AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Background

Human cryptosporidiosis is caused by infection with the Apicomplexa protozoans of the genus Cryptosporidium. Human illness was formerly thought to be caused by a single species, but recent molecular studies have demonstrated that several different species cause human cryptosporidiosis. Among the more common species are Cryptosporidium hominis, for which humans are the only natural host and Cryptosporidium parvum, which infects bovines as well as humans. Cryptosporidiosis mainly affects children. It causes a self-limited diarrheal illness in healthy individuals. Cryptosporidiosis is also recognized as a cause of persistent diarrhea in children and severe prolonged diarrhea in patients with AIDS. The source of most endemic cryptosporidiosis cases is human-to-human fecal-oral transmission, but infection may also result from animal-to-person transmission and waterborne transmission. Major outbreaks resulting from waterborne transmission have been recorded.

Pathophysiology

Cryptosporidium oocysts are highly infectious, requiring only 10¹-10³ oocysts to cause human disease (50% infectious dose, 10²). The oocysts are infectious immediately, and the life cycle of the parasite produces forms that invade the intestine. Location of the parasite in the intestine is intracellular but extracytoplasmic, which may contribute to the marked resistance of Cryptosporidium species to treatment. Large numbers of oocysts are excreted and are resistant to harsh conditions, including chlorine at levels usually applied in water treatment.

The mechanism by which Cryptosporidium causes diarrhea includes a combination of increased intestinal permeability, chloride secretion, and malabsorption, which are all thought to be caused by the host response to infection. In patients who are not immunocompromised, the infection is usually limited to the small intestines. In patients with AIDS or some congenital immunodeficiencies, the biliary tract may be involved.

Frequency

United States

The frequency of cryptosporidiosis has not been well defined. About 30% of the adult population is seropositive, but only approximately 3,000 cases are reported each year. This may in part reflect the fact that most laboratories do not routinely test for this organism, and, when testing for Cryptosporidium, many laboratories use insensitive tests. Recent studies have documented cryptosporidiosis in about 4% of stools sent for parasitologic examination. Prior to the availability of highly active antiretroviral therapy, approximately 10-15% of patients with AIDS developed cryptosporidiosis over their lifetime. Like other opportunistic infections, the prevalence of cryptosporidiosis in AIDS patients has dropped dramatically.

International

In developing countries, most people are infected as children. For example, studies in Brazil documented 90% of children in slums were infected before age 5 years. Serologic and stool studies have documented high rates of infection in Latin America, Africa, the Middle East, and South Asia. Overall, about 13% of stool studies submitted for parasitologic studies in developing countries reveal Cryptosporidium oocysts. In patients with AIDS, the rate of cryptosporidiosis is higher in developing countries, ranging from 12-48% of patients with diarrhea.

Mortality/Morbidity

Cryptosporidiosis is an important cause of persistent diarrhea in developing countries. Children with persistent diarrhea develop worsening malnutrition, which may result in cognitive and fitness problems that persist for years. Chronic cryptosporidiosis may be complicated by biliary tract disease, malabsorption, and death in AIDS patients and malnourished children.

Age

Peak incidence is in children younger than 5 years. Infection is rare in immunocompetent adults in developing countries but can occur in patients with AIDS.

CLINICAL

Section 3 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

History

After an incubation period of 5-10 days (range 2-28 d), the patient develops watery diarrhea, which may be associated with abdominal cramps and a low-grade fever. Parasitologically diagnosed cases typically last for about 5-10 days and may persist for 2-4 weeks. Patients with AIDS and very low CD4 cell counts may develop a profuse, choleralike diarrhea, which can be complicated by volume depletion and malabsorption. Biliary tract involvement is seen in AIDS patients with very low CD4 cell counts and is common in children with X-linked immunodeficiency with hyper-IgM. Biliary involvement may include acalculous cholecystitis, sclerosing cholangitis, papillary stenosis, or pancreatitis. All are associated with right upper quadrant pain, nausea, and vomiting.

Physical

Physical findings are nonspecific. Temperature higher than 39°C is not characteristic of cryptosporidiosis and warrants investigation for other infections. Patient may have signs of volume depletion or wasting from malabsorption.

DIFFERENTIALS

Section 4 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Other Problems to be Considered

Cyclospora cayetanensis infection

WORKUP

Section 5 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Lab Studies

• Stool microscopy: Modified acid-fast staining of stool shows red-stained round oocysts against a blue-green background (see Image 1). White and red blood cells should not be seen in the stool. Antigen-detection assays are more sensitive and include immunofluorescent assays, enzyme-linked immunosorbent assay (ELISA), and immunochromatographic tests. Polymerase chain reaction (PCR) assays, when available, are more sensitive than other tests.
• Stool culture: Perform a stool culture to rule out the presence of other bacterial pathogens.
• Urea and electrolytes: These tests are used to assess electrolyte replacement requirements and the presence of prerenal uremia.
• Liver function tests: Elevated alkaline phosphatase and glutamyl transpeptidase without hyperbilirubinemia are typical signs of biliary infection.
• Lymphocyte subset analysis: CD4⁺ lymphocyte counts predict the duration of disease in patients infected with HIV. When the counts are greater than 150, the diarrhea is likely to resolve spontaneously but may be chronic with lower counts. Counts are typically less than 50 in patients with either biliary involvement or choleralike syndromes.

Imaging Studies

• Abdominal ultrasound: Dilated or irregular intrahepatic and extrahepatic bile ducts, along with a thickened gallbladder, indicate biliary involvement.
• Endoscopic retrograde cholangiopancreatography (ERCP): ERCP is often needed to diagnose sclerosing cholangitis or papillary stenosis.

Procedures

• ERCP: Identification of Cryptosporidium oocysts in bile or intracellular forms on biopsy confirms the diagnosis of biliary cryptosporidiosis. Papillary stenosis may be present and responds symptomatically to endoscopic sphincterolotomy, often with stent placement.

Histologic Findings

Histological examination of the small intestine is not required to confirm the diagnosis of cryptosporidiosis. The small intestine shows the parasite projecting from the brush border of the mucosal surface. Parasites may also be identified in bile or biliary tract biopsies.

TREATMENT

Section 6 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical Care

• Nitazoxanide significantly shortens the duration of diarrhea and can decrease mortality in malnourished children. Trials have also demonstrated efficacy in adults.
• Initial studies with antiparasitic drugs in AIDS patients with cryptosporidiosis were disappointing. Nitazoxanide, paromomycin, and azithromycin are partially active. Combination antiretroviral therapy that includes an HIV protease inhibitor is associated with dramatic improvement in many cases. Improvement is likely to result from immune reconstitution but may in part reflect the antiparasitic activity of the protease inhibitors. Nucleoside antiretroviral drugs are malabsorbed in chronic cryptosporidiosis. For that reason, it is probably wise to use partially active antiparasitic drugs (eg, nitazoxanide or paromomycin combined with azithromycin) prior to initiating antiretroviral therapy.
• Symptomatic therapy includes replacement of fluids, nutrition, and treatment with antimotility agents. Loperamide or diphenoxylate-atropine may help in some cases. More potent opiates, including anhydrous morphine (Paregoric), may work in some cases not responding to milder agents. Patients should avoid dietary lactose.

Surgical Care

Patients with acalculous cholecystitis should generally be treated with cholecystectomy.

Consultations

• Infectious disease specialist - For consideration of antiparasitic and antiretroviral therapy
• Gastroenterologist - For ERCP and sphincterotomy; endoscopy sometimes required for diagnosis
• General surgeon - For suspected acalculous cholecystitis

Diet

Attention to nutritional aspects of patient care is crucial because malnutrition can cause death. Lactose intolerance is common in cryptosporidiosis, and lactose-containing foods should be avoided. Enteral nutrition is usually sufficient and studies have not supported the use of parenteral nutrition.

MEDICATION

Section 7 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Recent studies of healthy hosts and malnourished children have demonstrated the importance of nitazoxanide treatment. Since the advent of highly active antiretroviral therapy (HAART), cryptosporidiosis is much less common in patients with AIDS. Stabilize patients who are not on HAART and present with cryptosporidiosis by using the treatments described below, and then commence antiretroviral therapy. Antiparasitic drugs aim to treat diarrhea by a direct anticryptosporidial effect, but maintenance treatment is often required. Antimotility agents are administered for symptomatic relief and to increase exposure to the antiparasitic and antiretroviral agents. Somatostatin analogues are partially beneficial for reducing secretory diarrhea in some refractory cases.

Drug Category: Antiparasitic drugs

Nitazoxanide, paromomycin, and azithromycin have activity against Cryptosporidium.

Drug Name	Azithromycin (Zithromax)
Description	Macrolide antibiotic. In clinical study, the combination with paromomycin gave good symptom control.
Adult Dose	600 mg PO qd for 28 d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; hepatic impairment; do not administer with pimozide
Interactions	May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Diarrhea common; site reactions can occur with IV route; bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in impaired hepatic function and prolonged QT intervals

Drug Name	Nitazoxanide (Alinia)
Description	Inhibits growth of C parvum sporozoites and oocysts and Giardia lamblia trophozoites. Elicits antiprotozoal activity by interfering with pyruvate-ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction, which is essential to anaerobic energy metabolism. Available as a 20 mg/mL PO susp.
Adult Dose	500 mg PO bid for 3 d in healthy hosts; dose may be safely increased to 1 g PO bid in AIDS patients and the duration may be prolonged
Pediatric Dose	<1 year: Not established 1-4 years: 100 mg (5 mL) PO q12h for 3 d with food 4-12 years: 200 mg (10 mL) PO q12h for 3 d with food >12 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Tizoxanide (nitazoxanide metabolite) is >99.9% bound to plasma protein and may displace other highly plasma protein–bound drugs, resulting in increased toxicity
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	May cause abdominal pain, diarrhea, vomiting, or headache; administer with food; caution when coadministered with other highly plasma protein–bound drugs with narrow therapeutic indices

Drug Category: Antidiarrheal agents

Used to decrease the frequency of diarrheal stools and possibly the duration of episodes.

Drug Name	Diphenoxylate and atropine (Lomotil)
Description	Pethidine analogue that reduces intestinal motility but not as effective as loperamide hydrochloride. Drug combination that consists of diphenoxylate, which is a constipating meperidine congener, and atropine to discourage abuse; inhibits excessive GI propulsion and motility.
Adult Dose	15-20 mg/d PO divided tid/qid Maintenance dose: 5-15 PO mg/d
Pediatric Dose	<12 years: Not recommended >12 years: Administer as in adults
Contraindications	Documented hypersensitivity; narrow-angle glaucoma or hepatic insufficiency; not for use in colitis resulting from invasive bacterial infection
Interactions	May delay metabolism of drugs in liver; CNS depressants, MAOIs, and antimuscarinic agents may increase the toxicity of this drug combination
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Opiate toxicity present in overdosage; in young children, dehydration may influence variability of response and predispose patient to delayed diphenoxylate intoxication; caution in ulcerative colitis; decrease in intestinal motility be detrimental to patients with diarrhea resulting from Shigella and Salmonella species and toxigenic strains of Escherichia coli

Drug Name	Anhydrous morphine (Paregoric)
Description	More potent opiates can decrease motility more than is achieved by loperamide or diphenoxylate and atropine.
Adult Dose	2 mg/5 mL take 5-10 mL PO qid as needed for diarrhea; dose may be titrated upward as needed to produce firm stools
Pediatric Dose	0.25-0.5 mL/kg PO qid prn diarrhea
Contraindications	Marked inflammatory diarrhea associated with passing blood or pus
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Overdose may be associated with constipation and respiratory depression

Drug Category: Somatostatin analogues

Inhibit secretion of hormones involved in vasodilation.

FOLLOW-UP

Section 8 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

In/Out Patient Meds

• In AIDS patients, cryptosporidiosis usually cannot be eradicated prior to restoration of the CD4 cell count in response to HAART. During early immune reconstitution, patients should generally continue antiparasitic therapy (such as nitazoxanide or paromomycin) and antimotility agents as needed.

Deterrence/Prevention

• Drinking water should be purified by filtration. This can be accomplished using 1-micron water filters when drinking tap water. AIDS patients should only drink filtered water.
• Boil or filter water in countries with high risk of transmission.
• Avoid newborn animals (eg, calves, lambs), including domestic animals. New pets for patients with AIDS should be older than 6 months and should not have diarrhea.
• Health care worker, childcare workers, and health-compromised patients should avoid fecal-oral spread by wearing gloves and washing their hands after contact with human feces. Spread can occur after activities such as changing diapers.

Complications

• Sclerosing cholangitis, acalculous cholecystis, papillary stenosis, and pancreatitis may develop with biliary involvement.
• Patients with AIDS may develop respiratory tract infections.
• Rare cases of pancreatitis have been recorded in patients who are not immunocompromised.

Prognosis

• Prolonged diarrhea (ie, >1 mo) and biliary disease indicate a poor prognosis in patients with AIDS.

Patient Education

• Encourage patients who are immunocompromised to consider using 1-micron water filters when drinking tap water.
• Instruct patients to boil or filter water in countries with high risk of transmission.
• Instruct immunocompromised patients to avoid newborn animals (eg, calves, lambs), including domestic animals, and people with diarrhea. New pets for patients with AIDS should be older than 6 months and should not have diarrhea.
• Instruct patients with AIDS, daycare workers, and health care workers to avoid fecal-oral spread by wearing gloves and washing their hands after contact with human feces. Spread can occur after activities such as changing diapers.

MISCELLANEOUS

Section 9 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical/Legal Pitfalls

• Prolonged diarrhea caused by cryptosporidiosis may lead to the need for HIV testing. Provide appropriate counseling before and after administration of the HIV test.
• Outbreaks of cryptosporidiosis should be detected by vigilant observation for increased case numbers at primary and public health care levels.

ACKNOWLEDGMENTS

Section 10 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous coauthor Damon Eisen, MD, to the development and writing of this article.

MULTIMEDIA

Section 11 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Media file 1:  Modified acid-fast stain of stool shows red oocysts of Cryptosporidium parvum against the blue background of coliforms and debris.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

• Amadi B, Mwiya M, Musuku J, et al. Effect of nitazoxanide on morbidity and mortality in Zambian children with cryptosporidiosis: a randomized controlled trial. Lancet. Nov 2 2002;360(9343):1375-80. [Medline].
• Blackburn BG, Mazurek JM, Hlavsa M, et al. Cryptosporidiosis associated with ozonated apple cider. Emerg Infect Dis. Apr 2006;12(4):684-6.
• Buch K, Nguyen S, Divino CM, et al. Cryptosporidiosis presenting as acute appendicitis: a case report. Am Surg. Jun 2005;71(6):537-8.
• Bushen OY, Lima AA, Guerrant RL. Cryptosporidiosis. In: Guerrant RL, Walker DH, Weller PF, eds. Tropical Infectious Diseases. Principle, Pathogens, and Practice. Philadelphia, PA:. Elsevier-Churchill Livingstone;2006:1003-1014.
• Cunha BA. Antibiotic Essentials. 5th ed. Royal Oak, Mich:. Physicians Press;2006.
• Huang DB, Chappell C, Okhuysen PC. Cryptosporidiosis in children. Semin Pediatr Infect Dis. Oct 2004;15(4):253-9.
• Insulander M, Lebbad M, Stenstrom TA, Svenungsson B. An outbreak of cryptosporidiosis associated with exposure to swimming pool water. Scand J Infect Dis. 2005;37(5):354-60.
• Kosek M, Alcantara C, Lima AA, Guerrant RL. Cryptosporidiosis: an update. Lancet Infect Dis. Nov 2001;1(4):262-9.
• Mac Kenzie WR, Hoxie NJ, Proctor ME, et al. A massive outbreak in Milwaukee of cryptosporidium infection transmitted through the public water supply. N Engl J Med. Jul 21 1994;331(3):161-7. [Medline].
• Mahdi NK, Ali NH. Cryptosporidiosis and other intestinal parasitic infections in patients with chronic diarrhea. Saudi Med J. Sep 2004;25(9):1204-7.
• Ramirez NE, Ward LA, Sreevatsan S. A review of the biology and epidemiology of cryptosporidiosis in humans and animals. Microbes Infect. Jul 2004;6(8):773-85.
• Roy SL, DeLong SM, Stenzel SA, et al. Risk factors for sporadic cryptosporidiosis among immunocompetent persons in the United States from 1999 to 2001. J Clin Microbiol. Jul 2004;42(7):2944-51.
• Smith HV, Corcoran GD. New drugs and treatment for cryptosporidiosis. Curr Opin Infect Dis. Dec 2004;17(6):557-64. [Medline].
• Thompson RC, Olson ME, Zhu G, et al. Cryptosporidium and cryptosporidiosis. Adv Parasitol. 2005;59:77-158.
• White AC Jr. Cryptosporidiosis (Cryptosporidium hominis, Cryptosporidium parvum, other species). In: Mandell GL, Bennett JE, Dolin R, ed. Principles and Practice of Infectious Diseases. 6th ed. Philadelphia, PA:. Elsevier Churchill Livingstone;2005:3215-3228.
• Zardi EM, Picardi A, Afeltra A. Treatment of cryptosporidiosis in immunocompromised hosts. Chemotherapy. Jul 2005;51(4):193-6.

Article Last Updated: Jun 29, 2006