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Cryptosporidiosis

By Richard D. Pearson, MD, Emeritus Professor of Medicine, University of Virginia School of Medicine

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Cryptosporidiosis is infection with Cryptosporidium. The primary symptom is watery diarrhea, often with other signs of GI distress. Illness is typically self-limited in immunocompetent patients but can be persistent and severe in patients with AIDS. Diagnosis is by identification of the organism or antigen in stool. Treatment of immunocompetent people, when necessary, is with nitazoxanide. For patients with AIDS, highly active antiretroviral therapy and supportive care are used.

Pathophysiology

Cryptosporidia are obligate, intracellular coccidian protozoa that replicate in small-bowel epithelial cells of a vertebrate host.

After Cryptosporidium oocysts are ingested, they excyst in the GI tract and release sporozoites, which parasitize GI epithelial cells. In these cells, the sporozoites transform into trophozoites, replicate, and produce oocysts.

Two types of oocysts are produced:

  • Thick-walled oocysts, which are commonly excreted from the host

  • Thin-walled oocysts, which are primarily involved in autoinfection

The thick-walled infective oocysts are shed into the lumen and passed in stool by the infected host; they are immediately infective and can be transmitted directly from person to person by the fecal-oral route. Very few oocysts (eg, <100) are required to cause disease, thus increasing risk of person-to-person transmission.

When the infective oocysts are ingested by humans or another vertebrate host, the cycle begins again.

Oocysts are resistant to harsh conditions, including chlorine at levels usually used in public water treatment systems and swimming pools despite adherence to recommended residual chlorine levels.

Epidemiology

Cryptosporidium parvum (bovine genotype) and C. hominis (human genotype) are responsible for most human cases of cryptosporidiosis. Infections result from the following:

  • Ingestion of fecally contaminated food or water (often water in public and residential pools, hot tubs, water parks, lakes, or streams)

  • Direct person-to-person contact

  • Zoonotic spread

The disease occurs worldwide. Cryptosporidiosis is responsible for 0.6 to 7.3% of diarrheal illness in developed countries and an even higher percentage in areas with poor sanitation. It has been the cause of large waterborne diarrhea outbreaks in the US (1). In Milwaukee, Wisconsin, > 400,000 people were affected during a waterborne outbreak in 1993, when the city’s water supply was contaminated by sewage during spring rains and the filtration system was not working correctly.

Children, travelers to foreign countries, immunocompromised patients, and medical personnel caring for patients with cryptosporidiosis are at increased risk. Outbreaks have occurred in day care centers. The small number of oocysts required to cause infection, the prolonged excretion of oocysts, the resistance of oocysts to chlorination, and their small size raise concern about swimming pools used by diapered children.

Severe, chronic diarrhea due to cryptosporidiosis is a problem in patients with AIDS.

Epidemiology reference

  • 1. Painter JE, Gargano JW, Yoder JS, et al: Evolving epidemiology of reported cryptosporidiosis cases in the United States, 1995–2012. Epidemiol Infect 144(8):1792–1802, 2016. doi: 10.1017/S0950268815003131.

Symptoms and Signs

The incubation period is about 1 wk, and clinical illness occurs in > 80% of infected people. Onset is abrupt, with profuse watery diarrhea, abdominal cramping, and, less commonly, nausea, anorexia, fever, and malaise. Symptoms usually persist 1 to 2 wk, rarely 1 mo, and then abate. Fecal excretion of oocysts may continue for several weeks after symptoms have subsided. Asymptomatic shedding of oocysts is common among older children in developing countries.

In the immunocompromised host, onset may be more gradual, but diarrhea can be more severe. Unless the underlying immune defect is corrected, infection can persist, causing profuse intractable diarrhea for life. Fluid losses of > 5 to 10 L/day have been reported in some AIDS patients. The intestine is the most common site of infection in immunocompromised hosts; however, other organs (eg, biliary tract, pancreas, respiratory tract) may be involved.

Diagnosis

  • Enzyme immunoassay for fecal antigen

  • Microscopic examination of stool (special techniques required)

Identifying the acid-fast oocysts in stool confirms the diagnosis, but conventional methods of stool examination (ie, routine "stool for ova and parasites" testing) are unreliable. Oocyst excretion is intermittent, and multiple stool samples may be needed. Several concentration techniques increase the yield. Cryptosporidium oocysts can be identified by phase-contrast microscopy or by staining with modified Ziehl-Neelsen or Kinyoun techniques. Immunofluorescence microscopy with fluorescein-labeled monoclonal antibodies allows for greater sensitivity and specificity.

Enzyme immunoassay for fecal Cryptosporidium antigen is more sensitive than microscopic examination for oocysts. DNA-based assays for detection and speciation of C. parvum and C. hominis have been developed. They are being increasingly used in reference diagnostic laboratories.

Intestinal biopsy can demonstrate Cryptosporidium within epithelial cells.

Treatment

  • Nitazoxanide in patients without AIDS and with persistent infection

  • Antiretroviral therapy (ART) in patients with AIDS plus high-dose nitazoxanide

In immunocompetent people, cryptosporidiosis is self-limited. For persistent infections, oral nitazoxanide can be used; the recommended doses, given for 3 days, are as follows:

  • Age 1 to 3 yr: 100 mg bid

  • Age 4 to 11 yr: 200 mg bid

  • Age ≥ 12 yr: 500 mg bid

In patients with AIDS, immune reconstitution with ART is key. High-dose nitazoxanide (500 to 1000 mg bid) for 14 days has been effective in adults with a CD4 count > 50/μL. Symptoms have abated after effective ART in some patients.

Supportive measures, oral and parenteral rehydration, and hyperalimentation are indicated for immunocompromised patients.

Prevention

Stools of patients with cryptosporidiosis are highly infectious; strict stool precautions should be observed. Special biosafety guidelines have been developed for handling clinical specimens. Boiling water for 1 min (3 min at altitudes > 2000 m [6562 ft]) is the most reliable decontamination method; only filters with pore sizes 1 μm (specified as “absolute 1 micron” or certified under NSF International Standard No. 53 or No. 58) remove Cryptosporidium cysts.

Key Points

  • Cryptosporidiosis spreads easily because fecal excretion of oocysts persists for weeks after symptoms resolve, a very small number of oocysts are required for infection, and oocysts are difficult to remove by conventional water filtration and are resistant to chlorination.

  • Profuse, watery diarrhea with cramping is usually self-limited but can be severe and lifelong in patients with AIDS.

  • Diagnose using enzyme immunoassay for fecal Cryptosporidium antigen; microscopic stool examination is less accurate and requires specialized techniques (eg, phase-contrast microscopy, acid-fast staining).

  • For people without AIDS, use nitazoxanide if symptoms persist.

  • Treat people with AIDS with ART and high doses of nitazoxanide; symptoms may abate when the immune system improves with ART.

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