Gastroenterology and Hepatology Board Review: Pearls of Wisdom, Third Edition

Section I GASTROENTEROLOGY

CHAPTER 7. Travel Matters in Gastroenterology

Abinash Virk, MD, DTM&H

Image Name three clinical syndromes associated with neurologic abnormalities (parathesias, ataxia, hypotension, seizures, and muscle paralysis) that occur following ingestion of toxin-containing fish.

Puffer fish poisoning (tetrodotoxin), paralytic shellfish poisoning (saxitoxin), and ciguatera poisoning (ciguatoxin).

Image What is the most common cause of fish poisoning in the United States?

Ciguatera. This is commonly seen in Florida, Hawaii, and the Caribbean.

Image What is ciguatera fish poisoning?

Ciguatera poisoning occurs after consumption of ciguatoxins present in certain fish. Large carnivorous tropical fish such as grouper, amberjack, red snapper, barracuda, and sea bass can harbor a toxin that cannot be detected by odor, taste, or color. The ciguatoxin accumulates in carnivorous fish that have consumed smaller herbivorous fish that feed on dinoflagellates such as Gambierdiscus taxicus. Risk is higher at tropical destinations such as the Caribbean and Indo-Pacific Islands.

Image True/False: Ciguatera poisoning causes both gastrointestinal and neurological symptoms.

True. Acute gastrointestinal (nausea, vomiting, and cramps) and neurologic symptoms occur within 2–6 hours of ingestion and last for about 1 week. Rarely, the neurologic symptoms of paresthesias and motor weakness can persist for months to years.

Image Which contaminated fish poisoning may cause flushing, vertigo, and burning sensation and is effectively treated with antihistamines?

Scromboid.

Image What is scromboid poisoning?

Scromboid poisoning presents within 30 minutes of consumption of toxic fish. Scromboid results from improper cooling of fish and resultant bacterial growth that degrades histidine in the fish muscles into histamine and histamine-like products called saurine. The histamine consumption causes flushing, nausea, emesis, and abdominal cramps, and can cause anaphylactoid symptoms within minutes of ingestion of the fish. The fish looks and smells normal but is often reported to have a “peppery” taste. Spoiled tuna, mackerel, and skipjacks are often implicated. If any of these fish has an unpleasant odor or clouded eyes, it should be avoided.

Image What infectious organisms can a traveler acquire with raw oyster consumption?

Raw oyster consumption is associated with acquisition of hepatitis A, Vibrio vulnificus and Cryptosporidium parvum. A single oyster or mollusk can filter >14 liters of water and concentrate pathogens in the gills.

Image True/False: A causative agent is found in most patients with traveler’s diarrhea (TD) suffering from prolonged diarrhea.

False.

Image What microorganism is the most common cause of TD?

Enterotoxigenic Escherichia coli is the most common cause of TD when a pathogen is isolated. In approximately 40%–50% patients with TD, no pathogen is isolated in stool cultures suggesting a possible viral etiology.

Image What is an approach to patients with persistent (TD) in whom a specific pathogen cannot be identified?

1. Treatment with an antibiotic directed at common bacterial pathogens.

2. Empiric course of antiprotozoal therapy if the above approach does not alleviate symptoms.

3. Endoscopic evaluation if the above fails.

Image What is the current recommendation for the treatment of TD?

For mild to moderate diarrhea (fewer than 4 bowel movements per day without blood or fever), either loperamide or bismuth subsalicylate can be used effectively. For more severe diarrhea, an antimicrobial drug should be used, usually a fluoroquinolone or trimethoprim-sulfamethoxazole. Rifaximin is also approved for the treatment of TD. Antimotility agents should not be used when bloody stools or high fever is present.

Image What are potential infectious causes of bloody diarrhea in a traveler?

Campylobacter and Shigella are the most common causes of bloody diarrhea in a short-term traveler. Other causes of bloody diarrhea include SalmonellaE. coli O157:H7, and Entamoeba histolytica. Acute amebic bloody diarrhea should be considered particularly in those returning after prolonged travel, especially if off the beaten track. Clostridium difficile colitis must also be considered in the differential diagnosis in patients on doxycycline for malaria prophylaxis or taking antibiotics for other reasons.

Image What is the most likely cause of diarrhea after trekking in Nepal during the rainy season?

Cyclospora should be considered high in the differential diagnosis.

Image What infection should be considered in a patient with fever, elevated transaminases, and doughnut-shaped granulomas on liver biopsy who recently returned from travels to a New Zealand farm?

Coxiella burnetii or Q or “Query” fever is a zoonosis that occurs worldwide. Transmission is primarily by inhalation of small droplets of barnyard dust or ingestion of contaminated dairy products; however, tick bites or human-to-human transmission can occur. Symptomatic acute infections may present with nonspecific generalized febrile illness with or without signs or symptoms of pneumonia and/or hepatitis or other organ involvement. Biopsy of the liver shows pathognomonic doughnut-shaped epithelioid granulomas.

Image What infection needs to be considered in a traveler with diarrhea, right lower quadrant pain, and mesenteric lymphadenitis?

Yersinia enterocolitica infection can mimic acute appendicitis. This will resolve spontaneously; however, in severe presentations, antibiotic therapy with trimethoprim/sulfamethoxazole, quinolones, or doxycycline is effective.

Image What condition predisposes to Yersinia enterocolitica septicemia?

Iron overload states such as in hemochromatosis, cirrhosis, and hemolytic processes.

Image What vaccines are contraindicated in patients receiving immunosuppressive medications including TNF-alpha antagonists?

Live-attenuated viral or bacterial vaccines such as Varicella–Zoster vaccine, live-attenuated influenza vaccine (LAIV), yellow fever, measles, mumps, and rubella (MMR), oral typhoid vaccine, or oral polio (not available in the United States).

Image What vaccines are recommended for the short-term healthy traveler to a developing country?

Hepatitis A and, in some cases, depending on destination risk, typhoid vaccines would be the most commonly recommended vaccines. Both diseases are food and water transmitted. Routine vaccines should be up to date for the age and underlying medical history of the patient. Japanese encephalitis, hepatitis B, and rabies vaccines would be recommended in addition if traveling for several months in South East Asia, while travel to some countries in Africa and South America may require yellow fever vaccine. Meningococcal vaccine is recommended for travel to certain countries in Africa and to Saudi Arabia during Hajj pilgrimage.

Image What are the adverse effects from yellow fever vaccination?

Yellow fever vaccine is a live-attenuated vaccine which can cause a multisystemic organ failure (with 50% mortality) in 1 in 250,000 doses in otherwise healthy adults. The risk is higher in adults over 60 years of age and immunocompromised hosts. Affected individuals develop fever, constitutional symptoms, jaundice, hematemesis, hypotension, and shock. Laboratory findings show transaminitis with aspartate aminotransferase being significantly higher than alanine aminotransferase. Yellow fever vaccine also has a neurotropic adverse effect which is lethal but less frequent.

Image What protozoal conditions are potential causes of constipation, ileus, or intestinal obstruction in travelers or immigrants from developing countries?

Amebiasis due to Entamoeba histolytica from many developing countries and Chagas disease due to Trypanosoma cruzii among those returning or immigrating from Central and South American countries.

Image What are common clinical presentations of trichinosis?

Trichinosis is acquired by ingestion of raw or undercooked pork, bear, or walrus meat. Initial symptoms include nonspecific diarrhea and abdominal discomfort. However, in the subsequent 1–2 weeks, fever with peri-orbital edema, shortness of breath (diaphragm involvement), and myalgias may occur. A leukemoid reaction with eosinophilia and normal sedimentation rate are unique to trichinosis.

Image What are adverse gastrointestinal effects of scuba diving?

Nitrogen gas expansion, related to Boyle’s law, may result in expansion of the gases and stretching of the intestines. Rarely, this can result in bowel overdistention and rupture. Barotrauma may also cause an insufficiency of mesenteric blood flow.

Image Consumption of unpasteurized milk is associated with what infections?

Brucella melitensis or abortusListeria species, and Mycobacterium bovis (presents just like Mycobacterium tuberculosis) can be acquired by the consumption of unpasteurized milk or milk products. Populations at risk particularly for Listeria monocytogenes include pregnant women and immunosuppressed persons. Meningitis can be a fatal occurrence with this infection.

Image What infection is associated with raw or improperly stored seafood or food contaminated with seawater?

Vibrio parahemolyticus.

Image What is the significance of isolating Entamoeba hartmanni, Endolimax nana, or Iodamoeba butschlii in stool?

None. These are nonpathogenic protozoa along with Entamoeba coli. The presence of these usually indicates consumption of contaminated food and water. No intervention is needed.

Image Lack of stomach acid (achlorhydria) increases the vulnerability to what infectious diseases?

Giardiasis, cholera, salmonellosis, tuberculosis, and enterotoxigenic E. coli.

Image What is the most likely infectious organism if a patient calls to report having seen a worm in his stool months after travel to a developing country?

Ascaris lumbricoides or round worm is large and the most commonly seen worm passed in stool or occasionally from other orifices. It can also migrate into and cause obstruction of the common bile duct.

Image What are some noninfectious causes of posttravel fatigue, anorexia, nausea, and elevated liver tests?

The liver dysfunction may be due to “Gordo-lobo yerba tea,” which, like germander and comfrey teas, contains pyrrolizidine alkaloids. Hepatic veno-occlusive disease may follow.

Image What parasite may cause inflammatory colon polyps?

Schistosomal infection may result in inflammatory colon polyps that appear grossly similar to hyperplastic and adenomatous lesions. Identifying the worm and/or the ova in tissue biopsy or in stool ova and parasite examination can make a definitive diagnosis. Serology is also available.

Image What are the differences between the enterotoxins produced by Vibrio cholera and Clostridium perfringens?

Clostridial enterotoxin has maximal activity in the ileum and minimal activity in the duodenum, just the opposite of cholera toxin.

Image What is the most common vehicle for Clostridium perfringens gastroenteritis?

Meat or poultry that is cooked, stored, and then reheated. Heat-resistant spores that survive the cooking process germinate within the food during the cooling period. On reheating, sporulation of the cells occurs with subsequent enterotoxin production.

Image What is the optimal management of patients with cholera?

The key components of management are aggressive rehydration along with electrolyte replacement, antibiotic therapy (such as doxycycline, azithromycin, or ciprofloxacin), and management of complications such as hypoglycemia or electrolyte imbalance.

Image What is the most likely diagnosis of persistent fevers, weight loss, diarrhea, shortness of breath, splenomegaly, and pancytopenia in an immunocompromised individual who went spelunking in Mexico 2 months ago?

Disseminated histoplasmosis from exposure to bat droppings in the caves. Histoplasma capsulatum can be identified in the GI tract of 70%–90% of patients with progressive disseminated histoplasmosis, although only 3%–12% have symptoms.

Image What are gastrointestinal manifestations of chronic Chagas disease?

Trypanosoma cruzi infection causes destruction of the autonomic and enteric innervation leading to dysfunction of the digestive system especially the esophagus and colon. Mega-esophagus is more frequently seen than megacolon. Symptoms include dysphagia, chest pain, active and passive regurgitation, heartburn, hiccups, cough, ptyalism (drooling), enlargement of the salivary glands—mainly the parotids—and emaciation. Thirty percent will have cardiac problems as well. The risk of acquiring Chagas disease in the course of usual travel itineraries is low. Chronic Chagas disease can be seen in the United States among immigrants from endemic countries in Central and South America.

Image Mild elevation of transaminases along with fever and rash presenting within 1 week of return from a 1-week trip to Haiti is most likely caused by what infection?

Dengue fever, transmitted by the Aedes sp. mosquitoes, which is present in more than 100 tropical countries. Infected persons usually have fever, chills, frontal headache, characteristic blanching rash, severe myalgias, and malaise. Laboratory tests often show mild neutropenia, thrombocytopenia, and mild elevations of transaminases. Diagnosis is clinical and based on short incubation period of about 7 days. Repeat infection with another strain of dengue virus can result in dengue shock or dengue hemorrhagic syndrome. Insect precautions are advised for travelers to endemic countries.

Image What parasites do you need to consider in a Chinese immigrant with eosinophilia, low-grade fever, and right upper quadrant pain?

Liver flukes such as Clonorchis sinensis and Opisthorchis viverrini infect and reside in the biliary tract. Fascioliasis, contracted from water vegetation, often produces a right upper quadrant “hot sensation,” hepatomegaly, and ascending cholangitis. Raw fish ingestion may lead to clonorchiasis that presents as pancreatitis. Cholangiography may detect the characteristic sacculated and dilated biliary tree of opisthorchiasis or brown leaflike fasciola fluke. Diagnosis is often made by finding typical eggs in stool or duodenal aspirates. Cholangiocarcinoma has been associated with chronic Clonorchis infection.

Image What are some adverse effects of transdermal scopolamine patches commonly used for motion sickness prevention?

A transdermal scopolamine patch is very effective for the prevention of motion sickness but anticholinergic reactions are occasionally seen. Anticholinergic reactions can result in dry mouth, urinary retention, and/or unilateral or bilateral blurred vision (dilation of the pupil [mydriasis] and paralysis of accommodation [cycloplegia]). Removal of the patch results in the resolution of symptoms within 12 hours.

Image Profuse diarrhea, fatigue, and weight loss in a Guatemalan immigrant unresponsive to metronidazole would most likely be due to which of the following:

1. Helicobacter pylori infection?

2. Necator americanus contracted from walking barefoot in the muddy soil?

3. Leptospira canicularis associated with the domestic dogs?

4. Cryptosporidium parvum from drinking the well-water?

5. Cyclospora cayetanensis?

Cyclospora cayetanensis is prevalent in developing countries. Outbreaks in the United States have occurred following importation of Guatemalan raspberries, pesto dishes, and mesclun lettuce. Fecal contamination of water and food is often the source.

Image What is the drug of choice for the treatment of Cyclosporiasis?

The drug of choice for cyclosporiasis in adults is trimethoprim-sulfamethoxazole (TMP-SMX; one double-strength 160 mg/800 mg tablet orally twice daily) for 7–10 days. Longer duration may be required for an immunocompromised host. Alternatives include ciprofloxacin or nitazoxanide in sulfa allergic patients.

Image What is Anisakiasis?

Anisakiasis is an acute infection caused by Anisakis simplex or Pseudoterranova decipiens larvae (fish roundworms) imbedded in salmon, cod, tuna, pike, herring, or squid. Risk of infection occurs with consumption of raw, undercooked, pickled, or salted fish. Most infections are with a single larva and, uncommonly, by two or more larvae. The larvae try to attach to the gastric mucosa but eventually die. Very few get beyond the stomach but all eventually die since humans are not the final host.

Image What are the classical symptoms of Anisakiasis? How is it treated?

Classical symptoms of anisakiasis are acute onset of excruciating abdominal pain, nausea, and emesis associated with sweating beginning a few hours after eating undercooked fish. Extraction by endoscopic forceps provides immediate relief. No antiparasitic medication is available for treatment. Freezing fish to -35°C for 15 hours or cooking the fish will prevent the infection.

Image What parasite is most frequently found in stool in the United States?

Giardia lamblia. It is found in 4%–7% of stools tested in US laboratories. The overall rate of detection is 7.4 cases per 100,000 population with a higher incidence in late summer or early fall.

Image What are the most common symptoms of Giardiasis?

Diarrhea with foul-smelling stools, malaise, flatulence, and nausea are the most common symptoms. Diarrhea is usually without fever or blood.

Image What is the best test to diagnose Giardiasis?

Giardia stool antigen. Due to intermittent shedding, it is best to obtain at least two stools separated by a few days. The enterocapsule “string test” is seldom utilized in present day, but can identify Giardia in the duodenum with a 96% success rate.

Image What is the optimal treatment for Giardiasis?

Tinidazole 2 g as a single dose has been shown to be more effective than metronidazole. Alternative treatments include metronidazole 250 mg orally three times a day for 5–7 days or nitazoxanide 500 mg orally twice a day for 3 days. In 2002, nitazoxanide was the first new drug to be FDA-approved for the treatment of Giardia in 40 years.

Image Which of the following statements below is correct in relation to a 43-year-old woman who presents with malaise, 10-pound weight loss, low-grade fever, mucoid diarrhea with flatulence and right lower quadrant aching and presence of fecal “green-tinted crystals” and hypochromic microcytic anemia following a recent trip to rural Mexico?

a. A colonoscopy would aid in the diagnosis.

b. The persistent mucoid discharge suggests a right-sided colonic lesion.

c. Ameboma, chronic appendiceal abscess, Crohn’s ileitis, and tubercular or yersinea infections are all diagnostic considerations.

d. A limited trial of medical therapy, while avoiding alcohol, is justified before surgical intervention.

All are correct. A constricting cecal ameboma associated with colonic ulcerations was visualized on colonoscopy. These regressed on metronidazole and paromomycin therapy with negative biopsies 2 months later. Pineapple crystals display a greenish tinge with long acicular forms and are often mistaken for Charcot–Leyden and fatty acid crystals. The simple use of a flurochrome, calcoflor compound as a wet mount will enhance the detection of not only amebic cysts but filamentous fungi, microsporidia, and Pneumocystis carinii.

Image A 50-year-old Somali male immigrant, who immigrated 6 years ago, presents with low-grade fever, weight loss, intermittent massive hematemesis, and left upper abdominal pain. Evaluation confirms splenomegaly. He is noted to have mild eosinophilia. What is the most likely diagnosis?

Schistosomiasis is most likely caused by Schistosoma mansoni and secondary complications of hepatic cirrhosis and portal hypertension. Diagnosis can be confirmed by stool ova and parasite evaluation, serology, and/or rectal squish biopsy. Chronic complications are irreversible but treatment with praziquantel may decrease progression.

Image What is the most common infectious cause of chronic nonbloody diarrhea in the United States?

Cryptosporidium parvum. The testing for Cryptosporidium should be specifically requested; otherwise, it can be missed on routine stool ova and parasite examination. The best method for detection is immunofluorescence microscopy followed closely by enzyme immunoassays.

Image What is the treatment of choice for Cryptosporidium?

Most infections will be self-limiting and do not require pharmacological treatment; however, if symptoms persist, then treatment is with nitazoxanide 500 mg orally twice a day for 3 days. Alternatives are paromomycin, azithromycin, or a combination of the two. There is no clearly effective regimen in advanced HIV/AIDS patients. Treatment with highly active antiretroviral therapy (HAART) appears to decrease the risk of infection and symptoms.

Image Massive hepatosplenomegaly with cachexia, pancytopenia, and reversed albumin: gamma-globulin ratio in a soldier returning home from Afghanistan is suggestive of what infectious disease?

Visceral leishmaniasis is caused by Leishmania donovani and other species. It is transmitted by the bite of the female sandfly, Phlebotomus sp. Visceral leishmaniasis is endemic in 88 countries with more than 90% of cases occurring in India, Nepal, Bangladesh, Brazil, and Sudan. Diagnosis is mostly by demonstration of the parasite in macrophages in bone marrow specimen or other tissue biopsies.

Image What food is usually implicated in the vomiting syndrome caused by Bacillus cereus?

Fried rice.

Image Improperly canned products may contain what potentially lethal infection?

Clostridium botulinum. Its spores are resistant to heat and its neurotoxin can block acetylcholine at the neuromuscular junction, resulting in fatal respiratory muscle paralysis.

• • • SUGGESTED READINGS • • •

Practice Guidelines for the Management of Infectious Diarrhea. Clin Infect Dis. 2001;32(3):331-351.

Drugs for Parasitic Infections. Treatment Guidelines from the Medical Letter. 2007;5(suppl):e1-e15.

Rosenblatt JE. Approach to diarrhea in returned travelers. In: Elaine Jong and Christopher Sanford, eds. The Travel and Tropical Medicine Manual. 4th ed. Philadelphia, PA: Saunders-Elsevier, 2003:430-447.