Clinical Manual for Management of the HIV-Infected Adult
2006 Edition

Section 6: Disease-Specific Treatment

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 is usually 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. It can also cause cholangitis and pancreatitis, through infection of the biliary tract and pancreatic duct. Those at greatest risk for cryptosporidiosis are patients with CD4 counts of <100 cells/µL.

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 (mean 3.6 L, and up to 10 L/d 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
• Recent CD4 cell count (highest risk is in patients with CD4 count <100 cells/µL)

O: Objective

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

• Vital signs
• Hydration status (eg, orthostatic vital signs, mucous membrane moistness, skin turgor)
• Weight (compare with previous values; document weight loss)
• Signs of malnourishment (eg, cachexia, wasting, thinning hair, pallor)
• Abdominal examination for bowel sounds (usually hyperactive), tenderness (can be diffuse), rebound
• Recent CD4 count (likely to be <150 cells/µL and can be significantly lower)

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.
  • Be sure to ask that the laboratory look for Cryptosporidium; certain laboratories do not look for these parasites unless requested. For profuse diarrhea, a single sample is usually adequate for diagnosis; repeat sampling can be useful if the first round of test results is negative.
  • Test for fecal leukocytes. This is usually negative in cryptosporidiosis; if positive, consider the possibility of a second enteric infection, especially if the CD4 count is low.
• If the stool is negative for ova and parasites after 3 tests, consider a referral for biopsy of the gastrointestinal mucosa or flexible sigmoidoscopy.
• If cholangitis is suspected, consider abdominal ultrasound to detect biliary ductal dilatation, and endoscopic retrograde cholangiopancreatography (ERCP).
• Check electrolytes; conduct liver function studies including alkaline phosphatase and bilirubin.
• If fever is present, obtain blood cultures.
• Conduct other diagnostic testing as indicated by the history and physical examination (eg, evaluation for CMV, MAC, and other infectious causes of diarrhea or cholangitis) (see chapter Diarrhea).

Treatment

• 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, intravenous 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 (Tucks pads, sitz baths)
• No antiparasitic therapy has been proven to cure or prevent cryptosporidiosis. Most patients experience symptom improvement or resolution with immune reconstitution achieved by effective antiretroviral therapy (ART), especially if the CD4 count increases to >100 cells/µL. All patients with cryptosporidiosis should be treated with ART, unless it is contraindicated, as early in the course of cryptosporidiosis therapy as possible (see chapter Antiretroviral Therapy).
• Antiparasitic agents have not been proven effective, but are sometimes used. These include:
  • Paromomycin (Humatin), which may result in initial response, although its efficacy remains unclear. The usual adult dosage is 500 mg orally 4 times daily or 1,000 mg twice daily, with meals.
  • Paromomycin in combination with azithromycin. One study found substantial short-term benefit from this combination, although cure rates were low.
  • Nitazoxanide (Cryptaz), 500 mg orally twice daily. This agent is approved for use in children with diarrhea caused by C parvum. Its usefulness in adults and those with immunodeficiency has not been demonstrated consistently.
• For patients with weight loss, nutritional supplementation is usually an important 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 in children <2 years of age.

The prognosis for HIV-infected patients with cryptosporidiosis and without access to ART is poor. In one study, the mean survival time of coinfected patients was 25 weeks.

Patient Education

• Recommend scrupulous handwashing for the patient and all contacts, especially household members and sexual 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.
• Educate the patient about healthful food choices that increase calories and nutrition.
• Provide supportive counseling; discuss how to manage symptoms and the isolation that may accompany chronic diarrhea.

References

• Bartlett JG, Gallant JE. 2005-2006 Medical Management of HIV Infection. Baltimore: Johns Hopkins University Division of Infectious Diseases; 2005. Available online at hopkins-aids.edu/mmhiv/order.html.
• Centers for Disease Control and Prevention, National Institutes of Health, HIV Medicine Association/Infectious Diseases Society of America. Treating Opportunistic Infections Among HIV-Infected Adults and Adolescents. MMWR Recomm Rep. 2004 Dec 17; 53(RR15);1-112. Available online at aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?GuidelineID=14. Accessed June 1, 2006.
• Leder K, Weller PF. Cryptosporidiosis [online resource]. Waltham, MA: Up to Date; April 2005. Available online at www.uptodate.com/index.asp. [Fee required.]