Parasitic diarrhea

Parasites are the final category of infectious agents causing acute diarrheal illness. In the developed world, parasites are the least common etiologic agents, causing fewer than 10% of infections, most of which are due to Cryptosporidium and Giardia lamblia.22 Both of these organisms are transmitted fecal-orally. Cryptosporidium causes a self-limited, watery diarrhea that presents within hours after oocyst ingestion in immunocompetent persons but has a severe, prolonged course in the elderly and immunocompromised; it is a major cause of wasting in patients who have AIDS.23 In industrialized countries, Cryptosporidium is acquired mainly through contaminated swimming pools and drinking water because the durable cysts are chlorine-resistant. In the United States, most Cryptosporidium infections are reported in children during the summer months, correlating with the opening of community swimming pools.24 The infection can also spread quickly from person to person in places where hygiene is poor, and outbreaks occur in day care facilities and hospitals less commonly.25 Travelers to developing countries often acquire cryptosporidiosis from contaminated drinking water or animal contact.22 Giardia causes a delayed infection 7 to 14 days after ingestion of the cysts25 in which large-volume steatorrhea is often associated with weight loss. The infection is self-limited but often lasts more than 7 days; in some patients it persists to become a chronic infection, lasting more than 14 days.25 Giardia infection is acquired via contaminated water and food and during person-to-person contact in places with poor hygiene. Less commonly, Giardia infection can be sexually transmitted during anal intercourse. Other parasites, including Entamoeba, Cyclospora, and Microspora, are uncommonly found among the immunocompetent population in developed countries, but organisms may persist in returning travelers and cause opportunistic infections in patients with AIDS in industrialized countries.22

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Further workup

After a thorough history and physical examination have been conducted, there are still times when it is necessary to pursue further testing. Using clinical judgment is crucial to provide a cost-effective yet revealing diagnostic workup.2 Studies have shown that diagnostic yields from stool cultures are as low as 1.5% to 5.6%.2 Extrapolation of data leads to estimated costs for each positive culture result ranging from $952 to $1200.2,9,26 Although a negative stool culture result can still hold valuable information, the poor sensitivity of stool cultures and their broad misuse inflate costs.9 That information notwithstanding, diagnostic testing can be useful in a number of situations. Avoiding testing can increase the use of inappropriate empirical antibiotic therapies, with a subsequent increase in resistant bacterial strains and side effects.9 Also, the use of antibiotics in some cases of diarrhea prolongs and worsens the illness.9 Lastly, a properly selected antibiotic regimen reduces the strain of disease and in some cases is life-saving.9

Because most cases are self-limited and last less than a day,4 and given the potentially high costs and low yields of diagnostic tests in most cases of diarrhea,2,9 fecal testing should be reserved for patients with features indicating severe illness, such as the following: persistent diarrhea, diarrhea accompanied by fever, recent antibiotic use, and the presence of blood and/or pus, tenesmus, and dehydration.2,9 In the presence of these factors, it is appropriate to test for causes of inflammatory diarrhea, such as Salmonella, Shigella, Campylobacter, and Shiga toxin–producing E. coli (STEC, especially in patients with dysentery).2 Other important situations to consider are elderly patients (especially those in nursing homes), those who are immunocompromised, food handlers, day care center employees, and suspected outbreaks.8

If inflammatory diarrhea is being considered, fecal microscopic neutrophils or lactoferrin can supplement a diagnosis.2,9 The sensitivity and specificity of fecal leukocytes in diagnosing inflammatory diarrhea are relatively high, 73% and 84%, respectively.2,26 For lactoferrin, the sensitivity and specificity are 92% and 79%, respectively.2,26 The acute onset of dysentery and/or the presence of HUS should trigger specific testing for Shiga toxin and culture for E. coli O157:H7.2 Entamoeba histolytica testing should be considered when bloody stools are found in recent travelers and immigrants from regions of endemicity, “such as tropical Africa, Asia, or Latin America.”2,3 A history suggestive of recent seafood consumption may prompt a culture for Vibrio species.2 A presentation mimicking persistent appendicitis with diarrhea can suggest Yersinia enterocolitica or Yersinia pseudotuberculosis.2

A common cause of nosocomial diarrhea is C. difficile. Stool cultures and tests for toxins should be promptly considered in hospitalized patients with an acute onset of diarrhea, especially in those who are of advanced age or have recently taken antibiotics.2,19 Any antibiotic may be the cause, but the most common agents are clindamycin, the broad-spectrum penicillins, and the cephalosporins.19 Toxin screens have proved to be the gold standard for diagnosing C. difficile colitis.19 Imaging studies such as abdominal radiography and computed tomography along with endoscopic procedures can be helpful, but they are not as sensitive or specific, and they are more expensive than toxin assays.19

Some important caveats about fecal testing should be mentioned.19 Researchers found that to prevent unnecessary testing, fecal tests other than those for C. difficile should not be performed on patients hospitalized for more than 3 days unless they are older than 65 years of age, immunocompromised, or neutropenic, are infected with HIV, or have other pre-existing comorbidities.2,19

Other, less likely causes of diarrhea may be considered given the appropriate clinical history. A history of persistent diarrhea following exposure to untreated water, such as occurs during camping or hiking, should trigger a workup for protozoa such as Giardia and Cryptosporidium.2 The sensitivity of enzyme immunoassays is very high, about 95%, and they are more effective than simple microscopic fecal analysis.2 Furthermore, in those patients who have advanced AIDS and CD4 cell counts below 50/mm3 with persistent diarrhea, “stool studies for Cryptosporidium, Microsporidia, Cyclospora, and Isospora” are appropriate.2 Other causes of diarrhea in patients with advanced HIV infection can be explored by collecting blood cultures or taking biopsy specimens to evaluate for Mycobacterium avium complex and cytomegalovirus.2

Persistent diarrhea with fecal indicators of inflammation in the face of a negative workup for infectious causes should prompt an evaluation for inflammatory bowel disease.2,27

In most cases of acute diarrhea, a single stool sample should be sufficient for licensed laboratories.11 The sample should be studied as soon as possible (within 4 hours) for microscopic analysis and within 12 hours for stool cultures or other standard tests.8 Multiple stool samples may be needed for some cases of C. difficile colitis, inflammatory bowel disease, and diarrhea caused by parasites.2,28

The role of endoscopy in the investigation of diarrhea is essentially limited to cases in which the previous workup has remained inconclusive, symptoms have persisted, or treatment has failed.2,29,30 Specifically, endoscopy is indicated in cases of suspected C. difficile colitis and dysentery in which the results stool studies, including toxin assays and cultures, have proved negative.8 Flexible sigmoidoscopy has a role and may be used initially to investigate acute diarrhea in several situations: patients with suspected C. difficile colitis, pregnant patients, those with significant comorbidities, and those with symptoms that are largely left-sided.30 Endoscopic findings can help differentiate infectious diarrhea from inflammatory bowel disease.8 Routine esophagogastroduodenoscopy (EGD) is not indicated.30 Instead, EGD should be reserved for patients with negative results of laboratory studies and lower gastrointestinal tract endoscopy because inflammatory bowel disease is a rare cause of diarrheal symptoms.30 The working differential at that time should include celiac disease and Crohn disease, intestinal Giardia infection, and pancreatic insufficiency, among others.30

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The choice of any further diagnostic studies, including serum studies, imaging, urinalysis, and anoscopy or endoscopy, should be determined by the severity of illness along with the clinical and epidemiological features.9