|Cryptosporidium muris oocysts found in human feces.|
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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. It is spread through the fecal-oral route, often through contaminated water; the main symptom is self-limiting diarrhea in people with intact immune systems. In immunocompromised individuals, such as AIDS patients, the symptoms are particularly severe and often fatal. Cryptosporidium is the organism most commonly isolated in HIV positive patients presenting with diarrhea. Treatment is symptomatic, with fluid rehydration, electrolyte correction and management of any pain. Despite not being identified until 1976, it is one of the most common waterborne diseases and is found worldwide. The parasite is transmitted by environmentally hardy microbial cysts (oocysts) that, once ingested, exist in the small intestine and result in an infection of intestinal epithelial tissue.
Cryptosporidium is a protozoan pathogen of the Phylum Apicomplexa and causes a diarrheal illness called cryptosporidiosis. Other apicomplexan pathogens include the malaria parasite Plasmodium, and Toxoplasma, the causative agent of toxoplasmosis. Unlike Plasmodium, which transmits via a mosquito vector, Cryptosporidium does not utilize an insect vector and is capable of completing its life cycle within a single host, resulting in microbial cyst stages which are excreted in feces and are capable of transmission to a new host.
A number of Cryptosporidium infect mammals. In humans, the main causes of disease are C. parvum and C. hominis (previously C. parvum genotype 1). C. canis, C. felis, C. meleagridis, and C. muris can also cause disease in humans.
Cryptosporidiosis is typically an acute short-term infection but can become severe and non-resolving in children and immunocompromised individuals. In humans, it remains in the lower intestine and may remain for up to five weeks. The parasite is transmitted by environmentally hardy microbial cysts (oocysts) that, once ingested, excyst in the small intestine and result in an infection of intestinal epithelial tissue.
The genome of Cryptosporidium parvum was sequenced in 2004 and was found to be unusual amongst Eukaryotes in that the mitochondria seem not to contain DNA . A closely-related species, C. hominis, also has its genome sequence available . CryptoDB.org is a NIH-funded database that provides access to the Cryptosporidium genomics data sets.
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Infection is through contaminated material such as earth, water, uncooked or cross-contaminated food that has been in contact with the feces of an infected individual or animal. Contact must then be transferred to the mouth and swallowed. It is especially prevalent amongst those in regular contact with bodies of fresh water including recreational water such as swimming pools. Other potential sources include insufficiently treated water supplies, contaminated food, or exposure to feces. The high resistance of Cryptosporidium oocysts to disinfectants such as chlorine bleach enables them to survive for long periods and still remain infective . Some outbreaks have happened in day care related to diaper changes.
Symptoms appear from two to ten days after infection, with an average of 7 days  , and last for up to two weeks, or in some cases, up to one month . There are 3 possible forms of the illness in immunocompetent people. The disease can be asymptomatic or cause acute diarrhea or persistent diarrhea that can last for a few weeks. Diarrhea is usually watery with mucus. It is very rare to find blood or leukocytes in the diarrhea . As well as watery diarrhea, there is often stomach pains or cramps and a low fever. Other symptoms include nausea, vomiting , malabsorption  and dehydration. Anorexia can occur, as can weight loss. The individuals who are asymptomatic (have no symptoms) are nevertheless infective, and thus can pass on the infection to others. Even after symptoms have finally subsided an individual is still infective for some weeks.
Immunocompromised people, as well as very young or very old people, can develop a more severe form of cryptosporidiosis. There are 4 clinical presentations for patients with AIDS. 4% have no symptoms, 29% have a transient infection, 60% have chronic diarrhea, and 8% have a severe, cholera-like infection. With transient infections diarrhea ends within 2 months and Cryptosporidium is no longer found in the feces. Chronic diarrhea is diarrhea that lasts for 2 or more months. The most severe form results in the patients excreting at least 2 liters of watery diarrhea per day. They can lose up to 25 liters per day. AIDS patients can have up to 10 stools per day. They experience severe malabsorption and can have 10% weight loss. Many of them never completely eliminate Cryptosporidium from their bodies.
When Cryptosporidium spreads beyond the intestine, as it can predominantly in patients with AIDS, it can reach the lungs, middle ear, pancreas, and stomach. Thus, one symptom is pain in the right upper quadrant. The parasite can infect the biliary tract, causing biliary cryptosporidiosis. This can result in cholecystitis and cholangitis.
The life cycle of Cryptosporidium parvum consists of an asexual stage and a sexual stage. After being ingested the oocysts excyst in the small intestine. They release sporozoites that attach to the microvilli of the epithelial cells of the small intestine. From there they become trophozoites that reproduce asexually by multiple fission, a process known as schizogony. The trophozoites develop into Type 1 meronts that contain 8 daughter cells. These daughter cells are Type 1 merozoites, which get released by the meronts. Some of these merozoites can cause autoinfection by attaching to epithelial cells. Others of these merozoites become Type II meronts , which contain 4 Type II merozoites. These merozoites get released and they attach to the epithelial cells. From there they become either macrogamonts or microgamonts. These are the female and male sexual forms, respectively. This stage, when sexual forms arise, is called gametogony. Zygotes are formed by microgametes from the microgamont penetrating the macrogamonts. The zygotes develop into oocysts of two types. 20% of oocysts have thin walls and so can reinfect the host by rupturing and releasing sporozoites that start the process over again. The thick-walled oocysts are excreted into the environment. The oocysts are mature and infective upon being excreted. They can survive in the environment for months.
The oocysts are ovoid or spherical and measure 5 to 6 micrometers across. When in flotation preparations they appear highly refractile. The oocysts contains up to 4 sporozoites that are bow-shaped.
As few as 2 to 10 oocysts can initiate an infection. The parasite is located in the brush border of the epithelial cells of the small intestine. They are mainly located in the jejunum. When the sporozoites attach the epithelial cells’ membrane envelops them. Thus, they are “intracellular but extracytoplasmic”. The parasite can cause damage to the microvilli where it attaches. The infected human excretes the most oocysts during the first week. Oocysts can be excreted for weeks after the diarrhea subsides.
The immune system reduces the formation of Type 1 merozoites as well as the number of thin-walled oocysts. This helps prevent autoinfection. B cells do not help with the initial response or the fight to eliminate the parasite.
There are many diagnostic tests for Cryptosporidium. They include microscopy, staining, and detection of antibodies. Microscopy  can help identify oocysts in fecal matter. To increase the chance of finding the oocysts the diagnostician should inspect at least 3 stool samples. There are several techniques to concentrate either the stool sample or the oocysts. The modified formalin-ethyl acetate (FEA) concentration method concentrates the stool. Both the modified zinc sulfate centrifugal flotation technique and the Sheather’s sugar flotation procedure can concentrate the oocysts by causing them to float. Another form of microscopy is fluorescent microscopy done by staining with auramine.
Other staining techniques include acid-fast staining, which will stain the oocysts red. One type of acid-fast stain is the Kinyoun technique. Giemsa staining can also be performed. Part of the small intestine can be stained with hematoxylin and eosin (H & E), which will show oocysts attached to the epithelial cells.
Detecting antigens is yet another way to diagnose the disease. This can be done with direct fluorescent antibody (DFA). It can also be achieved through indirect immunofluorescence assay. Enzyme-Linked ImmunoSorbent Assay (ELISA) also detects antigens.
Polymerase chain reaction (PCR) is another way to diagnose cryptosporidiosis. It can even identify the specific species of Cryptosporidium. If the patient is thought to have biliary cryptosporidiosis then an appropriate diagnostic technique is ultrasonography. If that returns normal results the next step would be to perform endoscopic retrograde cholangiopancreatography.
There is no reliable treatment for cryptosporidium enteritis; certain agents such as paromomycin, atovaquone, nitazoxanide, and azithromycin are sometimes used, but they usually have only temporary effects.
Treatment is primarily supportive. Fluids need to be replaced orally. A lactose-free diet should be taken as tolerated. In rare situations, intravenous fluids may be required. Antibiotics are not usually helpful, and are primarily reserved for persons with severe disease and a weak immune system. Sometimes relapses happen.
The majority of immuno-competent individuals suffer a short (less than 2 weeks) self-limiting course that requires supportive care with re-hydration and occasionally anti-diarrhoeal medication and ends with spontaneous recovery. Nitazoxanide is one drug that the US FDA has approved for use in immunocompetent people to combat diarrhea. Spiramycin can help shorten the amount of time oocysts are passed as well as the duration of diarrhea in children.
In immunocompromised individuals—such as AIDS patients—cryptosporidiosis resolves slowly or not at all, and frequently causes a particularly severe and permanent form of watery diarrhea coupled with a greatly decreased ability to absorb key nutrients through the intestinal tract. The result is progressively severe dehydration, electrolyte imbalances, malnutrition, wasting, and eventual death. Spiramycin can help treat diarrhea in patients who are in the early stages of AIDS. The mortality rate for infected AIDS patients is generally based on CD4+ marker counts; patients with CD4+ counts over 180 cells/mm³ generally recover with supportive hospital care and medication, but in patients with CD4+ counts below 50 cells/mm³, the effects are usually fatal within three to six months. During the Milwaukee cryptosporidiosis epidemic (the largest of its kind), 73% of AIDS patients with CD4 counts lower than 50 cells/mm³ and 36% of those with counts between 50 and 200 cells/mm³ died within the first year of contracting the infection.. In one AIDS patient from Iran, who had pulmonary cryptosporidiosis in addition to intestinal cryptosporidiosis, azithromycin and paromomycin helped to clear the infection .
Currently, the best approach is to improve the immune status in immunodeficient individuals. The probiotic Saccharomyces boulardii sold over the counter in pharmacies and health shops (Brand name Florastor in US and DiarSafe in UK) has been found to be a helpful natural treatment in managing diarrhoea of various infectious origins including cryptosporidium. Parenteral octreotide acetate can help decrease the number of stools passed. A treatment for patients with biliary cryptosporidiosis who have cholangitis in addition to papillary stenosis is endoscopic sphincterotomy.
Currently research is being done in molecular-based immunotherapy. For example, synthetic isoflavone derivates have been shown to fight off Cryptosporidium parvum in vitro and in a gerbil. Derivates of nitazoxanide, which are synthetic nitro- or non nitro- thiazolide compounds, have also shown promising results in vitro.
Many treatment plants that take raw water from rivers, lakes, and reservoirs for public drinking water production use conventional filtration technologies. This involves a series of processes including coagulation, flocculation, sedimentation, and filtration. Direct filtration, which is typically used to treat water with low particulate levels, includes coagulation and filtration but not sedimentation. Other common filtration processes including slow sand filters, diatomaceous earth filter and membranes will remove 99% of Cryptosporidium. Membranes and bag and cartridge filters remove Cryptosporidium product-specifically.
While Cryptosporidium is highly resistant to chlorine disinfection, with high enough concentrations and contact time Cryptosporidium will be inactivated by chlorine dioxide and ozone treatment. The required levels of chlorine generally preclude the use of chlorine disinfection as a reliable method to control Cryptosporidium in drinking water. Ultraviolet light treatment at relatively low doses will inactivate Cryptosporidium. Water Research Foundation-funded research originally discovered UV's efficacy in inactivating Cryptosporidium.
One of the largest challenges in identifying outbreaks is the ability to identify Cryptosporidium in the laboratory. Real-time monitoring technology is now able to detect Cryptosporidium with online systems, unlike the spot and batch testing methods used in the past.
The most important zoonotic reservoirs are cattle, sheep and goats. Additionally, in recent years, cryptosporidiosis has plagued many commercial Leopard gecko breeders. Several species of the Cryptosporidium family (C. serpentes and others) are involved, and outside of geckos it has been found in monitor lizards, iguanas and tortoises, as well as several snake species. Cryptosporidiosis has no vectors.
Cryptosporidiosis is found worldwide. It causes 50.8% of water-borne diseases that are attributed to parasites. In developing countries 8-19% of diarrheal diseases can be attributed to Cryptosporidium. 10% of the population in developing countries excretes oocysts. In developed countries the number is lower at 1-3%. The age group most affected is children from 1 to 9 years old.
The following groups have an elevated risk of being exposed to Cryptosporidium:
Cases of cryptosporidiosis can occur in a city that does not have a contaminated water supply. In a city with clean water, it may be that cases of cryptosporidiosis have different origins. Testing of water, as well as epidemiological study, are necessary to determine the sources of specific infections. Note that Cryptosporidium typically does not cause serious illness in healthy people. It may chronically sicken some children, as well as adults who are exposed and immunocompromised. A subset of the immunocompromised population is people with AIDS. Some sexual behaviours can transmit the parasite directly.
Statistics for the United States - number of cases :
In the US the law requires doctors and labs to report cases of cryptosporidiosis to local or state health departments. These departments then report to the Center for Disease Control and Prevention. The best way to prevent getting and spreading cryptosporidiosis is to have good hygiene and sanitation. An example would be hand-washing. Prevention is through washing hands carefully after going to the bathroom or contacting stool, and before eating. People should avoid contact with animal feces. They should also avoid possibly contaminated food and water. Additionally, people should refrain from engaging in sexual activities that can expose them to feces.
Standard water filtration may not be enough to eliminate Cryptosporidium; boiling for at least 1 minute (3 minutes above 6,500 feet (2,000 m) of altitude) will decontaminate it. Heating milk at 71.7 °C for 15 seconds pasteurizes it and can destroy the oocysts' ability to infect. Water can also be made safe by filtering with a filter with pore size not greater than 1 micrometre, or by filters that have been approved for “cyst removal” by the US National Science Foundation (NSF). Bottled drinking water is less likely to contain Cryptosporidium, especially if the water is from an underground source.
People who have cryptosporidiosis should not swim in communal areas because Cryptosporidium can reside in the anal and genital areas and be washed off. They should wait until at least two weeks after diarrhea stops before entering public water sources since oocysts can still be shed for a while. Also, they should stay away from immunosuppressed people. Immunocompromised people should take care to protect themselves from water in lakes and streams. They should also stay away from animal stools and wash their hands after touching animals. To be safe they should boil or filter their water. They should also wash and cook their vegetables.