Cryptosporidium Infections in Cats and Dogs - VetLearn.com

Article #3
CE
ABSTRACT:
Cryptosporidiosis was recognized as an important zoonosis in the early 1980s. Early
studies assumed that all infections in mammals, including humans, were caused by the
parasite Cryptosporidium parvum. Recent studies using molecular biologic tools and hostspecificity
studies indicate that cats and dogs have their own unique species of Cryptosporidium
(C. felis and C. canis, respectively). Surveys indicate that up to 38.5% of cats and
up to 44.8% of dogs are infected with Cryptosporidium spp. Initial studies indicate that
owning a cat or dog does not increase the risk of humans acquiring cryptosporidiosis,
although human infections with C. felis and C. canis have been found in patients with
AIDS, immunosuppressed patients, and children from impoverished areas. Clinical signs
of cryptosporidiosis in cats and dogs vary from none to chronic or intermittent diarrhea.
Fluids and other supportive measures should be used in animals with diarrhea, but
there is no proven safe and effective treatment of cryptosporidiosis.
embers of the genus Cryptosporidium
are in the protozoan phylum Apicomplexa.
They are coccidia-like parasites
that develop in the microvillous border of
epithelial cells in the digestive, respiratory, and
urinary tracts of vertebrates. 1 Recent molecular
phylogenetic studies indicate that cryptosporidia
are more closely related to the gregarine
parasites of invertebrates than to the true coccidial
parasites of vertebrates. 2 This may explain
why cryptosporidia are not sensitive to chemotherapeutic
agents normally used to treat coccidial
infections. 1 M
In the early 1980s, Cryptosporidium
parvum was identified as a major
cause of intestinal disease in patients with
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Cryptosporidium Infections
in Cats and Dogs
David S. Lindsay, PhD a
Anne M. Zajac, DVM, PhD
Virginia-Maryland Regional College of Veterinary Medicine
a Dr. Lindsay receives funding
from Bayer Animal Health and
Merck & Company. Neither
company has been involved in
the preparation of this article.
AIDS, and it was later found in immunocompetent
humans who had been exposed to
infected dairy calves. 3 Several groups of
researchers conducted studies in which C.
parvum was successfully transmitted from
calves to young animals, including cats and
dogs. 1,3 Successful cross-species transmission
studies with C. parvum led to the proposal that
the organism was responsible for all infections
in mammals. 4 Most parasitologists embraced
this concept, which has been taught in most
veterinary schools since the 1980s. Recent studies
of Cryptosporidium spp from cats, 5–10
dogs, 11–13 and humans 14 indicate that these
organisms are biologically and genetically different
from C. parvum; thus they are now considered
separate species. Cryptosporidium felis is
primarily found in cats 5 and Cryptosporidium
canis in dogs 11 ; Cryptosporidium hominis is the
newly recognized parasite in humans. 14
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Ingestion
Excystation
Thick-walled
oocyst
Exits body
Sporozoite
Host
Excystation epithelial
cell
Autoinfection
Thin-walled oocyst
Mature
oocyst
Trophozoite
Immature
oocyst
LIFE CYCLE
Sporulated oocysts are ingested via direct contact with
the feces of an infected host or contaminated food or
water (Figure 1). The oocysts excyst in the digestive
tract, and the sporozoites penetrate the microvilli of a
variety of epithelial cells. The location of the infected
host cells depends on the species of Cryptosporidium. The
elongated sporozoite rounds up and becomes a trophozoite.
The trophozoite becomes a multinucleated type I
schizont and produces eight type I merozoites, which
penetrate other microvilli and become type II schizonts.
Type II schizonts repeat this developmental cycle, resulting
in four type II merozoites. Recycling of asexual
stages may occur. Type II merozoites penetrate microvilli
and become sexual stages. The male stage (i.e., microga-
Cryptosporidium Infections in Cats and Dogs CE 865
Microgamont
Macrogamont
Type I meront
Merozoite
Merozoite
Type II meront
Figure 1. Life cycle of Cryptosporidium spp. (Adapted from Dubey JP, Speer CA, Fayer R: Cryptosporidiosis of Man and Animals. Boca Raton, FL,
CRC Press, 1990)
mont) produces nonflagellated microgametes. In the
female stage (i.e., macrogamont), fertilization occurs and
oocysts are produced. Two types of oocysts are produced,
both of which sporulate endogenously and contain four
sporozoites, an oocyst residuum, and no sporocysts.
Thin-walled oocysts are autoinfective. Thick-walled
oocysts are excreted in the feces. 5,11,14
Cryptosporidium spp contain approximately 5,000
members, including Plasmodium (malaria), Toxoplasma,
Babesia, Neospora, Sarcocystis, and Eimeria spp. Most are
obligate intracellular parasites. Apicomplexans lack
appendages for locomotion and instead move by a “gliding”
motion. Cell entry by this group is mechanically
distinct from uptake of viruses, bacteria, and other parasites.
Cryptosporidium, Eimeria, and Toxoplasma spp
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Cryptosporidium Infections in Cats and Dogs
form oocysts that are shed in the feces of infected hosts.
Cryptosporidia oocysts are very resistant to environmental
damage, chlorination, and standard cleansers.
This makes Cryptosporidium spp an important foodand
waterborne pathogen. Extreme temperatures and
prolonged contact with ammonia destroy the oocysts.
PATHOGENESIS
The mechanisms by which Cryptosporidium spp
induce diarrhea, malabsorption, and wasting in humans
and animals are not well understood. 15 Cryptosporidial
parasites can develop in a variety of epithelial cells in the
body, not just in enterocytes in the intestines. This can
lead to respiratory, ocular, pancreatic, and hepatic infections
in humans; fortunately, these extraintestinal loci of
cryptosporidial infection have not been reported in dogs
or cats. Cryptosporidia develop in the microvillous border
and displace it, eventually leading to loss of mature
Dogs
Most reported cases of cryptosporidiosis in dogs involve
young animals. 13,28–33 Cases in adult dogs are rare. 34
Clinical signs can vary from none to chronic or intermittent
diarrhea and wasting. Immunosuppression due
to canine distemper may exacerbate infections in
dogs. 29,31 Concurrent canine parvovirus infection and
intestinal Isospora spp infection may also enhance cryptosporidiosis
in immunosuppressed dogs. 13,32 Two recent
reports used molecular methods to determine the Cryptosporidium
spp in a fatal case involving an 8-week-old
Yorkshire terrier from Georgia 33 and a nonfatal case involving
a 9-week-old bullmastiff from Australia, 13 and
both reports found that C. canis organisms were present.
DIAGNOSIS
The small size of Cryptosporidium oocysts makes them
difficult to detect. Oocysts are often overlooked unless
Oocysts of C. felis and C. canis are structurally similar
to the well-known and zoonotic C. parvum.
surface epithelium. 15 This causes shortening and fusion
of villi and lengthening of the crypts due to acceleration
of cell division to compensate for loss of cells. 15 This
causes reduced uptake of fluids, electrolytes, and nutrients
from the gut lumen. 15
The minimum infective dose of Cryptosporidium oocysts
for cats and dogs is unknown. Experimental studies in
humans using C. parvum oocysts collected from calves
indicate that 10 or fewer oocysts can cause infection. 16
Differences in infectivity among different C. parvum isolates
in human volunteers have been documented. 15
CLINICAL SIGNS
Cats
Most cats that are excreting Cryptosporidium oocysts
do not have clinical signs. 5,7,17–20 Young 17,18 or immunocompromised
18,21 animals are more likely to be infected.
Chronic or intermittent diarrhea, anorexia, and wasting
are common clinical signs in symptomatic cats. 21–25
Coinfection with Giardia spp or Tritrichomonas foetus
may exacerbate clinical signs of cryptosporidiosis in
cats. 26,27 Administering prednisolone (10 mg/kg/day SC
for 4 to 9 days 7 or 2.8 to 3.8 mg/kg/day PO for 26
days 27 ) may cause oocysts to reappear in feline feces.
an examiner is specifically looking for them, and this is
especially true if few oocysts are present in the sample.
Fecal flotation techniques used routinely in veterinary
laboratories are adequate to demonstrate Cryptosporidium
oocysts if large numbers are present. The slide
should be examined using the high-power objective.
Sheather’s sugar solution is the best flotation medium. 3
Because oocysts are small, they float in a plane higher
than that of helminth ova and other protozoal cysts.
They are light pink, and a central residual body is usually
visible in Cryptosporidium oocysts in fecal flotations.
C. felis oocysts are smaller 9,17,35 than those of C. parvum,
but morphology alone cannot be used to determine the
species of Cryptosporidium in a sample. 36 Many small
animal technicians are not taught to recognize Cryptosporidium
oocysts and may have difficulty identifying
them when the tests are run only infrequently. In these
cases, it is probably better for samples to be sent to diagnostic
reference laboratories for testing.
Fecal samples sent to diagnostic laboratories can be
tested using a number of procedures. 37 More than 10 different
types of staining methods have been developed for
use with fecal smears to aid in detecting Cryptosporidium
oocysts via standard light microscopy. 37 The Ziehl-Neelsen
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Cryptosporidium Infections in Cats and Dogs
Table 1. Transmission Studies with C. felis and
C. canis Oocysts
Source Recipient Results Study
Cat Guinea pigs Negative Iseki 5 , Arai et al 17
Cat Mice Negative Iseki 5 , Arai et al 17
Cat Newborn mice Negative Mtambo et al 8 ,
Arai et al 17
Cat Lambs Positive Mtambo et al 8
Cat Immunosuppressed mice Negative Mtambo et al 8
Cat Rats Negative Arai et al 17
Cat Dogs Negative Arai et al 17
Dog Newborn mice Negative Fayer et al 11
Dog Immunosuppressed mice Negative Fayer et al 11
Dog Calves Positive Fayer et al 11
Table 2. Prevalence of Cryptosporidium spp in Cats
Number Prevalence
Examined Location Test (%) Study
600 United States Serology 8.3 McReynolds et al 50
418 Australia Fecal 0 McGlade et al 52
40 Australia PCR 10 McGlade et al 52
102 Australia Fecal 1.2 Sargent et al 9
10 France Fecal 0 Chermette and
Blondel 53
300 Germany Fecal 1.3 Augustin-Bichl 55
13 Japan Fecal 38.5 Iseki 5
507 Japan Fecal 20 Uga et al 54
608 Japan Fecal 3.8 Arai et al 17
57 Scotland Fecal 12.3 Nash et al 19
235 Scotland Fecal 8.1 Mtambo et al 18
205 Colorado Fecal 5.4 Hill et al 51
263 New York Fecal 3.8 Spain et al 20
acid-fast staining technique is most often used and produces red-stained oocysts
against a blue–green background of fecal material. Fluorescently labeled monoclonal
antibodies to the oocyst stage of C. parvum have been made and are used
in a commercial direct immunofluorescent antibody (IFA) test. 38 Most Cryptosporidium
spp, including C. felis and C. canis, cross-react in commercial IFAbased
diagnostic tests developed to detect C. parvum. 39,40 Cross-reactivity also
occurs in many ELISAs for C. parvum. 38 Polymerase chain reaction (PCR) can
detect Cryptosporidium spp in fecal samples, and PCR is more sensitive than
IFA testing. 41 Most PCR-based tests indicate only the presence of Cryptosporidium
spp, but a recently developed set of PCR tests can differentiate between C.
felis, C. canis, C. parvum, and C. hominis. 42
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TREATMENT
Chemotherapy for Cryptosporidium
infections in animals and humans has
been actively investigated over the past
two decades (see box on page 871).
Over 100 compounds have been tested
in laboratory animal models, but none
is highly effective clinically. 43 Paromomycin
44 and nitazoxanide (NTZ) 27
are compounds that have shown some
efficacy in animal models and have
also been used to treat intestinal cryptosporidiosis
in cats. Treatment with
paromomycin (165 mg/kg PO bid for
5 days) resulted in resolution of diarrhea
and disappearance of oocysts
from the feces of a 6-month-old cat
with persistent diarrhea. 44 Paromomycin
is potentially nephrotoxic,
and acute renal failure was reported in
four cats that received paromomycin
for cryptosporidiosis or trichomoniasis.
45 Treatment using NTZ (25 mg/kg
PO bid for 28 days) eliminated Cryptosporidium
oocysts from the feces of
naturally infected laboratory cats. Use
of NTZ was associated with vomiting
and the presence of dark brown–black, foul-smelling
diarrhea while treating these cats. 27 Chlorpromazine (0.5
to 1.5 mg SC once daily) was given to alleviate vomiting
in NTZ-treated cats. 27 Fenbendazole administered at 50
mg/kg PO for 5 days did not affect Cryptosporidium
oocyst excretion in cats. 26
Treatment of an 18-month-old cat with inflammatory
bowel disease and Cryptosporidium infection was successful
using a course of clindamycin (25 mg/kg/day
[three-fourths of the total dose was administered in the
morning and one-fourth of the total dose at night] PO
for 60 days) and then tylosin (11 mg/kg PO bid with
food for 28 days). 15 Interpretation of these results was
hampered because of the presence of Clostridium perfringens
in the cat’s intestinal tract. Clindamycin administered
at 15 mg/kg PO q8h for 6 days did not eliminate
Cryptosporidium oocysts from a 5-year-old pointer. 34
STUDIES ON HOST SPECIFICITY OF
C. FELIS AND C. CANIS
Transmission studies with C. felis and C. canis indicate
that these species are relatively host-specific (Table 1).
Cryptosporidium Infections in Cats and Dogs CE 869
Table 3. Prevalence of Cryptosporidium spp in Dogs
Number Prevalence
Examined Location Test (%) Study
421 Australia Fecal/PCR 0 Bugg et al 62
493 Australia Fecal 11 Johnston and Gasser 65
195 Australia Fecal 7.1 Milstein and
Goldsmith 66
25 Egypt Fecal 12 El-Hohary and
Abdel-Latif 67
57 Finland Fecal 0 Pohjola 68
29 France Fecal 44.8 Chermette and
Blondel 53
200 Germany Fecal 0 Augustin-Bichl et al 55
213 Japan Fecal 1.4 Uga et al 54
140 Japan PCR 9.3 Abe et al 63
257 Korea Fecal 9.7 Kim et al 40
81 Spain Fecal 7.4 Causape et al 61
101 Scotland Fecal 0 Simpson et al 59
100 Scotland Fecal 1 Grimason et al 69
200 California Fecal 2 el-Ahraf et al 60
130 Colorado Fecal 3.8 Hackett and Lappin 64
49 Georgia Fecal 10.2 Jafri et al 70
100 Kentucky Fecal 17 Juett et al 71
However, additional well-controlled PCR-based and
PCR species–validated transmission studies need to be
conducted before these earlier observations can be completely
accepted. C. felis was not infectious in dogs or laboratory
rodents in a limited number of studies. It is infectious
in lambs 8 and has been found in a naturally infected
cow. 35 C. canis is not infectious in laboratory rodents but
is mildly infectious in calves. 11 The infectivity of C. canis
oocysts in cats has not been examined. C. parvum oocysts
are moderately infectious in cats and dogs. 3,11 Molecularly
confirmed natural cases of C. parvum or C. hominis have
not been reported in cats or dogs.
Several studies have suggested that humans have been
infected with Cryptosporidium spp from kittens or
cats. 46–48 None of these studies conducted genotyping or
other studies, and they should be viewed as only circumstantially
incriminating cats in the transmission of
Cryptosporidium spp to humans.
One study indicated that a veterinary student caring
for an adult dog with cryptosporidiosis developed cryptosporidiosis.
34 The parasite in the dog or the veterinary
student was not genotyped or further characterized.
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Cryptosporidium Infections in Cats and Dogs
Table 4. Reports of C. felis, C. canis, C. parvum, and C. hominis
in Humans Who Tested Positive for Oocysts a
Number and Type
Percentage with
of Patients C. felis C. canis C. parvum C. hominis Study
30 with HIV 30% 10% 10% 50% Pieniazek et al 72
22 with HIV 27% 0% 32% 9% Morgan et al 73
1 with HIV 100% NA NA NA Caccio et al 74
34 with HIV 9% 6% 15% 50% Gatei et al 75
25 with HIV 4% 0% 56% 32% Alves et al 76
80 children b 1% 3% 10% 84% Xiao et al 77
1,680 (mixed)

On the Horizon a
The genome sequence for C. parvum has recently been
generated. C. parvum lacks many typical metabolic
pathways, including Krebs cycle and de novo synthesis
of amino acids and nucleotides. In addition,
Cryptosporidium spp contain many plant-like enzymes
that are absent or very different from those usually found
in mammals. Further analysis of this genome could
provide important clues in developing an effective drug
against this parasite.
a Abrahamsen et al: Science 304:441, 2004.
mans, 72–76 children, 77 or humans with cryptosporidiosis
and some underlying immunosuppressive conditions 78–87
(Table 4). The prevalence of C. felis and C. canis in humans
is less than that of C. hominis and C. parvum. Some
studies have not found C. felis or C. canis in humans.
PREVALENCE OF CRYPTOSPORIDIUM
SPECIES IN THE ENVIRONMENT
Cryptosporidium oocysts are common in the environment
and have been found in surveys of nondrinking
surface and waste waters. 88–91 However, genotyping
Cryptosporidium isolates from nondrinking water sources
indicates little contamination by C. felis or C. canis. 90
One study documented C. felis or C. canis oocysts in raw
waste water but found none in raw surface water. 90
Although major outbreaks of human cryptosporidiosis
have been linked to contaminated drinking water, 92–95
molecular studies indicate that C. hominis 96–98 and C.
parvum 96,98 have been responsible for drinking water–
associated outbreaks of human cryptosporidiosis. No
reports indicate that C. felis or C. canis has been associated
with waterborne outbreaks of human disease.
CONCLUSION
Despite extensive experimental and epidemiologic literature
on Cryptosporidium spp, the primary species
infecting dogs and cats, C. canis and C. felis, respectively,
have been identified only recently, and there is little
experimental work documenting their pathogenicity or
Cryptosporidium Infections in Cats and Dogs CE 871
Resources
avma.org/noah/resources/zoonosis/crypto.asp
(password protected)
The AVMA Network of Animal Health provides
zoonosis updates.
vin.com (password protected)
Search “cryptosporidiosis” photographs: Kirsten Vance’s
Arthropod and Protozoa slide show
Lindsay D: Proc West Vet Conf: Giardia and
Cryptosporidia: Really Zoonotic
zoonotic potential. The contribution of canine and
feline Cryptosporidium spp to clinical disease in pets
does not seem to be great at this time but may be underestimated
because so few cats and dogs are tested for
infection. In contrast, the risk of zoonotic infection has
received considerably more attention. Many practicing
veterinarians are unaware that, to minimize exposure to
Cryptosporidium spp, current guidelines from the US
Public Health Service and Infectious Diseases Society
of America recommend that HIV-infected humans
should not take into their homes stray dogs or cats, animals
with diarrhea, or dogs and cats younger than 6
months of age. 99 They further recommend that if a dog
Clinical signs of Cryptosporidium infection in cats and dogs
vary from none to chronic or intermittent diarrhea.
or cat younger than 6 months of age is acquired by an
HIV-infected person, the animal should be tested for
Cryptosporidium spp. These recommendations, dating
from 1999, may be more stringent than necessary, but
further molecular analysis of human and animal infections
is needed to realistically assess potential transmission
from pets to humans. Until more is known, practitioners
should recognize that Cryptosporidium infection
in dogs and cats is not uncommon in North America
and that zoonotic transmission from pets could cause
serious disease in immunocompromised humans.
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Cryptosporidium Infections in Cats and Dogs
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ARTICLE #3 CE TEST
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1. Which Cryptosporidium spp was, until recently,
believed to be responsible for all cases of cryptosporidiosis
in humans and other mammals?
a. C. hominis
c. C. felis
b. C. canis
d. C. parvum
2. Waterborne outbreaks of cryptosporidiosis have
been associated with
a. C. parvum and C. hominis.
b. C. felis and C. parvum.
c. C. felis and C. canis.
d. C. felis and C. hominis.
3. Paromomycin therapy for cryptosporidiosis in
cats has been associated with
a. vomiting.
b. diarrhea.
c. kidney failure.
d. liver failure.
4. NTZ therapy for cryptosporidiosis in cats has
been associated with
a. vomiting.
b. pneumonia.
c. kidney failure.
d. liver failure.
5. What is the best fecal flotation medium for finding
Cryptosporidium oocysts?
a. zinc sulfate solution
b. Sheather’s sugar solution
c. saturated salt solution
d. sugar–salt solution
6. Because Cryptosporidium oocysts are small, they
a. float in a plane higher than that of helminth ova and
other protozoal cysts.
b. can be seen only by using oil immersion.
c. look like Isospora spp.
d. look like Giardia cysts.
7. Administering ________ may cause oocysts to
reappear in cat feces.
a. NTZ
b. paromomycin
c. clindamycin
d. prednisolone
8. Developmental stages of Cryptosporidium spp can
be found in a host cell’s
a. nucleus.
b. microvilli.
c. cytoplasm.
d. neurons.
9. Immunofluorescent detection tests for Cryptosporidium
oocysts
a. are not reliable.
b. cross-react with most Cryptosporidium spp.
c. are highly specific for C. canis but not C. felis.
d. are highly specific for C. hominis but not C. felis.
10. Lesions and subsequent clinical signs of cryptosporidiosis
are associated with
a. reduced uptake of fluids, electrolytes, and nutrients
from the gut lumen.
b. hemorrhagic diarrhea due to invasive stages.
c. excretory diarrhea due to parasite toxins.
d. fatty diarrhea due to infection of the upper small
intestine.
COMPENDIUM November 2004