mL) 4 times daily
1 to 4 years—1 teaspoon to 11/2 teaspoons (5 mL to 7.5 mL) 4 times daily
1 month to 1 year—1/2 teaspoon to 1 teaspoon (2.5 mL to 5 mL) 4 times daily
Trimethoprim/Sulfamethoxazole (TMP/SMX, Bactrim, Co-trimoxazole) Because of widespread resistance, TMP/SMX is now considered a last-choice drug for the treatment of travelers’ diarrhea.
Adult dosage: One double-strength tablet every 12 hours for 1 to 3 days
Child dosage: 8 mg/kg trimethoprim and 40 mg/kg sulfamethoxazole per 24 hours, given in two divided doses every 12 hours
- Note: TMP/SMX is effective for cyclosporiasis. Cyclosporiasis is a gastrointestinal disease caused by the parasite Cyclospora. Symptoms include prolonged watery diarrhea, abdominal cramping, weight loss, anorexia, myalgia, and occasionally vomiting and/or fever. Symptoms generally begin approximately 1 week (5-8 days) after ingestion of the oocysts and these may persist for a month or more. Cyclospora is treatable with trimethoprim-sulfamethoxazole (Bactrim).
- Adult dosage: One double-strength tablet every 12 hours for 7 days
Read more about cyclosporiasis.
Metronidazole (Flagyl) If you have diarrhea that persists longer than 2 weeks, you could be harboring Giardia parasites. It is reasonable to start self-treatment for giardiasis if you will be unable to get timely medical consultation.
Adult dosage: 250 mg three times daily for 5 to 7 days; don’t drink alcohol when taking metronidazole; severe nausea and vomiting may occur.
Tinidazole (Fasigyn, Tindamax), a derivative of metronidazole, is now the drug of choice for giardiasis. Tinidazole is an anti-parasitic drug used against protozoan infections. It is widely known throughout Europe and the developing world as treatment for a variety of amoebic and parasitic infections. Tinidazole is FDA approved for the treatment of giardiasis, amebiasis and trichomoniasis. Tinidazole has similar side effects to metronidazole, but has a shorter (single dose) treatment course. Adult dosage: Single 2-gram dose Child dosage: Up to 40 kg in weight, single 50mg/kg dose
Nitazoxanide (Alinia) Nitazoxanide oral suspension was approved in November 2002 for the treatment of diarrhea caused by Cryptosporidium parvum and Giardia lamblia in children aged 1-11 years. In July 2004, nitazoxanide was approved for the treatment of diarrhea caused by Giardia lamblia in patients > 12 years old. Adult dosage: 500 mg orally twice daily for 3 days Child dosage: An oral suspension is available for children under age 11.
Note: Nitazoxanide is also effective against C. difficile colitis. In one study, a 10-day course of treatment showed a 90% cure rate.
Treatment of Children and Pregnant Women
Children The quinolones are currently the most effective treatment for travelers’ diarrhea. In some experimental animals, these compounds damage cartilaginous end plates of long bones, but there are no data that show a similar process in humans. Children with cystic fibrosis and cancer have been treated with long courses of ciprofloxacin without apparent complications.
Many travel experts now believe that it is unacceptable for a child, who may be more likely to get travelers’ diarrhea, may become more dehydrated with it, and may have a more prolonged illness, to receive less effective treatment than an adult. The illness can result in significant suffering for the child and have a major impact on the travel experience for the whole family.
Standby treatment for children should consist of either ciprofloxacin or azithromycin. Ciprofloxacin may be the preferred agent. Because it is not routinely recommended for use in children in the United States or Canada, careful discussion with parents is necessary, weighing the very low risks of giving ciprofloxacin for a very short course against the need for off-label use of an effective, proved therapeutic agent. When using ciprofloxacin for children, give 20 to 30 mg/kg/day, divided into two doses per day, for 3 days. When using azithromycin for children, prescribe 10 mg/kg orally, once daily for 3 days.
Pregnant Women The same reasoning also justifies the use of quinolones during pregnancy. If antibiotic treatment of diarrhea is indicated, then the most effective drug should be used, especially if the woman could face a prolonged illness with toxicity and dehydration. According to the Physicians’ Desk Reference (PDR), “quinolones should be used during pregnancy only if the potential benefit justifies the potential risk.” In other words, quinolones are not contraindicated during pregnancy (as some would have you believe); they should be administered when untreated maternal illness may result in harm to the mother as well as the fetus.
Standby treatment for pregnant women should consist of a quinolone antibiotic such as ciprofloxacin or azithromycin. Because rifaximin is not absorbed, it should be safe in pregnancy; however, it may have little efficacy against invasive bacteria that cause the most severe illness.
Always follow this principle: The mother’s health takes priority. In the case of infectious diarrhea, if her illness is severe, treatment with a quinolone antibiotic should not be withheld because of a theoretical concern about risk to the fetus.
SUMMARY OF TREATMENT OF TRAVELERS’ DIARRHEA
- Every traveler to the developing world should carry an antibiotic and loperamide (Imodium) for self-treatment of traveler’s diarrhea.
- Treatment options include loperamide (Imodium), antibiotics, or an antibiotic plus loperamide. If your symptoms are relatively mild, you could start treatment with loperamide. If you are not better after 4 to 6 hours, start antibiotics, preferably a quinolone or azithromycin.
- If you have copious or explosive diarrhea, take an antibiotic and loperamide immediately. Start oral rehydration therapy, as needed. A 1- to 3-day course of an antibiotic combined with loperamide is usually curative.
- Always treat dysentery (bloody diarrhea, high fever) with antibiotics.
- Quinolones are the most effective antibiotics and should not be withheld from pregnant women or children, especially from those who have more severe symptoms.
- Azithromycin is the best alternative drug, particularly for pregnant women and infants or children.Azithromycin may be more effective than a quinolone against E, coli and Vibrio cholerae in certain countries, such as Thailand.
- In Mexico and Latin America, Rifaximin is an excellent alternative drug because of the high incidence of ETEC-caused diarrhea. Problem: High cost may be a problem.
- Diarrhea danger signs include bloody diarrhea, high fever, persistent vomiting, severe abdominal pain, prostration, and dehydration. Seek qualified medical care if your symptoms are not improved after 48 hours of antibiotic treatment, or if you are becoming dehydrated.
- Soup or broth, salted crackers, and extra water will help maintain hydration, and also provide nutrients. Try to eat a normal diet as much as possible, even in the face of diarrhea.
- If you have mostly vomiting—and minimal diarrhea—sipping plenty of slightly salty fluids and taking Pepto-Bismol is a good treatment.
- About 10% of diarrhea is caused by a parasitic disease such as giardiasis or amebiasis. Treat with metronidazole (Flagyl) or tinidazole (Fasigyn).
- Antacids containing magnesium, aluminum, or calcium; sucralfate; iron tablets; or multivitamins containing iron or zinc, or Pepto-Bismol, may interfere with the absorption of quinolone antibiotics. They should not be given with, or within 2 hours, of the administration of a quinolone.
Oral Rehydration Therapy
The initial treatment of moderate to severe travelers’ diarrhea begins by replacing the salt and water lost through your intestinal tract. Severe watery diarrhea (as seen with cholera, for example) can cause life-threatening fluid losses from the intestine of one liter or more per hour. Treating dehydration of this magnitude is an urgent priority, especially in infants, young children, and the elderly. Early, vigorous treatment is even more important in hot, tropical climates where fluid requirements are higher. Hospitalization and intravenous fluid therapy may be required if oral intake cannot keep up with fluid losses. (Additional information on treating dehydration in infants and children is found in Chapter 21).
The first mistake that most people make when treating copious diarrhea is that they don’t drink enough fluids. The second mistake they make is using the wrong fluids. They may drink salt-free, high-sugar beverages or a too-salty beverage without the correct glucose concentration necessary to optimize salt and water absorption. Not drinking enough, or using the wrong fluids to treat severe diarrhea, can make matters worse, especially in infants.
Alternatively, you may be in a remote location where you can’t get appropriate fluids or the necessary ingredients to prepare a balanced rehydration solution. Under these circumstances, just about any kind of beverage (disinfected tap water, bottled water, tea, coffee, diluted soda pop, etc.) is better than no fluid replacement at all. This will buy enough time (hopefully) to procure the necessary ingredients and prepare a proper solution—or get to a medical treatment facility if you don’t improve. First, though, review these basic facts about how the body absorbs salt and water.
Facts About Food, Sugar, Salt, and Water
Your body cannot absorb water by itself. Water absorption only follows the absorption of glucose (or amino acids) and sodium. This fact forms the basis of oral rehydration therapy.
- Glucose (also known as dextrose) rarely occurs by itself in a normal diet. The glucose you consume is mostly in the form of complex carbohydrates (starches) and sugars (disaccharides), such as sucrose, lactose, and maltose. These compounds are broken down by intestinal enzymes to provide free glucose.
- Glucose is transported across the intestinal cell membrane only in conjunction with sodium. Once absorbed through the intestinal wall, glucose and sodium create an osmotic force that pulls in water. The movement of water across cell membranes into the body is entirely passive.
- Table sugar (sucrose) is broken down into one molecule of glucose and one molecule of fructose. Fructose is not co-transported with sodium; it is transported separately and converted to glucose (and fat) in the liver.
- A too-high sugar concentration in the intestine inhibits water absorption. Highly sweetened sugar drinks, especially those with a high fructose content, can actually increase diarrhea by inhibiting water absorption. Apple juice, Gatorade, non-diet cola drinks, and Jell-O have glucose/fructose concentrations of about 6%. Maximum absorption of water occurs when the glucose concentration in your intestine is about 2.5%.
Starchy foods promote water absorption better than simple sugars. This is because starch solutions in the intestine, before they are broken down to glucose, have less osmotic “back pull” on water.
- Even in the presence of diarrhea, your intestine is still able to absorb glucose, salt, water, and other nutrients. When diarrhea occurs, “resting the intestine” in an attempt to reduce stool output is harmful.
- Rehydration strategies can involve simply the consumption of food plus additional water—or balanced salt/sugar rehydration solutions when diarrhea is more severe.
Oral Rehydration Solutions
Premixed Oral Rehydration Solutions (ORS) WHO and CeraLyte rehydration salts contain the optimum balance of sodium, potassium, bicarbonate, plus a source of glucose. The WHO formula is glucose-based, whereas Ceralyte uses the advantages of rice carbohydrate as the glucose source. These convenient products are best suited for treating more severe diarrhea and dehydration, especially in infants and children. One packet is added to 1 liter (or 4 cups) of potable water.
Quick ORS formulas If you don’t have packets of ORS formula, you can prepare a basic solution by adding one teaspoon of salt and 2 to 3 tablespoons of sugar or honey to a liter of water. This solution will effectively maintain blood volume and tissue hydration. Another option is to mix one 8-oz. cup of orange juice (or other fruit juice) with three cups of water and add one teaspoon of salt.
Complex Carbohydrate- and Food-Based Rehydration
The glucose-based ORS can keep you hydrated, but they do not decrease stool volume or shorten the duration of acute diarrhea. Cereal- and food-based ORS do both. They also supply up to four times more calories during a time when appetite may be suppressed. With cereal-based ORS, starches (complex carbohydrates) are broken down enzymatically into glucose directly on the intestinal wall with less “osmotic penalty,” resulting in better absorption of glucose, salt, and water.
Hydrating Older Children and Adults
This treatment is simple and straightforward, as long as the person is not vomiting:
- Step 1. Drink 2 to 4 liters, or more, of full-strength oral rehydration solution over 2 to 4 hours. Drink enough to restore urine output.
- Step 2. Diet and maintenance fluids—After you are rehydrated and urine output is restored, start to eat (see later) and continue to drink enough fluids to maintain hydration.
- Step 3. If diarrhea continues, continue your diet but drink 8 to 12 oz. of full-strength ORS each time you have a watery stool.
Hydrating Infants and Younger Children
You should know when a child has the potential to become dehydrated. The history is critical: How long has the child had diarrhea, and what are the frequency and volume? Has the child been unable to take oral fluids because of vomiting?
Signs of Dehydration Observe the child for increased thirst, listlessness or lethargy, decreased urine output, dark urine, and dry mucous membranes. Severe dehydration requires hospitalization and intravenous fluid therapy. Early, vigorous administration of ORS usually keeps a child from reaching that stage.
Children with diarrhea should continue to be fed, but you can interrupt these feedings to administer fluids. Give a dehydrated infant or child 1 to 1-1/2 oz. (30-45 mL of ORS per pound of body weight.) Administer this amount of fluid over 2 to 4 hours. A dehydrated 22-lb. infant, for example, might require as much as 1 quart of ORS during the first 3 to 4 hours of treatment. If the child is not vomiting, give ORS as rapidly as the infant or child will accept it. Use a spoon, dropper, or a baby bottle for infants. Some parents squirt the solution into the child’s mouth with a small syringe (ask your doctor for one before leaving or purchase the EZY DOSE syringe, or similar product; these are available in most pharmacies). Watch for the return of urine output and improvements in the child’s appearance and behavior.
Vomiting Don’t let it deter you from giving ORS. Even if the child has been vomiting, continue to administer ORS in small amounts. Giving a teaspoon (5 mL) of ORS every 1 to 2 minutes avoids stomach distention, but provides an hourly intake of up to 10 oz. (300 mL). If available, use a feeding syringe (see earlier), an infant bottle, or a medicine cup. This process often requires time and patience, and it may take you 4 to 6 hours to rehydrate the child. Seek medical care if vomiting continues to interfere significantly with oral feedings. Intravenous fluids, or fluids via nasogastric tube, may be required.
Feeding Infants and Children Early feeding is important. The intestine continues to absorb water and nutrients despite diarrhea. The World Health Organization, in fact, advises parents not to stop giving infants with diarrhea their regular formula or food. Starving an infant to rest the intestine will only make matters worse. Therefore, restore a child’s regular diet as soon as possible. Avoid the so-called BRAT diet (bananas, rice, apple sauce, and toast)—it provides insufficient calories and nutrients, and a consensus has developed among pediatricians that this diet is too low in protein, fat, and energy content and may impede the recovery process. Children, like adults, recover more quickly when fed a normal diet.
What Not to Eat and Drink
In moderate to severe diarrhea, avoid fatty foods and also drinks high in simple sugars, including undiluted fruit juices, sport drinks, and soft drinks. These drinks are not appropriate because their carbohydrate concentration is too great and the electrolyte concentration (especially sodium) is too low. Apple and pear juices have greater concentrations of fructose over glucose, and this excess fructose may also aggravate diarrhea. If you do give a child a sugar-containing soft drink, dilute it 2:1 with water and add a teaspoon of salt per liter of diluted drink.
General Dietary Recommendations
Appropriate foods include lean meats, yogurts, fruits and vegetables, as well as complex carbohydrates (starches) such as pasta, rice, potatoes, bread, crackers, and cereals. Cream of Wheat and Gerber Rice Cereal are good choices. It is not clear whether spicy foods (e.g., hot curry) aggravate diarrhea, but these are best avoided unless there is no alternative. Tea is recommended, but alcoholic beverages should be avoided.
TRAVELERS’ DIARRHEA FACTS
- Bacteria cause about 80% of travelers’ diarrhea.
- Contaminated food causes more illness than contaminated water.