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 (i.e., individuals with a normal functioning immune system) and immunocompromised (e.g., persons with HIV/AIDS or autoimmune disorders) 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. Cryptosporidium is commonly isolated in HIV-positive patients presenting with diarrhea.
The organism was first described in 1907 by Tyzzer, who recognised it was a coccidian.
On January 8, 2025, a group of scientists from the Cryptosporidiosis Therapeutics Advocacy Group (CTAG) released an article in the newsletter Global Health NOW advocating for Cryptosporidiosis to be raised to the status of Neglected Tropical Disease (NTD) by the World Health Organization (WHO).
Signs and symptoms Cryptosporidiosis may occur as an asymptomatic infection, an acute infection (i.e., duration shorter than 2 weeks), as recurrent acute infections in which symptoms reappear following a brief period of recovery for up to 30 days, and as a chronic infection (i.e., duration longer than 2 weeks) in which symptoms are severe and persistent. It may be fatal in individuals with a severely compromised immune system. Symptoms usually appear 5–10 days after infection (range: 2–28 days) and normally last for up to 2 weeks in immunocompetent individuals; symptoms are usually more severe and persist longer in immunocompromised individuals. Following the resolution of diarrhea, symptoms can reoccur after several days or weeks due to reinfection. The likelihood of is high in immunocompromised adults, and low in those with normal immune systems.
In immunocompetent individuals, cryptosporidiosis is primarily localized to the distal small intestine and sometimes the respiratory tract as well. In immunocompromised persons, cryptosporidiosis may disseminate to other organs, including the hepatobiliary system, pancreas, upper gastrointestinal tract, and urinary bladder; pancreatic and biliary infection can involve acalculous cholecystitis, sclerosing cholangitis, papillary stenosis, or pancreatitis.
Intestinal cryptosporidiosis
Common signs and symptoms of intestinal cryptosporidiosis include: Moderate to severe watery diarrhea, sometimes contains mucus and rarely contains blood or leukocytes In very severe cases, diarrhea may be profuse and cholera-like with malabsorption and hypovolemia Low-grade fever Crampy abdominal pain Dehydration Weight loss Fatigue Nausea and vomiting – suggests upper GI tract involvement and may lead to respiratory cryptosporidiosis Epigastric or right upper quadrant tenderness
Less common or rare signs and symptoms include: Reactive arthritis (may affect the hands, knees, ankles, and feet) Jaundice – suggests hepatobiliary involvement Ascites – suggests pancreatic involvement
Respiratory cryptosporidiosis
Symptoms of upper respiratory cryptosporidiosis include: Inflammation of the nasal mucosa, sinuses, larynx, or trachea Nasal discharge Voice change (e.g., hoarseness)
Symptoms of lower respiratory cryptosporidiosis include: Cough Shortness of breath Fever Hypoxemia
Cause
Cryptosporidium is a genus of protozoan pathogens which is categorized under the phylum Apicomplexa. Other apicomplexan pathogens include the malaria parasite Plasmodium, and Toxoplasma, the causative agent of toxoplasmosis. Several Cryptosporidium species 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. Cryptosporidium is capable of completing its life cycle within a single host, resulting in microbial cyst stages that are excreted in feces and are capable of transmission to a new host via the fecal-oral route. Other vectors of disease transmission also exist.
The pattern of Cryptosporidium life cycle fits well with that of other intestinal homogeneous coccidian genera of the suborder Eimeriina: macro- and microgamonts develop independently; a microgamont gives rise to numerous male gametes; and oocysts serve for parasites' spreading in the environment. Electron microscopic studies made from the 1970s have shown the intracellular, although extracytoplasmic localization of Cryptosporidium species.
These species possess several unusual features: an endogenous phase of development in microvilli of epithelial surfaces two morphofunctional types of oocysts the smallest number of sporozoites per oocyst a multi-membraneous "feeder" organelle
DNA studies suggest a relationship with the gregarines rather than the coccidia. The taxonomic position of this group has not yet been finally agreed upon.
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.
Transfer 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 remain infective. Some outbreaks have happened in day care related to diaper changes.
The following groups have an elevated risk of being exposed to Cryptosporidium: Child care workers Parents of infected children People who take care of other people with cryptosporidiosis International travelers Backpackers, hikers, and campers who drink unfiltered, untreated water People, including swimmers, who swallow water from contaminated sources People who handle infected cattle People exposed to human feces through sexual contact
Cases of cryptosporidiosis can occur even in cities that have a properly decontaminated water supply. In a city with clean water, it may be that cases of cryptosporidiosis have other origins. Testing of water, as well as epidemiological study, is necessary to determine the sources of specific infections. Cryptosporidium causes serious illness more frequently in immunocompromised than in apparently healthy individuals. 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 behaviors can transmit the parasite.
Agricultural transmission
Cryptosporidiosis can occur in agricultural environments where humans have close contact with livestock and contaminated water sources. The parasite Cryptosporidium is shed in the feces of infected animals, particularly young calves, and the infectious oocysts can contaminate soil and surface water. Humans may become infected through direct contact with infected animals or through ingestion of contaminated drinking water or food. Agricultural runoff and improper manure management may contribute to environmental contamination, increasing the risk of transmission to nearby communities.
Life cycle Cryptosporidium spp. exist as multiple cell types which correspond to different stages in an infection (e.g., a sexual and asexual stage). As an oocyst – a type of hardy, thick-walled spore – it can survive in the environment for months and is resistant to many common disinfectants, particularly chlorine-based disinfectants. After being ingested, the sporozoites within oocysts excyst (i.e., are released) in the small intestine. The released sporozoites subsequently 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 are 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.Murray, Patrick R., Ken S. Rosenthal, and Michael A. Pfaller. Medical Microbiology. 5th ed. Philadelphia: Elsevier Inc., 2005: 855–856.
Zygotes are formed by microgametes from the microgamont penetrating the macrogamonts. The zygotes develop into two types of oocysts. 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.
Pathogenesis The oocysts are ovoid or spherical and measure 5 to 6 micrometers across. When in flotation preparations, they appear highly refractile. The oocysts contain 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 to 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 from infections by C. parvum or C. hominis; however, immunocompetent individuals with C. muris infections have been observed excreting oocysts for seven months.
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. Previous infection in immunocompetent individuals produces little resistance to future infection; however, it may decrease the severity of disease and the number of oocysts excreted.
Diagnosis 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.