Cryptosporidiosis Case File

Cryptosporidiosis Case File

Eugene C.Toy, MD, Cynthia Debord, PHD, Audrey Wanger, PHD, Gilbert Castro, PHD, James D. Kettering, PHD, Donald Briscoe, MD

CASE 46

A 32-year-old man with known HIV is brought to the hospital with diarrhea. He has had between 15 and 25 watery stools a day for the past 2 weeks. He has had a low grade fever and felt very fatigued, but denies vomiting. He has not passed any blood in his stool. He says that he has lost 8 lb in this time

frame. He is on a “triple therapy cocktail” of AZT, 3TC, and a protease inhibitor for his HIV. His last CD4 cell count was 150 cells/mm3. On examination, his temperature is 37.2°C (98.9°F), pulse is 110 beats per minute, blood pressure is 95/75 mm Hg, and respiratory rate is 24 breaths per minute. In general, he appears cachectic. His eyes are dry and sunken. His mucous membranes are moist. His cardiovascular exam is notable for tachycardia, and he has orthoscopic changes on sitting up from lying down. His abdomen has hyperactive bowel sounds, but is soft and only mildly tender. His stool is heme negative. A modified acid-fast stained stool sample reveals multiple red and pink, round oocysts.

◆ What is the most likely cause of diarrhea?

◆ How is this infection most commonly acquired?

ANSWERS TO CASE 46: CRYPTOSPORIDIOSIS

Summary: A 32-year-old man with HIV and diarrhea. A modified acid-fast stained stool sample reveals multiple red and pink, round oocysts.

◆ Most likely etiologic agent: Cryptosporidium parvum.

◆ The most common mode of acquiring this infection: Ingestion of oocysts in contaminated water or food or fecal-oral transmission from infected animals or person to person.

CLINICAL CORRELATION

Cryptosporidium parvum belongs to a group of protozoans known as coccidians. The infective oocyst is approximately 3–8 μm in diameter. The parasite, on emerging from the oocyst, attaches to the surface of intestinal epithelium where it multiplies both asexually and sexually. The parasite causes changes in the mucosa that include crypt hyperplasia and villous atrophy. Associated with its presence in the intestine, and after an incubation period of approximately 2–12 days, is an acute illness characterized by nausea, abdominal cramps, weight loss, anorexia, malaise, low-grade fever, and diarrhea. The frequency of diarrheal episodes and voluminous fluid loss is often debilitating. During infection there may be periods in which symptoms are absent. Although any individual can acquire the infection, children in day care centers and individuals with AIDS or HIV infection represent populations that are especially vulnerable to cryptosporidiosis. In immunocompetent individuals, the disease will resolve on its own, usually within 7–14 days. In immunocompromised hosts, the disease is generally more severe and chronic, sometimes lasting for life. Five to ten percent of patients with AIDS acquire infection with Cryptosporidium. Persistence of infection in HIV-infected individuals is closely associated with CD4 lymphocyte counts of less than 180 cells/mm3. Protracted diarrhea may lead to dehydration, wasting, and death. Severe intestinal distress, usually in immunodeficient individuals, is sometimes associated with pulmonary and tracheal cryptosporidiosis that is associated with coughing and low-grade fever. The strains that infect the intestine and lungs are, to date, indistinguishable.

APPROACH TO SUSPECTED Cryptosporidium INFECTION

Objectives

1. Learn the life cycle of C. parvum and the epidemiology and clinical course of cryptosporidiosis, and compare this disease with those caused by related organisms, such as Cyclospora and Isospora.

2. Be able to describe the three basic aspect of infection: transmission, diagnosis, and treatment/prevention.

Definitions

Coccidia: The specific taxonomic group of protozoans to which C. parvum belongs.

Oocyst: The stage in the life cycle of C. parvum that transmits the disease and is also sought in making a definitive diagnosis. Each oocyst contains four sporozoites.

Sporozoite: The stage released from the oocyst following ingestion and which initiates infection.

Zoonosis: A disease that is transmitted from lower vertebrate hosts to humans.

Acid-fast stain: A type of stain that renders oocysts highly visible in a fecal sample. It is used to support the microscopic diagnosis of the parasite.

DISCUSSION

Characteristics of Cryptosporidium That Impact Transmission

Cryptosporidium species are ubiquitous, worldwide enteric pathogens of humans and multiple other animal species. Of the many species of the genus, C. parvum is responsible for most clinical disease in humans and other mammals. The life cycle of C. parvum occurs within a single host and, like other coccidia, involves sexual and asexual reproduction. Misdiagnosis with cyclosporiasis may be made, in part because clinical symptoms are similar. Protracted, watery diarrhea is the hallmark of infection. Cyclospora cayetanensis, which infects humans, has a worldwide distribution. Another related organism that causes diarrhea in humans is Isospora belli.

The small intestine is the usual host habitat for Cryptosporidium, where it lives in a unique intraepithelial niche. The life cycle is initiated with the ingestion of oocysts that contain four sporozoites. When oocysts are ingested, they undergo excystation as the outer wall is removed by digestive processes. Sporozoites that are released attach to the host’s intestinal epithelial cells and become surrounded by a host-derived membrane, making them intracellular but extracytoplasmic. Sporozoites undergo multiple fission to form meronts that contain multiple merozoites. The merozoites are released to infect other cells. Following another round of asexual division and on release of the second and subsequent generations of merozoites, they penetrate new cells to form gametes. Most gametes undergo enlargement into macrogametes (female). Some become microgametocytes that undergo fission multiple times to form sperm-like microgametes (male). Microgametes leave the microgametocyte and fertilize a macrogamete to form a zygote. The zygote then becomes covered by a wall, forming an oocyst that is highly resistant to chemical and physical changes in the internal and external environment. Sporozoites develop within the oocyst that are sloughed, along with intestinal epithelial cells, and voided in the feces. Because oocysts are passed in the feces in a sporulated stage (i.e., contain sporozoites), they are immediately infective and can retain infectivity for long periods because of their protective wall. In having oocysts that are immediately infective, Cryptosporidium is different from Cyclospora, which has oocysts that require 1–2 weeks to develop to an infective stage.

Presumably ingestion of one oocyst can initiate an infection that can be contracted by eating contaminated food or drinking contaminated water. Touching the stool of infected individuals or animals or anything contaminated with feces and then touching your mouth can also initiate infection.

Infection can be transmitted by ingestion of oocysts passed in feces of infected humans or animals. Thus, infection can be transmitted from one person to another or from animals to humans, from eating and drinking food or water contaminated with fecal material or from transfer of oocysts from contaminated material to the mouth or from person to person.

Diagnosis

A definitive diagnosis is based on identifying oocysts in a fecal sample. A technique, such as sugar flotation, is used to concentrate the oocysts and acidfast staining is used to identify them. A fluorescent antibody technique is also available to stain the isolated oocysts, augmenting visualization. Oocysts contain four sporozoites. It is important to make a differential diagnosis with Cyclospora oocysts, which are similar in size but are not sporulated when passed. Cryptosporidium oocysts contain four sporozoites and are approximately 8 μm in diameter. When sporulated, the oocysts of Cyclospora are the same size, but contain two sporocysts, each with two sporozoites. Isospora oocysts can also be found in the stool; however, they can be differentiated by their larger size, 15 by 30 μm ovoid. Like Cyclospora, oocysts of Isospora are excreted in an unsporulated stage, and, after becoming sporulated, contain two sporocysts, each with two sporozoites. Pulmonary infections of Cryptosporidium are diagnosed by biopsy and staining (Table 46-1).

Table 46-1

DIFFERENTIATION OF HUMAN COCCIDIAN OOCYSTS

Treatment and Prevention

As noted, infection is self-limiting in immunocompetent hosts and chronic in immunosuppressed individuals. While nitazoxanide is effective in the treatment of immunocompetent hosts, it has not proven so for immunosupressed patients. Because of massive fluid loss, due to diarrhea, infected individuals may require rehydration therapy.

Because there is no effective agent to treat infection specifically in immunosuppressed patients, the best measure to control infection is avoidance of situations that are conducive to transmission. Thus, knowledge about sources of infection and how infection is transmitted is the key to prevention. Most surface water, such as streams, lakes, and rivers contain some Cryptosporidium oocysts. Many public supplies of treated and filtered water derived from these sources are contaminated with low levels of oocysts. Cryptosporidiosis can be prevented by thoroughly washing hands before eating and after any contact with animals or soil or after changing diapers. In people with weakened immune systems, cryptosporidiosis can be lifethreatening. These individuals must take extra precautions to drink only water that has been purified; wash with purified water; cook all food; do not swim in lakes, rivers, streams, or public pools; avoid sexual practices that might involve contact with stool; and avoid touching farm animals.

Synopsis

The synopsis of cryptosporidiosis is presented in Table 46-2.

Table 46-2

COMPREHENSION QUESTIONS

[46.1] A 33-year-old woman has chronic diarrhea. A fecal sample is obtained. Microscopic identification of which of the following stages of the organism would provide the strongest evidence for cryptosporidiosis?

A. Cyst

B. Oocyst

C. Egg

D. Sporocysts

E. Merozoites

[46.2] A 24-year-old male scientist is diagnosed with chronic cryptosporidiosis. He asks about the epidemiology of this disorder. Which of the following accurately describes the disease or the etiologic agent?

A. Is self-limiting in immunocompromised patients

B. Reproduces sexually and asexually in different hosts

C. Can be acquired through sporozoites transmitted by an insect vector

D. Is transmitted through drinking water contaminated with animal feces

E. Is the only human parasite that produces oocysts

[46.3] Chronic, debilitating cryptosporidiosis is most likely to affect which of the following individuals?

A. Dairy farmers

B. Individuals with AIDS

C. Infants placed in day care centers

D. Zoo animal handlers

E. Hikers who drink from streams and lakes

Answers

[46.1] B. Oocyst is the correct answer. Egg and cyst stages are not part of the life cycle of Cryptosporidium. Eggs are produced by helminths, and cyst stages are produced by other intestinal protozoans, such as Entamoeba and Giardia. Merozoites occur within infected epithelial cells but are not the target of diagnostic tests or procedures. Sporocysts are not found in the life cycle of cryptosporidium as a feature of the oocyst. Sporocysts are a feature of the genus Cyclospora and important in differential diagnosis.

[46.2] D. Infection can be acquired from oocysts transferred from farm animals. In immunocompromised individuals, such as those with AIDS or cancer patients being treated with immunosuppressive agents, infection is not self-limiting but rather chronic and sometimes lifethreatening. The life cycle of Cryptosporidium involves both asexual and sexual reproduction, but both forms occur in a single host. Sporozoites are stages in the life cycle that are released from ingested oocysts. There is no insect that serves as a biological or mechanical vector in the life cycle. Oocysts are also produced by other species of coccidians that infect humans, such as Isospora, Cyclospora, Toxoplasma, and Plasmodium. Toxoplasma oocysts only occur in feline hosts; Plasmodium species cause malaria in which only the mosquito definitive host harbors oocysts; Isospora and Cyclospora are intestinal coccidian parasites that produce oocysts that are passed in the feces and must be considered in making a differential diagnosis.

[46.3] B. All individuals (A–E) are susceptible to infection. However, persons that are at high risk of severe, protracted infection are those with AIDS, or those who have cancer or organ transplants who are treated with drugs that weaken the immune system, or individuals who are genetically immunodeficient.

MICROBIOLOGY PEARLS ❖ Often there is misdiagnosis between cryptosporidiosis and cyclosporiasis. ❖ Immunologically compromised patients with cryptosporidiosis do not respond to specific therapy with nitazoxanide.

REFERENCES

Centers for Disease Control. DPDx. Laboratory identification of parasites of public concern. Cryptosporidiosis. 2007. http://www.dpd.cdc.gov/dpdx/HTML/ Cryptosporidiosis.htm. 

Centers for Disease Control. DPDx. Laboratory identification of parasites of public concern. Image Library. Cryptosoridiosis. 2007. http://www.dpd.cdc.gov/ dpdx/HTML/ImageLibrary/Cryptosporidiosis_il.htm. 

Medical Letter on Drugs and Therapeutics. Drugs for parasitic infections. New Rochelle, NY. 2004. http://www.medletter.com/freedocs/parasitic.pdf. This reference has been updated and “superseded by the special report Drugs for Parasitic Infections, which can be purchased (on-line) for $25.” This reference has been provided because it is a comprehensive and clinically useful reference that is regularly updated and could be of value to those who are involved in treating parasitic infections.

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