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Infectious Diseases of the Dog and Cat, 3rd Edition

CHAPTER 82 Cryptosporidiosis and Cyclosporiasis

Stephen C. Barr

CRYPTOSPORIDIOSIS

Etiology and Epidemiology

Cryptosporidiumis a ubiquitous coccidian genus in the phylum Apicomplexa, suborder Eimeria, family

Cryptosporidiidae, that inhabits the epithelium of the respiratory and digestive systems of reptiles, birds, and

mammals. Infections of the ileum are most common, but gastric, respiratory, and conjunctival infections have

been observed in immunosuppressed hosts. Most species may be relatively host specific. Cryptosporidium

found in reptiles and birds apparently do not infect mammals. The multiple genospecies of Cryptosporidium

include Cryptosporidium felisand Cryptosporidium canis.*Only two morphologically distinct species are

recognized mammals based on the very small oocyst size, namely Cryptosporidium parvum(4 to 5 m indiameter) and Cryptosporidiumsp. (= Cryptosporidium muris; 6 to 8 m in diameter). Strains that infect cats

and dogs cannot be morphologically differentiated from those that infect people. However, genetic methods can

be used to differentiate different isolates of C. parvum. New species designations have been made for these

distinct isolates (Table 82-1). Many of the newly described genospecies from animals were originally thought

to be host specific. However, the host restriction may be less strict given the evidence of a complex circulation

of the cryptosporidial species in the environment.15

Oocysts are often difficult to demonstrate in the feces

without special techniques. The biology of C. murisis not well known and its host range is limited,5and it will

not be considered further. C. parvumsubtype 1 is the cause of most human infections and is anthroponotic. In

contrast, subtype 2 is zoonotic, with cattle being a principal reservoir host. The organism is thought to be by far

the most commonly occurring species in mammals and, similar to Toxoplasma, has a wide mammalian host

range.97

Cryptosporidiumhas been reported in rodents, domestic livestock, cats, dogs, people, and numerous

wild mammals. Ruminants, especially calves, are considered reservoir hosts for the cattle subtype. Crossinfection between various mammalian hosts occurs with this strain.

93Despite their host specificity,

experimentally, C. parvumfrom calves can induce respiratory signs in chickens103

; however most such

attempts have failed.97

Canada geese (Branta canadensis)have been shown to be vectors of C. parvum

infection and they may cause fecal contamination far from the site of its origin.36

A high prevalence of serum

antibodies to cryptosporidia in most species tested, including cats, suggests that exposure to the parasite is

common.92

Prevalence of serum antibodies to C. parvumin cats in various geographic regions in the United

States ranges from 1.3% to 14.7%, with older animals in the southeastern states showing the highest exposure

rate (15.3%).80,81

However, young stray cats are more likely to excrete cysts in their feces. In New York, 3.8%

of shelter cats between 1 and 12 months of age were excreting cysts in their feces, while in Colorado, 5.4% of

cats were positive.47

In the Colorado study, dogs and cats with diarrhea were more likely to shed cysts in their

feces compared with clinically normal animals.47In a clinical and postmortem study in metropolitan domestic

and feral cats, the prevalence of infection was 5.1% and 12.1%, respectively.90

In rural cats from the

surrounding area, the prevalence was 12.3%.94

Fecal cyst excretion rates in dogs in California and Colorado

were 2% and 3.8%, respectively, suggesting that the number of dogs excreting oocysts at any one time may be

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lower than that in cats.24,47

Ranges for prevalence of fecal oocysts in various populations have been 038.5% in

cats and 044.8% in dogs.70a

The life cycle of cryptosporidians differs from most other coccidians (Fig. 82-1). All stages of development(asexual and sexual) of cryptosporidia occur within one host.

97After ingestion, oocysts excyst in the

gastrointestinal (GI) tract, releasing infective sporozoites, which become enclosed as trophozoites within

parasitophorous vacuoles of the microvillous surface of enterocytes rather than in the cytoplasm (Fig. 82-2).

The trophozoites proliferate (asexually) by merogony to produce, sequentially, two types of meronts. Within 24

hours, type I meronts (containing eight merozoites) leave the parasitophorous vacuole to invade other epithelial

cells where they develop into more type I meronts or type II meronts (containing four merozoites). The type II

meronts do not undergo merogony but produce sexual reproductive stages (gamonts). The zygotes formed by

sexual reproduction (gametogony between male microgamonts and female macrogamonts) form either thick

walled (excreted in the feces) or thin walled (autogenous reinfection) oocysts each containing four sporozoites.

Oocysts of cryptosporidia are highly resistant and spread via the fecal oral route. Fecal contamination of food or

drinking water is a common source of infection. Large outbreaks can occur when a community water source

becomes contaminated.25aThe organism is extremely infective; as few as 100 oocysts are necessary to

precipitate disease in people.76

* References: 2, 53, 88, 89, 109, 120.

Pathogenesis

Cryptosporidia are either primary pathogens or secondary invaders in a variety of immunosuppressive diseases

of animals and people. Crowding and unsanitary practices increase the risk of exposure. Cryptosporidial

diarrhea is common among calves in intensive raising units and among children in day care centers.

Cryptosporidiosis may cause malabsorption or secretory diarrhea, but the underlying mechanisms are complex

and still not fully understood and have been reviewed elsewhere.34

The organism remains just beneath the

luminal cell membrane of the intestinal epithelial mucosa. Functional impairment (glucose stimulated sodium

and water absorption) and morphologic changes (villous atrophy, crypt hyperplasia, and inflammatory cell

infiltration) have been reported in pigs experimentally infected with C. parvum.4,86

Although secretory toxins

have been implicated in the electrogenic chloride secretory stimulation,39

the mechanism of action is unclear.76

Substance P, a neuropeptide in the tachykinin family, is increased in symptomatic as compared with

asymptomatic people with cryptosporidiosis related to acquired immunodeficiency syndrome (AIDS).116

Neuropeptides such as SP are known to mediate many inflammatory processes in the intestine. Tumor necrosis

factor and prostaglandins, which are released during infection, may also be involved in a disturbance of the

epithelial cell function. The net effect of the cellular mediators and villous atrophy is nutrient and electrolyte

malabsorption and shifts in water balance in favor of net secretion.34

Lymphocytic duodenitis and intestinal

bacterial overgrowth have been documented in a young cat with cryptosporidiosis; however, whether

Cryptosporidiumsp. caused the lesion is unknown.46

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Fig 82-1 Life cycle of Cryptosporidium. A, Oocysts are ingested by the host and

these excyst in the intestinal tract. B, They undergo replication in the

intestine by two generations of merogony. C, Meronts thendifferentiate into male and female gamonts which form a zygote that

matures into a sporulated oocyst within the intestine. Sporozoites from

thin-walled oocysts can reinfect new cells. D, Thick-walled oocysts are

environmentally resistant and infectious as they are passed in the stool.

(Courtesy University of Georgia, Athens, Ga.)


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Both humoral and cell mediated immunity (CMI) participate in the host response to infection with C. parvum.35

CMI appears to be the major component of the protective response; the role of antibodies is unclear. In affected

people, causes of immunodeficiency such as chemotherapy, IgA deficiency or interferon-deficiency have been

associated with an increased risk infection. Although cryptosporidial cysts are excreted by asymptomatic cats or

dogs, most case reports document a potential cause of systemic (feline leukemia virus [FeLV], feline

immunodeficiency virus, canine distemper, parvovirus) or local (GI lymphoma, coronavirus, Campylobacter,

Isosporaspp., Toxocara cati) immunosuppression in infected symptomatic animals.19,32,67,113

Concurrent

infections with various organisms (Capillariaspp., T. cati, Isospora felis,Pharyngostomum cordatum) were

detected in normal cats excreting cryptosporidial oocysts in the feces. Cryptosporidiosis was found to be more

common among asymptomatic young and newborn kittens as compared with older (6 months or older) cats.83

Clinical Findings

Cats

Because experimental inoculations in healthy adult cats or 6 week old kittens with C. parvumresulted in

asymptomatic infections, whether cryptosporidial infections can cause diarrhea in healthy animals is

questionable. Diarrhea can be self limiting or absent in naturally infected immunocompetent cats.

Pathogenicity undoubtedly is greater in immunodeficient cats. Intestinal cryptosporidiosis in other FeLV

negative or FeLV positive cats has also been associated with chronic anorexia, marked weight loss, and

persistent diarrhea.113

The diarrhea is usually of a small bowel nature, characterized by high volume, low

frequency stools with significant weight loss. Tenesmus, fresh blood, swelling, and discomfort may be seen

with chronicity. C. felishas been identified as a cause of infection in people associated with cats (see Public

Health Considerations). Clinical illness, when reported, has been that of diarrhea with occasional blood.88

Many cats are possible carriers for this species, and clinical illness may only occur following stress or

immunosuppression.

Dogs

In older reports in which the infecting species was unknown, experimental infection of healthy pups resulted

in oocyst shedding without accompanying disease.113

In subsequent reports in which the infecting

genospecies has been identified, a majority of dogs infected with C. canishave been asymptomatic.

However, in two dogs, with concurrent parvovirus infection or immune-mediated thrombocytopenia, the

dogs had hemorrhagic diarrhea.19,89

In one pup, C. caniswas found in the stomach mucosae, as a novel

finding.82

Naturally occurring cryptosporidiosis has been reported in a 1 week old pup that died after an

episode of diarrhea and dyspnea,97

whereas other pups infected with cryptosporidia did not show clinical

signs suggestive of infection.113

As in cats, signs of diarrhea have been most severe in immunosuppressed

dogs. Cryptosporidiosis has been described in immunosuppressed pups with distemper

113

and in dogs withGI lymphoma.

7Cryptosporidial infection has been diagnosed in an adult dog with persistent diarrhea, weight

loss, and malabsorption syndrome and no obvious cause for immunosuppression.37

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Calves and Other Animals

Although cryptosporidial infection in calves without clinical signs of diarrhea is common, it is an important

cause of diarrhea of varying severity (from mild intermittent to profuse watery with dehydration) among

calves younger than 3 weeks.98

The organism has also been identified in the bronchial epithelium of a calf.77

Cryptosporidial diarrhea is also an important disease among young ruminants found in zoos. Less severe

infections have been reported in young swine, lambs, and foals. The coccidian is fairly common in birds,

infecting the digestive and respiratory tracts and the bursa of Fabricius, and may be a primary pathogen. In

captive snakes, cryptosporidia causes gastritis and subsequent vomiting because it parasitizes the stomachs of

these reptiles.97

People

People of all ages can become infected with cryptosporidia, and the severity of disease depends on the

immunocompetence of the host. Most people develop transient clinical signs and recover. Cryptosporidiosisis an increasingly common cause of death in people with AIDS.

122Individuals with congenital

immunodeficiency disease may survive for years with cryptosporidiosis when fed parenterally.

Immunocompetent persons may be infected readily with Cryptosporidium, as demonstrated when more than

400,000 people in Milwaukee developed diarrhea as a result of contracting the organism via the public water

supply.73

Enzootic infections by this means are very common.11,31,74

Infection among veterinary students is

common after contact with infected calves and has been documented after contact with infected lambs,28

a

dog,37

and cats.23,60,69

Canine and feline isolates have been found in human immunodeficiency virus (HIV)

-infected people, but cat ownership by people with HIV is not associated with an increased risk to

cryptosporidiosis.30,109

Severe stress or concurrent infection by viruses or bacteria serves to exacerbate the

diarrheal syndrome.

In people, a causal connection has been cited between oocysts being shed in the stool and GI signs.56The

typical prepatent period is 5 to 7 days. Clinical signs, which may last from 2 to 26 days in immunocompetent

people, may include nausea, abdominal cramps, low grade fever, and anorexia. Occasionally, episodes last

longer. Diarrhea may be profuse, and dehydration is a common sequela. Asymptomatic infections do occur,

especially in recovery phases of the illness. Conversely, symptomatic patients can have intermittently

negative stools.56

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Fig 82-3 Fecal float with unstained oocysts suspended in water and viewed

with bright-field microscopy (1500). (From Gardiner CH, Fayer R,

Dubey JP. 1988. An atlas of protozoan parasites in animal tissues,USDA Agricultural Handbook No. 651, USDA, Beltsville, Md.)

Diagnosis

Fecal Examination

Fecal oocyst excretion directly coincides with the onset and duration of clinical signs. Because

cryptosporidial oocysts are directly infective when shed in the feces, caution must be used to avoid

accidental infection. To destroy the oocyst, one part 100% formalin (38% formaldehyde) should be mixed

with nine parts fluid feces before performing fecal examination procedures. Sodium acetateacetic acid

formalin is another acceptable fixative, but polyvinyl alcohol fixatives are not compatible with most staining

procedures. Samples should also be formalinized before shipment to a diagnostic laboratory and should be

placed in a nonbreakable container. The outside of the container should be disinfected to avoid accidental

infection of laboratory personnel. The laboratory should be notified of suspicion of cryptosporidial infection.

Oocysts may be seen microscopically on direct smears of feces, but concentration techniques, such as

Sheather's sugar solution, can be used (see Fecal Examination, Chapter 70). Because oocysts are slightly

smaller compared with erythrocytes, and because of transparency, unstained preparations using conventional

light microscopy do not permit accurate identification.113

When searching for cryptosporidial oocysts on

unstained preparations, phase contrast microscopy is often recommended; however, bright field microscopy

can be used (Fig. 82-3). A wet preparation in which crystal violet is applied to fluid stools enhances

visualization of organisms. Oocysts can readily be seen because they do not stain. Because the small and

refractile oocysts cling to the coverslip on Sheather's flotation, focusing immediately beneath the coverslip is

imperative. Oocysts appear as circular, sometimes concave, disks that are refractile and pink with bright field

microscopy. Dark shadows of sporozoites may be seen within the oocysts.

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Beagle pups experimentally infected with C. parvumof calf origin commenced shedding oocysts 3 to 5 days

postinoculation (PI), with a peak shedding at 7 to 9 days PI. Shedding lasted for at least 80 days at a low or

intermittent level.

Other procedures, used by diagnostic laboratories to demonstrate cryptosporidial oocysts in fluid stools,

include formalin ethyl acetate (FEA) sedimentation technique or examination of direct smears of feces or

intestinal contents with positive stains, such as Giemsa (Fig. 82-4), or acid-fast, negative stains, such as

Kinyoun's modified carbolfuchsin malachite green, and crystal violet (Fig. 82-5).*The negative stains give a

clear halo around the oocysts. Using the FEA concentration method on watery stool specimens provided

100% detection with direct fluorescent antibody (FA) or acid fast staining when 104oocysts/g or more were

present.136

For formed stools, 5 104oocysts/g or more was needed for direct FA and 5 10

5oocysts/g or

more for acid fast staining. A modification of the acid fast technique using dimethyl sulfoxide has simplified

the procedure by staining the internal structure of the organism. Newer but more expensive auramine

rhodamine staining techniques are very sensitive.75

Staining methods allow for easier detection of the

oocysts and their differentiation from yeasts, which stain darker, are oval, appear in clumps, and may show

budding, and are slightly smaller than cryptosporidia. Commercial kit staining methods are available.97

A

direct FA kit for staining cryptosporidial oocysts (and Giardiacysts) in feces is commercially available

(Merifluor, Meridian Diagnostics, Cincinnati, Ohio). Although few evaluations have been reported in dogs

and cats,75b

the test is effective for oocyst detection in fecal samples from calves and sheep.145

Several

enzyme-linked immunosorbent assays (ELISA) (ProSpecT and ProSpecTR, CryptosporidiumMicrotiter

Assay, Alexon, Sunnyvale, Calif.; Color Vue Cryptosporidium, Seradyn, Indianapolis, Ind.) for the detection

of cryptosporidial antigen in feces are also available, but whether these tests will consistently reveal C. felis

or C. canisis unknown. ELISA tests were more sensitive in detecting Cryptosporidiumoocysts in a single

fecal specimen of kittens compared to acid-fast staining and direct FA methods.75b

Nested polymerase chain

reaction (PCR) has been used to detect C. parvumDNA in feces of symptomatic people with 500 oocysts/g

of feces, some of whom had negative results with acid fast staining.6Similar high sensitivity has been

reported for PCR detection in calf feces.136

PCR has been used for the diagnosis and the molecular typing ofisolates causing cryptosporidiosis in dogs.

3,2,121aA nested multiplex PCR was developed that can

simultaneously detect and distinguish between four zoonotic species: C. parvumgenotypes 1 and 2, C. canis,

and C. felis.70

When compared with immunofluorescence, PCR has been shown to be 10 to 100 times more

sensitive for the diagnosis of cryptosporidiosis in cats.63,121,121a

Flow cytometry has also been used to

increase the sensitivity of oocyst detection.133

See Appendix 5for the laboratories that perform diagnostic

tests and Appendix 6for further information on test kits available for diagnosis of this disease.

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Fig 82-4 Fecal smear with cryptosporidial oocysts stained blue (Giemsa, 750).

(From Gardiner CH, Fayer R, Dubey JP. 1988. An atlas of protozoan

parasites in animal tissues, USDA Agricultural Handbook No. 651,USDA, Beltsville, Md.)

Fig 82-5 Acid-fast stained preparation of Cryptosporidiumoocysts. Organisms

are outlined well with negative staining method (1000). (Courtesy

University of Georgia, Athens, Ga.)


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* References: 25, 52, 71, 75, 91, 96.

Serologic Testing

An ELISA was developed to measure Cryptosporidiumspecific IgG in feline sera.65

Positive antibody titers

were correlated with exposure but not necessarily active infection or oocyst shedding. This test has been used

as an epidemiologic surveillance tool.80

Animal Inoculation

Oocysts for animal inoculation may be harvested by sugar centrifugation and stored in a refrigerator in 2.5%

potassium dichromate for up to 6 months without appreciable loss of viability. Neonatal mice are inoculated

per os, and the intestinal tissues are examined microscopically 1 week later.

Intestinal Biopsy

Gross lesions consist of enlarged, congested mesenteric lymph nodes, and changes are most severe in the

distal ileum. The mucosa is hyperemic and may contain watery, yellow contents. Giemsa and routine

hematoxylin and eosin stains are effective given that most parasite stages are basophilic (Fig. 82-6). As a

routine method of diagnosis, biopsy is costly, time consuming, and lacks sensitivity because only small

amounts of tissue can be examined.

Specimens may be fixed in Bouin's or formalin solutions. Samples must be fixed within hours of biopsy

procedure, otherwise cellular death associated with autolysis causes rapid loss of the intestinal surface that

contains the organisms. Microscopic lesions vary in degree of villous atrophy, reactive lymphoid tissue, and

inflammatory infiltrates in the lamina propria, consisting of neutrophils, macrophages, and lymphocytes.

Blunting of the intestinal villi and crypt hyperplasia is apparent. Parasites may be found throughout the

intestines but are usually most numerous in the distal small intestine. Electron microscopy (EM) readily

identifies organisms by their unique ultrastructural characteristics and location within distinctive

parasitiferous vacuoles.97

EM shows that the organism is covered by the host cell microvillous membrane

and therefore is intracellular but extracytoplasmic in location.

Therapy

Infections in immunocompetent animals or people are usually self limiting, and full recovery soon ensues. To

date, few drugs have been used successfully for treating cryptosporidiosis, although more than 100 have been

screened.58

Spiramycin showed early promise, but subsequent studies did not corroborate its efficacy.108

Eflornithine,117

oral bovine dialyzable extract,79

and hyperimmune bovine colostrum112

have shown clinical

benefit. The aminoglycoside antibiotic, paromomycin (Humatin, Parke Davis, Morris Plains, N.J.), is effective

in treating acute intestinal cases of cryptosporidiosis in people,18

calves,26

mice,42

and rats.135

Clinical signs ofdisease and oocyst shedding were eliminated in cats and dogs after paromomycin was administered for 5 days

(Table 82-2).7,8

Paromomycin is not absorbed from the GI tract unless gut epithelium is injured. If injured, a

resulting absorption of paromomycin, renal damage, or deafness similar to that caused by other

aminoglycosides may occur. Acute renal failure has been described in four cats receiving excessive doses of

paromomycin for the treatment of hemorrhagic diarrhea presumably caused by cryptosporidiosis.35

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Paromomycin was effective in preventing cryptosporidial enteritis in a controlled study in goats.55

See the Drug

Formulary, Appendix 8, for further information on this drug. Although paromomycin seems effective against

ileal infections, it was ineffective against cecal and biliary tract infections in immunosuppressed rats.115

Tylosin (11 mg/kg, orally, twice daily for 28 days) was helpful in relieving diarrhea in a cat withcryptosporidiosis and lymphocytic duodenitis,

46,64which may be related to its antibacterial effects. Neither

prior treatment with clindamycin nor metronidazole was effective in treating this cat. Pretreatment with

paromomycin was effective in prolonging the prepatent period of infection in a controlled study of calves with

experimentally induced infections; however, it did not reduce the severity or occurrence of infection.38

Paromomycin was no more effective than placebo was in treating human patients with advanced AIDS.45

Azithromycin, a macrolide antibiotic, was more effective than paromomycin was when used at identical

regimens against cryptosporidial infection involving the ileum, cecum, or biliary tract of immunosuppressed

rats.115

Azithromycin has been effective in treating an immunocompetent man with cryptosporidiosis acquired

from a calf.10

Azithromycin is being tested in human trials but has not been extensively studied for the

treatment of infected dogs or cats. Azithromycin, combined with paromomycin, was highly effective in treating

an immunocompromised person with AIDS.

124

Clarithromycin, a related derivative to azithromycin, was highlyeffective in preventing development of cryptosporidiosis in human patients with AIDS when it was combined

with a rifabutin as prophylaxis for mycobacterial infections.50

Nitazoxanide has shown some efficacy in people

infected with cryptosporidiosis and has been licensed for treatment.118,138

In one study, cats treated with

nitazoxanide showed immediate cessation of cyst excretion in their feces, but administration was complicated

by vomiting soon after the cats received the oral drug.35

This drug needs further study in cats and dogs.

Lasalocid, an ionophorous antibiotic, had in vitro and in vivo activity against cryptosporidia,43

although further

studies are needed. For additional information on the above drugs, see Chapter 34, and the Drug Formulary,

Appendix 8.

Fig 82-6 Cryptosporidium (arrows)in intestine from an infected calf is

characteristically located at the microvillous border (H and E stain,

250). (Courtesy University of Georgia, Athens, Ga.)


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Table 82-2 Drug Therapy for Cryptosporidiosis

DRUG

a SPECIES

DOSE

b

(mg/kg)

ROUTE INTERVAL (HOURS)DURATION (DAYS)

Paromomycin B 125165 PO 12 57,8

Azithromycinc D 510 PO 12 57

C 715 PO 12 57

B,Dog and cat; D,dog; C,cat; PO,by mouth.

a See Drug Formulary,Appendix 8, for specific information on drugs.

b Dose per administration at specified interval.

c Dose for systemic infections; effective level for this disease has not been established.

Parenteral fluid replacement is usually indicated if dehydration is severe. Antibiotic therapy for eliminating

secondary bacterial invaders may be necessary. Because absorptive-cell surface epithelium is lost and

developing glutamine-dependent epithelium predominates, oral rehydration solutions containing glutamine may

be helpful as supportive care.

40

Public Health Considerations

Cryptosporidial infections in people were not recognized until 1976. Since that time, it has been diagnosed with

increasing frequency. Animal handlers, medical personnel, people living or traveling in developing countries,

and children in day care facilities have the highest risk of exposure. Infection is not restricted to, but is more

severe in, immunocompromised hosts. Between 4% and 7% of human patients admitted to hospitals for

gastroenteritis have cryptosporidiosis, and infections are more common during the warm, humid months.

Aquatic transmission via drinking water, the source of infection for more than 400,000 people in Milwaukee in

1993,73

and swimming pools74,78

have been major sources of infection. One outbreak in the United States has

also been associated with a recreational lake.62

Although major human outbreaks of cryptosporidiosis caused by

C. hominisand C. parvumhave been linked to contaminated drinking water, none has incriminated C. felisorC. canis.

70aReports of food contamination with feces from infected people or animals are less common.

58

Owning a dog or cat does not increase the risk of humans developing cryptosporidiosis.70a

Although

epidemiologic data implicating household pets as sources of cryptosporidiosis in people is weak, several reports

have been issued of human infection after contact with infected cats60

and a dog.37

C. parvumof the cattle genotype has been considered as the predominant zoonotic risk for people. Dogs may

also be infected with the cattle genotype, which they may conceivably pass on to people. Dogs are most

commonly infected with the host-restricted species C. canis. Therefore dogs are not a significant reservoir for

human infection. The dog isolate has been identified only in a few reports of human infection.*The people in

these reports have generally been immunocompetent and nonsymptomatic. Similarly, human infection with C.

felishas been an uncommon occurrence; however, clinical illness has been more apparent. Fourteen cases of C.

felisinfection of people have been documented with genetic methods.Clinical illness, characterized by watery

diarrhea, was observed in immunocompetent (n = 4) and immunosuppressed (n = 10) people.12

Reports of

human cryptosporidiosis acquired from cats have been published in which the infecting species was unknown.30

A nosocomial outbreak of C. parvuminfection in animals and people in a veterinary teaching hospital was

associated with infection from a hospitalized calf.61

Numerous reports of transmission from calves to humans

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have been issued.66,68,83

Genetic analyses of human and bovine isolates have shown that two types of C.

parvumexist.107

One is involved with calf to human, human to human, human to calf, and other interspecies

transmissions. The other is an exclusive anthroponotic cycle, with people being both the reservoir and affected

population. Because cryptosporidiosis can be fatal in immunocompromised people, especially those with AIDS,owners of infected animals must be made aware of the zoonotic risks. C. muris, predominantly a rodent species

that can experimentally infect dogs and cats among other animals, has been isolated from immunocompromised

people.104

Whether dogs can be reservoirs for this species is uncertain.

In immunocompetent people, GI signs, in decreasing frequency, include profuse watery diarrhea, low grade

fever, vomiting, and abdominal discomfort. Diarrhea usually lasts 3 to 12 days. Infants, children, and older

adults have more chronic persistent diarrhea and dehydration. In immunodeficient individuals, especially those

with AIDS, the diarrhea becomes chronic (usually 20 or more weeks), debilitating, and potentially fatal. In

addition, respiratory tree, biliary, and pancreatic duct colonization has been reported in immunodeficient people

with associated clinical signs.17

Cryptosporidia are resistant to commercial bleach (5.25% sodium hypochlorite); routine chlorination of

drinking water does not affect oocyst viability.114

Of the common disinfectants, only formol saline (10%

solution) and ammonia (5% solution) were effective in destroying the viability of cryptosporidial oocysts.

However, oocysts had to be in contact with the disinfectants for 18 hours. More concentrated (50%) ammonia

solutions have been effective after 30 minutes. Moist heat (steam or pasteurization [over 55 C]), freezing and

thawing, or thorough drying are more practical means of disinfection. Swimming pools can be disinfected by

using high-chlorine concentrations for long periods (3 mg/L of water for 53 hours or 8 mg/L for 20 hours).57

Excellent sanitation and liberal use of boiling water for scalding food and water bowls should minimize

contamination in a clinical environment. Chlorination of drinking water is not effective, and because filtration

of this small organism is difficult, the organism can enter treated municipal supplies. Even bottled

noncarbonated mineral water has been contaminated.95

* References: 2, 87, 106, 109, 144.

References: 12, 14, 87, 106, 109, 144.

CYCLOSPORIASIS

Cyclospora cayetanensisis a member of subclass Coccidia in the phylum Apicomplexa that infects people and

animals in warm or tropical climates worldwide. For many years, C. cayetanensiswas considered a

cyanobacterium, a blue green alga, or a large (8 to 10 m) strain of Cryptosporidium. Phylogenetically, the

organism is most closely related toEimeria.110

Veterinarians should be aware that this parasite may be mistaken

for Cryptosporidium, and parasites closely resembling Cyclosporahave been found in animals. Both Cyclospora

and other coccidia have similar appearing oocysts in feces and produce similar GI signs.143

The morphology and

features of Cyclosporathat distinguish it from other coccidial oocysts are listed in Table 82-3. The life cycle of

Cyclosporais unknown, but transmission occurs through contaminated water.75a

Oocysts are passed in a

noninfectious state and must survive long enough to sporulate and to be ingested by a susceptible host. The oocyst

dies immediately when desiccated. Cyclosporaoocysts have only been recovered in limited quantities from water

sources because of technological limitations of recovery methods. At least 2 weeks at a temperature range of 25

C to 30 C (77 F to 86 F) are required outside the host for sporulation of oocysts to be infectious.127

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Outside this range, oocyst sporulation does not occur, or the time interval is markedly prolonged. Following

ingestion, sporulated oocysts excyst in the small bowel and enter epithelial cells. The upper small intestine is the

site of replication in immunocompetent hosts, and more diffuse intestinal involvement occurs in the

immunosuppressed hosts.105Asexual replication is thought to occur in the small bowel with extruded merozoites

penetrating new epithelial cells. Sexual reproduction occurs in the small bowel epithelium as unsporulated oocysts

are shed in the stool.101

Malabsorption is caused by inflammation, villous atrophy, and crypt hyperplasia.

Cholecystitis has also been reported in people.148

Outbreaks correspond to the time of the rainy season in endemic countries. Drinking contaminated water or eating

unwashed berries (e.g., raspberries) or other plants (e.g., basil, salad leaves) imported from some countries in

South America or Southern Europe have been implicated as risk factors in the United States,*where the

prevalence in stool specimens submitted to diagnostic laboratories is generally less than 0.5%.51,125

Carriage rates

of up to 20% of people with diarrhea are found in endemic tropical countries. Animals or insects may act as

reservoir hosts maintaining the organism in nature. Although other animals might be infected, this has been

currently identified only as a human pathogen. Cyclospora-like organisms have been recovered from dogs,

chickens, ducks, and primates.127

Only in primates has the organisms been confirmed as Cyclospora. In other

animals, inert passage through the intestinal tract cannot be eliminated. Two cases in dogs in Sao Paulo, Brazil,

have been reported.147

However, when dogs were experimentally inoculated orally with Cyclosporacysts,

infection did not occur.22

In Mexico, feces of cats were examined to no avail; however, a large number of oocysts

morphologically and biologically resembling C. cayetanensiswas found in poultry feces.29

Fowl feces may be

involved in contamination of poultry meat, water supplies, vegetables and fruits, or any combination of these.

Animal to human or person to person transmission is not yet documented.

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Table 82-3 Comparison of Coccidial Oocysts and Transmission

VARIABLE CYCLOSPORA CRYPTOSPORIDIUM ISOSPORA TOXOPLASMA

Definitive host People, possibly animals People, dog, cat, other

animals

People, dog, cat other

animals

Cat

Intestinal biopsy

Intracellular stages T, S, M T, S, M, G T, S, M, G T, S, M, G

Intracellular location Deep seated Intramembranous,

extracytoplasmic

Deep seated Deep seated

Size in tissue (mm) 416 25 315 315

Feces

Oocyst size (mm) 810 46 1019 2030 Varies

with species

12 10

Sporulated oocyst

Number sporocysts 2 0 2 2

Number sporozoites per

sporocyst

2 4 per oocyst (naked) 4 4

Acid-fast staining Variable Yes Yes Yes

Ultraviolet

autofluorescence,

365-nm filter

Blue-green Circles None Yes None

Auramine fluorescence Weak Bright Variable Variable

Infectivity in fresh feces

(already sporulated)

No Yes No No

Zoonotic transmission Unknown Many animals None, host specific Cat

Host-to-like-host

transmission

Unknown Yes Yes Yes, uncommon via

oocyst

Modified from Soave R. 1996. Cyclospora:an overview, Clin Infect Dis23:429437, with permission of the University of

Chicago Press; Sun T, Ilardi CF, Asnis D, et al. 1996. Light and electron microscopic identification of Cyclosporaspecies in the

small intestine: evidence of the presence of asexual life cycle in human host, Am J Clin Pathol105:216220; copyright

1996, by the American Society of Clinical Pathologists. Reprinted with permission.

T,Trophozoite;S,schizont; M,merozoitel G,gametocyte.

Cyclosporiasis produces relapsing watery diarrhea, fatigue, systemic influenza-like manifestations, and weight loss

in susceptible people such as those infected with HIV, those receiving organ transplants or immunosuppressants,

and those traveling to different geographic areas. Clinical signs usually begin after 1 week following exposure.

Clinical signs are infrequent or transient in immunocompetent hosts, who usually recover within several weeks.101

Diagnosis is made by microscopic detection of oocysts in fecal specimens. At present, definitive oocysts have only

been identified in human feces. These oocysts can be confused with CryptosporidiumandIsospora, which also

stain acid-fast in stool specimens. However, Cyclosporahas a variable staining intensity on an individual

preparation. The organisms are passed unsporulated in fresh feces and on superficial examination, they may be

misidentified as a fungal spore. Although PCR has been used for specific detection of the organism in fecal

specimens, cross amplification with other coccidia has not been determined.99,111

Organisms can also be detected

on jejunal aspiration or biopsy. Unlike cryptosporidiosis, cyclosporiasis in people responds to 7 days of treatment

with trimethoprim sulfonamides with rapid cessation of diarrhea and shedding of oocysts.49,134Should a dog or

cat be diagnosed with clinical cyclosporiasis or pose a potential risk for human infection, routine dosages of

trimethoprim-sulfonamide can be used (see Drug Formulary, Appendix 8). As with other coccidia, chlorine bleach

is not an effective disinfectant for Cyclosporaspp. oocysts.


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C. cayetamensisrequires a period in the environment to sporulate into the infectious oocysts. Therefore direct

animal-to-person or person-to-person spread would be minimal. People tend to acquire their infection from

consuming contaminated water or produce. Nevertheless, cyclosporiasis in Peru has been epidemiologically

associated with ownership of domestic animals, especially birds, guinea pigs, and rabbits.9

* References: 16, 20, 44, 48, 72.

Suggested Readings*

* See the CD-ROM for a complete list of references.

2. Abe, N, Kimata, I, Iseki, M: Identification of genotypes of Cryptosporidium parvumisolates from a

patient and a dog in Japan.J Vet Med Sci. 64, 2002, 165168.

34. Gookin, JL, Nordone, SK, Argenzio, RA: Host responses to Cryptosporidiuminfection.J Vet Intern

Med. 16, 2002, 1221.

35. Gookin, JL, Riviere, JE, Gilger, BC, et al.: Acute renal failure in four cats treated with paromomycin.J

Am Vet Med Assoc. 215, 1999, 18211823.

82. Miller, DL, Liggett, A, Radi, ZA, et al.: Gastrointestinal cryptosporidiosis in a puppy. Vet Parasitol.

115, 2003, 199204.

88. Morgan, UM, Sargent, KD, Elliot, A, et al.: Cryptosporidiumin catsadditional evidence for C. felis.

Vet J. 156, 1998, 159161.

89. Morgan, UM, Xiao, L, Monis, P, et al.: Cryptosporidiumspp. in domestic dogs: the dog genotype.

Appl Enviro Microbiol. 66, 2000, 22202223.

121. Scorza, AV, Brewer, MM, Lappin, MR: Polymerase chain reaction for the detection of

Cryptosporidiumspp. in cat feces.J Parasitol. 89, 2003, 423426.

Uncited references

119. Saini, PK, Ransom, G, McNamara, AM: Emerging public health concerns regarding cryptosporidiosis.

J Am Vet Med Assoc. 217, 2000, 658663.

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82 Cryptosporidiosis and Cyclosporiasis