Cryptosporidium Case Study Cryptosporidium is reported as a "coccidian protozoan parasite" and one that has received a great deal of attention over the past two decades as a "clinically important human pathogen." (Hannahs, nd, p.1) The discovery of Cryptosporidium is reported as associated with E.E. Tyzzer who described a "cell-associated organism in the gastric mucosa of mice" in 1907 as reported in the work of Keusch et al. (1995). (Hannahs, nd, p.1) Cryptosporidium was believed for several decades to be a "rare, opportunistic animal pathogen." (Hannahs, nd, p.1)

The first case of human cryptosporidiosis occurred in a three-year-old girl in rural Tennessee in 1976 suffering from severe gastroenteritis for two weeks and reported in the work of Flanigan and Soave (1993). Cryptosporidium parvum was discovered through use of an electronic microscopic examination of the intestinal mucosa. Cryptosporidium parvus was associated with AIDS cases in the 1980s and this resulted in renewed attention of this infection as a "ubiquitous human pathogen." (Hannahs, nd, p.1)

Cryptosporidium oocysts is an infection that is water-borne and is often contracted in drinking water, which has placed further emphasis on this particular infection. There is not much known about the pathogenesis of the parasite and to date there is not a safe or effective treatment established for combating cryptosporidiosis. Cryptosporidium is unlike other intestinal pathogens in that it can infect several different hosts and has the capacity to survive most environments for long periods of time reported to be due to its "hardy cyst" (Keusch, et al., 1995 in: Hannahs, nd, p.1) This parasite inhabits all climates and locales as well. (Hannahs, nd, p.1) The following illustration shows a duodenal biopsy sample taken from an AIDS patient who has cryptosporidiosis.

Figure 1

Duodenal Biopsy Sample From AIDS Patient with Cryptosporidiosis

Source: Hannahs (nd)

The arrow indicates the parasites in the microvillus border.

I. Life Cycle of Cryptosporidium

The taxonomical classification of Cryptosporidium is as a Sporozoa because its oocyst is known to release four sporozoites, which are its motile infectious agents upon excystation. The life cycle of Cryptosporidium is complex in nature as there are both sexual and asexual cycles and six developmental stages of a distinct nature are noted in the work of Keusch et al. (1995) as follows:

(1) Stage one: excystation of the orally ingested oocyst in the small bowel with release of the four sporozoites;

(2) Stage two: invasion of intestinal epithelial cells via the differentiated apical end of the sporozoite within a vacuole formed of both host and parasite membranes and the initiation of the asexual intracellular multiplication stage;

(3) Stage three -- differentiation of microgametes and macrogametes;

(4) Stage Four -- fertilization that initiates sexual replication;

(5) Stage Five -- development of oocysts;

(6) Stage Six -- Formation of new, infectious sporozoites within the oocyst, which is then excreted in the stool. (Hannahs, nd, p.1)

This cycle is such that starts all over when the oocysts are ingested by a new host. The following figure illustrates the Cryptosporidium life cycle as noted in Hayworth (1992).

Figure 2

Cryptosporidium Life Cycle

Source: Hannahs (nd)

II. Clinical manifestations

There is a wide range of variation in the symptoms of cryptosporidiosis in individuals who are immunocompetent and immunocompromised in that cryptosporidiosis in the immunocompetent patients involves "an acute, yet self-limiting diarrheal illness lasting one to two weeks in during with symptoms including frequent and watery diarrhea, nausea, vomiting, abdominal cramps, and a low-grade fever. For the individual who is immunocompromised the illness is much more severe and involves cholera type diarrhea, severe cramps in the abdominal area, malaise, a low-grade fever accompanied by weight loss and anorexia. This infection is also indicated as responsible for thickening of the gallbladder wall and known to infection the individual's respiratory system. (Hannahs, nd, paraphrased)

III. Epidemiology of Cryptosporidium

The Cryptosporidiosis infection has been reported in six continents and known to infection individuals from three days of age to 95 years of age with transmission generally being through feces or oral transmission and many times through livestock mammal feces contaminating water sources. The most likely individuals to be infected by this parasitic infection are infants and younger children who attend daycare centers, individuals with unfiltered and untreated drinking water, individuals involved in farming operations and specifically those delivering lambs, calves and who spread muck, individuals who practice sex that bring the person in contact with the feces of another individual infected with Cryptosporidium, patients in a healthcare setting with other infected patients as well as healthcare workers in this setting, veterinarians who attend farm animals, travelers to areas where water is untreated, individuals living in urban...

(Hannahs, nd, paraphrased)
IV. Transmission of Cryptosporidial Infection

The Cryptosporidial infection is transmitted from food and water that has been contaminated by feces and also from contact with animals or other individuals who have this infection. Only a small amount of contamination is needed for transmission of this infection. Avoiding contracting this infection makes a requirement of the following as stated by the Mayo Clinic:

(1) Wash hands thoroughly with soap and water (and supervise children's handwashing) after using the toilet or changing diapers, after handling animals or cleaning up feces, after working in soil or touching any objects such as shoes that may have been contaminated with fecal matter, and before preparing, serving, or eating food;

(2) Avoid drinking untreated water from lakes, streams, and other surface water bodies;

(3) Because of possible contamination with manure, peel or rinse fruits or vegetables to be eaten raw;

(4) Take extra care in selecting food and drink when traveling to places with poor sanitation;

(5) Follow any water advisory issued by local health departments, state authorities, or the National Centers for Disease Control and Prevention;

(6) To treat contaminated water before drinking it, bring it to it a rolling boil for at least one minute to kill oocysts or remove them with a filter with an absolute pore size of one micron or smaller. (Mayo Clinic, 2012, p.1)

V. Pathogenesis

Four sporozoites are released upon oocyst excystation and these are reported to "adhere their apical ends to the surface of the intestinal mucosa." (Hannahs, nd, p.1) The following illustrates a phase contrast photograph of the sporozoite release form the Cryptosporidium oocyst which has been adapted from the work of Flanigan and Soave (1993) and Hannahs (nd).

Figure 3

The agent of attachment to the intestinal surface has been identified as A sporozoite-specific lectin adherence factor. Following attachment, Hannahs (nd) reports that it has been "…hypothesized that the epithelial mucosa cells release cytokines that activate resident phagocytes" as cited in the work of Goodgame (1996). It is reported that thee activated cells "… release soluble factors that increase intestinal secretion of water and chloride and also inhibit absorption. These soluble factors include histamine, serotonin, adenosine, prostaglandins, leukotrienes, and platelet-activating factor, and they act on various substrates, including enteric nerves and on the epithelial cells themselves" again as cited in the work of Goodgame (1996) and reported in the work of Hannahs (nd). The result is that there is damage to epithelial cells in one of two ways as follows:

(1) Cell death is a direct result of parasite invasion, multiplication, and extrusion or (2) Cell damage could occur through T cell-mediated inflammation, producing villus atrophy and crypt hyperplasia. (Hannahs, nd, p.1)

Either method of damage is due to "…distortion of villus architecture and is accompanied by nutrient malabsorption and diarrhea" according to Goodgame (1996). (Hannahs, nd, p.1) Evidence derived from experiments supports this pathogenic hypothesis and specifically as reported in a pig model system in which "… decreased intestinal sodium absorption has been correlated with "both decreased villus surface area and inhibition by prostaglandin E2 produced by inflammatory cells" as reported by Goodgame (1996) and cited in the work of Hannahs (nd, p.1)

V. Detection and Diagnosis

Detection of C. parvum was initially accomplished through biopsy of intestinal tissue as reported in the work of Keusch et al. (1995). This method of testing however renders false positives since the intestinal parasitic infection is known to be somewhat patchy as noted by Flanigan and Soave (1993). The next method used was staining to detect the oocysts directly from the individual's samples of stool. However, the identified best method for use is that of the "modified acid-fast stain" as it is most reliable in detection of cryptosporidial oocysts. (Hannahs, nd, p.1) Hannahs (nd) states that anti -- cryptosporidial IgM, IgG, and IgA can be "immunologically…detected by the enzyme-linked immunoabsorbent assay (ELISA) or by the antibody immunofluorescence assay (IFA), but neither of these assays can provide a direct diagnosis of cryptosporidiosis.

Recently, new genetic methods of detecting C. parvum have been developed, using PCR (Polymerase Chain Reaction) or other DNA-based detection methods." (p.1)

VI. Treatment

While there is no effective treatment for patients with cryptosporidiosis, antiparasitic therapy is reported to be combined with symptomatic treatment which includes nutritional therapy for avoidance of fatal malnutrition. (Medscape, 2011, p.1) Patients with acalculous cholecystitis are reported as generally being treated by cholecystectomy. (Medscape, 2011, p.1) Nitazoxanide is reported to shorten the duration of diarrhea significantly and to decrease the "risk of mortality in…