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 areas that are densely populated, and in rare cases, owners of pets which have become infected with Cryptosporidium. (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 “immunologicallydetected 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 malnourished children.” (Medscape, 2011, p.1) It is reported that research trials have demonstrated the efficacy of using Nitazoxanide in adults as well. (Medscape, 2011, p.1) The report states that in earlier studies with antiparasitic drugs in patients with AIDS and cryptosporidiosis, that the results were a disappointment. Reported as well is:
“Nitazoxanide, paromomycin, and azithromycin are partially active. Combination antiretroviral therapy that includes an HIV protease inhibitor is associated with dramatic improvement in many cases. Improvement is likely to result from immune reconstitution but may in part reflect the antiparasitic activity of the protease inhibitors. Nucleoside antiretroviral drugs are malabsorbed in chronic cryptosporidiosis. For that reason, the use of partially active antiparasitic drugs (eg, nitazoxanide or paromomycin combined with azithromycin) should be considered prior to initiating antiretroviral therapy.” (Medscape, 2011, p.1)
It is reported that in patients with AIDS “cryptosporidiosis usually cannot be eradicated prior to restoration of the CD4 cell count in response to combination antiretroviral therapy. During early immune reconstitution, patients should generally continue antiparasitic therapy (such as nitazoxanide or paromomycin) and antimotility agents, as needed.” (Medscape, 2011, p.1) Symptomatic therapy is reported to include fluid replacement, appropriate nutrition provision, and antimotility agent treatment. It is reported that Loperamide or diphenoxylate-atropine is helpful in some cases and that the more potent opiates including “anhydrous morphine (Paregoric)” are effective in cases that do not respond to milder agents.
Dietary lactose should be avoided by patients. Attention to the nutrition of the patient’s care is critical since malnutrition can result in death. Stated is that enteral nutrition is generally found to be sufficient. Avoidance of infection involves purification of drinking water by filtration accomplished through use of a 1-um water filter when drinking tap water. AIDS patients should drink filtered water only and water in countries with a high transmission risk should boil all drinking water.
Avoidance of newborn animals including those which are domestic animals is important and in those with AIDS no animal younger than six months in age should be considered. Healthcare workers, childcare workers, food handlers and patients who are health compromised should wear gloves and wash their hands after potential contact with animal or human feces including changing of diapers.
In the event this infection is contracted the individual should consult the following specialists:
(1) Infectious disease specialist – For consideration of antiparasitic and antiretroviral therapy;
(2) Gastroenterologist – For ERCP and sphincterotomy; endoscopy sometimes required for diagnosis;
(3) General surgeon – For suspected acalculous cholecystitis; and (4) Studies of healthy hosts and malnourished children have demonstrated the importance of nitazoxanide treatment. (Medscape, 2011, p.1)
Since the advent of combination antiretroviral therapy, cryptosporidiosis is much less common in persons with AIDS. Patients not receiving combination antiretroviral therapy need to be stabilized with the drugs described below before starting HIV treatment. Antiparasitic drugs are geared toward treatment of diarrhea by “a direct anticryptosporidial effect, but maintenance treatment is often required. Antimotility agents are administered to relieve symptoms and to increase exposure to the antiparasitic and antiretroviral agents. Somatostatin analogues are partially beneficial for reducing secretory diarrhea in some refractory cases.” (Medscape, 2011, p.1) Activity against Cryptosporidium is contained in “Nitazoxanide, paromomycin, and azithromycin.” (Medscape, 2011, p.1)
VII. Medications
Specific information on the medications are listed as follows:
(1) Paromomvcin is an oral “nonabsorbed aminoglycoside that is partially active in cryptosporidiosis. It is an amebicidal and antibacterial aminoglycoside obtained from a strain of Streptomyces rimosus that is active in intestinal amebiasis. Paromomycin is recommended for treatment of Diphyllobothrium latum, Taenia saginata, Taenia solium, Dipylidium caninum, and Hymenolepis nana.” (Medscape, 2011, p.1)
(2) Azithromvcin (Zithromax, Zmax): this is an “a macrolide antibiotic. In a clinical study, it provided good symptom control in combination with paromomycin.” (Medscape, 2011, p.1)
(3) Nitazoxide (Alinia): This medication serves to “inhibit the growth of Cryptosporidium parvum sporozoites and oocysts and Giardia lamblia trophozoites. It elicits antiprotozoal activity by interfering with pyruvate-ferredoxin oxidoreductase (PFOR) enzyme — dependent electron transfer reaction, which is essential to anaerobic energy metabolism.” (Medscape, 2011, p.1)
VII. Alternatives to Tap Water
In the event the individual is advised not to drink tap water the stated alternatives includes the following:
(1) One option is to boil water prior to drinking or using for cooking. Water should be brought to a rolling boil for at least five minutes. (Illinois Department of Public Health, 2012, p.1)
(2) The second stated option is to use a “point-of-use (personal use, end-of-tap, under sink) filter. Only point-of-use filters that remove particles one micrometer or less in diameter should be considered.” (Illinois Department of Public Health, 2012, p.1)
(3) The third option is to use bottled water however, it is not wise to assume that all bottled waters are 100% free of Cryptosporidium. While Cryptosprodius has been known to be acquired by drinking well water, however water treated by passing through a filter will nearly meet the same standards as distillation or reverse osmosis. (Illinois Department of Public Health, 2012, p.1)
Summary and Conclusion
In review Cryptosporidium is a coccidian protozoan parasite which attaches itself to the intestinal tissue of the host. This infection is not easily cured and there is no known specific effective treatment although there are medications that assist with the symptoms of infection and which deter the progression of the infection. It is important that human beings and animals alike, whether livestock or domestic animals, drink water that has gone through the proper distillation, reverse osmosis, or filtering to cleanse this parasite from the water.
Bibliography
Cabada, MM (2011) Cryptosporidiosis Medication. MedScape. Retrieved from: http://emedicine.medscape.com/article/215490-medication#2
Cabada, MM (2011) Crytosporidiosis Treatment and Management. MedScape. Retrieved from: http://emedicine.medscape.com/article/215490-treatment#aw2aab6b6b6
Casemore, D.P., Garder, C.A., and O’Mahony, C. “Cryptosporidial infection, with special reference to nosocomial transmission of Cryptosporidium parvum: a review.” Folia Parasitol, 1994; 41 (1): 17-21.
Cryptosporidiosis in Immunocompromised Persons (2012) Illinois Department of Health. Healthbeat. Retrieved from: http://www.idph.state.il.us/public/hb/hbcrypto.htm
Doyle, P.S., Crabb, J., and Petersen, C. “Anti-Cryptosporidium parvum antibodies inhibit infectivity in vitro and in vivo.”Infect Immun, 1993 Oct; 61 (10): 4079-84.
Flanigan, T.P. And Soave, R. “Cryptosporidiosis.” Prog Clin Parasitol, 1993; 1-20.
Goodgame, R.W. “Understanding intestinal spore-forming protozoa: cryptosporidia, microsporidia, isospora, and cyclospora.” Ann Intern Med, 1996 Feb 15; 124 (4): 429-41.
Hannahs, G. (nd) Cryptosporidium parvum: an emerging pathogen. Kenyon College. Retrieved from: http://biology.kenyon.edu/slonc/bio38/hannahs/crypto.htm
Johnson, D.W., Pieniazek, N.J., Griffin, D.W., Misener, L., and Rose, J.B. “Development of a PCR protocol for sensitive detection of Cryptosporidium oocysts in water samples.” Appl Environ Microbiol, 1995 Nov; 61 (11): 3849-55.
Keusch, G.T., Hamer, D., Joe, A., Kelley, M., Griffiths, J., and Ward, H. “Cryptosporidia — who is at risk?” Schweiz Med Wochenschr, 1995 May 6; 125 (18): 899-908.
Korich, D.G., Mead, J.R., Madore, M.S., Sinclair, N.A., and Sterling, C.R. “Effects of ozone, chlorine dioxide, chlorine, and monochlorine on Cryptosporidium parvum oocyst viability.” Appl Envion Microbiol, 1990 May; 56 (5): 1423-8.
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