Approach

The presentation of cryptosporidiosis is nonspecific watery diarrhea with no pathognomonic features; laboratory testing is necessary to make a diagnosis, usually by detection of Cryptosporidium oocysts, antigens, or DNA in stools. Other samples (intestinal fluid, tissue samples, biopsy specimens, and sputum) may also be tested if considered appropriate: for example, in an immunocompromised patient with complicated disease.

Populations at risk

Physicians should consider cryptosporidiosis as a cause for prolonged diarrhea in the following populations:

  • Severely immunocompromised or immunosuppressed individuals and those living with advanced HIV/AIDS

  • Malnourished infants and young children

  • Young children, especially those in day care

  • People who have recently been in contact with farm animals, and visitors to farms or petting zoos

  • Those who have drunk contaminated water

  • Travelers returning from nonindustrialized countries

  • Swimmers or bathers

  • Those in contact with other people with diarrhea

  • Those who toilet or change diapers of young children.

As with other causes of infectious diarrhea, it is important to note occupation as a food handler or caregiver, as this may have implications for exclusion from work.

Clinical evaluation

Cryptosporidiosis should be considered in any individual who presents with diarrhea, particularly if duration is >7 days or the patient is immunocompromised. Clinical history should be taken as epidemiologic risk factors will guide testing and hygiene advice (including medical history, household, daycare, travel, recreational water exposure, animal contact, and drinking water). The spectrum of illness ranges from mild to severe. Patients may present with symptoms characteristic of acute disease or of severe, chronic, or intractable diarrheal disease. It is rare for the diarrhea to be bloody but coinfections with other pathogens may occur. Asymptomatic carriage also occurs.[74]

Acute disease

  • Typical symptoms are watery diarrhea, nearly always accompanied by abdominal cramps and often loss of appetite, low-grade fever, nausea, and/or vomiting. Symptoms relapse in 30% to 40% of cases.[38][73] Symptoms can be persistent, lasting for up to 4 weeks. Significant weight loss can also occur.

Severe, chronic, or intractable diarrheal disease

  • Severe, chronic, or intractable diarrheal disease, associated with increased morbidity and mortality, may occur in people with acquired or congenital T-cell immune deficiency. Diarrhea is watery, of large volume (sometimes >2 liters per day), and is often associated with profound weight loss and prostration. Right upper quadrant abdominal pain is a sign of cholangitis, which is a feature of pancreatobiliary disease occasionally found in severely immunocompromised people. Jaundice may signify sclerosing cholangitis, which can lead eventually to liver cirrhosis, but occurs only in severely immunocompromised people. Sinusitis has very rarely been described in severely immunocompromised people. Tracheobronchial involvement, signified by cough and dyspnea, occurs rarely in immunocompromised patients.

  • Patients with HIV infection with CD4+ counts >180/mm^3 are more likely to have transient or self-limited disease.[75][76]​ Fulminant disease (marked by the passing of >2 liters stool per day) has only occurred in patients with CD4+ counts <50/mm^3.[76] Lower CD4+ counts were predictive of chronic diarrhea.[77] Four distinct clinical syndromes of cryptosporidiosis have been identified in patients with AIDS with CD4+ counts <200/mm^3: transient diarrhea, relapsing illness, chronic diarrhea, and cholera-like illness.[11] In this patient group, chronic diarrhea and cholera-like illness with severe weight loss predominated. Although cryptosporidiosis significantly influenced survival rates, this was not linked to individual cryptosporidiosis clinical syndromes.[11]

Asymptomatic carriage

  • Asymptomatic carriage also occurs, at least among young children, including those in industrialized countries.[12][13][14][15][16][17][18]​ In low-middle income countries, large scale studies have demonstrated that Cryptosporidium infection causes lasting health impacts and high mortality in malnourished infants and young children. Ongoing malnutrition, stunted growth, wasting and cognitive deficit are among the impacts across sub-Saharan Africa, South America and South East Asia.[3][19][20][21][22][23]​​​​

  • Asymptomatic carriage occurs in both immunocompetent and immunocompromised patients.

Laboratory evaluation

The initial assessment for patients with any suspected infectious diarrhea is traditionally stool microscopy and culture.[74] Increasingly, detection of pathogen nucleic acid: for example, by polymerase chain reaction (PCR)-based methods, is used for diagnosing cryptosporidiosis.[74]​ These are often provided as multiplex panels with other gastrointestinal pathogens; Cryptosporidium must be included. A positive Cryptosporidium PCR result can be reported without confirmation using another test.[78]​ If microscopy is used, healthcare providers must include relevant information such as travel history or immunocompromise, or they must specifically request testing for Cryptosporidium. This is because regular stool microscopy for ova, cysts, and parasites will not detect Cryptosporidium oocysts, and tests such as staining for Cryptosporidium may not be routinely undertaken.[69][79]​​ The diagnosis cannot be excluded by one negative stained microscopy test result, and several samples should be tested (3 are recommended).[80] Oocyst concentration by formalin ethyl acetate sedimentation is recommended for formalin-preserved stools before stained microscopy for Cryptosporidium.[80] Staining techniques used in stool microscopy for Cryptosporidium oocysts are acid-fast staining, [Figure caption and citation for the preceding image starts]: Acid-fast-stained Cryptosporidium oocystsFrom the Cryptosporidium Reference Unit collection; used with permission [Citation ends].com.bmj.content.model.Caption@12802778​​​​ fluorescent staining (e.g., auramine phenol), [Figure caption and citation for the preceding image starts]: Auramine-phenol-stained Cryptosporidium oocystsFrom the Cryptosporidium Reference Unit collection; used with permission [Citation ends].com.bmj.content.model.Caption@7daf2240​​​​ and direct fluorescent antibody staining. [Figure caption and citation for the preceding image starts]: Direct-immunofluorescent-stained Cryptosporidium oocystsFrom the Cryptosporidium Reference Unit collection; used with permission [Citation ends].com.bmj.content.model.Caption@1962453

Alternatively, enzyme immunoassays or immunochromatographic assays may be used to detect oocyst antigens. Cryptosporidium antigen detection methods provide an alternative to labor-intensive highly skilled stained microscopy. Enzyme immunoassays are reportedly superior to acid-fast microscopy and can be comparable to direct fluorescent antibody microscopy in terms of sensitivity and specificity. Combined kits for the detection of Cryptosporidium and Giardia, or Cryptosporidium, Giardia, and Entamoeba histolytica are available. Rapid immunochromatographic assays are comparable to acid-fast microscopy but not direct fluorescent antibody staining.[81]​ The test kit performance should be monitored, as false positives have been reported.[80][81]​​[82] CDC: laboratory identification of parasitic diseases of public health concern - cryptosporidiosis Opens in new window​​​​ Positive reactions should be confirmed by a different test.

Specialist testing

Detection of DNA by PCR-based methods may be requested for the detection of other lifecycle stages in specimen types other than stool (intestinal fluid, bronchoalveolar washings, antral washings, tissue samples, biopsy specimens) from immunocompromised patients.

None of the methods used in routine primary diagnostic laboratories will identify the Cryptosporidium species present; these PCR-based genotyping tests are available in reference laboratories.

Imaging

Where biliary tract involvement is suspected in an immunocompromised patient, ultrasound or CT scan of the biliary tract is indicated. Confirmation of biliary cryptosporidiosis is possible using endoscopic retrograde cholangiopancreatography to obtain histologic biopsies and bile for laboratory testing.

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