Cryptosporidium parvum

Cryptosporidium parvum
Immunofluorescence image of C. parvum oocysts.
Scientific classification
Kingdom:	Chromalveolata
Phylum:	Apicomplexa
Class:	Conoidasida
Subclass:	Coccidiasina
Order:	Eucoccidiorida
Family:	Cryptosporidiidae
Genus:	Cryptosporidium
Species:	C. parvum
Binomial name
Cryptosporidium parvum

Cryptosporidium parvum is one of several protozoal species that cause cryptosporidiosis, a parasitic disease of the mammalian intestinal tract.

Primary symptoms of C. parvum infection are acute, watery, and non-bloody diarrhoea. C. parvum infection is of particular concern in immunocompromised patients, where diarrhea can reach 10–15L per day. Other symptoms may include anorexia, nausea/vomiting and abdominal pain. extra intestinal sites include the Lung and liver where is causes respiratory cryptosporidosis, hepatitis n cholecystisis.^[1]

Infection is caused by ingestion of sporulated oocysts transmitted by the fecal-oral route. In healthy human hosts, the median infective dose is 132 oocysts.^[2] The general C. parvum life cycle is shared by other members of the genus. Invasion of the apical tip of ileal enterocytes by sporozoites and merozoites causes pathology seen in the disease.

Infection is generally self-limiting in immunocompetent people. In immunocompromised patients, such as those with AIDS or those undergoing immunosuppressive therapy, infection may not be self-limiting, leading to dehydration and, in severe cases, death.

The diagnosis of C. parvum consists of serological tests and microscopic evaluation of oocysts in stools using Kinyoun acid-fast staining.

C. parvum is considered to be the most important waterborne pathogen in developed countries. It is resistant to all practical levels of chlorination, surviving for 24hrs at 1000 mg/L free chlorine. It is an obligate intracellular pathogen.^[3]

Genome

The genome of C. parvum (sequenced in 2004^[4]) have a relatively small size and simple organization of 9.1 Mb, which is composed of eight chromosomes ranging from 1.04 to 1.5 Mb. The genome is very compact, and is one of the few organisms without transposable elements. Unlike other apicomplexans, C. parvum has no genes in its plastids or mitochrondria.^[4]

Treatment

Supportive therapy such as IV fluids is the primary for C. parvum infection. Paromomycin and Nitazoxanide may alleviate some of the diarrheal symptoms, however the latter is contraindicated for AIDS patients. Continuing antiretroviral drugs to boost the immune system may also control infection. Research into other potential drugs and therapeutics targets, as well as vaccine candidates, is ongoing. Spiramycin for immunosuppressed patients.

Important C. parvum proteins and drug targets

Lipid metabolism

C. parvum is incapable of de novo lipid synthesis, making its lipid trafficking machinery an important potential therapeutic target. C. parvum possesses multiple oxysterol-binding proteins (OSBPs), and oxysterol related proteins (OSRPs). Only OSBPs are capable of lipid binding, while both contain Pleckstrin homology domains, which function in cell signalling pathways.

Surface glycoproteins

C. parvum possesses numerous surface glycoproteins thought to play a role in pathogenesis. An immunodominant >900kDa protein, known as GP900, localizes to the apical end of sporozoites and in micronemes of merozoites. Its high molecular mass is most likely due to heavy post-translational glycosylation. Indeed, the structure of GP900 is similar to that of a family of glycoproteins known as mucins. GP900 is thought to mediate attachment and invasion to host cells. GP900 may also play a role in C. parvum’s resistance to proteolysis by the numerous proteases found in the mammalian gut.

In vitro, hyperimmune sera as well as antibodies directed at specific epitopes on the GP900 protein inhibit the invasion of C. parvum sporozoites into MDCK cell monolayers. Additionally, competitive inhibition using native GP900 or purified GP900 fragments reduces cell invasion.^[5]

Further experiments have confirmed the importance of the mucin-like glycosylations. Lectins directed at GP900 carbohydrate moieties (alpha-N-galactosamine) were able to block adhesion and prevent C. parvum invasion.^[6]

C. parvum glycoproteins have the characteristics of attractive vaccine candidates. Many are immunodominant, and antibodies against select domains block invasion of host cells.

References

1. ^ ”Cryptosporidiosis.” Laboratory Identification of Parasites of Public Health Concern. CDC. 5 Sept 2007. <http://www.dpd.cdc.gov/dpdx/HTML/Cryptosporidiosis.htm>
2. ^ DuPont HL, Chappell CL, Sterling CR, Okhuysen PC, Rose JB, Jakubowski W (March 1995). "The infectivity of Cryptosporidium parvum in healthy volunteers". N. Engl. J. Med. 332 (13): 855–9. doi:10.1056/NEJM199503303321304. PMID 7870140. http://content.nejm.org/cgi/pmidlookup?view=short&pmid=7870140&promo=ONFLNS19. 
3. ^ PMID 14711592 (PubMed)
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4. ^ ^{a b} Abrahamsen MS, Templeton TJ, et al. (2004). "Complete genome sequence of the apicomplexan, Cryptosporidium parvum". Science 304 (5669): 441–5. doi:10.1126/science.1094786. PMID 15044751. http://www.sciencemag.org/cgi/content/abstract/304/5669/441. Retrieved 2008-05-25. 
5. ^ Barnes DA, Bonnin A, Huang JX, et al. (October 1998). "A novel multi-domain mucin-like glycoprotein of Cryptosporidium parvum mediates invasion". Mol. Biochem. Parasitol. 96 (1–2): 93–110. doi:10.1016/S0166-6851(98)00119-4. PMID 9851610. http://linkinghub.elsevier.com/retrieve/pii/S0166-6851(98)00119-4. 
6. ^ Cevallos AM, Bhat N, Verdon R, et al. (September 2000). "Mediation of Cryptosporidium parvum Infection In Vitro by Mucin-Like Glycoproteins Defined by a Neutralizing Monoclonal Antibody". Infect. Immun. 68 (9): 5167–75. doi:10.1128/IAI.68.9.5167-5175.2000. PMC 101770. PMID 10948140. http://iai.asm.org/cgi/pmidlookup?view=long&pmid=10948140.