Cryptosporidium parvum
Encyclopedia
Cryptosporidium parvum is one of several protozoa
l species that cause cryptosporidiosis
, a parasitic disease
of the mammal
ian 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.
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. The general C. parvum life cycle is shared by other members of the genus. Invasion of the apical tip of ileal enterocyte
s 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.
ns, C. parvum has no genes in its plastid
s or mitochrondria.
may alleviate some of the diarrheal symptoms, however the latter is contraindicated for AIDS patients. Continuing antiretroviral drug
s 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.
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.
s thought to play a role in pathogenesis. An immunodominant >900kDa 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.
Protozoa
Protozoa are a diverse group of single-cells eukaryotic organisms, many of which are motile. Throughout history, protozoa have been defined as single-cell protists with animal-like behavior, e.g., movement...
l species that cause cryptosporidiosis
Cryptosporidiosis
Cryptosporidiosis, also known as crypto, is a parasitic disease caused by Cryptosporidium, a protozoan parasite in the phylum Apicomplexa. It affects the intestines of mammals and is typically an acute short-term infection...
, a parasitic disease
Parasitic disease
A parasitic disease is an infectious disease caused or transmitted by a parasite. Many parasites do not cause diseases. Parasitic diseases can affect practically all living organisms, including plants and mammals...
of the mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
ian intestinal tract
Intestine
In human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...
.
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
Anorexia (symptom)
Anorexia is the decreased sensation of appetite...
, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
/vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
and abdominal
Abdomen
In vertebrates such as mammals the abdomen constitutes the part of the body between the thorax and pelvis. The region enclosed by the abdomen is termed the abdominal cavity...
pain. extra intestinal sites include the Lung and liver where is causes respiratory cryptosporidosis, hepatitis n cholecystisis.
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. The general C. parvum life cycle is shared by other members of the genus. Invasion of the apical tip of ileal enterocyte
Enterocyte
Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells found in the small intestines and colon. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase surface area for the digestion and transport of molecules from the intestinal...
s 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
Chlorination
Chlorination is the process of adding the element chlorine to water as a method of water purification to make it fit for human consumption as drinking water...
, surviving for 24hrs at 1000 mg/L free chlorine. It is an obligate intracellular pathogen.
Genome
The genome of C. parvum (sequenced in 2004) 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 apicomplexaApicomplexa
The Apicomplexa are a large group of protists, most of which possess a unique organelle called apicoplast and an apical complex structure involved in penetrating a host's cell. They are unicellular, spore-forming, and exclusively parasites of animals. Motile structures such as flagella or...
ns, C. parvum has no genes in its plastid
Plastid
Plastids are major organelles found in the cells of plants and algae. Plastids are the site of manufacture and storage of important chemical compounds used by the cell...
s or mitochrondria.
Treatment
Supportive therapy such as IV fluids is the primary for C. parvum infection. Paromomycin and NitazoxanideNitazoxanide
Nitazoxanide, also known by the brand names Alinia and Annita is a synthetic nitrothiazolyl-salicylamide derivative and an antiprotozoal agent.Nitazoxanide is a light yellow...
may alleviate some of the diarrheal symptoms, however the latter is contraindicated for AIDS patients. Continuing antiretroviral drug
Antiretroviral drug
Antiretroviral drugs are medications for the treatment of infection by retroviruses, primarily HIV. When several such drugs, typically three or four, are taken in combination, the approach is known as Highly Active Antiretroviral Therapy, or HAART...
s 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.
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 proteinOxysterol-binding protein
Oxysterol-binding proteins are evolutionary related proteins involved with sterol synthesis and/or its regulation . These include mammalian oxysterol-binding protein , a protein of about 800 amino-acid residues that binds a variety of oxysterols ; yeast OSH1, a protein of 859 residues that also...
s (OSBPs), and oxysterol related proteins (OSRPs). Only OSBPs are capable of lipid binding, while both contain Pleckstrin homology domain
Pleckstrin homology domain
Pleckstrin homology domain is a protein domain of approximately 120 amino acids that occurs in a wide range of proteins involved in intracellular signaling or as constituents of the cytoskeleton....
s, which function in cell signalling pathways.
Surface glycoproteins
C. parvum possesses numerous surface glycoproteinGlycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
s thought to play a role in pathogenesis. An immunodominant >900kDa protein, known as GP900, localizes to the apical end of sporozoites and in microneme
Microneme
Micronemes are cellular organs, or organelles, possessed by Apicomplexa protozoans that are restricted to the apical third of the protozoan body. They are surrounded by a typical unit membrane. On electorn microscopy they have an electron-dense matrix due to the high protein content...
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
Mucin
Mucins are a family of high molecular weight, heavily glycosylated proteins produced by epithelial tissues in most metazoans. Mucins' key characteristic is their ability to form gels; therefore they are a key component in most gel-like secretions, serving functions from lubrication to cell...
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
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
by the numerous proteases found in the mammalian gut.
In vitro, hyperimmune sera as well as antibodies directed at specific epitope
Epitope
An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that recognizes the epitope is called a paratope...
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.