| Cryptosporidiosis | |
|---|---|
 | |
| Micrograph showing cryptosporidiosis. The cryptosporidium are the small, round bodies in apical vacuoles on the surface of the epithelium.H&E stain.Colonicbiopsy. | |
| Specialty | Infectious disease |
| Symptoms | Watery diarrhea, nausea, abdominal pain, fever |
| Causes | Cryptosporidium infection |
| Risk factors | Immunocompromisation |
| Prevention | Avoid contaminated water |
| Treatment | Nitazoxanide |
Cryptosporidiosis, sometimes informally calledcrypto,[1] is aparasitic disease caused byCryptosporidium, a genus ofprotozoanparasites in the phylumApicomplexa. It affects thedistal small intestine and can affect therespiratory tract in bothimmunocompetent (i.e., individuals with a normal functioningimmune system) andimmunocompromised (e.g., persons withHIV/AIDS orautoimmune disorders) individuals, resulting inwatery diarrhea with or without an unexplained cough.[2] In immunosuppressed individuals, the symptoms are particularly severe and can be fatal. It is primarily spread through thefecal-oral route, often through contaminated water;[2][3] recent evidence suggests that it can also be transmitted viafomites contaminated with respiratory secretions.[2]Cryptosporidium is commonly isolated inHIV-positive patients presenting with diarrhea.[4][5]
The organism was first described in 1907 by Tyzzer, who recognised it was acoccidian.[6]
On January 8, 2025, a group of scientists from the Cryptosporidiosis Therapeutics Advocacy Group (CTAG) released an article in the newsletterGlobal Health NOW advocating for Cryptosporidiosis to be raised to the status of Neglected Tropical Disease (NTD) by the World Health Organization (WHO).[7]
Cryptosporidiosis may occur as anasymptomatic 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.[2][8][9][10] It may be fatal in individuals with a severely compromisedimmune system.[2][8]Symptoms usually appear 5–10 days after infection (range: 2–28 days) and normally last for up to 2 weeks inimmunocompetent individuals;[2][8][9] symptoms are usually more severe and persist longer inimmunocompromised individuals.[2][8][9] Following the resolution of diarrhea, symptoms can reoccur after several days or weeks due to reinfection.[8][9][10][11] The likelihood ofre-infection is high in immunocompromised adults, and low in those with normal immune systems.[11][12]
In immunocompetent individuals, cryptosporidiosis is primarily localized to thedistal small intestine and sometimes therespiratory tract as well.[2][9] In immunocompromised persons, cryptosporidiosis may disseminate to other organs, including thehepatobiliary system,pancreas,upper gastrointestinal tract, andurinary bladder;[2][9] pancreatic and biliary infection can involveacalculous cholecystitis,sclerosing cholangitis,papillary stenosis, orpancreatitis.[9][13]
Common signs and symptoms of intestinal cryptosporidiosis include:
Less common or rare signs and symptoms include:
Symptoms ofupper respiratory cryptosporidiosis include:
Symptoms oflower respiratory cryptosporidiosis include:
Cryptosporidium is a genus ofprotozoanpathogens which is categorized under thephylumApicomplexa. Other apicomplexan pathogens include themalaria parasitePlasmodium, andToxoplasma, the causative agent oftoxoplasmosis. SeveralCryptosporidium species infect mammals. In humans, the main causes of disease areC. parvum andC. hominis (previouslyC. parvum genotype 1).C. canis,C. felis,C. meleagridis, andC. 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 infeces and are capable of transmission to a new host via thefecal-oral route. Other vectors of disease transmission also exist.[2][14]
The pattern ofCryptosporidium life cycle fits well with that of other intestinal homogeneous coccidian genera of the suborderEimeriina: 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 ofCryptosporidium species.[citation needed]
These species possess several unusual features:[citation needed]
DNA studies suggest a relationship with the gregarines rather than the coccidia.[15] The taxonomic position of this group has not yet been finally agreed upon.
Thegenome ofCryptosporidium parvum was sequenced in 2004 and was found to be unusual amongstEukaryotes in that themitochondria seem not tocontain DNA.[16] A closely related species,C. hominis, also has its genome sequence available.[17] CryptoDB.org is aNIH-funded database that provides access to theCryptosporidium genomics data sets.[18]
Infection is through contaminated material such as earth,water, uncooked or cross-contaminatedfood that has been in contact with the feces of an infected individual oranimal. 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.[3] The high resistance ofCryptosporidiumoocysts todisinfectants such aschlorinebleach enables them to survive for long periods and remain infective.[19] Some outbreaks have happened in day care related to diaper changes.[20]
The following groups have an elevated risk of being exposed toCryptosporidium:[3]
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.[3] Testing of water, as well asepidemiological study, is necessary to determine the sources of specific infections.Cryptosporidium is causing serious illness[21] 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.[3]
Cryptosporidiumspp. exist as multiple cell types which correspond to different stages in an infection (e.g., a sexual and asexual stage).[1] As anoocyst – a type of hardy, thick-walledspore – it can survive in the environment for months and is resistant to many common disinfectants, particularly chlorine-based disinfectants.[22][23] 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 1meronts [1] that contain 8 daughter cells.[24]
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,[25] which contain 4 Type II merozoites.[24] These merozoites get released and they attach to the epithelial cells. From there, they become either macrogamonts or microgamonts.[25] These are the female and male sexual forms, respectively.[24] This stage, when sexual forms arise, is called gametogony.[26]
Zygotes are formed bymicrogametes from the microgamont penetrating the macrogamonts. The zygotes develop into two types of oocysts.[25] 20% of oocysts have thin walls and so can reinfect the host by rupturing and releasing sporozoites that start the process over again.[24] The thick-walled oocysts are excreted into the environment.[25] The oocysts are mature and infective upon being excreted.[24]
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.[27]
As few as 2 to 10 oocysts can initiate an infection.[28] The parasite is located in the brush border of the epithelial cells of the small intestine.[29] They are mainly located in the jejunum. When the sporozoites attach to the epithelial cells' membrane envelops them. Thus, they are "intracellular but extracytoplasmic".[24] The parasite can cause damage to the microvilli where it attaches.[27] The infected human excretes the most oocysts during the first week.[24] Oocysts can be excreted for weeks after the diarrhea subsides from infections byC. parvum orC. hominis;[1] however, immunocompetent individuals withC. muris infections have been observed excreting oocysts for seven months.[30]
The immune system reduces the formation of Type 1 merozoites as well as the number of thin-walled oocysts.[24] This helps prevent autoinfection. B cells do not help with the initial response or the fight to eliminate the parasite.[28]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.[31][32]
There are many diagnostic tests forCryptosporidium. They include microscopy, staining, and detection ofantibodies.Microscopy[1] can help identify oocysts in fecal matter.[29] To increase the chance of finding the oocysts, the diagnostician should inspect at least 3 stool samples.[26] There are several techniques to concentrate either the stool sample or the oocysts. The modifiedformalin-ethyl acetate (FEA) concentration method concentrates the stool.[27] Both the modified zinc sulfate centrifugal flotation technique and the Sheather's sugar flotation procedure can concentrate the oocysts by causing them to float.[26] Another form of microscopy isfluorescent microscopy done by staining withauramine.[29]
Other staining techniques includeacid-fast staining,[28] which will stain the oocysts red.[27] One type of acid-fast stain is theKinyoun stain.[23]Giemsa staining can also be performed.[24] Part of the small intestine can be stained withhematoxylin andeosin (H & E), which will show oocysts attached to theepithelial cells.[27]
Detectingantigens is yet another way to diagnose the disease. This can be done withdirect fluorescent antibody (DFA) techniques.[1] It can also be achieved throughindirect immunofluorescence assay.[26]Enzyme-linked immunosorbent assay (ELISA) also detects antigens.[29]
Polymerase chain reaction (PCR) is another way to diagnose cryptosporidiosis. It can even identify the specific species ofCryptosporidium.[1] If the patient is thought to have biliary cryptosporidiosis, then an appropriate diagnostic technique isultrasonography. If that returns normal results, the next step would be to performendoscopic retrograde cholangiopancreatography.[28]
Manytreatment plants that take raw water fromrivers,lakes, andreservoirs for publicdrinking water production use conventional filtration technologies. This involves a series of processes, includingcoagulation,flocculation,sedimentation, andfiltration. Direct filtration, which is typically used to treat water with low particulate levels, includes coagulation and filtration, but not sedimentation. Other common filtration processes, includingslow sand filters,diatomaceous earth filters, and membranes will remove 99% ofCryptosporidium.[33] Membranes and bag and cartridge filters removeCryptosporidium product-specifically.[citation needed]
WhileCryptosporidium is highly resistant to chlorine disinfection,[34] with high enough concentrations and contact time,Cryptosporidium will be inactivated bychlorine dioxide and ozone treatment. The required levels of chlorine generally preclude the use of chlorine disinfection as a reliable method to controlCryptosporidium in drinking water. Ultraviolet light treatment at relatively low doses will inactivateCryptosporidium. Water Research Foundation-funded research originally discovered UV's efficacy in inactivatingCryptosporidium.[35][36]
One of the largest challenges in identifying outbreaks is the ability to identifyCryptosporidium in thelaboratory. Real-time monitoring technology is now able to detectCryptosporidium with online systems, unlike the spot and batch testing methods used in the past.[citation needed]
The most reliable way to decontaminate drinking water that may be contaminated byCryptosporidium is to boil it.[37][38]
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 theCenters for Disease Control and Prevention.[1] The best way to prevent getting and spreading cryptosporidiosis is to have good hygiene and sanitation.[26] An example would be hand-washing.[1] Prevention is through washing hands carefully after going to the bathroom or contactingstool, and before eating. People should avoid contact with animal feces.[29] They should also avoid possibly contaminated food and water.[1] In addition, people should refrain from engaging in sexual activities that can expose them to feces.[26]
Standard water filtration may not be enough to eliminateCryptosporidium; 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 (161 °F) for 15 seconds pasteurizes it and can destroy the oocysts' ability to infect.[39] 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 NSF InternationalNational Sanitation Foundation.[1] Bottled drinking water is less likely to containCryptosporidium, especially if the water is from an underground source.[39]
People with cryptosporidiosis should not swim in communal areas because the pathogen 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.[1] Immunocompromised people should take care to protect themselves from water in lakes and streams.[28] 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.[1]
The US CDC notes the recommendation of many public health departments to soak contaminated surfaces for 20 minutes with a 3%hydrogen peroxide[clarification needed] (99% kill rate) and then rinse them thoroughly, with the caveat that no disinfectant is guaranteed to be completely effective against Cryptosporidium. However, hydrogen peroxide is more effective than standard bleach solutions.[40]
Symptomatic treatment primarily involvesfluid rehydration,electrolyte replacement (sodium, potassium, bicarbonate, and glucose), andantimotility agents (e.g.,loperamide).[41][42] Supplemental zinc may improve symptoms,[41] particularly in recurrent or persistent infections or in others at risk forzinc deficiency.
Immunocompetent individuals with cryptosporidiosis typically experience a short (i.e., duration of less than 2 weeks) self-limiting course of diarrhea that may requiresymptomatic treatment and ends with spontaneous recovery; in some circumstances, antiparasitic medication may be required (e.g., recurrent, severe, or persistent symptoms);[11] however reinfection frequently occurs.[11]
As of 2015[update],nitazoxanide is the onlyantiparasitic drug treatment with proven efficacy for cryptosporidiosis in immunocompetent individuals;[11][41][42][43] however, it lacks efficacy in severelyimmunocompromised patients.[43] Certain agents such asparomomycin andazithromycin are sometimes used as well, but they only have partial efficacy.[41]
Inimmunocompromised individuals, such as AIDS patients, cryptosporidiosis resolves slowly or not at all. It frequently causes a particularly severe and persistent form of watery diarrhea coupled with a greatly decreased ability to absorb key nutrients through the intestinal tract. As a result, infected individuals may experience severe dehydration, electrolyte imbalances, malnutrition, wasting, and potentially death. In general, the mortality rate for infected AIDS patients is based onCD4+ marker counts. Patients with CD4+ counts over 180 cells/mm3 recover with supportive hospital care and medication; but, in patients with CD4+ counts below 50 cells/mm3, the effects are usually fatal within 3 to 6 months. During the1993 Milwaukee cryptosporidiosis outbreak (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.[44]
In individuals with HIV and cryptosporidiosis, theprimary treatment is the prompt initiation ofeffective antiretroviral therapy (ART) to restore immune function, typically using anintegrase strand transfer inhibitor (INSTI)–based regimen rather than older protease-inhibitor combinations (National Institutes of Health, 2025). Restoration of immune competence is the single most important factor in clearing infection.
Supportive care—including hydration, nutritional maintenance, and symptom control—is essential.Nitazoxanide may be considered as an adjunct, although itsbenefit in immunocompromised individuals remains limited, and clinical studies have shown reduced or absent efficacy in patients with advanced HIV (Centers for Disease Control and Prevention [CDC], 2025a). Evidence for other antiparasitic agents such asparomomycin orazithromycin is inconclusive; none have demonstrated consistent benefit in people with severe immune suppression (CDC, 2025b).
Older reviews, such as the Cochrane Collaboration analysis, noted potential activity of nitazoxanide primarily inimmunocompetent hosts and regarded its use in immunocompromised individuals asexperimental or adjunctive rather than standard therapy. Current guidelines emphasize thatimmune reconstitution through ART, not antiparasitic drug therapy, remains the cornerstone of management.
Recent evidence indicates that respiratory cryptosporidiosis may occur commonly in immunocompetent children with cryptosporidial diarrhea and unexplained cough. Findings from animal models, human case reports, and a few epidemiological studies suggest that Cryptosporidium may be transmitted via respiratory secretions, in addition to the more recognized fecal-oral route. ... Upper respiratory cryptosporidiosis may cause inflammation of the nasal mucosa, sinuses, larynx, and trachea, accompanied by nasal discharge and voice change (54, 61, 62). Cryptosporidiosis of the lower respiratory tract typically results in productive cough, dyspnea, fever, and hypoxemia (63,–66). ... While fecal-oral transmission is indisputably the major route of infection, transmission via coughing and fomites is also possible in situations of close contact (20). ... Because they lacked gastrointestinal symptoms and oocyst excretion, the latter cases establish the possibility of primary respiratory infection with Cryptosporidium, which may have been acquired by inhalation of expectorated droplets or by contact with fomites. ... This finding suggests that respiratory cryptosporidiosis may occur commonly in immunocompetent individuals.
After an incubation period of 5–10 days (range 2–28 days), an infected individual develops watery diarrhea ... fever may be low grade or nonexistent; ... Diarrhea, with or without crampy abdominal pain, may be intermittent and scant or continuous, watery, and copious; sometimes, the diarrhea is mucoid. ... Biliary tract involvement is seen in persons with AIDS who have very low CD4 cell counts and is common in children with X-linked immunodeficiency with hyper–immunoglobulin M (IgM). ... Other signs related to GI illness include right upper-quadrant or epigastric tenderness, icterus, and, rarely, ascites related to pancreatic involvement. Reactive arthritis that affects the hands, knees, ankles, and feet has been described.
Healthcare professionals might consider re-testing stool at least 1 week after the last dose of nitazoxanide only if symptoms do not resolve. In such cases, longer courses of treatment might be needed. Persistent symptoms may also represent re-infection
All 58 patients reported resolution of diarrhoea after 7 days of treatment with nitazoxanide. However, 40 (70.1%) patients reported recurrence of diarrhoea within 6 weeks of treatment. ... Our study demonstrates a high prevalence of cryptosporidiosis in immunocompetent adult patients. Nitazoxanide is the recommended antimicrobial drug for cryptosporidiosis. ... The frequency of cryptosporidiosis has not been well-defined. About 30% of the adult population of the United States is seropositive, with over 10,500 cases reported in 2008. ... Although we gave 7 days of therapy, and a satisfactory treatment response was obtained in the short term, there was a high recurrence rate.21 Paromomycin and/or azithromycin in combination with nitazoxanide have been tested in double blind randomized trials for the treatment of cryptosporidiosis in immunocompromised patients, such as those with HIV/AIDS, and the results have been encouraging.18,22,23
Trial subscription required to access
C. muris-infected subjects shed oocysts longer than occurred with other species studied in healthy volunteers. Three volunteers shed oocysts for 7 months. ... Thus, healthy adults are susceptible to C. muris, which can cause mild diarrhea and result in persistent, asymptomatic infection.
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] ... Use of partially active antiparasitic drugs (eg, nitazoxanide or paromomycin combined with azithromycin) should be considered along with initiating antiretroviral therapy. ... 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.
The results indicate that nitazoxanide reduces the load of parasites and may be useful in immunocompetent individuals. Due to the seriousness of the potential outcomes of cryptosporidiosis, the use of nitazoxanide should be considered in immunocompromised patients. The absence of effective therapy highlights the need to ensure that infection is avoided. ... For HIV-infected persons, highly active antiretroviral therapy (HAART) is the mainstay of preventing and managing cryptosporidiosis. HAART can lead to complete resolution of clinical symptoms and oocysts (Grube 1997; Maggi 2000; Miao 2000). This intervention is not available for HIV patients who are failing HAART or those unable to access HAART in developing countries. Among these immunocompromised persons without the option of an effective treatment for the underlying disease, supportive management, including rehydration therapy, electrolyte replacement, and anti-motility agents, will remain the only alternatives for care until better drugs emerge.
Currently, research is being done in molecular-basedimmunotherapy. For example, synthetic isoflavone derivatives have been shown to fight offCryptosporidium parvum bothin vitro and in animal studies.[1] Derivates of nitazoxanide, known asthiazolides, have also shown promising resultsin vitro.[2] rifaximin is also sometimes used for immunocompromised patients/patients with severe disease.
Cryptosporidiosis is found worldwide. It causes 50.8% of water-borne diseases that are attributed to parasites.[3] In developing countries, 8–19% of diarrheal diseases can be attributed toCryptosporidium.[4] Ten percent 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.[5][6]
In Eastern Europe, cryptosporidiosis in humans and animals is common, but there are considerable gaps in surveillance and a lack of comparable methods, which limit the understanding of the disease and the detection of outbreaks. Research shows a rich diversity of zoonotic subtypes of the parasite in animals, indicating a rich potential of animal-to-human transmission.[7][8]
Roughly 30% of adults in the United States areseropositive for cryptosporidiosis, meaning that they contracted the infection at some point in their lives.[9]
A recombinantCryptosporidium parvumoocyst surface protein (rCP15/60) vaccine has produced an antibody response in a large group of cows and also an antibody response in calves fed rCP15/60-immunecolostrum produced by these vaccinated cows. This is very promising. HumanCryptosporidium parvum infections are particularly prevalent and often fatal in infants in developing countries and toimmunocompromised people, such as AIDS patients. There is no commercially available effective vaccine againstCryptosporidium parvum, although passive immunization utilizing different zoite surface (glyco)proteins has shown promise. Developmental stages of the life cycle of the parasite might act as possible targets for vaccine development. The organism is detected in 65–97% of thesurface-water supply in the United States and is resistant to most disinfectants used for the treatment of drinking water.Antibodies in the serum of humans and animals infected withCryptosporidium parvum react with several antigens, one of which is a 15 kDaTooltip kilodalton protein (CP15) located on the surface of the organism. This protein is a good candidate for use as a molecular vaccine because previous studies have shown that amonoclonal antibody to CP15 conferspassive immunity to mice. Currently, there is no vaccine or completely effective drug therapy againstCryptosporidium parvum in HIV/AIDS individuals.[10][11]
A summary of discoveries presented at the most recent (June 2019) international symposium onCryptosporidium has been published in 2020.[12]
The most importantzoonotic reservoirs arecattle,[13]sheep andgoats. In addition, in recent years, cryptosporidiosis has plagued many commercialleopard 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.[citation needed]
gideon was invoked but never defined (see thehelp page).ChenW was invoked but never defined (see thehelp page).pmid25252476 was invoked but never defined (see thehelp page).MS Crypto treatment was invoked but never defined (see thehelp page).Cochrane immunocompromised was invoked but never defined (see thehelp page).
