MICROBIOLOGY

  • Major human pathogens:
    • Cryptosporidium parvum (most common)
    • C. hominis
    • C. meleagridis
  • Time from acquisition to symptoms: range 2-10 d, average 7d.
  • Sporulated oöcyst (with four sporozoites) are spread through fecal material from infected host. Mostly acquired through drinking contaminated water with infective oöcysts [ Fig].
  • Highly infective, few oöcysts can result in infection.
  • High tolerance to chlorine.

CLINICAL

  • Epidemiology: three usual populations affected.
    • Major cause of epidemic diarrhea from contaminated water
    • Severe diarrhea in AIDS patients with low CD4 cell counts
    • Sporadic diarrhea in immunocompetent patients.
  • ~ 748,000 cryptosporidiosis case reports occur in the U.S. annually.
  • Acquisition: cause is ingestion of oöcysts after person-person contact or contaminated food or water.
    • Risks: children attending daycare centers, child care workers, travelers or backpackers/hikers/swimmers. May also be found in shallow, contaminated water wells.
  • Symptoms:
    • Acute or subacute large volume secretory diarrhea, often with nausea, cramps, vomiting, weight loss.
    • Fever found in one third.
  • Course:
    • Self-limited in the immune competent, but often lasts 2-3 wks.
    • In AIDS patients, it causes severe diarrhea lasting >2 mos in 60% of cases.
  • Diagnosis:
    • oöcyst detection exam with AFB stain (~70% sensitive) [Fig], IFA (most sensitive and specific) or EIA stains.
        • Note: routine O & P does not detect.
          • Must request detection of Cryptosporidia specifically on O & P specimen.
        • A single specimen is usually adequate, occasionally multiple specimens required.
    • Antigen detection
      • Current test of choice for Dx.
      • Fresh or frozen stool samples.
      • There are several commercial kits, many are combined tests for Cryptosporidium, Giardia, and E. histolytica.
      • The most sensitive (99%) and specific (100%) method is reported to be the direct immunofluorescence assay (DFA) test.

SITES OF INFECTION

  • GI: intestine, small intestine most commonly
  • Extra-gastrointestinal: rarely found in extraluminal locations (e.g., pulmonary)

TREATMENT

Antimicrobials

  • No definitive evidence for effective agents in the management of cryptosporidiosis in either immunocompetent or immunocompromised hosts [1].
  • Preferred:
    • Nitazoxanide: effective for treatment of immune competent patients (FDA approved).
      • Adult and children > 12 yrs: 500mg PO three times a day
        • Duration: 3d
      • Pediatric dosing:
        • 1-3 yrs: 100mg PO twice daily
        • 4-11 yrs: 200mg PO twice daily
  • Advanced HIV:
    • HAART with immune reconstitution is the only proven treatment.
      • Even minor increases in CD4 count often work.
    • Possibly effective: nitazoxanide or 0.5-1.0 gm PO twice daily with food x 14 days
    • Paromomycin 500mg QID: no proven benefit at 3 or 6 w treatment in HIV infected patients [7].

Antiperistaltic agents

  • Loperamide 4mg PO, then 2mg PO with each loose stool up to 16 mg/day max.
  • Lomotil 2.5mg PO four times a day.
  • Codeine 15-60mg (usually 30mg) PO q3-6h prn.
  • Deodorized tincture of opium (DTO) 0.3-1ml (usually 0.6ml) PO 3-4x/d prn.

Non-antimicrobial treatments

  • Diet: frequent, small feedings, low-fat, lactose- and caffeine-free, high fiber, bland foods.
  • Fluid support, losses may be up to 10 L/d with AIDS.
  • Oral feedings to replace NaHCO3, K+, Mg++, P04--, glucose.
  • Non-specific agents: NSAIDs, bismuth subsalicylate (PeptoBismol).
  • Food supplements for AIDS patients: Vivonex, TEN, etc.
  • Octreotide: not effective.
  • Probiotics: helpful in improving intestinal function after infection [21].

Prevention

  • Interventions below may be especially important for patients with advanced HIV or other immunosuppression.
  • Avoid contaminated water or foods.
    • Avoid raw oysters.
  • Maintain good hand hygiene.
  • Lakes, rivers, salt water beaches and swimming pools may be contaminated; avoid them or at least avoid drinking. Some municipal water supplies may be contaminated.
    • During "boil water advisory," follow any of the below options.
      • Boil x 3 minutes
      • Use submicron personal use water filter (1um filter, www.nsf.org or 800-673-6275)
      • Use bottled water
    • Remember that ice may also be a source.
    • The parasite can survive in water at CDC-recommended chlorine levels (1–3 mg/L) and pH (7.2–7.8) for >10 days.
    • 3% hydrogen peroxide more effective than standard bleach solution.
  • Safe: nationally distributed bottled water, canned carbonated soft drinks, frozen fruit concentrates and pasteurized drinks.
  • Avoid exposure to fecal material during sexual activity.

Selected Drug Comments

Drug

Recommendation

Clarithromycin

(Biaxin) Role in treating cryptosporidiosis is unclear. When combined with rifabutin (RBT) for MAC prophylaxis there is a reduced rate of cryptosporidiosis, but some would question the wisdom of combining RBT and clarithromycin due to drug interaction plus efficacy is a long shot.

Nitazoxanide

Therapeutic trial (ACTG 192) showed marginal effect. Drug is now FDA-approved for treatment in the immunocompetent patient. Drug usually taken as capsules, but liquid form available. Should be taken with food.

Paromomycin

Trials show modest benefit at best. Often mentioned, but no longer advocated.

Atovaquone

Sometimes tried in desperation. Utility unproven and cost is high. Dose: 750mg PO twice daily with meals.

OTHER INFORMATION

  • Healthy host may have self-limited disease lasting 2-3 wk; compromised hosts (CD4 < 100) may have very severe and debilitating chronic diarrhea.
  • Supportive care: rehydration and antiperistaltics.
  • Cryptosporidiosis is a reportable disease.

Basis for recommendation

  1. Abubakar I et al: Treatment of cryptosporidiosis in immunocompromised individuals: systematic review and meta-analysis. Br J Clin Pharmacol 63:387, 2007  [PMID:17335543]

    Comment: Authors were unable to demonstrate the effectiveness of any therapeutic agent in the treatment of immunocompromised patients with cryptosporidiosis. A significant effect on parasitological clearance was observed with nitazoxanide when all patient groups were included.
    Supportive management including rehydration therapy, electrolyte replacement and antimotility agents will remain the main treatment strategies until better drugs emerge.

  2. Masur H et al: Prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Updated Guidelines from the Centers for Disease Control and Prevention, National Institutes of Health, and HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 58:1308, 2014  [PMID:24585567]

    Comment: Source of recommendation for primary use of ART and immune reconstitution for HIV-related cryptosporidial infection, as well as prevention.

  3. Rossignol JF, Ayoub A, Ayers MS: Treatment of diarrhea caused by Cryptosporidium parvum: a prospective randomized, double-blind, placebo-controlled study of Nitazoxanide. J Infect Dis 184:103, 2001  [PMID:11398117]

    Comment: Nitazoxanide (500mg twice daily x 3d) vs placebo in 100 HIV-negative patients with cryptosporidiosis. THERE WAS A SUPERIOR RESPONSE IN THE NITAZOXANIDE GROUP (80% vs 51%).

  4. The Medical Letter. Drugs for Parasitic Infections 2013

    Comment: Recommendations for non-HIV related infections, including pediatric dosing.

References

  1. Miao YM et al: Eradication of cryptosporidia and microsporidia following successful antiretroviral therapy. J Acquir Immune Defic Syndr 25:124, 2000  [PMID:11103042]

    Comment: 5 of 6 patients with cryptosporidiosis or microsporidiosis cleared PARASITE AFTER 6 MONTHS ON HAART; one failed to respond to HAART and had persistent symptoms.
    Rating: Important

  2. Rossignol JF et al: A double-'blind' placebo-controlled study of nitazoxanide in the treatment of cryptosporidial diarrhoea in AIDS patients in Mexico. Trans R Soc Trop Med Hyg 92:663, 1998 Nov-Dec  [PMID:10326116]

    Comment: 66 HIV-infected patients with cryptosporidiosis randomized to placebo, nitazoxanide 500mg twice daily or NITAZOXANIDE 1000mg twice daily. Microbiologic cure achieved in 22/34 (65%) of pts given nitazoxanide (p=0.016) 19 of these 22 had clinical resolution. Both dose regimens well tolerated.

  3. Hewitt RG et al: Paromomycin: no more effective than placebo for treatment of cryptosporidiosis in patients with advanced human immunodeficiency virus infection. AIDS Clinical Trial Group. Clin Infect Dis 31:1084, 2000  [PMID:11049793]

    Comment: ACTG trial: 35 HIV infected adults with cryptosporidiosis and CD4 counts <150 randomized to receive paromomycin (500mg four times a day) or placebo. Analysis after 21 days of therapy showed NO DIFFERENCE IN CLINICAL RESPONSE RATES.
    Rating: Important

  4. Chappell CL et al: Cryptosporidium hominis: experimental challenge of healthy adults. Am J Trop Med Hyg 75:851, 2006  [PMID:17123976]

    Comment: C. hominis given orally to 21 healthy adults showed 76% had diarrhea as evidence of infection, the ID50 was 10-83 oocysts and increasing the dose increased infectivity.

  5. Checkley W et al: A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium. Lancet Infect Dis 15:85, 2015  [PMID:25278220]

    Comment: Review of the topic. Cryptosporidiasis is recognized as a world-wide cause of diarrhoea and childhood malnutrition. Diagnostic tests for cryptosporidium infection are suboptimal. Therapy has some effect in healthy hosts and no proven efficacy in immunocompromised hosts. Several vaccines are in development.
    Rating: Important

  6. Clarke SH: Reducing the public health risk of cryptosporidiosis by optimizing treatment processes at a military water system. US Army Med Dep J 2011 Jul-Sep  [PMID:21805455]

    Comment: Public health implications of clean water with emphasis on need for optimizing current practices and changing coagulant chemical is the best response to Cryptosporidiosis contamination.

  7. Rossignol JF: Nitazoxanide in the treatment of acquired immune deficiency syndrome-related cryptosporidiosis: results of the United States compassionate use program in 365 patients. Aliment Pharmacol Ther 24:887, 2006  [PMID:16918894]

    Comment: Compassionate use nitazoxanide (500-1500 mg twice daily for average 60 days) in 365 AIDS patients showed the drug was safe and it appeared effective.
    Rating: Important

  8. DPDx, CDC. Diagnostic Procedures (for parasites). https://www.cdc.gov/dpdx/diagnosticProcedures/stool/antigendetection.html (accessed 6/27/16)

    Comment: List of all available antigen detection kits for Cryptosporidium.
    Rating: Important

  9. Hadfield SJ et al: Detection and differentiation of Cryptosporidium spp. in human clinical samples by use of real-time PCR. J Clin Microbiol 49:918, 2011  [PMID:21177904]

    Comment: PCR method for detection of C. hominis and C. parvum. Sensitivity and specificity was 100% and 99%, respectively.

  10. Hlavsa MC et al: Outbreaks of Illness Associated with Recreational Water--United States, 2011-2012. MMWR Morb Mortal Wkly Rep 64:668, 2015  [PMID:26110837]

    Comment: This report from the CDC on outbreak illness related to recreational water use during 2011-2012 indicates that Cryptosporidium continues to be the dominant cause of recreational water–associated outbreaks.
    Rating: Important

  11. Kothavade RJ: Challenges in understanding the immunopathogenesis of Cryptosporidium infections in humans. Eur J Clin Microbiol Infect Dis 30:1461, 2011  [PMID:21484252]

    Comment: Pathophysiology of cryptosporidiosis is complicated by complex epidemiology (environment, human, food, water and animal sources) and complex intestinal immune issues.

  12. Mor SM et al: Cryptosporidiosis in the elderly population of the United States. Clin Infect Dis 48:698, 2009  [PMID:19199827]

    Comment: The rate of cryptosporidiosis was significantly increased in persons >65 years (1,304 cases for 1991-04 in Medicare database). Mortality was 8% in persons >85 years and 10% in persons with AIDS.
    Rating: Important

  13. Bruce BB et al: Risk of Cryptosporidium parvum transmission between hospital roommates. Clin Infect Dis 31:947, 2000  [PMID:11049775]

    Comment: No cases of cryptosporidiosis among 37 HIV-infected hospital roommates of 21 patients with cryptosporidiosis, suggesting that ISOLATION is unnecessary.

  14. Painter JE et al: Cryptosporidiosis surveillance -- United States, 2011-2012. MMWR Surveill Summ 64 Suppl 3:1, 2015  [PMID:25928581]

    Comment: Cryptosporidiosis incidence rates remain elevated nationally. Rates remain highest in young children, although rates among elderly adults are increasing. Transmission of Cryptosporidium occurs throughout the United States. Seasonal onset peaks coincide with the summer recreational water season and might reflect increased use of communal swimming venues
    Rating: Important

  15. Carr A et al: Treatment of HIV-1-associated microsporidiosis and cryptosporidiosis with combination antiretroviral therapy. Lancet 351:256, 1998  [PMID:9457096]

    Comment: Patients with AIDS and chronic cryptosporidiosis had a GOOD RESPONSE WHEN IMMUNE RECONSTITUTION was achieved with HAART. Patients who had subsequent failure with HAART experienced relapses. Patients with sustained elevations of CD4 counts had complete and sustained clinical, microbiological, and histological responses.
    Rating: Important

  16. Hunter PR et al: Health sequelae of human cryptosporidiosis in immunocompetent patients. Clin Infect Dis 39:504, 2004  [PMID:15356813]

    Comment: Questionnaires from 235 immunocompetent persons with lab proven cryptosporidiosis. Of them 111 had stain typing- 61 were C. hominis and 50 were C. parvum. Relapses were reported in 40% and some had extraintestinal disease- eye pain, dizziness, headache, joint pain, etc.
    Rating: Important

  17. Sindhu KN et al: Immune Response and Intestinal Permeability in Children With Acute Gastroenteritis Treated With Lactobacillus rhamnosus GG: A Randomized, Double-Blind, Placebo-Controlled Trial. Clin Infect Dis 58:1107, 2014  [PMID:24501384]

    Comment: This randomized double-blind placebo-controlled trial evaluated the effect of probiotics (Lactobacillus rhamnosus) in children aged 6 months-5 years infected with either rotavirus (n=82) or cryptosporidium (n=42). Probiotics had a positive immunomodulatory effect and treated children had fewer recurrences of rotavirus diarrhea. There was an improvement in intestinal function in children with rotavirus and cryptosporidial gastroenteritis who received probiotics.
    Rating: Important

  18. Smith NH et al: Combination drug therapy for cryptosporidiosis in AIDS. J Infect Dis 178:900, 1998  [PMID:9728569]

    Comment: Uncontrolled trial of PAROMOMYCIN + AZITHROMYCIN, which appeared promising; azithromycin alone was not effective. The combination produced some improvement in diarrhea, reducing stool frequency from a median of 6.5 to 3.0/day at week 12. There was also a decrease in cyst excretion.

Media

Cryptosporidia

Left: Cryptosporidium sp. oocysts stained with Ziehl-Neelson modified acid-fast. Right: Cryptosporidium sp. oocysts stained with safranin. Source credit: CDC, DPDx

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Last updated: August 1, 2016