Cryptosporidium Parvum
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''Cryptosporidium parvum'' is one of several species that cause
cryptosporidiosis Cryptosporidiosis, sometimes informally called crypto, is a parasitic disease caused by ''Cryptosporidium'', a genus of protozoan parasites in the phylum Apicomplexa. It affects the ileum, distal small intestine and can affect the respiratory tr ...
, a
parasitic disease A parasitic disease, also known as parasitosis, is an infectious disease caused by parasites. Parasites are organisms which derive sustenance from its host while causing it harm. The study of parasites and parasitic diseases is known as parasitol ...
of the
mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...
ian
intestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. ...
. Primary symptoms of ''C. parvum'' infection are acute, watery, and nonbloody
diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...
. ''C. parvum'' infection is of particular concern in
immunocompromised Immunodeficiency, also known as immunocompromise, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that affe ...
patients, where diarrhea can reach 10–15 times per day. Other symptoms may include
anorexia Anorexia nervosa (AN), often referred to simply as anorexia, is an eating disorder characterized by Calorie restriction, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. Individuals wit ...
,
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...
/
vomiting Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...
, and
abdominal The abdomen (colloquially called the gut, belly, tummy, midriff, tucky, or stomach) is the front part of the torso between the thorax (chest) and pelvis in humans and in other vertebrates. The area occupied by the abdomen is called the abdominal ...
pain. Extra-intestinal sites include the lung, liver, and gall bladder, where it causes respiratory
cryptosporidiosis Cryptosporidiosis, sometimes informally called crypto, is a parasitic disease caused by ''Cryptosporidium'', a genus of protozoan parasites in the phylum Apicomplexa. It affects the ileum, distal small intestine and can affect the respiratory tr ...
, hepatitis, and
cholecystitis Cholecystitis is inflammation of the gallbladder. Symptoms include Right upper quadrant (abdomen), right upper abdominal pain, pain in the right shoulder, nausea, vomiting, and occasionally fever. Often gallbladder attacks (biliary colic) precede ...
, respectively. Infection is caused by ingestion of sporulated oocysts 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 Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase ...
s by
sporozoite Apicomplexans, a group of intracellular parasites, have life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an apicomplexan organis ...
s and
merozoite Apicomplexans, a group of intracellular parasites, have life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an apicomplexan organism i ...
s causes pathology seen in the disease. Infection is generally self-limiting in immunocompetent people. In
immunocompromised Immunodeficiency, also known as immunocompromise, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that affe ...
patients, such as those with
AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...
or those undergoing immunosuppressive therapy, infection may not be self-limiting, leading to dehydration and, in severe cases, death.


Detection

''Cryptosporidium parvum'' oocysts are very difficult to detect; their small size means they are difficult to detect in fecal samples. A fecal
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay is a solid-phase type of enzyme immunoassay (EIA) to detect the presence of ...
could detect the presence of the parasite. A serological ELISA is unable to distinguish between past and present infections. ''Cryptosporidium 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 Milwaukee is the List of cities in Wisconsin, most populous city in the U.S. state of Wisconsin. Located on the western shore of Lake Michigan, it is the List of United States cities by population, 31st-most populous city in the United States ...
, 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.


Prevention

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.


Oocyst stage

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.


Genome

The
genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
of ''C. parvum'' (sequenced in 2004) is of relatively small size and simple organization of 9.1 Mb, which is composed of eight
chromosome A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...
s ranging from 1.04 to 1.5 Mb. The genome is very compact, and is one of the few organisms without
transposable element A transposable element (TE), also transposon, or jumping gene, is a type of mobile genetic element, a nucleic acid sequence in DNA that can change its position within a genome. The discovery of mobile genetic elements earned Barbara McClinto ...
s. Unlike other
apicomplexa The Apicomplexa (also called Apicomplexia; single: apicomplexan) are organisms of a large phylum of mainly parasitic alveolates. Most possess a unique form of organelle structure that comprises a type of non-photosynthetic plastid called an ap ...
ns, ''C. parvum'' has no genes in its
plastid A plastid is a membrane-bound organelle found in the Cell (biology), cells of plants, algae, and some other eukaryotic organisms. Plastids are considered to be intracellular endosymbiotic cyanobacteria. Examples of plastids include chloroplasts ...
s or
mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...
.


Treatment

Treatment of gastrointestinal infection in humans involves fluid rehydration, electrolyte replacement, and management of any pain. ,
nitazoxanide Nitazoxanide, sold under the brand name Alinia among others, is a broad-spectrum antiparasitic and broad-spectrum antiviral medication that is used in medicine for the treatment of various helminthic, protozoal, and viral infections. It is ...
is the only drug approved for the treatment of
cryptosporidiosis Cryptosporidiosis, sometimes informally called crypto, is a parasitic disease caused by ''Cryptosporidium'', a genus of protozoan parasites in the phylum Apicomplexa. It affects the ileum, distal small intestine and can affect the respiratory tr ...
in
immunocompetent In immunology, immunocompetence is the ability of the body to produce a normal immune response following exposure to an antigen. Immunocompetence is the opposite of immunodeficiency (also known as ''immuno-incompetence'' or being ''immuno-comprom ...
hosts. Paromomycin may alleviate some of the diarrhoeal symptoms and is registered for it in UK for non-ruminating calves (Parofor Crypto, Huvepharma). Continuing
antiretroviral drug The management of HIV/AIDS normally includes the use of multiple Antiviral drug, antiretroviral drugs as a strategy to control HIV/AIDS, HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV li ...
s for HIV infection to boost the immune system may also control infection.


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 domain Pleckstrin homology domain (PH domain) or (PHIP) 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. This domain can bind phosph ...
s, which function in cell signalling pathways.


Surface glycoproteins

''Cryptosporidium parvum'' possesses numerous surface
glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...
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 Micronemes are secretory organelles, possessed by parasitic apicomplexans. Micronemes are located on the apical third of the protozoan body. They are surrounded by a typical unit membrane. On electron microscopy they have an electron-dense ma ...
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 Mucins () are a family of high molecular weight, heavily glycosylated proteins ( glycoconjugates) produced by epithelial tissues in most animals. Mucins' key characteristic is their ability to form gels; therefore they are a key component in ...
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 is the breakdown of proteins into smaller polypeptides or amino acids. Protein degradation is a major regulatory mechanism of gene expression and contributes substantially to shaping mammalian proteomes. Uncatalysed, the hydrolysis o ...
by the numerous
proteases A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products. They do ...
found in the mammalian gut. ''In vitro'', hyperimmune sera, as well as antibodies directed at specific
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 binds to the epitope is called a paratope. Although e ...
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. ''Cryptosporidium parvum'' glycoproteins have the characteristics of attractive vaccine candidates. Many are immunodominant, and antibodies against select domains block invasion of host cells.


References

{{Authority control Conoidasida Rodent-carried diseases