Zoonosis: Cryptosporidiosis

The owner-opeartors of a 50-cow dairy herd reported that one of their children (a 4-year-old boy) had diarrhea for 3 weeks. The child had been under the outpatient care of a physician for 2 weeks. The clients stated that the cause of the diarrhea was not known. The child started accompanying his parents to the barn daily about a month before developing diarrhea. The clients had read (in the lay press) about cryptosporidiosis in cattle spreading to people, and about persistent cryptosporidiosis in people with the acquired immune deficiency syndrome and other immunologic deficiencies. The clients suspected that the child may have had persistent cryptosporidiosis acquired from calves on their farm. Their physician recommended that they contact their veterinarian to determine whether their cattle had cryptosporidiosis.

Cryptosporidiosis had not been diagnosed in the herd, and enteric disease had not been considered to be a serious problem in the herd for 3 years. During the previous 3 years, however, about 20% of the calves raised in the herd developed mild diarrhea for 1 to 3 days during the first month after birth. Examinations of the herd indicated that the cows and replacement heifers were healthy, but that 4 of 26 calves (1 day to 12 weeks old) had mild diarrhea.

Cryptosporidium spp were not detected in fecal specimens selected randomly from 10 cows and 2 replacement heifers. Cryptosporidium spp oocysts were found in fecal specimens from 3 of the 4 diarrheic calves and from 2 of the 22 healthy calves.

Rotavirus was isolated from a fecal specimen from a diarrheic calf. Salmonella spp were not isolated.

The child did not have cryptosporidiosis, and the specific cause of the diarrhea was not determined.

A: Yes, readily so, directly via the fecal-oral route or via contaminated food, water, or fomites.^1-6

A: Cryptosporidia are coccidian parasites of the genus Cryptosporidium, sub-order Eimeriorina.⁷

Q: What are some of the characteristics that distinguish Cryptosporoidium spp from other coccidia such as Eimeria spp?

A: Cryptosporidia are smaller. The oocysts of the Cryptosporidium spp that parasitize the intestinal tracts of calves are 4 to 5 µm in diameter (Fig 1).^1,2,8

Figure 1--Photomicrograph of 2 oocysts of cryptosporidia in a smear of a fecal specimen from a calf. The oocysts are stained negatively and refractile against a dark background. Kinyoun's carbol fuchsin stain; x 980.

Cryptosporidia do not invade beyond the apical surfaces of parasitized epithelial cells. They protrude into the intestinal lumen from the brush border of the epithelial cells (Fig 2),

Figure 2--Transmission electron micrograph of cryptosporidia protruding from the apical surface of a villous epithelial cell in the ileum of a calf. The plasma membrane (arrow) of the host cell envelops the parasite. Several epithelial cell microvilli remain on either side of the parasite. Reproduced with permission from Vet Pathol 1978;15:417-427.
Photo50(fig 2)

and are covered by the epithelial cell membrane, but do not enter into the host cell cytoplasm.⁹ This unique location has been described as intracellular-extracytoplasmic.¹⁰

A: The life cycles are similar, but there are important differences. In contrast to other coccidia (which require time outside the host to become infective), Cryptosporidium spp oocysts are sporulated and infectious at the time of excretion.^1,2,6 Thus, removal of manure every 2 to 3 days (as done before sporulation of Eimeria spp) is less effective for controlling cryptosporidiosis than for other types of coccidiosis. Furthermore, sporulated Cryptosporidium spp oocysts can excyst in the intestine before being excreted in the feces. Thus, the infection persists until the immune response of the host clears the parasite. Calves that recover from C parvum infection are not chronic carriers and do not recrudesce when treated with dexamethasone.¹¹ Infections with Cryptosporidium spp may persist indefinitely in people with some types of immunodeficiencies.⁴

Q: Are cryptosporidia primary pathogens or do they only cause disease secondary to, or in concert with, other pathogens?

A: They are primary pathogens. Cryptosporidium spp cause enteric lesions and diarrhea in monoinfected calves.¹¹ However, calves often develop mixed infections of Cryptosporidium spp and other enteric pathogens such as coronavirus and rotavirus.^12-14

A: Macroscopically, the intestine usually appears normal. Microscopic lesions can extend throughout the intestine in clinically affected calves; however, they usually are found in the ileum, where epithelial cell destruction results in villous atrophy and infiltration of the mucosa with neutrophils and lymphocytes.^11,13 In many low-grade (subclinical) infections, only a few parasites are found, with no apparent histologic damage to the intestine.

A: Yes. However, at high magnification (x 450), cryptosporidia can be found in the brush border of the villous epithelium (Fig 3).

Figure 3--Photomicrograph of the tip of a villus in a histologic section from the ileum of a calf; H&E stain; x 450. numerous cryotosporidia (arrows) are attached to the epithelial surface. Epithelial cells are low columnar to cuboidal, their nuclei are not aligned, and a cellular infiltrate is seen in the lamina propria. Reproduced with permission from J infect Dis 1984;150:768-775.
Photo(fig 3)

In contrast to rotaviruses, Cryptosporidium spp frequently affect both the large and the small intestine.^6,11,13

A: Cryptosporidia parasitize the intestinal tracts of various vertebrate species.^1,12 Cryptosporidia are prevalent particularly in neonates of ruminant species and are ubiquitous in the intestinal tracts of beef and dairy calves.^3,10,15,16 Most calves become infected (clinically or subclinically) before 6 weeks of age. About 25% of diarrheic calves 5 days to 1 month old are infected with C parvum.^6,14 Clinical and subclinical infections also develop in human beings. The reported prevalence of cryptosporidia in fecal specimens from people with diarrhea is 1.4% to 10.8%.^4,5,13,17 Unlike cattle, human beings of all ages are susceptible. Subclinical or clinical infections also can develop in swine, cats, dogs, horses, chickens, turkeys, geese, reptiles, rodents, rabbits, nonhuman primates, and exotic and wild animals.^1,2,6,12

A: Frequently, but not always. Respiratory, conjunctival, and gastric infections also have been reported.^1,2,4,5,6,16

A: At least 2 species in mammals and at least 2 species in birds.⁸ Cryptosporidium parvum commonly parasitizes the intestinal tracts of calves and man, is transmitted readily to the newborn of several species of mammals, and produces oocysts 4 to 5 µm in diameter. Cryptosporidium muris infects the stomachs of mice, produces oocysts nearly 8 µm in diameter, and is thought to be more host- and tissue-specific than C parvum. The 2 species in birds are C baileyi and C meleagridis.⁷

Q: Do all strains of C parvum have the same host range and potential for zoonotic infection?

A: The strains predominant in calves and man are cross-transmissible, and can infect various other host species.^1,2,4,6 Isolates from guinea pigs and calves probably have different host ranges.¹⁸

Q: Do human beings acquire cryptosporidiosis from domestic poultry via the food chain or occupational exposure?

A: An isolate of a Cryptosporidium sp from chickens was not infectious for infant mice or for goat kids.⁷ Therefore, mammals may be resistant to avian cryptosporidia.

A: Endogenous stages of the parasite in the brush border of epithelial cells can be detected histologically in H&E-stained intestinal specimens fixed within 1 or 2 hours after death.^1,6,12 Oocysts can be seen microscopically in direct smears of feces or intestinal contents stained with Kinyoun's carbolfuchsin stain, modified acid-fast stain, Giemsa stain, or various other stains.^3,19,20 Concentration techniques, such as Sheather's sugar flotation (before microscopic examination), can also be used.²⁰ Oocysts remain demonstrable in fecal specimens or intestinal contents for > 24 hours afterthe death ofthe host, and such specimens can be preserved for weeks if kept moist and stored at 4 C.

Subclinical infections are common.^1,12,13 Thus, as with rotavirus or enterotoxigenic Escherichia coli, finding the agent in a diseased animal is the basis for a presumptive diagnosis. However, finding the agent does not prove that it caused the disease. If the diarrhea is the result of intestinal cryptosporidiosis, the feces should contain 10⁵ to 10⁷ C parvum oocysts per ml. Sometimes shedding can be detected several hours before or after the onset of diarrhea.

Q: In view of the high prevalence of C parvum in calves and the ease of transmission between species, one would expect a high prevalence of cryptosporidiosis among people who are working with calves. Why is diarrhea due to cryptosporidiosis not a common problem among dairy farmers, cattle ranchers, veterinarians, and their families?

A: Cryptosporidiosis may be one of the causes of undiagnosed transient diarrhea that develops commonly among these groups, as well as among the rest of the population. Preliminary surveys for antibody against cryptosporidia in human serum indicate that a high percentage of the population has been exposed to the organism.^6,15,17

A: Various compounds, including many of those effective against other coccidia and other protozoan parasites, have been ineffective against cryptosporidiosis.^4-6 Therefore, treatment with antimicrobial drugs is contraindicated. Treatment consists of supportive therapy. Keep affected animals warm, dry, well fed, and at a constant ambient temperature (> 5 C), to minimize their energy requirements during the course of clinical disease. If managed in this fashion, most calves with uncomplicated infections will recover in 5 to 10 days. Calves that become dehydrated and acidotic should be given appropriate fluids IV or orally.

A: The logical approach to prevention is to minimize fecal-oral transmission between calves. Reducing the number of oocysts ingested probably will reduce severity of the infection and will allow the calf to develop immunity to the organism. Calves should be born and raised in a clean, dry environment. Dairy calves should be housed in individual hutches or boxes. Healthy calves should be confined separately from sick calves and, if possible, healthy and sick calves should be cared for by different people, using different equipment. Calf rearing areas should not be occupied continuously. Use all-in, all-out management, with thorough cleaning and several weeks of drying between batches of calves. Rats and mice should be controlled, because they probably are a reservoir for C parvum infection of calves. If the herd is free of the infection, maintaining a closed herd and following these hygienic practices will increase the probability that the herd will remain free of cryptosporidiosis.

A: Cryptosporidium spp oocysts are resistant to most chemical disinfectants.⁶ Emphasis should be on cleanliness and removal of all fecal material, rather than on the selection of a chemical disinfectant in an attempt to kill the oocysts. Suspension of the oocysts in ammonia (5% solution) or 10% formalin for 18 hours has been shown to kill the oocysts.⁶ Moist heat [pasteurization (> 55 C) or live steam], freezing, or thorough drying are probably the most effective practical means for killing oocysts.²¹ Pens, crates, and utensils should be cleaned thoroughly with an ammonia solution and dried thoroughly for several days before introduction of a new group of calves. In the winter, an area that has been cleaned and frozen probably is free of infectious cryptosporidia.

A: By using good sanitation and hygiene practices when handling young animals (particularly calves) Do not allow infants or immunologically compromised adults to handle animals with diarrhea. Because the disease is so severe and persistent in immunologically compromised individuals,⁴ people who have immunologic deficiencies or who are receiving immunosuppressive therapy should not work with calves, lambs, or other neonatal ruminants.

Most people and animals infected with C parvum develop immunity and recover from the infection. However, the disease is persistent and life-threatening in individuals with certain types of immunologic impairment such as acquired immune deficiency syndrome.⁴ Prognosis for immunologically compromised individuals with cryptosporidiosis is grave, because an effective chemotherapeutic means of eliminating the parasite is not available.

Cryptosporidiosis may be a common cause of self-limited diarrhea in man.^5.17.22-25 Animal handlers, medical personnel, human beings living or traveling in developing countries, and children in day care centers appear to have the greatest risk of exposure to cryptosporidia. Person-to-person transmission and zoonotic infections have been reported.^5,22 Subclinical infections can develop in cats and dogs. Human infections acquired from cats and dogs may be possible.^6,13,16 Kittens, pups, and mice are susceptible to infection with human isolates of C parvum. Infected calves probably do not become chronic carriers of C parvum.¹¹ The prevalence of C parvum in adult cattle appears to be much lower than among calves. In addition to specific acquired immunity, adults of several species appear to develop an innate age-dependent resistance to cryptosporidiosis.^6,11 Thus, young animals probably are a more important source of infection than are adults. However, immunity and age-dependent resistance are not universal because infections develop in adult human beings and guinea pigs. Although many strains of C parvum have a broad host range and some calf strains of C parvum cause human infections, all strains may not have the same zoonotic potential. Two strains of cryptosporidia with different host ranges parasitize the intestinal tracts of guinea pigs.¹⁸

Cryptosporidium muris infection has been reported in cattle in the United States.⁸ Oocysts of C muris can be differentiated from those of C parvum on the basis of size (7.4 x 5.6 µm, C muris; 5.0 x 4.5 µm, C parvum). In contrast with C parvum, C muris has been found in adult cattle.⁸ Cryptosporidium muris infects the gastric glands of mice and cattle. Cryptosporidium baileyi infects the intestinal tracts of chickens in the United States.⁷ Oocysts of C baileyi (6.2 x 4.6 µm) can be differentiated from those of C muris and C parvum on the basis of size. Cryptosporidium baileyi hosts include chickens, geese, ducks, and turkeys. In contrast to C parvum, C baileyi does not infect (experimentally) newborn mice and goats.⁷ Therefore, mammals may not be susceptible to infection with C baileyi. Morphologic and host range differences indicate that birds can be infected by at least 2 species, C baileyi and C meleagridis.⁷ Data on the zoonotic potential of avian cryptosporidia are needed.

1. Angus KW. Cryptosporidiosis in man, domestic animals and birds: a review. J R Soc Med 1983; 76:62-70.

3. Kirkpatrick CE. Cryptosporidium infection as a cause of calf diarrhea. Vet Clin North Am: Food Anim Pract 1985; 1:515-528.

4. Navin TR, Juranek DD. Cryptosporidiosis: clinical, epidemiologic, and parasitologic review. Rev Infect Dis 1984; 6:313-327.

5. Scully RE, Mark EJ, McNeely BU. Case records of the Massachusetts general hospital: case 39-1985. New Engl J Med 1985; 313:805-815.

6. Tzipori S. Cryptosporidiosis in animals and humans. Microbiol Rev 1983; 47:84-96.

7. Current WL, Upton SJ, Haynes TB. The life cycle of Cryptosporidium baileyi n sp (Apicomplexa, Cryptosporidiidae) infecting chickens. J Protozool 1986;33:289-296.

8. Upton SJ, Current WL. The species of Cryptosporidium (Apicomplexa: Cryptosporidiidae) infecting mammals. J Parasitol 1985; 71:625-629.

9. Marcial MA, Madara JL. Cryptosporidium: cellular localization, structural analysis of absorptive cell-Darasite membrane-membrane interactions in guinea pigs, and suggestion of protozoan transport by M cells. Gastroenterology 1986; 90:583-594.

10. Boch VJ, Gobel E, Heine J, et al: Kryptosporidien-Infektion bei Haustieren. Berl Munch Tieraerztl Wochenschr 1982; 95:361-367.

11. Moon HW, Pohlenz JFL, Woodmansee DB, et al. Intestinal cryptosporidiosis. pathogenesis and immunity, in Proceedings. 10th Intl Symp Intest Microecology 1985;1:29-33.

12. Anderson BC. Cryptosporidiosis: a review. J Am Vet Med Assoc 1982; 180:1455-1457.

13. Tzipori S. Cryptosporidium: notes on epidemiology and pathogenesis. Parasitol Today 1985; 1:159-165.

14. Tzipori S. The relative importance of enteric pathogens affecting neonates of domestic animals. Adv Vet Sci Comp Med 1985; 29:103-206.

15. Current WL. Cryptosporidium and cryptosporidiosis of domestic animals and man, in Proceedings. Vet Infect Dis Org,4th Intl Symp Neonatal Diarrhea, Oct 3-5, 1983; 293-305.

16. Current WL. Cryptosporidium and cryptosporidiosis, in Proceedings. 10th Intl Symp Intest Microecology 1985; 10:58-76.

17. Ungar BLP, Soave R, Fayer R, et al. Enzyme immunoassay detection of immunoglobulin M and G antibodies to Cryptosporidium in immunocompetent and immunocompromised persons. J Infect Dis 1986; 153:570-577.

18. Angus KW, Hutchison G, Munro HMC. Infectivity of a strain of Cryptosporidium found in the guinea-pig (Cavia porcellus) for guinea pigs, mice and lambs. J Comp Pathol 1985; 95:151-165.

19. Anderson BC. Quick and easy diagnosis of cryptosporidiosis and Johne's disease. Vet Med 1985; 80:87-89.

20. Current WL. Human enteric coccidia. I. Cryptosporidium. Clin Microbiol (Newsletter) 1985; 7:167-170.

21. Anderson BC. Moist heat inactivation of Cryptosporidium sp. Am J Public Health 1985; 75:1433-1434.

22. Casemore DP, Jackson FB. Hypothesis: cryptosporidiosis in human beings is not primarily a zoonosis. J Infect 1984; 9:153-156.

23. Koch KL, Phillips DJ, Aber RC, et al. Cryptosporidiosis in hospital personnel. Ann Intern Med 1985; 102:593-596.

24. Sterling CR, Seegar K, Sinclair NA. Cryptosporidium as a causative agent of traveler's diarrhea. J Infect Dis 1986; 153:380-381.

25. Weikel CS, Johnston LI, De Sousa MA, et al. Cryptosporidiosis in northeastern Brazil: association with sporadic diarrhea. J Infect Dis 1985; 151:963-965.

Q: How has our understanding of zoonotic cryptosporidiosis changed since 1986 when this article was originally published?

A: The major waterborne episode of human illness in Milwaukee, Wisconsin was covered extensively by the national press, and raised public awareness immensely.¹ The Milwaukee episode emphasized the fact that the chemical resistance and small size of Cryptosporidium parvum oocytes pose a particular problem for human sewage treatment and drinking water treatment facilities. Sewage treatment cannot be relied on to completely remove the oocysts. Removal from heavily contaminated drinking water requires that filtration and coagulation systems be in place and functioning optimally.^1-3 That episode also raised concern about the relative potential for contributions from human beings, cattle, and wildlife to surface water contamination, leading to waterborne human infection.

We now know that C muris infects the abomasum of adult cattle.⁴ The prevalence of C muris is not known, but is thought to be lower that that of C parvum. There is no evidence that C muris can infect human beings. Cryptosporidium baileyi infection in an immune-suppressed man has been reported.⁵ However, zoonotic cryptosporidiosis remains restricted principally to C parvum infection.

Additional data on the prevalence of Cryptosporidium spp among companion animals are available. Cryptosporidium sp (thought to be C parvum) was detected among 5% of domestic cats and 12% of feral cats during a study in Glasgow, Scotland.

2. LeChevallier MW, Norton WD, Lee RG. Giardia and Cryptosporidium spp in filtered drinking water supplies. Appl Environ Microbiol 1991;57:2617-2621.

3. LeChevallier MW, Norton WD, Lee RG. Occurrence of Giardia and Cryptosporidium spp in surface water supplies. Appl Environ Microbiol 1991;57:2610-2616.

4. Anderson BC. Abomasal cryptosporidiosis in cattle. Vet Pathol 1987;24:235-238.

5. Ditrich O, Palkovi L, t rba J, et al. The first finding of Cryptosporidium baileyi in man. Parasitol Res 1991;77:44-47.

6. Mtambo MMA, Nash AS, Blewett DA, et al. Cryptosporidium infection in cats: Prevalence of infection in domestic and feral cats in the Glasgow area. Vet Rec 1991;139:502-504.