Cryptosporidium Species

The Pathogen

Organisms of the genus Cryptosporidium are 2- to 6-μm coccidian parasites that infect the epithelial cells lining the digestive and respiratory tracts of vertebrates, including fish, birds, reptiles, and mammals as well as humans. The organism lacks host specificity; however, most human infections are caused by Cryptosporidium hominis or C. parvum . The life cycle of Cryptosporidium is similar to that of other true coccidia that infect mammals. Infectious oocysts excyst within the lumen of the intestine and release sporozoites. The released sporozoites penetrate host cells, where they develop into trophozoites. Trophozoites can undergo asexual division, resulting in autoinfection in adjacent cells, or undergo sexual reproduction, resulting in the formation of oocysts. After fertilization of gametes, a thick-walled oocyst is formed. The oocysts of Cryptosporidium undergo sporogony within the host cells and are infectious when released in feces.

Epidemiology

Oocysts of Cryptosporidium withstand adverse environmental conditions and can survive for long periods if stored moist and cold. Oocysts are resistant to common disinfectants, including disinfectants recommended for hospital use. One study found that ammonia concentrations of >50% and formalin concentrations of ≥10% were necessary to kill the organism.

Infection occurs after ingestion or, possibly, inhalation of infectious spores. In healthy adult volunteers with no serologic evidence of past infection with C. parvum, the median infective dose was 132 oocysts. Spread to humans occurs through person-to-person transmission, contact with contaminated objects or surfaces, and from ingestion of environmentally contaminated water or contaminated food. ^, During 2009–2017, the number of reported outbreaks in the US has increased an average of approximately 13% per year. Leading causes include: swallowing contaminated water in pools or water playgrounds, contact with infected cattle, and contact with infected persons in childcare settings. Cryptosporidium also causes traveler’s diarrhea. Person-to-person sexual transmission also is reported among men who have sex with men. In the US, reported cases of cryptosporidiosis are highest among young children (ages 1–4 years) with an estimated incidence rate of 6.6 per 100,000 population during 2011–2012. Symptoms peak in the summer and early fall (June through October), coinciding with the summer recreational water season. ^,

Zoonotic transmission from calves has been well documented, and other animals such as rodents, puppies, and kittens probably also serve as reservoir hosts. ^, Zoonotic transmission occurs in people living and working in close association with animals and is most often caused by C. parvum . A recent review of the waterborne parasitic outbreaks reported worldwide between 2004 and 2010 found that Cryptosporidium spp. were the etiologic agent in 60% of the outbreaks.

Outbreaks of cryptosporidial infection have been associated with contaminated community water supplies in several US states and the UK. ^, In 1993 a waterborne outbreak in Milwaukee, Wisconsin caused approximately 400,000 cases of diarrhea. Consumption of untreated surface water or inadequate water filtration has occurred in some waterborne outbreaks. Swimming pool water and water from decorative fountains have been linked to outbreaks. An accidental fecal spillage into a community swimming pool resulted in 44 persons contracting diarrhea in one outbreak. Attack rates in different groups of swimmers ranged from 47%–100% of exposed group members, with the highest rate in people with prolonged water exposure. Waste water in the form of raw sewage and runoff from dairies and grazing lands can contaminate drinking and recreational water. ^, Molecular techniques allow specific linkages of outbreaks of Cryptosporidium disease to human versus animal contamination of water.

Cryptosporidiosis is associated with diarrheal illness worldwide but is more prevalent in resource-poor countries and in children aged <2 years. ^{, ,} Surveys of selected populations have shown that infection rates in resource-rich countries range from 0.6%–20% compared with rates as high as 32% in resource-poor countries. ^, Seroprevalence studies confirm that cryptosporidiosis is more common in resource-poor countries. In Europe and North America, approximately 25%–35% of people have antibodies against Cryptosporidium, compared with 64% in Peru and Venezuela. Increased infection rate probably is due to poor sanitation, lack of clean water, crowded living conditions, and close association with animals.

Clinical Manifestations

Cryptosporidiosis is characterized by profuse watery diarrhea that can contain mucus but rarely contains white or red blood cells. Fifty percent of affected people have crampy abdominal pain, nausea, and vomiting. Nonspecific symptoms such as myalgia, fatigue, weakness, headache, anorexia, weight loss, and low-grade fever also may occur, as well as asymptomatic infection. ^{, , ,} Severity of symptoms correlates with density of oocyst shedding, which can be intermittent. Symptoms may vary based on the species of infecting Cryptosporidium . Malabsorption, lactose intolerance, dehydration, and malnutrition often occur in severe cases. Radiographic findings are nonspecific and include prominent mucosal folds and thickening of intestinal walls.

The incubation period is 2–10 days (average 7 days). Infection can be asymptomatic, self-limited, or protracted, with severity linked to immunosuppression. Most immunocompetent hosts have a self-limited diarrheal illness that usually resolves within 7–14 days, although diarrhea can persist for as long as 5 weeks. Oocyst shedding can continue for up to 2 weeks after clinical improvement. Prolonged, debilitating disease can occur in immunocompromised hosts, including people with HIV infection, malignancy, CD40 ligand deficiency, severe combined immunodeficiency syndrome, other T-lymphocyte abnormalities, or selective immunoglobulin A deficiency, and in solid-organ or stem cell transplant recipients, patients with end-stage renal disease undergoing hemodialysis, or people who are undernourished. ^,

Biliary tract disease is well documented in immunocompromised hosts and is characterized by fever, right upper quadrant pain, nausea, vomiting, and diarrhea. Jaundice and elevated serum levels of alkaline phosphatase, γ-glutamyltranspeptidase, and bilirubin can occur. The gallbladder can appear dilated and thick-walled on radiography and ultrasonography. If stenosis of the common bile duct occurs, the extrahepatic ducts usually are dilated. Approximately 15% of patients with AIDS who have cryptosporidiosis have biliary tract involvement. Cryptosporidium also has been detected in the pancreatic duct of a child with AIDS and has been associated with pancreatitis and sclerosing cholangitis in an immunocompetent host. ^{, , , ,}

Cryptosporidium has been detected in people with respiratory tract symptoms, including cough, shortness of breath, wheezing, croup, and hoarseness. These symptoms can occur with or without diarrhea. Oocysts have been identified in sputum and bronchoalveolar lavage specimens. However, not all of these respiratory tract symptoms can be attributed to cryptosporidiosis because other pathogens often are present, especially in HIV-infected patients. Further study of respiratory tract disease, including the potential for airborne spread of the organism, is warranted. ^{, ,}

Laboratory Diagnosis

Most clinical laboratories use enzyme immunoassays or immunofluorescence assays to detect Cryptosporidium antigens in stool specimens. Polymerase chain reaction (PCR) analysis also has been reported to have an increased sensitivity over light microscopy and is now considered the diagnostic method of choice. In addition, PCR may be beneficial as an epidemiologic tool.

The definitive diagnosis of cryptosporidial infection relies on identifying oocysts in feces or body fluids or along the epithelial surface of biopsy tissue ( Fig. 261.1 ). On sections stained with hematoxylin and eosin, oocysts appear as small, spherical, basophilic bodies located along the microvilli of the epithelium lining of the gastrointestinal tract. Because not all areas of the intestinal tract may be affected, sampling errors can occur. An indirect immunofluorescence assay can be used to detect oocysts in embedded tissue. Histologic sections reveal villous atrophy and blunting, epithelial flattening, and inflammation of the lamina propria.

Fresh stool specimens should be placed in a fixative before submission to the laboratory to prevent infection of laboratory workers. At least three specimens should be examined in immunocompetent hosts and two specimens in immunocompromised hosts. Serodiagnostic assays are available for epidemiologic study; however, the role of serodiagnosis in acute diarrheal disease is undefined.