''Cryptosporidium parvum'' is one of several species that cause cryptosporidiosis
, a parasitic disease
of the mammal
ian intestinal tract
Primary symptoms of ''C. parvum'' infection are acute, watery, and nonbloody diarrhea
. ''C. parvum'' infection is of particular concern in immunocompromised
patients, where diarrhea can reach 10–15 times per day. Other symptoms may include anorexia
, and abdominal
pain. Extra-intestinal sites include the lung, liver, and gall bladder, where it causes respiratory cryptosporidosis, hepatitis, and cholecystitis, respectively.
Infection is caused by ingestion of sporulate
s transmitted by the faecal-oral route. In healthy human hosts, the median infective dose is 132 oocysts.
The general ''C. parvum'' lifecycle
is shared by other members of the genus. Invasion of the apical
tip of ileal enterocyte
s by sporozoite
s and merozoite
s 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.
''C. parvum'' oocysts are very difficult to detect; their small size means they are difficult to detect in fecal samples. A fecal ELISA could detect the presence of the parasite. A serological ELISA is unable to distinguish between past and present infections.
''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. It is resistant to all practical levels of chlorination
, surviving for 24 hours at 1000 mg/L free chlorine. It is an obligate intracellular pathogen
The most effective way to prevent the spread of ''C. parvum'' is to avoid contact with contaminated feces. 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. Hygiene is the most effective way to combat this difficult-to-prevent parasite.
Those visiting areas, such as petting zoos, where they might access affected animals should ensure good hygiene measures such as hand washing
The ''C. parvum'' oocysts are incredibly durable, which can cause extended problems when attempting to control the spread of the parasite. The oocyst stage can tolerate a vast number of environmental pressures. The oocyst can tolerate temperatures as low as −22 °C and for long periods of time, which means fecal contamination is possible even after going through deep freezing. The oocysts can also tolerate shifts in pH that are found in some water treatment processes, and careful attention to detail must be done to prevent the possibility of infection. The oocysts in fecal material are immediately infective and have the potential to find a new host if contamination occurs.
The genome of ''C. parvum'' (sequenced in 2004) is of 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 element
s. Unlike other apicomplexa
ns, ''C. parvum'' has no genes in its plastid
s or mitochondria
Treatment of gastrointestinal infection in humans involves fluid rehydration
, electrolyte replacement, and management of any pain. , nitazoxanide
is the only drug approved for the treatment of cryptosporidiosis
in immunocompetent hosts.
may alleviate some of the diarrhoeal symptoms and is registered for it in UK for non-ruminating calves (Parofor Crypto, Huvepharma). Continuing antiretroviral drug
s for HIV infection to boost the immune system may also control infection.
Important ''C. parvum'' proteins and drug targets
''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 protein
s (OSBPs), and oxysterol related proteins (OSRPs). Only OSBPs are capable of lipid binding, while both contain Pleckstrin homology domain
s, which function in cell signalling pathways.
''C. parvum'' possesses numerous surface glycoprotein
s thought to play a role in pathogenesis. An immunodominant >900 kDa protein, known as GP900, localizes to the apical end of sporozoites and in microneme
s 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 mucin
s. 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 epitope
s 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.
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.
''C. parvum'' glycoproteins have the characteristics of attractive vaccine candidates. Many are immunodominant, and antibodies against select domains block invasion of host cells.