Cryptosporidiosis

Cryptosporidiosis is contracted by ingestion of the oocysts of Cryptosporidium, which excyst in the small intestine, releasing motile sporozoites. These invade the epithelial cells, initiating asexual multiplication and subsequent sexual reproduction. Sporulation is in situ and facilitates autoinfection, leading to chronic infection in patients unable to mount an appropriate immune response.[40] Ingestion of single numbers of oocysts (<10) can cause disease. The incubation period usually ranges from 3-11 days; the median is 5-7 days.[2]

Oocysts are found in animal and human feces and in contaminated food, drinking water, recreational waters, and fomites. Transmission is waterborne, foodborne, animal to person, or person to person by the fecal-oral route. The oocysts are robust and survive chlorination in drinking water and swimming pools. Outbreaks associated with these transmission routes have been described.[32][41][42]

Two species cause most human cryptosporidiosis: C. parvum can be transmitted anthroponotically or zoonotically; C. hominis is anthroponotic.[38]

The small intestine is the main site of infection, but the entire GI tract and extraintestinal sites may be affected. In patients with HIV infection, more proximal small intestine infections generally cause most severe disease, and gastric involvement has also been reported.[43][44]

Invasion of host cells leads to loss of the surface epithelium and displacement of the microvillous border, leading to alteration in villous architecture, with villous atrophy, blunting, and crypt-cell hyperplasia, and mononuclear cell infiltration in the lamina propria.[45][46]

The causative mechanisms for the diarrhea are not fully understood: the large-volume, watery stool resembles secretory diarrhea, which may indicate an enterotoxin as a specific mechanism, but a Cryptosporidium toxin has not been isolated.[47][48] Increased intercellular permeability and inflammation in the lamina propria could contribute to secretory diarrhea via cytokines and neuropeptides.[49][50] Expression of a neuropeptide and pain transmitter, substance P, that is involved with chloride anion secretion in the gut, is elevated in Cryptosporidium-infected volunteers and patients with AIDS with cryptosporidiosis.[51] Crypt-cell hyperplasia causes increased chloride secretion, and villous blunting leads to decreased sodium absorption, also resulting in overall enhanced secretion.[52] Fecal leukocytes are usually absent, although infection has been associated with a persistent systemic inflammatory response.[53] In patients with HIV infection, histopathology shows evidence of mucosal injury and a variable inflammatory response that is often associated with coinfection with other pathogens.[54]

Diarrhea is often associated with malabsorption, demonstrated by, for example, abnormal D-xylose tests and radiographic studies.[44]

Cryptosporidiosis of extragastrointestinal sites occurs mainly in immunocompromised patients. Biliary and pancreatic cryptosporidiosis have been reported.[11][55][56]Cryptosporidium causes apoptosis of human biliary epithelial cell lines, an observation that may be relevant in the pathogenesis of sclerosing cholangitis, a well-described complication of biliary cryptosporidiosis.[57][58][59][60][61][62][63] Although very rare, tracheobronchial involvement and sinusitis have been described in severely immunocompromised patients.[64][65] The precise clinical significance of this is uncertain, however, as most have concomitant infection with an identified respiratory pathogen.[64] Respiratory cryptosporidiosis has been investigated in immunocompetent children with cryptosporidial diarrhea and unexplained cough, which was considered suggestive of respiratory transmission.[66]

Taxonomic classification[4][5][6]

Phylum Apicomplexa: affinity within the phylum, and the evolutionary relationship with Eimerid Coccidia in particular, has been debated, and the family Cryptosporidiidae has been placed in a new order (Cryptogregarida) within a new subclass (Cryptogregaria); however, single cell genomic and transcriptomic analyzes have led to the suggestion that Cryptosporidium is evolutionarily distinct.

Species delimination[7][8][9][10]

The family Cryptosporidiidae contains a single genus, Cryptosporidium. There are 48 species but the main human pathogens are:

C. hominis
C. parvum.

Other species and Cryptosporidium genotypes (isolates for which insufficient biologic data are available for species status) are occasionally found in humans. Although most are of uncertain pathogenicity, C meleagridis, C felis, and C canis have been linked to diarrhea in children in Peru, and C cuniculus (formerly the rabbit genotype) has caused a waterborne outbreak of human cryptosporidiosis in the UK.

Clinical manifestations[1][11]

Acute cryptosporidiosis

Presence of Cryptosporidium oocysts, antigens, or DNA in stool from patients with diarrhea, abdominal cramps, loss of appetite, low-grade fever, nausea, and/or vomiting. Symptoms may relapse and can be persistent, lasting for up to 4 weeks. Significant weight loss can also occur.

Severe, chronic, or intractable cryptosporidiosis

Severe, chronic, or intractable diarrheal disease and 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.
Complications of infection in this group include pancreatobiliary cryptosporidiosis, which may rarely lead to sclerosing cholangitis and liver cirrhosis. Respiratory cryptosporidiosis is also a rare complication.
Moderate to severe diarrheal disease with increased morbidity and mortality may occur in malnourished young children.

Pathophysiology

Classification

Taxonomic classification[4][5][6]

Species delimination[7][8][9][10]

Clinical manifestations[1][11]