- 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 from an infected host through fecal material, mainly acquired through drinking contaminated water with infective oöcysts [Fig].
- See life cycle, CDC
- Highly infective, few oöcysts can result in infection.
- High tolerance to chlorine.
- Epidemiology: three usual adult populations were affected.
- A leading cause of outbreaks of diarrhea linked to water and the third leading cause of diarrhea associated with animal contact
- 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, childcare workers, travelers or backpackers/hikers/swimmers. May also be found in shallow, contaminated water wells.
- Acute or subacute large-volume secretory diarrhea, often with nausea, cramps, vomiting, weight loss.
- Fever found in one third.
- In patients with prolonged disease, Cryptosporidium may infect the epithelium of the biliary tract and pancreatic duct and cause sclerosing cholangitis and pancreatitis.
- Self-limited in the immune-competent, but often lasts 2-3 wks.
- In AIDS patients, it causes severe diarrhea lasting >2 months in 60% of cases.
- PCR (multiplex methods, often part of a panel)
- Antigen detection
- 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.
- 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.
- Note: routine O & P does not detect.
SITES OF INFECTION
- GI: intestine, small intestine most commonly, biliary
- Extra-gastrointestinal: rarely found in extraluminal locations (e.g., pulmonary)
- No definitive evidence for effective agents in the management of cryptosporidiosis in either immunocompetent or immunocompromised hosts.
- Clinical cure 70-88%, parasitologic cure 60-75%
- Adult and children > 12 yrs: 500mg PO twice a day
- Duration: 3d, 14 days if HIV+ (see below)
- Pediatric dosing:
- 1-3 yrs: 100mg PO twice daily for 3 days
- 4-11 yrs: 200mg PO twice daily for 3 days
- Retesting not recommended (may consider if persistnet synmptoms).
- Advanced HIV:
- Aggressive oral rehydration
- Antimotility agents
- Antiretroviral therapy with immune reconstitution is key for the treatment of infection.
- Even minor increases in CD4 count often work, and immune restoration to CD4 count >100cells/mm3 usually leads to resolution of clinical cryptosporidiosis.
- Nitazoxanide 0.5-1.0 gm PO twice daily with food x 14 days--significant decrease in diarrhea and organism load in patients with HIV with CD4 counts >50 cells/mm3 -OR
- Paromomycin 500mg four times a day for at least 14-21 days
- Deodorized tincture of opium (DTO) 0.3-1ml (usually 0.6ml) PO 3-4x/d prn (may be more effective than loperamide)
- Loperamide 4mg PO, then 2mg PO with each loose stool up to 16 mg/day max.
- Lomotil 2.5mg PO four times a day.
- Diet: frequent, small feedings, low-fat, lactose-free 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.
- Nonspecific agents: NSAIDs, bismuth subsalicylate (Pepto-Bismol).
- Food supplements for AIDS patients: Vivonex, TEN, etc.
- Probiotics: helpful in improving intestinal function after infection.
- 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, saltwater 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 a standard bleach solution.
- During "boil water advisory," follow any of the below options.
- Safe: nationally distributed bottled water, canned carbonated soft drinks, frozen fruit concentrates and pasteurized drinks.
- Avoid exposure to fecal material during sexual activity.
- Patients with cryptosporidiasis should refrain from swimming until 2 weeks after resolution of symptoms.
Selected Drug Comments
The therapeutic trial (ACTG 192) showed a marginal effect. The drug is now FDA-approved for treatment in the immunocompetent patient. Usually taken as capsules, but liquid form available. Should be taken with food.
Trials show modest benefits at best. Often mentioned, but no longer advocated.
Sometimes tried in desperation. Utility unproven and cost is high. Dose: 750mg PO twice daily with meals.
- The 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.
- Because diarrhea can cause lactase deficiency, patients should avoid milk products.
Basis for recommendation
- Checkley W, White AC, Jaganath D, et al. A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium. Lancet Infect Dis. 2015;15(1):85-94. [PMID:25278220]
Comment: Review of the topic. Cryptosporidiosis is recognized as a worldwide cause of diarrhea 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.
- 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. 2001;184(1):103-6. [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%).
- Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Available at https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/cryptosporidiosis.... (accessed 2/27/2023)
Comment: The basis for treatment recommendations
- Hlavsa MC, Aluko SK, Miller AD, et al. Outbreaks Associated with Treated Recreational Water - United States, 2015-2019. MMWR Morb Mortal Wkly Rep. 2021;70(20):733-738. [PMID:34014907]
Comment: This study from CDC provides most recent data regarding infectious causes of outbreaks associated with recreational water. For outbreaks between 2015-2019, Cryptosporidium accounted for 2,492 (84%) of 2,953 cases resulting from the 155 outbreaks with a confirmed etiology, followed by Legionella. Unlike for Legionella, no deaths due to Cryptosporidium.
- Ryan UM, Feng Y, Fayer R, et al. Taxonomy and molecular epidemiology of Cryptosporidium and Giardia - a 50 year perspective (1971-2021). Int J Parasitol. 2021;51(13-14):1099-1119. [PMID:34715087]
Comment: Detailed description of all different types of Cryptosporidium species (currently at least 44 Cryptosporidium spp. and >120 genotypes).
- Gharpure R, Perez A, Miller AD, et al. Cryptosporidiosis Outbreaks - United States, 2009-2017. MMWR Morb Mortal Wkly Rep. 2019;68(25):568-572. [PMID:31246941]
Comment: An update on Cryptosporidiosis outbreaks in the US. This represents a 13% increase from the last report. Leading causes include swallowing contaminated water in pools or water playgrounds, contact with infected cattle, and contact with infected persons in childcare settings.
- Sindhu KN, Sowmyanarayanan TV, Paul A, 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. 2014;58(8):1107-15. [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.
- Hadfield SJ, Robinson G, Elwin K, et al. Detection and differentiation of Cryptosporidium spp. in human clinical samples by use of real-time PCR. J Clin Microbiol. 2011;49(3):918-24. [PMID:21177904]
Comment: PCR method for the detection of C. hominis and C. parvum. Sensitivity and specificity were 100% and 99%, respectively.
- Kothavade RJ. Challenges in understanding the immunopathogenesis of Cryptosporidium infections in humans. Eur J Clin Microbiol Infect Dis. 2011;30(12):1461-72. [PMID:21484252]
Comment: Pathophysiology of cryptosporidiosis is complicated by complex epidemiology (environment, human, food, water and animal sources) and complex intestinal immune issues.
- Mor SM, DeMaria A, Griffiths JK, et al. Cryptosporidiosis in the elderly population of the United States. Clin Infect Dis. 2009;48(6):698-705. [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.
- Abubakar I, Aliyu SH, Arumugam C, et al. Treatment of cryptosporidiosis in immunocompromised individuals: systematic review and meta-analysis. Br J Clin Pharmacol. 2007;63(4):387-93. [PMID:17335543]
Comment: The authors could not demonstrate any therapeutic agent’s effectiveness in treating immunocompromised patients with cryptosporidiosis. When all patient groups were included, nitazoxanide had a significant effect on parasitological clearance.
Supportive management, including rehydration therapy, electrolyte replacement and antimotility agents, will remain the primary treatment strategies until better drugs emerge.
- 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. 2006;24(5):887-94. [PMID:16918894]
Comment: Compassionate use nitazoxanide at the time of publication, (500-1500 mg twice daily for an average 60 days) in 365 AIDS patients showed the drug was safe and it appeared effective.
- Chappell CL, Okhuysen PC, Langer-Curry R, et al. Cryptosporidium hominis: experimental challenge of healthy adults. Am J Trop Med Hyg. 2006;75(5):851-7. [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.
- Fox LM, Saravolatz LD. Nitazoxanide: a new thiazolide antiparasitic agent. Clin Infect Dis. 2005;40(8):1173-80. [PMID:15791519]
Comment: This review article summarizes the evidence for clinical indications for nitazoxanide.
- Hunter PR, Hughes S, Woodhouse S, et al. Health sequelae of human cryptosporidiosis in immunocompetent patients. Clin Infect Dis. 2004;39(4):504-10. [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.
- Hewitt RG, Yiannoutsos CT, Higgs ES, 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. 2000;31(4):1084-92. [PMID:11049793]
Comment: ACTG trial: 35 HIV-infected adults with cryptosporidiosis and CD4 counts < 150 were randomized to receive paromomycin (500mg four times a day) or a placebo. Analysis after 21 days of therapy showed NO DIFFERENCE IN CLINICAL RESPONSE RATES.
- Bruce BB, Blass MA, Blumberg HM, et al. Risk of Cryptosporidium parvum transmission between hospital roommates. Clin Infect Dis. 2000;31(4):947-50. [PMID:11049775]
Comment: No cases of cryptosporidiosis among 37 HIV-infected hospital roommates of 21 patients with cryptosporidiosis, suggesting that ISOLATION is unnecessary.
- Smith NH, Cron S, Valdez LM, et al. Combination drug therapy for cryptosporidiosis in AIDS. J Infect Dis. 1998;178(3):900-3. [PMID:9728569]
Comment: An 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.
- DPDx, CDC. Diagnostic Procedures (for parasites). https://www.cdc.gov/dpdx/diagnosticProcedures/stool/antigendetection.html (accessed 2/12/2023)
Comment: List of all available laboratory detection tests for Cryptosporidium.
Left: Cryptosporidium sp. oocysts stained with Ziehl-Neelson modified acid-fast. Right: Cryptosporidium sp. oocysts stained with safranin.
Source credit: CDC, DPDx