Cryptosporidium parvum

Cryptosporidium parvum oocysts are very difficult to detect and therefore diagnose. The oocysts in fecal samples would indicate if the parasite is present in the body but they have a very small size and so detection is made very difficult. Doing a fecal ELISA method to detect the presence of the parasite would eliminate the difficulty due to the small size and many other methods are unable to distinguish between past and present infections; something serological ELISA would not allow to distinguish.^[3]

C. parvum is considered to be the most important waterborne pathogen in developed countries. The protozoa also caused the largest waterborne-disease outbreak ever documented in the United States, making 403,000 people ill in Milwaukee, Wisconsin in 1993.^[4] It is resistant to all practical levels of Water chlorination, surviving for 24hrs at 1000 mg/L free chlorine. It is an obligate intracellular pathogen.^[5]

The most effective way to prevent the spread of Cryptosporidium parvum is to avoid the contact of feces that are contaminated. Avoiding this contact, especially with young children is important, as they are more likely to come into oral contact and have the parasite transferred into the body. These ideas of hygiene are the most effective way to combat this difficult to prevent parasite.^[6]

The Cryptosporidium parvum oocysts are incredibly durable and this can cause extended problems when attempting to control the spread of the parasite. The oocyst stage can tolerate a vast number of environmental pressures that allows it to be more likely to survive. The oocyst can tolerate temperatures as low as -22C and for long periods of time which means fecal contamination is possible even after going through those environmental extremes. The oocysts can also tolerate shifts in pH that are found in some water treatment process and careful attention to detail must be done to prevent the possibility of infection. The oocysts that are in fecal material are immediately infective and have the potential to find a new host if contamination occurs.^[3][6]

The genome of C. parvum (sequenced in 2004^[7]) 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 mitochondria.^[7]

Cryptosporidium parvum infecton must be differentiated from other causes of viral, bacterial, and parasitic gastroentritis.

8Small bowel diarrhea: watery, voluminous with less than 5 WBC/high power field

Large bowel diarrhea: Mucousy and/or bloody with less volume and more than 10 WBC/high power field
† It could be as high as 1000 based on patient’s immunity system.

The table below summarizes the findings that differentiate inflammatory causes of chronic diarrhea^{[8][9][10][11][11]}

Supportive therapy such as IV fluids is the primary for C. parvum infection. Paromomycin and Nitazoxanide may alleviate some of the diarrhoeal 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.

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.

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.^[12]

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.^[13]

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