Approach

The presentation of cryptosporidiosis is non-specific watery diarrhoea 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 diarrhoea 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

  • Travellers returning from non-industrialised countries

  • Swimmers or bathers

  • Those in contact with other people with diarrhoea

  • Those who toilet or change nappies of young children.

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

Clinical assessment

Cryptosporidiosis should be considered in any individual who presents with diarrhoea, particularly if duration is >7 days, or the patient is immunocompromised. Clinical history should be taken as epidemiological 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 diarrhoeal disease. It is rare for the diarrhoea to be bloody but co-infections with other pathogens may occur. Asymptomatic carriage also occurs.[74]

Acute disease

  • Typical symptoms are watery diarrhoea, 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 diarrhoeal disease

  • Severe, chronic, or intractable diarrhoeal disease, associated with increased morbidity and mortality, may occur in people with acquired or congenital T-cell immune deficiency. Diarrhoea is watery, of large volume (sometimes >2 litres 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 dyspnoea, occurs rarely in immunocompromised patients.

  • Patients with HIV infection with CD4+ counts >180/mm^3 are more likely to have transient or self-limiting disease.[75][76]​ Fulminant disease (marked by the passing of >2 litres stool per day) has only occurred in patients with CD4+ counts <50/mm^3.[76] Lower CD4+ counts were predictive of chronic diarrhoea.[77] Four distinct clinical syndromes of cryptosporidiosis have been identified in patients with AIDS with CD4+ counts <200/mm^3: transient diarrhoea, relapsing illness, chronic diarrhoea, and cholera-like illness.[11] In this patient group, chronic diarrhoea 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 industrialised 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 assessment

The initial assessment for patients with any suspected infectious diarrhoea 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, fluorescent staining (e.g., auramine phenol), and direct fluorescent antibody staining.

Alternatively, enzyme immunoassays or immunochromatographic assays may be used to detect oocyst antigens. Cryptosporidium antigen detection methods provide an alternative to labour-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.

[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@2eff435f[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@5cf92a1f[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@7d889b5f

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, broncho-alveolar 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 histological biopsies and bile for laboratory testing.

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