HB3 S76 SGC GI Cases 2

How should you treat this case?

- Antibiotic treatment generally is not required because most cases self-resolve in a reasonable period of time. - However, treatment is indicated in patients presenting with fever and severe diarrhea lasting for more than five days. - The recommended treatment for severe febrile infections is azithromycin.

How is this disease transmitted?

- As noted above, humans are infected by ingesting pinworm eggs. - Many infected children and adults are asymptomatic and function as carriers. - Transmission occurs via person-to-person spread or via fomites. - Person-to-person spread is most frequent in crowded places like day care centers and schools. - Infected children who scratch their perianal area and pick up eggs on their hands can easily transfer them to the hands of other children, who then infect themselves when they put their fingers in the mouths. - Eggs and egg-laying adults are deposited and can survive on clothing, toys in daycare centers, and other fomites. - They can also survive for long periods of time in dust, so people can be infected by inhaling egg-infested dust. Infected food handlers also serve as significant reservoirs of infection.

Are any complications possible? If so, what are they?

- Between 10% and 20% of patients with Campylobacter enterocolitis develop bacteremia and serious inflammatory disease. - C. jejuni has been associated with Guillain-Barré Syndrome (GBS), an autoimmune disorder of the peripheral system in which symmetrical weakness develops over a few days. - Full recovery might require months or longer. - This complication occurs in only about 1 in 1000 cases of diagnosed C. jejuni infection, and it appears to be associated with specific serotypes. - Other possible but rare complications of C. jejuni infections include reactive arthritis and bacteremia. - Reactive arthritis is more frequent in people with the HLA-B27 gene phenotype.

A 57-year-old woman has been admitted to the hospital because she is experiencing a fourth episode of unexplained Gram-negative bacteremia. The only other significant aspect of this woman's medical history is that she recently started treatment with corticosteroids for asthmatic bronchitis. To her physician's surprise, her cough actually worsened after she was started on corticosteroid therapy and, not long afterwards, she developed persistent abdominal pain and diarrhea. The woman's un-explained episodes of bacteremia also began after she started taking the corticosteroid. What tests do you want to order? Explain your reasoning.

- Blood cultures could be ordered to identify the causative agent of the bacteremia and to obtain antibiotic sensitivity information that would help to optimize treatment. - The woman's cough could be caused by a respiratory infection, so a chest radiograph could be ordered and, if she is able to cough up sputum, it can be sent to the lab for microscopic examination, Gram staining, and culturing. - She also has persistent gastrointestinal symptoms, so a stool specimen can be sent for microscopic examination, testing for occult blood, and culturing. - Imaging might also be helpful with respect to finding out what is happening in her GI tract.

- Gram stains of the stool samples reveal the presence of comma-shaped, Gram-negative bacilli in each of the samples. - Isolates are obtained from each sample and identified as Campylobacter jejuni. What kind of damage does C. jejuni do in the GI tract?

- Campylobacter infections cause injury to the jejunum, ileum, and colon, technically making this disease an enterocolitis. - The mucosal surfaces appear ulcerated, edematous, and bloody, with abscesses in the epithelial glands. - Biopsies reveal an acute non-specific inflammatory reaction, with neutrophils, eosinophils, and monocytes in the lamina propria.

What is the causative agent of this condition? What is its host range?

- Enterobiasis is caused by Enterobius vermicularis, the pinworm. - Pinworms are small nematode (roundworm) parasites. - Humans are the only known hosts for this parasite

What specific agents in the category that you identified for the previous question are known to cause gastrointestinal diseases?

- Five types of nematodes commonly cause gastrointestinal diseases. - They are: Ascaris lumbricoides, Enterobius vermicularis (pinworm), Necator americanus/Anyclostoma duodenale (hookworms), Strongyloides stercoralis, and Trichuris trichiura (hookworm).

Seven UCF medical students who just completed their M1 year decide to take a break before starting work on the FIRE module projects they've been putting off until the summer. The students go to Col-o¬rado, where they climb a "14er" and take strenuous hikes through undeveloped areas of Rocky Mountain National Park. Near the end of their trip, they go on a white water rafting excursion down one of the more challenging rivers in the state. Unfortunately, their raft nearly capsizes in one of the rapids, spilling most of the riders, including the med students, into the river. No one was hurt and everyone was eventually pulled back into the raft, but those who were dumped out did swallow varying amounts of apparently pristine river water before they were picked up. About 11 days after returning from their Colorado trip, five of the students experience the sudden onset of a watery and unusually foul-smelling diarrhea consisting of pale, greasy stools (i.e., steator-rhoea). Their diarrhea is accompanied by abdominal cramps, occasional nausea and vomiting, bloat-ing, pronounced flatulence, and sulfurous belching. The ill students are not febrile, and they have not eaten any meals together since they returned to UCF. What do you think is the source of these students' gastrointestinal disease?

- GI diseases are usually associated with contaminated food or water. - The students must have contracted their disease in Colorado because they haven't eaten any meals together since returning to UCF and the public water supplies in Orlando are quite safe. - So, the only likely source of disease to which they were all exposed (as far as we know) was the river water.

Where does the causative agent live and how are humans exposed to it?

- Giardia lamblia occurs worldwide and has a sylvatic (or "wilderness") distribution in numerous streams, lakes, and mountain resort areas. - The organism is maintained in animal reservoirs (such as beavers and muskrats) that shed its cysts in their feces. - Humans can be infected by consuming contaminated water (which often appears crystal clear, since only a very small number of cysts—as few as 10 to 25—can initiate infection), by consuming uncooked fruits and vegetables that have been exposed to contaminated water, and by person-to-person transmission (via the fecal-oral and anal-oral routes).

People who are infected with Strongyloides stercoralis usually do not develop a large adult worm load and persistent notable symptoms, despite the worm's autoinfec-tion cycle, so why did the woman in this case develop a large adult worm load and associated symptoms?

- In an immunocompetent person, the immune response will pretty much keep the autoinfection cycle in check, so the adult worm load does not increase enough to cause problems. - In the absence of a normal immune response, however, the autoinfection cycle is not controlled and the adult worm load increases continually. - This can eventually lead to a hyperinfection in which larvae disseminate to multiple organs, a very dangerous condition with a mortality rate of about 85%. - The woman in this case apparently was infected with Strongyloides many years earlier (while growing up in Kentucky), and her immune system was able to keep the autoinfection cycle in check until it was suppressed when she started taking a corticosteroid.

If the chicken sandwiches were the source of this illness, why did only three of the five family members become ill?

- Most likely, the sandwiches eaten by the father and the child that did not become ill were cooked thoroughly enough either to kill the causative agent or to lower its numbers to a safe level. - All GI pathogens require a minimum inoculum (the number of bacteria swallowed) to get established and cause disease. - If cooking reduces the levels of a pathogen in the food below the minimum inoculum, the food is theoretically safe to eat even though some living pathogen cells are still present.

A 4-year-old boy is brought to your clinic because he is experiencing anal itching. He has been rubbing and scratching his anal area frequently for the past ten days. The itching worsens at night and is starting to keep the boy awake. The area around his anus is erythematous and raw from all the scratching. The boy's mother tried to treat him with a hydrocortisone cream, but that didn't relieve his symptoms at all. The boy hasn't had any obvious skin rashes and he is not scratching any other part of his body. He has not had diarrhea or any related GI symptoms. He is not on any medications and has no recent history of medical problems. On physical examination, he appears tired but well developed and well nourished. Except for erythema and excoriation in his anal area, there are no sig-nificant physical findings. On taking a history, you learn that the boy attends day care four days a week. What is your preliminary diagnosis? (What condition is most likely to cause anal itch-ing, especially nocturnal anal itching, in a young child?)

- Pinworm = enterobius vermicularis - Most typical GI pathogens are ruled out by the absence of symptoms like diarrhea or vomiting. - Various conditions can cause perianal pruritus (the only notable symptom), but the most frequent cause of perianal itching that worsens at night in young children is enterobiasis, commonly known as pin-worm.

What is the life cycle of the causative agent?

- Pinworm infection is initiated by ingestion of E. vermicularis eggs. - The eggs hatch in the small intestine, releasing larvae that migrate to the colon and mature into adults. - Fertilized adult females migrate to the perianal area at night and deposit eggs in folds of skin. - The eggs become infectious in just a few hours. - They can easily be transmitted to others, but some of them hatch in perianal folds, producing larvae that migrate back into the rectum and mature into adults. - This process allows untreated infections to persist for long periods of time. - Reinfection also occurs if eggs are carried to the mouth on unwashed hands.

How common is this disease?

- Pinworm infections occur worldwide (500 million new cases/year), especially in temperate zones. - Enterobiasis is the most frequently occurring helminthic (worm) infection in North America.

What is your preliminary diagnosis, based on the apparent source of the disease and the rather unusual combination of symptoms?

- Steatorrhoea, flatulence, bloating, and sulfurous belching suggest giardiasis caused by Giardia lamblia, a protozoan. - The apparent incubation period and all of the symptoms seen in the case are consistent with giardiasis. - Moreover, giardiasis is often associated with consumption of unfiltered water from "pristine" mountain streams or lakes. - Cryptosporidiosis is also possible because its presentation occasionally resembles that of giardiasis and there have been reports of cases from Colorado associated with mountain stream water.

What tests do you want to order? What will they tell you?

- Stool specimens should be sent for sent for microscopic analysis and culturing. - Microscopic analysis can distinguish between non-inflammatory and inflammatory GI disease, based on the absence or presence of WBCs and/or RBCs. - The lab can also check for ova and cysts, which would indicate a parasitic disease. - Culturing may reveal the identity of a bacterial causative agent. - Labs only do cultures for a limited set of common GI pathogens, so if you suspect anything else, you must order the appropriate additional tests.

How can you confirm your diagnosis? (What tests do you want to order?)

- Stool specimens should be sent to the lab for analysis, including microscopic analysis for the presence of protozoan cysts (resting forms) or trophozoites (active forms). - The lab should also run routine stool cultures on all of the specimens in order to eliminate common bacterial GI pathogens.

How can you confirm your diagnosis quickly?

- The "Scotch Tape" test is used to detect pinworm infections. - Enterobius eggs are usually present on the perianal skin during an infection. - They can be sampled by pressing a piece of cellophane tape against the skin in the perianal region. - The eggs picked up by the tape can then be visualized with a microscope.

Are these new findings consistent with the diagnosis you developed on the previous page? Why or why not? If not, what is your new diagnosis?

- The absence of mucus, WBCs, and RBCs is consistent with giardiasis. - The objects seen in the stool specimens are trophozoites of Giardia lamblia, the causative agent of giardiasis. - Their presence in the stools confirms the diagnosis. - Giardia trophozoites and cysts often occur in "showers" during giardiasis, meaning that many organisms may be visible in the stool one day, but not the next day. - Therefore, one stool specimen should be examined each day for three days before accepting a negative result as correct.

Microscopic examination of smears from stool samples detects numerous PMNs in all of the patient's stools and a little fresh blood in the stools of the two children. There are no ova or cysts. The mother relates her concerns about the undercooked chicken sandwiches, but she also dismisses them because only three of the five family members who ate fast-food chicken sandwiches that day are ill. How do these new findings affect your differential?

- The lack of ova or cysts makes a parasitic disease unlikely. - The presence of WBCs and RBCs, along with a fever, confirms that this is an inflammatory diarrhea, so bacterial agents that do not cause inflammatory GI infections (e.g., Staphylococcus aureus and enterotoxigenic E. coli) and most viral GI pathogens can be ruled out in this case. - The differential is thus narrowed to infections by Salmonella enterica, Yersinia enterocolitica, Campylobacter jejuni, enterohemorrhagic E. coli, and a few other GI pathogens.

What are objects seen in the image? Does this finding confirm your diagnosis?

- The objects seen on microscopic examination of the cellophane tape are eggs of Enterobius vermicu-laris. - Their presence in the perianal region confirms that the boy has a pinworm infection.

The woman in this case currently is a resident of Michigan, but she lived in rural eastern Kentucky as a young child and teenager. As her physicians obtain a more detailed history, it becomes clear that she has not been repeatedly reinfected by or even exposed to a nematode GI pathogen from the environment during the past two decades. Nematode GI infections are usually very mild or even asymptomatic unless one builds up a large load of adult worms, which for most GI nematodes, requires repeated reinfection from the environment. However, there is an exception. Which nematode GI pathogen can produce a large adult worm load in someone who is not repeatedly reinfected from the outside environment?

- The only nematode GI pathogen that can produce a large adult worm load in the absence of reinfections from the environment and that has a pulmonary cycle (don't forget what was detected in her sputum) is Strongyloides stercoralis.

How should this case be treated?

- The recommended drug for treatment of strongyloidiasis is ivermectin. - Albendazole is an effective alternative drug.

How would you treat the patients in this case?

- The recommended treatment for giardiasis is nitazoxanide or tinidazole. - Metronidazole is an acceptable alternative treatment.

Based on the above images, what major category of helminth is causing this wom-an's infection? (Into which major group of medically significant helminths would this one be classified?) Explain your reasoning.

- There are three major categories of medically significant helminths: cestodes (tapeworms), trematodes (flukes), and nematodes (roundworms). - If a cestode were causing this infection, the lab should have noticed proglottids in the stool specimen. - Fully developed adult tapeworms probably would have shown up in the CT scan as well. - The larvae shown in Figures 4.1 and 4.2 have round, cylindrical bodies, which is characteristic of nematodes (roundworms). - By comparison, trematodes have flat, leaf-like bodies.

A family of five with children aged 3, 4, and 5 stops at a fast-food restaurant for lunch after driving all morning. Everyone orders a chicken sandwich, with French fries and a soft drink. The mother notices that the chicken filet in her sandwich is a little pink in the middle and is tempted to take the food back to the counter. However, the children are very hungry and were starting to fuss in the car be-fore the family stopped, so they are likely to throw a tantrum if there is another delay. Their mother wants to avoid this. Besides, her sandwich tastes pretty good, so she figures there's no real reason to worry. The next day, the mother and two of the children begin to experience fever, headaches, myalgias, and malaise. They do not seek medical attention because their symptoms really aren't all that bad. How-ever, the symptoms persist throughout the next day, after which they develop abdominal cramps and watery diarrhea. By the next morning, they have all had about 10 bowel movements and it is appar-ent that additional movements are on the way, so they immediately go their family physician. On ex-amination, their vital signs are normal, except for fevers ranging from 100.4 to 101.3°F. Two children display mild signs of dehydration, but there are no other significant findings. What is the differential? (What conditions might explain the symptoms seen here?)

- This is clearly a form of enteritis. - Intoxications can be ruled out based on the incubation period (about 1 day), the persistence of the symptoms, and the presence of fever. - However, that leaves a wide range of infectious agents that cause similar symptoms (watery diarrhea and cramps), including bacteria, viruses, and protozoa. - More information will be needed to make a specific diagnosis in this case.

What specific pathogens are most often associated with the apparent source of this GI disease outbreak?

- Two bacterial GI pathogens frequently cause GI infections associated with undercooked poultry: Salmonella enterica and Campylobacter jejuni. - Other pathogens cannot be ruled out without more information but the source of infection does make these two organisms the most likely suspects in this case.

How should you treat this patient?

- mebendazole (microtubule inhibitor) in a single dose to be repeated in 2 weeks. - Pyrantel pamoate is a good alternative.

Pinworm infection

Enterobius vermicularis

How do you explain the woman's recurrent episodes of bacteremia?

The episodes of bacteremia probably developed when filariform larvae penetrated though the intesti-nal lining and carried intestinal bacteria with them into the bloodstream.

How does Strongyloides stercoralis cause disease? (What is the pathologic process?) What aspect of its life cycle allows it to increase the number of adult worms in the GI tract without repeated reinfection from the outside environment?

The infectious form of Strongyloides stercoralis—the filariform larva—occurs in soils contaminated with fecal material. Humans are infected when filariform larvae penetrate through intact skin. (Per-haps the woman in this case walked barefoot while growing up in rural eastern Kentucky.) After enter-ing through the skin, the filariform larvae enter the circulatory system and migrate to the lungs, where they cause irritation and a transient pneumonitis. The larvae are eventually coughed up and swal-lowed, after which they mature into adults in the small intestine. The adult females produce eggs (Figure 4.3) that hatch in the intestinal mucosa and develop into rhabditiform larvae, which are not in-fectious and that move into the lumen of the bowel. Most rhabditiform larvae are passed in the stool and, in soil contaminated with that stool, they mature into the infectious filariform larvae that can penetrate skin. The unique feature of the Strongyloides stercoralis life cycle that might eventually produce a large adult worm load without repeated reinfection from the environment (through intact skin) is its autoinfection cycle. A small percentage of non-infectious rhabditiform larvae in the bowel develop into the infec-tious filariform larvae before they can be excreted in feces. The filariform larvae in the bowel then penetrate the intestinal lining, migrate to the lungs, get coughed up and swallowed, and develop into adults in the small intestine, thereby increasing the adult worm load.