Cryptosporidiosis

Background

Cryptosporidiosis is caused by a species of protozoan parasite that typically infects the mucosa of the small intestine, causing watery diarrhea. Diarrhea may be accompanied by nausea, vomiting, abdominal cramping, and occasionally fever. The infection is spread by the fecal-oral route, usually via contaminated water, and is highly contagious. The course of infection depends on the immune status of the host. In immunocompetent individuals, cryptosporidiosis usually is self-limited and can cause a mild diarrheal illness. However, in HIV-infected patients with advanced immunosuppression, cryptosporidiosis can cause severe chronic diarrhea, electrolyte disturbances, malabsorption, and profound weight loss. Infection also can occur outside the intestinal tract and can cause cholangitis, pancreatitis, and hepatitis. In severe cases, cryptosporidiosis can be life-threatening without aggressive fluid, electrolyte, and nutritional support. Patients at greatest risk of acquiring cryptosporidiosis are those with CD4 counts of <100 cells/µL. Immune reconstitution inflammatory syndrome (IRIS) has not been described in association with cryptosporidiosis.

S: Subjective

The patient may complain of some or all of the following: watery diarrhea (can be profuse), abdominal pain or cramping, flatulence, nausea, vomiting, anorexia, fever, and weight loss.

The history should include questions about the presence and characteristics of the symptoms listed above, as well as the following:

• Stool frequency (typically 6-26 bowel movements daily)
• Stool volume (up to 10 liters per day and can be described as "cholera-like" in some patients with AIDS)
• Duration of symptoms (subacute or acute onset)
• Associated symptoms
• Exposures: recent travel to areas with unsafe water supply; ingestion of possibly contaminated water while swimming, boating, or camping; oral-anal contact, fecal exposures during sexual contact
• Recent CD4 cell count (highest risk is in patients with CD4 counts of <100 cells/µL)

O: Objective

Perform a thorough physical examination with particular attention to the following:

• Vital signs, hydration status
• Hydration status (e.g., orthostatic vital signs, mucous membrane moistness, skin turgor)
• Weight (compare with previous values; document weight loss)
• Signs of malnourishment (e.g., cachexia, wasting, thinning hair, pallor)
• Abdominal examination for bowel sounds (usually hyperactive), tenderness (can be diffuse), rebound
• Recent CD4 count

A: Assessment

In HIV-infected patients with advanced immunosuppression, the differential diagnosis includes other infectious causes of subacute or chronic diarrhea or cholangitis, such as microsporidia, Isospora, Giardia, cytomegalovirus (CMV), and Mycobacterium avium complex (MAC), as well as lymphoma.

P: Plan

Diagnostic Evaluation

• Test the stool for ova and parasites, including Cryptosporidium. Diagnosis is made by microscopic identification of the Cryptosporidium oocysts in stool.
  • Be sure to ask the laboratory to look for Cryptosporidium; certain labs do not look for these parasites or their precursor, the oocyst, unless requested.
  • Test for fecal leukocytes. The result usually is negative in cryptosporidiosis; if positive, consider the possibility of a second enteric infection, especially if the CD4 count is low, or a different infection.
• Among persons with profuse diarrhea, a single stool specimen usually is adequate for diagnosis.
• For patients with milder disease, repeat stool sampling is recommended.
• If stool is negative for ova and parasites, consider a referral for biopsy of the gastrointestinal mucosa or flexible sigmoidoscopy.
• If cholangitis is suspected, consider abdominal ultrasound to look for biliary ductal dilatation, and endoscopic retrograde cholangiopancreatography (ERCP).
• Check electrolytes; conduct liver function studies including alkaline phosphatase and bilirubin to check for possible biliary or hepatic infection.
• If fever is present, obtain blood cultures.
• Conduct other diagnostic testing as indicated by the history and physical examination (e.g., evaluation for CMV, MAC, and other infectious causes of diarrhea or cholangitis) (see chapter Diarrhea).

Treatment

• Effective antiretroviral therapy (ART) with immune reconstitution (and CD4 count of >100 cells/µL) can resolve cryptosporidiosis, and it is the primary treatment. All patients with cryptosporidiosis should be offered ART (see chapter Antiretroviral Therapy). Patients who are on incompletely suppressive ART should have their regimens optimized.
• Provide supportive care and symptomatic relief (this may require hospitalization in cases of severe dehydration), including the following:
  • Aggressive fluid and electrolyte replacement as needed
  • Oral rehydration (solutions containing glucose, sodium bicarbonate, potassium, magnesium, and phosphorus); in severe cases, IV hydration may be required
  • Antidiarrheal agents: atropine/diphenoxylate (Lomotil), loperamide (Imodium), tincture of opium (Paregoric)
  • Antispasmodics
  • Antiemetics
  • Topical treatment for the anorectal area, as needed (witch hazel pads [e.g., Tucks]), sitz baths)
• No antiparasitic therapy has been proven to consistently and effectively cure cryptosporidiosis if used without ART.
  • Nitazoxanide is approved for use in children and adults with diarrhea caused by Cryptosporidium parvum, the most common strain of Cryptosporidium. It may increase the likelihood of clinical response. It should be given in conjunction with ART, but never instead of ART.
    • Usual adult dosage: 500-1,000 mg PO BID for 14 days
    • Adverse events associated with nitazoxanide are limited and typically mild; there are no important drug-drug interactions
  • Paromomycin with or without azithromycin does not appear to be effective, especially for patients with CD4 counts of <100 cells/µL. Current data do not support a recommendation for use.
• For patients with weight loss, nutritional supplementation is a critical aspect of treatment. In some cases, partial or total parenteral nutrition may be necessary while patients are awaiting clinical improvement in response to ART or other therapies. Consult or refer to a dietitian or nutritionist, if available. If not, assess food intake and counsel the patient about increasing caloric and nutritional intake.

Cryptosporidiosis in Resource-Limited Settings

Cryptosporidium infection in HIV-uninfected populations is more common in countries with overcrowding and poor sanitary conditions. The disease is also associated with rainy seasons and is frequent among children <2 years of age.

The prognosis for HIV-infected patients with cryptosporidiosis who lack access to ART is poor. In one study, the mean survival time of coinfected patients was 25 weeks.

Prevention of Disease and Exposure

• Rifabutin or clarithromycin, when taken for MAC prophylaxis, have been found to protect against cryptosporidiosis. However, current data are insufficient to warrant a recommendation of their use as prophylaxis.
• Scrupulous handwashing can prevent the spread of cryptosporidiosis, and HIV-infected patients should be advised to wash their hands after potential contact with human feces (diapering small children, handling pets, gardening, and before and after sex)
• HIV-infected patients should avoid sexual practices that could lead to direct (e.g., oral-anal) or indirect (e.g., penile-anal) contact with feces and should be advised to use barrier methods during sex (e.g., condoms and dental dams).
• HIV-infected persons should avoid drinking water from lakes or rivers. Waterborne infection also can result from recreational activities such as boating, fishing, and swimming.
• HIV-infected patients should avoid raw oysters as the cryptosporidial oocysts can survive in oysters for >2 months.

Patient Education

• Recommend scrupulous handwashing for the patient and all contacts, especially household members and sex partners.
• Explain that effective ART is the best treatment for alleviating symptoms and helping the immune system eradicate the parasite.
• Advise the patient to increase fluid intake (not alcohol), and avoid foods that aggravate diarrhea. A lactose-free diet may improve symptoms.
• Educate the patient about healthful food choices that increase calorie intake and nutrition.
• Provide supportive counseling; discuss how to manage symptoms and the isolation that may accompany chronic diarrhea.

References

• Abubakar I, Aliyu SH, Arumugam C, et al. Treatment of cryptosporidiosis in immunocompromised individuals: systematic review and meta-analysis. Br J Clin Pharmacol. 2007 April;63(4);387-393.
• Centers for Disease Control and Prevention. Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents: Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. April 10, 2009.
• Leder K, Weller PF. Cryptosporidiosis [online resource]. Waltham, MA: Up to Date; May 2009. [Fee required.] Accessed June 12, 2012.
• Pantenburg B, Cabada MM, White AC. Treatment of cryptosporidiosis. Expert Rev Anti Infect Ther. 2009 May;7(4):385-91.