- Author: Miguel M Cabada, MD, MSc; Chief Editor: Michael Stuart Bronze, MD more...
Human cryptosporidiosis is caused by infection with apicomplexan protozoans of the genus Cryptosporidium. Human illness was formerly thought to be caused by a single species, but molecular studies have demonstrated that it is caused by at least 15 different species. Among the more common species are Cryptosporidium hominis, for which humans are the only natural host, and C parvum, which infects bovines as well as humans.[1, 2, 3] (See Etiology and Pathophysiology.)
Cryptosporidiosis mainly affects children. It causes a self-limited diarrheal illness in healthy individuals. Cryptosporidiosis is also recognized as a cause of prolonged and persistent diarrhea in children and of severe, prolonged diarrhea in persons with acquired immunodeficiency syndrome (AIDS). (See Prognosis and Presentation.)
Outbreaks of cryptosporidiosis should be detected by vigilant observation for increased case numbers at primary and public health care levels. (See Epidemiology, Workup, and Treatment.)
The genus Cryptosporidium consists of a group of protozoan parasites within the protist subphylum Apicomplexa. There are more than 26 known Cryptosporidium species, as recognized by host specificity, morphology, and molecular biology studies. Besides humans, the parasite can infect many other species of animals, such as mammals, birds, and reptiles, and is pathogenic to immunocompetent and immunocompromised hosts (see the image below). (See Etiology.)
See Common Intestinal Parasites, a Critical Images slideshow, to help make an accurate diagnosis.
Cryptosporidium species are able to infect and reproduce in the epithelial cell lining of the GI and respiratory tracts without causing cytopathic effects.[1, 2, 3] C hominis and C parvum cause most human infections. In immunocompetent individuals, the organisms are primarily localized to the distal small intestines, whereas in immunocompromised hosts, the parasites have been identified throughout the gut, biliary tract, and respiratory tract. (See Etiology and Pathophysiology.)
Children with persistent cryptosporidiosis may have villous atrophy; in children with heavier infections, crypt hyperplasia and lymphocyte infiltration are also seen.
The disease is transmitted via the fecal-oral route from infected hosts. Most sporadic infections occur through person-to-person contact. Nonetheless, transmission can also occur following animal contact, ingestion of water (mainly during swimming), or through food. Extensive waterborne outbreaks have resulted from contamination of municipal water and recreational waters (eg, swimming pools, ponds, lakes).[4, 5, 6]
Animal contact can also be associated with transmission of zoonotic species. (See Etiology and Treatment.)
Cryptosporidium has emerged as the most frequently recognized cause of recreational water–associated outbreaks of gastroenteritis, particularly in treated (disinfected) venues. This is because in the oocyst stage of its life cycle, Cryptosporidium can resist disinfection, including chlorination, and can survive for a prolonged period in the environment.
Cryptosporidium does not multiply outside of the host.[1, 2, 3] Cryptosporidium can complete its life cycle within a single host, including its asexual (merogony) and sexual (sporogony) reproductive cycles. Infection is initiated by ingestion of oocysts, which are activated in the stomach and upper intestines to release 4 infective sporozoites (see the first image below). These motile sporozoites bind to the receptors on the surface of the intestinal epithelial cells (see the second image below) and are ingested into a parasitophorous vacuole near the surface of the epithelial cell, separated from the cytoplasm by a dense layer.
Once inside the epithelial cell, the parasite goes through a series of sexual and asexual multiplication steps leading to the production of oocysts. Two morphologic forms of the oocysts have been described: thin-walled oocysts (asexual stage) excyst within the same host (causing self-infection), whereas the thick-walled oocysts (sexual stage) are shed into the environment. Oocyst shedding can continue for weeks after a patient experiences clinical improvement.
Etiology and Pathophysiology
Cryptosporidium oocysts are highly infectious, requiring only 101 -103 oocysts to cause human disease (50% infectious dose, 102). The oocysts are infectious immediately after excretion, and the life cycle of the parasite produces forms that reinvade the intestine. The location of the parasite in the intestine is intracellular but extracytoplasmic, which may contribute to the marked resistance of Cryptosporidium species to treatment. Large numbers of oocysts are excreted and are resistant to harsh conditions, including chlorine at levels usually applied in water treatment.
Cryptosporidiosis typically presents with watery diarrhea. The mechanism by which Cryptosporidium causes diarrhea includes a combination of increased intestinal permeability, chloride secretion, and malabsorption, which are all thought to be caused by the host response to infection. In immunocompetent persons, the infection is usually limited to the small intestine. In persons with AIDS or certain congenital immunodeficiencies, the biliary tract may be involved.
Although healthy individuals can become ill from exposure to Cryptosporidium, immunodeficiency places an individual at increased risk for cryptosporidiosis, particularly for more severe and disseminated disease.
Immunodeficiency may be congenital or may be secondary to HIV infection, malnutrition, cancer chemotherapy, diabetes mellitus, or bone marrow or solid organ transplantation.
The following people have greater exposure to contaminated materials and are at more risk for infection.[1, 2, 3, 4, 5, 6]
Children who attend day care centers - Daycare center-related outbreaks have a high infection rate (30-60%).
Child care workers
Parents of infected children
International travelers, including backpackers and hikers who drink unfiltered, untreated water
Swimmers who swallow contaminated recreational water
People who handle infected animals
People exposed to human feces through sexual contact
Hospital-associated infection in patients and health-care providers has also been reported. Pregnancy is another predisposing factor for cryptosporidiosis.
In developing nations, the prevalence of Cryptosporidium infection is significantly higher than in industrialized countries because of a lack of clean water and sanitary facilities, crowding, and animal reservoirs in close proximity to residences.
Occurrence in the United States
The frequency of cryptosporidiosis has not been well-defined in the United States. Most laboratories do not routinely test for Cryptosporidium. Laboratories that test for Cryptosporidium often use poorly sensitive tests.[1, 2]
The number of reported cases has increased with increased awareness and improved diagnostic testing. From 2006-2010, the rate was between 2.3 and 3.9 cases per 100,000 population, with the highest rate recorded in 2007. There were a total of 8,008 cases of cryptosporidiosis reported in 2012, with the rate that year reaching 3 cases per 100,000 population. However, estimates suggest that the frequency of infection is likely to be 100-fold higher than the number of reported cases.
Studies in the United States have documented cryptosporidiosis in about 4% of stools sent for parasitologic examination. Seroprevalence studies using antibody assays suggest that 25-35% of the population in industrialized countries (including the United States) have had cryptosporidiosis at some time in their life.
Cryptosporidium species also cause waterborne outbreaks of diarrhea. In 1993, more than 400,000 cases of diarrheal illness due to Cryptosporidium infection were reported in Milwaukee, Wisconsin. Waterborne outbreaks continue to be common worldwide.
Cryptosporidium parasites are ubiquitous, except in Antarctica, and infection is more common in warm, moist months. In the United States, incidence peaks from July through September. Wastewater sources, such as raw sewage and runoff from dairies and grazing fields, contaminate water sources. Outbreaks in daycare centers with incidence rates of 30-60% have been reported.
Prior to the availability of combination antiretroviral therapy, approximately 10-15% of patients with AIDS developed cryptosporidiosis over their lifetime. As with other opportunistic infections, the prevalence of cryptosporidiosis in AIDS patients has dropped dramatically.
Prevalence rates reported in large-scale surveys of fecal oocyst excretion generally range from 1-3% in developed countries in Europe and North America. Children, especially those younger than 2 years, appear to have a higher prevalence of infection than do adults.[1, 2, 3, 4, 5, 6]
Cryptosporidiosis is a notifiable disease at the European Union level, and surveillance data are collected through the European Basic Surveillance Network.[10, 11] The crude incidence rate was similar to that in the United States, although considerable differences in the rates of cryptosporidiosis between countries were observed.[6, 10, 11] A pronounced seasonal peak was observed in the autumn season, with 59% of cases reported between August and November. However, Ireland and Spain experienced a peak in spring and summer, respectively. Routine cryptosporidiosis surveillance in northwest England over 17 years revealed that cases predominantly occurred in spring and autumn. There, most infections are caused by C hominis, while C parvum is associated with rural areas and animal contact.
In August 2012, an unexpectedly large increase in Cryptosporidium infections occurred in the Netherlands, Germany, England, Wales, and Scotland. In the Netherlands, for instance, 8 medical microbiology laboratories reported the detection of 524 Cryptosporidium -positive fecal samples for weeks 31-42 of that year, compared with 115 in 2010. Reasons behind the increases in these countries were uncertain.
In developing countries, cryptosporidiosis causes approximately 10-15% of cases of acute diarrheal illness. Rates are often higher when molecular tests such as polymerase chain reaction (PCR) are used.[13, 14] In addition, investigations using PCR assays have found Cryptosporidium species in 6% of American travelers to Mexico.
In developing countries, most people are infected as children. For example, studies in Brazil documented an infection rate of 90% for children younger than 5 years who were living in slums.
In persons with AIDS, cryptosporidiosis is more common in developing countries, ranging from 12-48% of persons with AIDS who have diarrhea.[1, 16, 17, 18]
The peak incidence of cryptosporidiosis is in children younger than 5 years. Infection is infrequently diagnosed in immunocompetent adults in developing countries.[1, 2, 3, 4, 5, 6] A second peak includes women of childbearing age (likely due to contact with infected children). Cryptosporidiosis can occur in persons with AIDS of any age.
Children younger than 2 years may be more susceptible to infection, possibly because of increased fecal-oral transmission in this age group and because of a lack of protective immunity. Waterborne epidemics in industrialized countries affect all ages.
In most healthy individuals, Cryptosporidium -induced diarrhea is usually self-limited. However, diarrhea is often prolonged (>1 week) or persistent (>2 weeks). In patients who are severely immunocompromised, cryptosporidiosis may be chronic, severe, sometimes fatal, and with extraintestinal manifestations.
Individuals with AIDS and cryptosporidiosis tend to develop chronic symptoms more often and about 10% have a fulminant course.[1, 15] Antiretroviral treatment improves outcome.
Immunocompetent children infected with Cryptosporidium generally do well. However, persistent abdominal pain, loose stools, and extraintestinal sequelae (eg, joint pain, eye pain, headache, dizzy spells, fatigue) have been reported, especially with C hominis infection.
Morbidity and Mortality
Complications of cryptosporidiosis include the following:
Cryptosporidiosis is an important cause of persistent diarrhea in developing countries; children with persistent diarrhea develop worsening malnutrition, which may result in cognitive and fitness problems that persist for years [19, 20]
Sclerosing cholangitis, acalculous cholecystis, papillary stenosis, and pancreatitis may develop with biliary involvement in immune-compromised subjects
Respiratory track involvement has been described both in AIDS patients and in otherwise-healthy children with intestinal cryptosporidiosis
Chronic cryptosporidiosis may be complicated by malabsorption, malnutrition, and death in individuals with AIDS and in malnourished children 
Thorough hand washing should be practiced by patients with diarrhea to avoid the spread of the disease. The effectiveness of alcohol-based hand sanitizers has not been well studied and their use should not be recommended.
Subjects with diarrhea should avoid using public swimming pools during their illness and at least 2 weeks after diarrhea has subsided.
Encourage immunocompromised patients to consider using 1-μm water filters when drinking tap water. Also consider boiled or bottled drinking water for patients who are immunocompromised, particularly those with HIV who have fewer than 200 CD4 cells/µL. Persons living in countries with a high risk of transmission should also be encouraged to use bottled or filtered water.
Instruct immunocompromised patients to avoid newborn animals (eg, calves, lambs), including domestic animals, and people with diarrhea. They should also consider avoiding communal swimming pools. New pets for patients with AIDS should be older than 6 months and should not have diarrhea.
Instruct patients with AIDS, daycare workers, food handlers, and healthcare workers to avoid fecal-oral spread by wearing gloves and washing their hands after contact with human feces. Spread can occur after activities such as changing diapers.
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