Cryptosporidiosis

Cryptosporidia are coccidia and belong to the Apicomplexa phylum. Coccidia form an order of unicellular eukaryotic micro-organisms, which includes the following human pathogens: Toxoplasma gondii, Sarcocystis sp., Cryptosporidium parvum, Cyclospora cayetanensis, Isospora belli. Microsporidia do not belong to the Coccidia and form a totally different taxonomic group. DNA analysis of Cryptosporidium suggests that there could be more than twenty different species. C. parvum is the most common parasite in this group in human infections, but C. meleagridis, C. muris and C. felis are also found in persons with acute diarrhoea. C. parvum has two genotypes: genotype 1 is a purely human (anthroponotic) parasite while genotype 2 is zoonotic and can infect various animals as well as humans.

Cryptosporidia are very small parasites of the intestinal mucosa (2.5-5 m). They infect many vertebrates (various mammals [calves], birds, fish, and so on). They have been known since 1907, but were only described in humans in 1976. Several species can be differentiated according to the type of host, but the host specificity does not appear very precise. Transmission to humans occurs from calves, dogs and cats. Transmission via drinking water or via insufficiently chlorinated water in swimming pools happens frequently. This species is resistant to standard chlorination. In 1993 a huge epidemic took place in Milwaukee in which 403,000 persons were infected via drinking water. The parasite was first observed in humans in cases of persistent diarrhoea in patients with immunosuppression, and since 1981 in cases of AIDS. Since 1983 the infection has frequently been recognised as a cause of benign and brief diarrhoea, both in children and adults, and it is one of the more common aetiologies of travellers’ diarrhoea.

The complete cycle of the parasite, sporogony and schizogony, takes place in the same host. People become infected by swallowing thick-walled, resistant oocysts. Once in the intestine the parasites excyst and release sporozoites. They penetrate epithelial cells via the apical membrane. Then follows a reorganisation of the actin cytoskeleton of the host cell. The parasites are intracellular but extracytoplasmic. After maturation of the sporozoite there is asexual reproduction via schizogony with the formation of merozoites. These may either penetrate a new epithelial cell to repeat the cycle (type 1 merozoites) or undergo further intracellular changes (type 2 merozoites) to the sexual form of the parasite. The macrogamont is the female form, the microgamont the male form. The microgamont releases microgametes. After fertilisation and the formation of zygotes, thin-walled oocysts are produced, which after meiosis release sporozoites in their turn which amplifies the infection (auto-infection). Thick-walled oocysts are released into the lumen of the intestine, and are directly infectious via the faeco-oral route. C. parvum induces apoptosis in epithelial cells. It is assumed that an enterotoxin is produced, but this has not yet been proven.

The parasites may be found throughout the entire digestive tract and even in the mucosa of the respiratory tract, but are usually limited to the duodenum and jejunum. The incubation period is 4 to 12 days (usually 7-10 days) and is followed by moderately severe diarrhoea without fever and with little abdominal pain but no particular characteristics. Asymptomatic infections may occur. If there is no underlying immunosuppression, spontaneous recovery occurs within a few weeks. It is estimated that 4 to 10% of all commonplace cases of diarrhoea in children in tropical environments can be attributed to Cryptosporidium. In patients who have a deficiency in cellular immunity (such as in HIV infection), the diarrhoea is more pronounced, chronic for several months, and recurrent. This is accompanied by painful abdominal cramps, nausea, dehydration, loss of weight and mild fever. Fulminant infection with cholera-like diarrhoea may occur in patients with fewer than 50 CD4 T-cells/mm³. Sometimes the protozoa enter the biliary tract, resulting in sclerosing cholangitis, strictures and papillary stenosis. Diagnosis is difficult and requires invasive procedures such as retrograde cholangiography (ERCP [endoscopic retrograde cholangiography]). A biliary tract reservoir may contribute to the chronic course of infection. Other extra-intestinal manifestations include infections of the respiratory tract, pancreas and middle ear.

Diagnosis is based on looking for the parasite in the faeces on smears stained with modified Ziehl-Neelsen or Kinyoun staining. The small dimensions of the parasites and their similarity to yeast cells, were responsible for the fact that infection in humans was only recognised in 1976. The parasites can easily be recognised on intestinal biopsy material obtained by endoscopy. There is villous atrophy, hyperplasia of crypts and an inflammatory cellular infiltrate in the lamina propria. There are other diagnostic techniques, such as immunofluorescence, antigen-capture ELISA [enzyme-linked immunosorbent assay] and PCR [polymerase chain reaction], but these are not available in most tropical settings. Serology is of little benefit. It is possible to detect thickening of the wall of the biliary tract and/or dilation of the gall bladder by ultrasound.

Treatment is mainly symptomatic and can be quite difficult in AIDS patients. The best practical method in these patients is via HAART (highly active antiretroviral therapy). Good results have been described using colostrum from hyperimmune cows (Lactobin-R®). Paromomycin (Humatin®, Gabbroral®) is a non-absorbed aminoglycoside and is of limited use. A swift cure has been reported in infections with C. felis. Azithromycin and letrazuril are being investigated. Another experimental drug is nitazoxanide (Cryptaz®, 500 mg tablets). The activity spectrum of the latter is broader than Cryptosporidium, but its place in therapy has not yet been determined. If papillary stenosis exists, papillotomy may be carried out to achieve decompression of the biliary tract.

Category: Medicine Notes