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Cryptosporidiosis Workup

  • Author: Miguel M Cabada, MD, MSc; Chief Editor: Michael Stuart Bronze, MD  more...
 
Updated: Apr 11, 2016
 

Approach Considerations

Many laboratories do not routinely test for Cryptosporidium, and in many instances, the tests used to look for this organism are insensitive.[1] Studies in the United States have documented cryptosporidiosis in about 4% of stools sent for parasitologic examination, while overall, about 13% of stool studies submitted for parasitologic studies in developing countries reveal Cryptosporidium oocysts. However, these numbers likely underrepresent the true number of infections, owing to the poor sensitivity of commonly used techniques.

Cryptosporidium can be difficult to diagnose and usually is missed unless specific tests are performed. Most often, stool specimens are examined microscopically using different techniques (eg, acid-fast staining, direct fluorescent antibody [DFA], enzyme immunoassays, or immunochromatographic tests for detection of Cryptosporidium species’ antigens). (See the image below.)[23]

Modified acid-fast stain of stool shows red oocyst Modified acid-fast stain of stool shows red oocysts of Cryptosporidium parvum against the blue background of coliforms and debris.

Urea, electrolyte, and liver function tests

Urea and electrolyte tests are used to assess electrolyte replacement requirements and the presence of prerenal uremia.

Elevated alkaline phosphatase and glutamyl transpeptidase without hyperbilirubinemia are typical signs of biliary infection.

Imaging studies

Imaging studies are not indicated as a first-line diagnostic approach in cryptosporidiosis. Abdominal radiography and computed tomography (CT) scanning are nonspecific but may reveal distended loops of bowel, air-fluid levels, and disrupted bowel motility.

When indicated, as guided by symptoms, ultrasonography or CT scanning may reveal an enlarged gallbladder with a thickened wall, dilated or irregular intrahepatic and extrahepatic biliary ducts, and a normal or stenotic distal common bile duct. Cholangiography may reveal beading of the common bile duct or papillary stenosis.

In cases of respiratory involvement, chest radiography is unremarkable, with modest infiltrates or increased bronchial markings.

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Stool Tests

Processing

Unconcentrated, fresh specimens can be examined by wet mount preparations. Concentration by the formalin ethyl acetate method is preferable. Optimal centrifugation time and speed, 10 minutes at 500 X, are critical for concentrating Cryptosporidium oocysts.

Commercial fecal concentration tubes are available that decrease processing time and supplies needed for concentrating specimens (eg, Fecal Parasite Concentrator, Evergreen Scientific). Polyvinyl alcohol (PVA)-preserved specimens are not acceptable for modified acid-fast staining or antigen-detection assays for detection of Cryptosporidium.

Types of tests

Modified acid-fast staining procedure is useful for the identification of oocysts of the coccidian species, including those of Cryptosporidium (which may be difficult to detect with routine stains, such as trichrome). Cryptosporidium species stain a pinkish-red color. The background should stain uniformly green. Unlike the modified Ziehl-Neelsen acid-fast (MZN-AF) stain, this stain does not require the heating of reagents for staining. (See the images below.)

Cryptosporidium parvum oocysts revealed with modif Cryptosporidium parvum oocysts revealed with modified acid-fast stain. Against a blue-green background, the oocysts stand out with a bright red stain. Image courtesy of CDC DPDx parasite image library
Cryptosporidium oocysts revealed with modified aci Cryptosporidium oocysts revealed with modified acid-fast stain

Chalmers et al demonstrated that enzyme-linked immunosorbent assays and immunofluorescent tests have sensitivities above 90% and were significantly higher than that of modified Ziehl-Neelsen stains (75%).[23] Molecular tests such as PCR are even more sensitive and are increasingly being used for diagnosis. Immunochromatographic tests are less sensitive, especially for zoonotic species.

Specimen examination

Concentrated sediment of fresh (within 30 min after passage of stools) or formalin-preserved stool may be used. Other types of clinical specimens, such as duodenal fluid, bile, and pulmonary samples (induced sputum, bronchial wash, biopsies) may also be stained.

The formalin ethyl acetate method is used to concentrate stool before staining with a modified acid-fast stain, because routine laboratory examination of stool for ova and parasites does not detect Cryptosporidium.[1, 24] This technique stains oocysts pink or red, whereas fecal debris or yeast assumes the color of blue or green counterstain. Oocysts are small (4-6 μm in diameter) and can be missed without a very careful examination of the slide.

Because shedding may be intermittent, examine at least 3 stool specimens collected on separate days before considering the test results negative. Fecal leukocytes are not found in stool specimens, because invasion does not occur below the epithelial layer of the mucosa. Other testing strategies include the following:

  • GI biopsy specimens can be used instead of stool specimens; a high concentration of oocysts is seen in the jejunum
  • Electron microscopy of stool or biopsy specimens can also be performed for direct visualization of oocysts
  • For research purposes and for species identification, PCR assays are used
  • Serologic detection of specific anti- Cryptosporidium antibodies is primarily used as a research or epidemiologic tool
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Evaluation of Immune Function

Lymphocyte subset analysis

CD4+ lymphocyte counts predict the duration of disease in patients infected with HIV. When the counts are greater than 150 cells/μL, the diarrhea is likely to resolve spontaneously. With lower counts, however, the diarrhea may be chronic. Counts are typically less than 50 cells/μL in patients with either biliary involvement or choleralike syndromes.

HIV testing

Prolonged diarrhea caused by cryptosporidiosis may warrant HIV testing.

Primary immunodeficiencies

Children with chronic diarrhea from cryptosporidiosis should be screened for primary immunodeficiencies associated with depressed cellular immune function. The most commonly identified immunodeficiency is hyper-IgM syndrome, which can be identified by antibody screening. T-cell deficiencies can be identified by examining lymphocyte numbers and subsets.[25]

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Abdominal Ultrasonography and ERCP

Dilated or irregular intrahepatic and extrahepatic bile ducts, along with a thickened gallbladder, as detected with abdominal ultrasonography, indicate biliary involvement.

Endoscopic retrograde cholangiopancreatography (ERCP) is often needed to diagnose sclerosing cholangitis or papillary stenosis.

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 sphincterotomy, often with stent placement.

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Biopsy and Lavage

GI or liver biopsy

GI or liver biopsy may be indicated in cases of diagnostic uncertainty. Different parts of the intestinal tract may be affected. Liver biopsy findings may reveal the organism attached to bile duct epithelial cells. Concurrent infection with cytomegalovirus (CMV), Enterobacter cloacae, and microsporidia is common.

Bronchoalveolar lavage and lung biopsy

In patients with related symptoms, bronchoscopy may reveal the parasite in lavage fluid, in brushing specimens, and in biopsy specimens, attached to the surface of bronchial mucosal cells, or in macrophages. In most instances, another pulmonary pathogen, such as CMV or Pneumocystis (carinii) jiroveci, is concurrently detected; however, in a series of 4 patients infected with HIV, Cryptosporidium was the only pathogen identified in the respiratory tract. Clear association with intestinal cryptosporidiosis or diarrhea has not been shown in these cases.

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Histologic Findings

Histologic examination of the small intestine is not required to confirm the diagnosis of cryptosporidiosis, although the small intestine does show the parasite projecting from the brush border of the mucosal surface. Parasites may also be identified in bile or biliary tract biopsies.

Villous atrophy with blunting, epithelial flattening, and an increase in lamina propria lymphocytes are seen in patients with persistent cryptosporidiosis. In patients with heavier infection, crypt hyperplasia and marked infiltration with lymphocytes, plasma cells, and neutrophils are also noted.

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Contributor Information and Disclosures
Author

Miguel M Cabada, MD, MSc Instructor, Infectious Diseases Division, University of Texas Medical Branch School of Medicine; Director, Universidad Peruana Cayetano Heredia and University of Texas Medical Branch Collaborative Research Center in Cusco, Peru

Miguel M Cabada, MD, MSc is a member of the following medical societies: International Society for Infectious Diseases, International Society of Travel Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

A Clinton White, Jr, MD The Paul R Stalnaker, MD, Distinguished Professor of Internal Medicine, Director, Infectious Disease Division, Department of Internal Medicine, University of Texas Medical Branch School of Medicine

A Clinton White, Jr, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Federation for Medical Research, American Society of Tropical Medicine and Hygiene, Christian Medical and Dental Associations, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, Oklahoma State Medical Association, Southern Society for Clinical Investigation, Association of Professors of Medicine, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

Poothirikovil Venugopalan, MBBS, MD, FRCPCH Consultant Pediatrician with Cardiology Expertise, Department of Child Health, Brighton and Sussex University Hospitals, NHS Trust; Honorary Senior Clinical Lecturer, Brighton and Sussex Medical School, UK

Poothirikovil Venugopalan, MBBS, MD, FRCPCH is a member of the following medical societies: Royal College of Paediatrics and Child Health, Paediatrician with Cardiology Expertise Special Interest Group, British Congenital Cardiac Association

Disclosure: Nothing to disclose.

Jaya Sureshbabu, MBBS, MRCPCH(UK), MRCPI(Paeds), MRCPS(Glasg), DCH(Glasg) Consultant Pediatrician and Neonatologist, PRS Hospital, India

Disclosure: Nothing to disclose.

Acknowledgements

Jeffrey D Band, MD Professor of Medicine, Oakland University William Beaumont School of Medicine; Director, Division of Infectious Diseases and International Medicine, Corporate Epidemiologist, William Beaumont Hospital; Clinical Professor of Medicine, Wayne State University School of Medicine

Disclosure: Nothing to disclose.

Damon Eisen, MD Clinical Senior Lecturer, Department of Medicine, University of Queensland

Disclosure: Nothing to disclose.

Joseph F John Jr, MD, FACP, FIDSA, FSHEA Clinical Professor of Medicine, Molecular Genetics and Microbiology, Medical University of South Carolina College of Medicine; Associate Chief of Staff for Education, Ralph H Johnson Veterans Affairs Medical Center

Disclosure: Nothing to disclose.

Athena P Kourtis, MD, PhD Associate Professor, Department of Pediatrics, Divisions of Infectious Diseases and Epidemiology, Emory University School of Medicine; Senior Fellow, Centers for Disease Control and Prevention

Athena P Kourtis, MD, PhD is a member of the following medical societies: American Academy of Pediatrics and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Russell W Steele, MD Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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Modified acid-fast stain of stool shows red oocysts of Cryptosporidium parvum against the blue background of coliforms and debris.
Hematoxylin and eosin stain of intestinal epithelium. The blue dots (arrows) represent Cryptosporidium on the surface of the epithelial cells. Image courtesy of Carlos Abramowsky, MD, Professor of Pediatrics and Pathology, Emory University School of Medicine
Cryptosporidium species oocysts are rounded and measure 4.2-5.4 µm in diameter. Sporozoites are sometimes visible inside the oocysts, indicating that sporulation has occurred on wet mount.
Cryptosporidium parvum oocysts revealed with modified acid-fast stain. Against a blue-green background, the oocysts stand out with a bright red stain. Image courtesy of CDC DPDx parasite image library
Cryptosporidium oocysts revealed with modified acid-fast stain
 
 
 
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