Cryptosporidium parvum

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Cryptosporidium parvum
Cryptosporidium parvum 01.jpg
Immunofluorescence image of C. parvum oocysts
Scientific classification OOjs UI icon edit-ltr.svg
Domain: Eukaryota
Clade: Diaphoretickes
Clade: SAR
Clade: Alveolata
Phylum: Apicomplexa
Class: Conoidasida
Order: Eucoccidiorida
Family: Cryptosporidiidae
Genus: Cryptosporidium
Species:
C. parvum
Binomial name
Cryptosporidium parvum
Tyzzer, 1912

Cryptosporidium parvum is one of several species that cause cryptosporidiosis, a parasitic disease of the mammalian intestinal tract. [1]

Contents

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, nausea/vomiting, and abdominal pain. Extra-intestinal sites include the lung, liver, and gall bladder, where it causes respiratory cryptosporidiosis, hepatitis, and cholecystitis, respectively.[ citation needed ]

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. [2] The general C. parvum lifecycle 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.[ citation needed ]

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.[ citation needed ]

Detection

Cryptosporidium 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. [2]

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, Wisconsin, in 1993. [3] 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. [4]

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. [5] Those visiting areas, such as petting zoos, where they might access affected animals should ensure good hygiene measures such as hand washing. [6]

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. [2] [5]

Genome

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. [7] 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] [8]

Treatment

Treatment of gastrointestinal infection in humans involves fluid rehydration, electrolyte replacement, and management of any pain. As of January 2015, nitazoxanide is the only drug approved for the treatment of cryptosporidiosis in immunocompetent hosts. [9] Paromomycin may alleviate some of the diarrhoeal symptoms and is registered for it in UK for non-ruminating calves (Parofor Crypto, Huvepharma). Continuing antiretroviral drugs for HIV infection to boost the immune system may also control infection.[ citation needed ]

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.[ citation needed ]

Surface glycoproteins

Cryptosporidium parvum possesses numerous surface glycoproteins thought to play a role in pathogenesis. An immunodominant >900 kDa 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. [10]

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. [11]

Cryptosporidium parvum glycoproteins have the characteristics of attractive vaccine candidates. Many are immunodominant, and antibodies against select domains block invasion of host cells.[ citation needed ]

Related Research Articles

<span class="mw-page-title-main">Cryptosporidiosis</span> Parasitic disease

Cryptosporidiosis, sometimes informally called crypto, is a parasitic disease caused by Cryptosporidium, a genus of protozoan parasites in the phylum Apicomplexa. It affects the distal small intestine and can affect the respiratory tract in both immunocompetent and immunocompromised individuals, resulting in watery diarrhea with or without an unexplained cough. In immunosuppressed individuals, the symptoms are particularly severe and can be fatal. It is primarily spread through the fecal-oral route, often through contaminated water; recent evidence suggests that it can also be transmitted via fomites contaminated with respiratory secretions.

<span class="mw-page-title-main">Isosporiasis</span> Human intestinal disease

Isosporiasis, also known as cystoisosporiasis, is a human intestinal disease caused by the parasite Cystoisospora belli. It is found worldwide, especially in tropical and subtropical areas. Infection often occurs in immuno-compromised individuals, notably AIDS patients, and outbreaks have been reported in institutionalized groups in the United States. The first documented case was in 1915. It is usually spread indirectly, normally through contaminated food or water (CDC.gov).

<span class="mw-page-title-main">Coccidia</span> Subclass of protists

Coccidia (Coccidiasina) are a subclass of microscopic, spore-forming, single-celled obligate intracellular parasites belonging to the apicomplexan class Conoidasida. As obligate intracellular parasites, they must live and reproduce within an animal cell. Coccidian parasites infect the intestinal tracts of animals, and are the largest group of apicomplexan protozoa.

<i>Plasmodium ovale</i> Species of single-celled organism

Plasmodium ovale is a species of parasitic protozoon that causes tertian malaria in humans. It is one of several species of Plasmodium parasites that infect humans, including Plasmodium falciparum and Plasmodium vivax which are responsible for most cases of malaria in the world. P. ovale is rare compared to these two parasites, and substantially less dangerous than P. falciparum.

Coccidiosis is a parasitic disease of the intestinal tract of animals caused by coccidian protozoa. The disease spreads from one animal to another by contact with infected feces or ingestion of infected tissue. Diarrhea, which may become bloody in severe cases, is the primary symptom. Most animals infected with coccidia are asymptomatic, but young or immunocompromised animals may suffer severe symptoms and death.

<i>Eimeria tenella</i> Species of single-celled organism

Eimeria tenella is a species of Eimeria that causes hemorrhagic cecal coccidiosis in young poultry. It is found worldwide.

<i>Eimeria</i> Genus of single-celled organisms

Eimeria is a genus of apicomplexan parasites that includes various species capable of causing the disease coccidiosis in animals such as cattle, poultry and smaller ruminants including sheep and goats. Eimeria species are considered to be monoxenous because the life cycle is completed within a single host, and stenoxenous because they tend to be host specific, although a number of exceptions have been identified. Species of this genus infect a wide variety of hosts. Thirty-one species are known to occur in bats (Chiroptera), two in turtles, and 130 named species infect fish. Two species infect seals. Five species infect llamas and alpacas: E. alpacae, E. ivitaensis, E. lamae, E. macusaniensis, and E. punonensis. A number of species infect rodents, including E. couesii, E. kinsellai, E. palustris, E. ojastii and E. oryzomysi. Others infect poultry, rabbits and cattle. For full species list, see below.

<i>Cryptosporidium</i> Genus of single-celled organisms

Cryptosporidium, sometimes called crypto, is an apicomplexan genus of alveolates which are parasites that can cause a respiratory and gastrointestinal illness (cryptosporidiosis) that primarily involves watery diarrhea, sometimes with a persistent cough.

<i>Cyclospora cayetanensis</i> Species of single-celled organism

Cyclospora cayetanensis is a coccidian parasite that causes a diarrheal disease called cyclosporiasis in humans and possibly in other primates. Originally reported as a novel pathogen of probable coccidian nature in the 1980s and described in the early 1990s, it was virtually unknown in developed countries until awareness increased due to several outbreaks linked with fecally contaminated imported produce. C. cayetanensis has since emerged as an endemic cause of diarrheal disease in tropical countries and a cause of traveler's diarrhea and food-borne infections in developed nations. This species was placed in the genus Cyclospora because of the spherical shape of its sporocysts. The specific name refers to the Cayetano Heredia University in Lima, Peru, where early epidemiological and taxonomic work was done.

The 1993 Milwaukee cryptosporidiosis outbreak was a significant distribution of the Cryptosporidium protozoan in Milwaukee, Wisconsin, and the largest waterborne disease outbreak in documented United States history. It is suspected that The Howard Avenue Water Purification Plant, one of two water treatment plants in Milwaukee at the time, was contaminated. It is believed that the contamination was due to an ineffective filtration process. Approximately 403,000 residents were affected resulting in illness and hospitalization. Immediate repairs were made to the treatment facilities along with continued infrastructure upgrades during the 25 years since the outbreak. The total cost of the outbreak, in productivity loss and medical expenses, was $96 million. At least 69 people died as a result of the outbreak. The city of Milwaukee has spent upwards to $510 million in repairs, upgrades, and outreach to citizens.

<span class="mw-page-title-main">Nitazoxanide</span> Broad-spectrum antiparasitic and antiviral medication

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 indicated for the treatment of infection by Cryptosporidium parvum and Giardia lamblia in immunocompetent individuals and has been repurposed for the treatment of influenza. Nitazoxanide has also been shown to have in vitro antiparasitic activity and clinical treatment efficacy for infections caused by other protozoa and helminths; evidence as of 2014 suggested that it possesses efficacy in treating a number of viral infections as well.

Cryptosporidium hominis, along with Cryptosporidium parvum, is among the medically important Cryptosporidium species. It is an obligate parasite of humans that can colonize the gastrointestinal tract resulting in the gastroenteritis and diarrhea characteristic of cryptosporidiosis. Unlike C. parvum, which has a rather broad host range, C. hominis is almost exclusively a parasite of humans. As a result, C. hominis has a low zoonotic potential compared to C. parvum. It is spread through the fecal-oral route usually by drinking water contaminated with oocyst laden feces. There are many exposure risks that people can encounter in affected areas of the world. Cryptosporidium infections are large contributors of child death and illness in heavily affected areas, yet low importance has been placed on both identifying the species and finding more treatment options outside of nitazoxanide for children and AIDS patients.

<span class="mw-page-title-main">Apicomplexan life cycle</span> Apicomplexa life cycle

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 is typified by a cellular variety with a distinct morphology and biochemistry.

<i>Theileria parva</i> Species of single-celled organism

Theileria parva is a species of parasites, named in honour of Arnold Theiler, that causes East Coast fever (theileriosis) in cattle, a costly disease in Africa. The main vector for T. parva is the tick Rhipicephalus appendiculatus. Theiler found that East Coast fever was not the same as redwater, but caused by a different protozoan.

Circumsporozoite protein (CSP) is a secreted protein of the sporozoite stage of the malaria parasite and is the antigenic target of RTS,S and other malaria vaccines. The amino-acid sequence of CSP consists of an immunodominant central repeat region flanked by conserved motifs at the N- and C- termini that are implicated in protein processing as the parasite travels from the mosquito to the mammalian vector. The amino acid sequence of CSP was determined in 1984.

<i>Cystoisospora belli</i> Species of single-celled organism

Cystoisospora belli, previously known as Isospora belli, is a parasite that causes an intestinal disease known as cystoisosporiasis. This protozoan parasite is opportunistic in immune suppressed human hosts. It primarily exists in the epithelial cells of the small intestine, and develops in the cell cytoplasm. The distribution of this coccidian parasite is cosmopolitan, but is mainly found in tropical and subtropical areas of the world such as the Caribbean, Central and S. America, India, Africa, and S.E. Asia. In the U.S., it is usually associated with HIV infection and institutional living.

Cystoisospora canis, previously known as Isospora canis, is a microscopic, coccidian parasite that causes an intestinal tract infection in dogs. The intestinal tract infection is coccidiosis caused by a protozoa called coccidia.

Eimeria bovis is a parasite belonging to the genus Eimeria and is found globally. The pathogen can cause a diarrheic disease in cattle referred to as either eimeriosis or coccidiosis. The infection predominantly cause disease in younger animals.

Cryptosporidium varanii is a protozoal parasite that infects the gastrointestinal tract of lizards. C. varanii is often shed in the feces, and transmission is primarily via fecal-oral route. Unlike Cryptosporidium serpentis, C. varanii does not colonize the stomach, but rather the intestines of most infected lizards, such as geckos. An exception to this rule are monitor lizards, as gastric (stomach) lesions have been found in those species. Oocysts of lizard Cryptosporidium are larger than the snake counterpart.

Cryptosporidium serpentis is a protozoal parasite that infects the gastrointestinal tract of snakes. Sporated oocysts of C. serpentis are intermittently shed in the feces, and transmission is primarily via fecal-oral route. C. serpentis is a gastric parasite, primarily colonizing the stomach. Unlike mammalian Cryptosporidium - that is usually self-limiting - C. serpentis remains chronic and in most cases, eventually lethal in snakes once an animal has become symptomatic. However, recent advancements in detection have led to the identification of healthy carrier animals some of which have thus far remained in good health for years and cast doubt on previous assumptions about the lethality of the parasite, though it remains to be seen how many carriers will remain healthy and for how long as most such animals are euthanized immediately. Cryptosporidiosis infection has been documented in a variety of snake species worldwide, such as North American Corn snakes and Australian Taipans, both free-living and captive. Necropsy examinations of expired captive snakes infected with C. serpentis note characteristic gastric mucosal hypertrophy that, in time, narrows the gastric lumen, resulting in classic symptoms of repetitive regurgitation and anorexia. Due to the enlargement of the stomach lining, a noticeable midbody bulge can be palpable and commonly visible. Frequent mucoid stools have been reported. However, some snakes will display no external symptoms at all throughout their lifetime, yet still remain infectious to counterparts.

References

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  8. Keithly, Janet S. (2007). "The Mitochondrion-Related Organelle of Cryptosporidium parvum". In Tachezy, Jan (ed.). Hydrogenosomes and mitosomes mitochondria of anaerobic eukaryotes. Microbiology Monographs, vol 9. Microbiology Monographs. Vol. 9. Berlin: Springer. pp. 231–253. doi:10.1007/7171_2007_115. ISBN   978-3-540-76733-6.
  9. Cabada MM, White AC, Venugopalan P, Sureshbabu J (18 August 2015). Bronze MS (ed.). "Cryptosporidiosis Treatment & Management". Medscape. WebMD. Retrieved 8 January 2016. Infection may improve with nutritional supplementation, particularly with regimens including zinc or glutamine. ... Nitazoxanide significantly shortens the duration of diarrhea and can decrease the risk of mortality in malnourished children.[22] Trials have also demonstrated efficacy in adults.[26, 27] ... Symptomatic therapy includes replacement of fluids, provision of appropriate nutrition, and treatment with antimotility agents. ... Replacement of fluids and electrolytes is the critically important first step in the management of cryptosporidiosis, particularly in patients with large diarrheal losses. Fluids should include sodium, potassium, bicarbonate, and glucose.
  10. 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.
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