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virology > Multisystemic viral diseases of cats > Flashcards

Multisystemic viral diseases of cats Flashcards

1
Q

Feline Leukemia virus conditions

A

Lymphomas, Leukemia, and immunosuppression

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2
Q

lymphomas

A

solid lymphoid tumors composed of malignant proliferating lymphocytes

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3
Q

leukemia

A

myeloproliferative tumor of blood and bone marrow

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4
Q

distribution of feline leukemia

A

worldwide

most important viral disease of cats

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5
Q

most important viral disease of cats

A

Feline leukemia/lymphoma

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6
Q

classify feline leukemia/lymphoma

A

caused by feline leukemia virus

retrovirus

family Retroviridae

Genus Gammaretrovirus

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7
Q

subtypes of FeLV

A

3 subtypes: subtype A, B, and C

can be isolated singly or in combination in disease (A+B)

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8
Q

antigens associated with FeLV

A

4 proteins

1) p27: major internal structural protein, detectable by ELISA
2) gp70: envelope glycoprotein, neutralizing antibodies bind gp70, provides basis for subtypes
3) p15E: envelope glycoprotein, immunosuppressant
4) FOCMA: Feline oncorna cell membrane associated antigen: protein present on surface of TRANSFORMED cells from FeLV infection

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9
Q

what protein serves as basis for subtype differentiation of FeLV>?

A

gp70

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10
Q

which protein of FeLV does ELISA detect?

A

p27

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11
Q

What protein acts as an immunosuppressant with FeLV?

A

p15E

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12
Q

which protein of FeLV do neutralizing antibodies bind to?

A

gp70

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13
Q

what is the significance of FOCMA?

A

Feline oncorna cell membrane associated antigen

A protein that is only present in cells that have BEEN TRANSFORMED by FeLV… virus encoded tumor specific antigen

antibodies to this antigen induces lysis of FeLV transformed cells only

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14
Q

Is FeLV very environmentally resistant?

A

NO

labile virus- susceptible to drying and disinfectants

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15
Q

What environments have the highest FeLV rate?

A

higher incidence in urban cats (50%)

MULTI CAT HOUSEHOLDS are the highest incidence of infection (30% viremic)

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16
Q

How do cats transmit FeLV?

A

saliva (MUTUAL GROOMING, sharing of food/water bowl)
loving transmission

but also milk, urine, feces

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17
Q

Is FeLV contagious?

A

yes

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18
Q

what is the most susceptible type of cat to FeLV?

A

Young cat with prolonged exposure to a high dose of virus

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19
Q

what age is most susceptible to FeLV?

A

the younger, the more susceptible to develop disease

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20
Q

where does FeLV replicate?>

A

lymphoid tissue of oropharynx

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21
Q

does FeLV cause viremia?

A

YES

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22
Q

what is the time frame to develop neutralizing antibodies to FeLV??

A

develop Ab to gp70

if cats develop Ab within 3 weeks, they get over infection

if weak/no Ab produced, cats become persistently infected and 80% chance to die of FeLV associated disease within 3 years

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23
Q

look at the 2 charts of FeLV transmission

A

_

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24
Q

What is the ratio of FeLV neoplasia deaths to ono-neoplastic FeLV deaths?

A

for every cat that dies of FeLV neoplasia, 2.6 die of non-neoplastic FeLV complications

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25
Q

% of 16 week old kittens that develop viremia, transient viremia, and persistent viremia

A

15% chance of no viremia
35% chance of transient viremia
50% chance of persistent viremia

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26
Q

what percentage of all feline tumors are caused by FeLV?

What percentage of feline HEMATOPOIETIC tumors are caused by FeLV/

A

FeLV is responsible for 30% of all feline tumors

FeLV is reponsible for 90% of all hematopoietic tumors

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27
Q

most common signs of FeLV infection

A 
loss of appetite
progressive weight loss
anemia
persistent fever
gingivitis
lymphadenopathy
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28
Q

lymphomas

A

solid tumors consisting of accumulations of proliferating transformed malignant lymphocytes

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29
Q

what color are lymphoma masses in cats?

A

cream-white with red stippling on the cut surface

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30
Q

types of lymphomas from FeLV

A

1) multicentric- generalized lymphoma
2) Alimentary lymphoma (older cats, negative for FeLV ELISA, GI signs)
3) Thymic or Mediastinal Lymphoma (younger cats, can cause swallowing difficulties and pleural effusion)
4) unclassified lymphomas- miscellaneous category

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31
Q

what is the most common type of leukemia caused by FeLV?

A

Acute lymphocytic leukemia is most common

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32
Q

what is the most important presenting sign of leukemia from FeLV?

A

Anemia

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33
Q

Non-neoplastic diseases caused by FeLV?

A

non-regenerative anemia (normocytic, normochromic… 60-70% of cats presented with this syndrome are viremic… most commonly associated with subtypes A+C)

Enterocolitis (panleukopenia-like syndrome)

Thymus atrophy

Immunosuppression

Reproductive failure (seen in catteries, infertility)

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34
Q

Diagnosis of FeLV?

A

History (most important consequence of FeLV is immunosuppression)… refractory anemia is most important sign

Clin Path (leukemia [high WBC], lymphoblasts, NORMOCYTIC/NORMOCHROMIC ANEMIA)

pathology (lymphomas with cream-white color with red stippling on cut surface)

virus isolation

detection of viral nucleic acid (PCR detects proviral DNA, RT-PCR detects viral RNA, SNAP test)

Detection of viral antigen (ELISA/SNAP to detect p27 in blood, IFA)

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35
Q

What does the ELISA detect?

A

detects p27 antigen of FeLV in blood

DETECTS ANTIGENEMIA NOT VIREMIA

therefore, positive tests does not mean viremic

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36
Q

What do IFA tests detect for FeLV?

A

immunofluorescent antibody test

detects FeLV antigens on virus infected lymphocytes

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37
Q

How good is the IFA to detect FeLV viremia?

A

98% of cats positive by IFA are viremic

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38
Q

How good is ELISA to detect FeLV viremia?

A

70% of cats positive by ELISA are viremic

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39
Q

does a negative ELISA or IFA rule out FeLV?

A

no because of presence of non-virus producing LSA tumors

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40
Q

What are the possibilities for a negative ELISA

A

non-viremic, not exposed, or immune to FeLV

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41
Q

What are the possibilities for a positive ELISA

A

may be viremic

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42
Q

What if the cat is positive for ELISA and positive for IFA?

A

cat is VIREMIC and CONTAGIOUS

98% remain IFA positive for life

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43
Q

What if the cat is positive for ELISA but NEGATIVE for IFA?

A

DISCORDANT CAT

30% of ELISA positive cats are “Discordant Cats”

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44
Q

what are the causes of Discordant cats

A

typically test positive on initial tests, but then negative on subsequent tests

may be faulty ELISA
may be early in phase of infection (retest in 1 mnth)
may be immune cat with sequestered lesion

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45
Q

What is a sequestered lesion for FeLV?

A

can be present in healthy latently infected or in discordant cats

small foci of infected lymphocytes… immune response (neutralizing Ab) keeps virus in sequester from replication

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46
Q

what can induce sequestered lesions from causing antigenemia/replication?

A

stress

corticosteroid therapy

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47
Q

why is serological detection of FeLV pointless?

A

seropositive test indicates either that cat has recovered from infection or been vaccinated (does not obtain infection status of cat)

seronegative cat means cat 1)never was infected… or 2) may have FeLV (since diseased cats do not mount an Ab response well)

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48
Q

Vaccination for FeLV

A
  • whole virus inactivated vaccine
  • disrupted virus vaccine with adjuvant
  • genetically engineered gp70 with adjuvant
  • recombinant (live)canary poxvirus with FeLV gene inserted
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49
Q

vaccination protocol

A

vaccinate at 10-12 weeks with 2 doses and booster annually

vaccine prevents tumor, but cats can still become latently infected

vaccine can induce soft tissue sarcoma at injection site

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50
Q

control program

A

test and removal program in shelters

  • test all cats… if neg, retest after 3 months… if still negative then FeLV negative
  • if FeLV exists in cattery, all cats that test positive should be removed… retest after 2 months (and every 3 months thereafter)
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51
Q

how quickly can we clear a cattery of FeLV

A

within 6 months

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52
Q

Treatment of FeLV

A

chemotherapy- cyclophosphamide + vincristine + prednisone

or treat with AZT to decrease amount of virus shed

53
Q

Feline Sarcoma Virus

A

endogenous virus
highly oncogenic, defective virus associated with tumors
~fibrosarcoma of skin
carry v-onc gene that replaces part of ENV Gene
Lack capsid and envelope proteins

can hijack FeLV capsid and leave the cell this way

54
Q

FIV
classify
any subtypes?

A

Feline Immunodeficiency Virus
caused by a retrovirus within genus lentivirus
3 subtypes in US (differentiated by envelope glycoproteins)

55
Q

FIV family and genus

A

family Retroviridae, genus Lentivirus

56
Q

what percentage of clinically ill cats test positive for FIV

A

4-25%

57
Q

transmission of FIV

A

fighting disease
biting during cat fights OR saliva contamination of wounds OR blood transfusion

  • virus infects and circulates in CD4 Th cells as a PROVIRUS (integrated int he chromosome)
  • also present in blood as free virus
  • also present in saliva
58
Q

Is a blood transfusion a possible route of infection?

A

YES

because it infects Th cells, transmitted lymphocytes are infectious … also free virus in blood would infect

59
Q

how common is horizontal transmission of FIV in multi-cat housholds?

A

infrequent

60
Q

what gender and age of cats are more commonly infected with FIV?

A

2-3X higher incidence in males than females

Adults >6 years more often infected than kittens

61
Q

recap of transmission of FIV

A 
fighting
saliva contamination of wound
iatrogenic/needle/blood transfusion
transplacental
transmammary
62
Q

pathogenesis of FIV

A

after primary infection, virus replicates in lymphocytes within lymnphoid tissue
-THYMUS is primary site of replication
-FIV infects and replicates in T-cells (especially in Th cells/CD4), but eventually also infects B cells and mononuclear cells
-viremia occurs as result of primary infection
host mounts solid immune response within 2-4 weeks
-viremia decreases, infection goes latent
-latent period can last several years (chonically infected)
-during latent chronic period, FIV replicates in lymphocytes and can be isolated from lymphocytes… however, higher level of virus replication occurs during stress and episodes of illness

63
Q

what triggers FIV out of latent chronic phase?

A

stress or other infection/illness

64
Q

what clin path is seen with FIV infection?

A

progressive disruption of immunity

marked decrease in CD4 cells, disruption in cytokine production

secondary infections with resident microflora occur on skin and mucosal surfaces of chronicall infected cats

65
Q

what cats have more severe FIV infections?

A

young cats

cats with FeLV infections too

66
Q

clinical signs of FIV: 3 phases

A

1) acute phase
- may go unnoticed, fever with malaise (and general lymphadenopathy)

2) asymptomatic phase
- lasts weeks,months, or years

3) terminal phase
- “wasting syndrome”… stomatitis and gingivitis common… most consistent neurological sign is behavioral changes, but also paresis and seizures

67
Q

What is the most common neoplasia associated with FIV?

A

Lymphomas of B-cell origin

68
Q

Diagnosis of FIV

A

History
-older male cat with recurrent infections, stomatitis/gingivitis, abnormal behavior

Clin Path

Pathology… NOT (none are specific for FIV)
-ANEMIA, NEUTROPENIA, and LYMPHOPENIA are seen in 1/3 of ill cats

Virus Isolation (difficult)

Detection of viral antigen (NOT DONE)

Detection of Virus/Viral Nucleic Acid
-RT-PCR to test for FIV provirus (viral DNA) in lymphocytes

detection of circulating Ab (serology)
-IgG response… ELISA test

69
Q

what is the most important test to diagnose FIV infection?

A

serology- look for Ab in blood (IgG)

ELISA

70
Q

when is IgG detectable to FIV?

A

within 8 weeks post infection, remain seropositive from then on
… cats in acute phase may be seronegative because they haven’t had enough time to develop IgG, so retest in 6 weeks

71
Q

If a cat is seropositive, assume that RT-PCR positive

A

_

72
Q

If seropositive on ELISA, how long do they stay seropositive?

A

FOREVER, through all 3 phases of infection

exceptions:
some cats may become seronegative during terminal stage of infection

kittens are seropositive if they acquire maternal antibodies from a positive dam (retest in 6 months)

73
Q

major drawback of ELISA test/serology?

A

Since we are detecting IgG (not IgM), we cannot differentiate current infection from vaccinated cats

74
Q

Prevention of FIV

A

there is an inactivated vaccine for FIV, but efficacy is debatable

75
Q

Treatment of FIV

A

AZT gives mixed results

in cats with stomatitis, antibiotics + dental hygiene

76
Q

recommendation for HEALTHY FIV positive cats

A

vaccinate them routinely to prevent infection with other pathogens (prevent as much immunosuppression from FIV as possible)

77
Q

FIP/Feline Coronavirus Infection

A

Feline Infectious peritonitis

SPORADIC but HIGHLY FATAL disease

78
Q

cause of FIP

A

Feline Enteric coronavirus (FeCoV) from family Coronaviridae

79
Q

what is the virus that is isolated from cats with FIP?

A

a type of FeCoV that has mutated into FELINE INFECTIOUS PARITONITIS VIRUS (FIPV)

80
Q

How does FIPV differ from FeCoV?

A

differs genetically but not antigenically

FIPV arises naturally in vivo by mutating and acquiring enhanced ability to replicate in tissue macrophages and circulating macrophages

81
Q

what aged cats is FIP most common in?

A

young cats <2 years, sometimes very old cats

multi-cat households

82
Q

GeCoV seropositive?

A

40% of cats in US are seropositive for FeCoV… but FIP is a SPORADIC disease even though FeCoV is common

83
Q

what types of cats does FIP affect?

A

all cats, even wild cats–> lion, leopard, cheetah, lynx

84
Q

transmission of FIP

A

ingestion
inhalation is possible, but not common
also by saliva

85
Q

FeCoV is shed by what?

A

shed in feces of infected cats during active infection

remains in dry feces for a few weeks, serves as source of infectious FeCoV

86
Q

Is FeCoV similar to other coronaviruses?

A

yes, similar to coronaviruses of pigs, dogs, and humans

87
Q

Risk factors of FIP

A

repeated exposure
large quantities of FeCoV
stress

88
Q

incubation period of FeCoV vs incubation of FIP

A

FeCoV incubation is just a few days

FIP incubation is > 4 months

89
Q

pathogenesis of FIP

A
  • cats infected with FeCoV by ingestion, virus replicates in intestinal epithelial cells, shed in feces
  • virus enters blood and infects circulating macrophages
  • immune response is induced (IgA, IgG, T cells)
  • cat recovers from disease and stops shedding
  • minority of cats don’t stop shedding upon recovery, remain shedders as a persistent infection in healthy cat
90
Q

How does FIP cause disease

A

via immune-complexes, antiviral antibodies, and complement

**Cats that have no antibodies to FeCoV DO NOT develop FIP

**Cats with no complement system DO NO develop FIP lesions

91
Q

what % of cats that have been infected with FeCoV develop antibodies to FeCoV and develop FIP?

A

1-2%

92
Q

what is associated with development of FIP?

A

Stress and environments where cat is exposed to high concentrations of FeCoV

93
Q

describe cellular pathogenesis of FIP

A
  • infection with FeCoV results in seropositive cat with persistent infection (low levels of virus in tissue macrophages)
  • when immunosuppressed with Stress, CMI is depressed… allows latent FeCoV to replicate and acquire mutations to replicate even better in macs
  • binding of virus to pre-existing Ab cause more macs to get infected when they phagocytose the FeCoV/Ab complex
  • infected macs leave blood and enter tissue… virus replication in macs in teh vicinity of blood vessels attracts more Ab, and these Ab fix complement
  • C3a and C5a release results in anflammation, which attracts NEUTROPHILS, eventually forms PYOGRANULOMA around the blood vessels

–>causes vasculitis

94
Q

what are the clinical signs seen with FIP?

A

VASCULITIS

inflammation leads to increased vascular permeability
-protein-rich exudates (in wet form)

95
Q

clinical signs of FeCoV infection

A

diarrhea or upper respiratory infection

96
Q

3 disease forms of FIP

A

1) effusive form (wet form)
2) Granulomatous form (dry form)
3) mixed form of both 1 and 2

97
Q

Effusive form of FIP

A

development of excessive fluid in chest or abdomen (thoracic effusion of ascites)

anorexia, weight loss, depression, dehydration, and anemia

unresponsive fever

icterus

98
Q

non-effusive/dry form of FIP

A

granulomatous lesions or pyogranuloma in many areas of body

same general signs (anorexia, weight loss, depression, dehydration, anemia, unresponsive fever)

OCULAR lesions: iritis with color change in iris, keratic precipitates caused by fibrin clot in anterior chamber, retinal hemorrhage, and “cuffing” of retinal vasculature

BEHOVIORAL changes- CNS lesions in 12% of cats with FIP… incoordination, paralysis, seizures

GRANULOMATOUS LESIONS

99
Q

Diagnosis of FIP

A

History (multicat environment, history of stress in last few months)

clinical pathology (effusive fluid in wet form is clear, straw-colored, clots on standing, and slimy… cellularity is low consisting of macrophages mostly, A:G ratio is 3.5… non-regenerative anemia common, neurtophilia with left shift, hypergammaglobulinemia, increase in acute phase proteins)

Pathology
(if wet form, see rough white deposit on serosal surfaces of abdomen and thorax- exudate is fibrinous… can see pyogranulomas on serosal surface)
(if dry form, see pyogranulomas on various organs… can also see necrotic vasculitis in organs)

Detection of viral antigen (IHC, easily done)

Detection of Virus/Viral nucleic acid
(RT-PCR to detect viral RNA… but RT-PCR also picks up FeCoV that is present in tissues/macrophages of persistently infected cats that do not have FIP)

Detecting of viral specific Ab
(immunofluorescence, monoclonal Ab kit… but problems with these tests)

100
Q

FIP A:G ratio

A

must be less than 0.45

if >0.8, then it is not FIP

101
Q

what is the only definitive way to make a positive FIP diagnosis

A

histopathology

102
Q

what is the problem with diagnosing FIP using antibody tests?

A

presence of circulating Ab to FeCoV does not tell you much, even if it is high… the test cannot distinguish cats infected with FIP from cats infected with FeCoV

“more cats have died of FIP Ab tests than of FIP”

if Ab test comes back negative, you can rule out FIP ONLY if no clinical signs present

advanced cases of FIP can come back Ab negative

103
Q

what has to happen to cause effusion due to FIP

A

Ab-Ag complex deposited in the vascular bed

104
Q

Vaccine for FIP

A

Primucell vaccine (attenuated temperature sensitive vaccine)… given IN

-virus vaccine replicates in respiratory tract and does not go systemic, causes good CMI response

105
Q

what is the problem with Primucell vaccine

A

safe but only partially effective

106
Q

Treatment of FIP

A

NO TREATMENT

best rpevention is good hygiene and disinfection… can have test and slaughter to reduce FeCoV carrier cats

107
Q

Feline Panleukopenia synonyms

A

Feline Distemper
Feline Infectious Enteritis
Cat Fever
Cat Plague

108
Q

Feline Panleukopenia characteristics

A

highly contagious, sometimes fatal viral disease of cats

vomiting, sever dehydration, and neutropenia

109
Q

age most susceptible to panleukopenia

A

kittens… primarily young unvaccinated kittens (<6months)

110
Q

what causes panleukopenia

A

a parvovirus (very resistant, can persist for months)

family Parvoviridae (only one serotype is recognized)

111
Q

in natural population, what % is seropositive?

A

70% of cats

75% of unvaccinated cats become seropositive within 1 year of age

112
Q

How susceptible is the panleukopenia virus?

A

Parvoviridae family (unenveloped)

very resistant, can only be killed by 1:32 bleach or formalin

not killed by iodides, phenol, or alcohol

113
Q

what is panleukopenia virus related to antigenically?

A

mink enteritis virus and canine parvovirus-2

114
Q

what species can panleukopenia cause disease in?

A

domestic and wild cats
mink
raccoons

115
Q

how is panleukopenia transmitted?

A

orally by contact with infected cats or contaminated fomites (fecal-oral)

infected cats can shed virus for 6 weeks after initial infection

116
Q

who is most susceptible to panleukopenia?

A

all ages susceptible, but mostly seen in unvaccinated young kittens (2-6 months)

117
Q

pathogenesis of panleukopenia

A

primary site of repliaction is oropharynx

viremia follows, and lymphocytes and fast dividing cells are infected

virus replicates only in fast-dividing cells

118
Q

what cells does panleukopenia virus infect

A

ONLY fast dividing cells (high mitotic index)

1) lymphocytes in bone marrow, thymus, spleen, LN
2) undifferentiated epithelial cells at the base of crypts
3) myeloid cell precursors- neutrophils

119
Q

what is the result of panleukopenia virus infecting cells

A

infects myeloid precursors/neutrophils–> SEVERE NEUTROPENIA

infects crypt cells–> necrosis of villi, shortening of villi in jejunum and ileum

120
Q

Can panleukopenia be transmitted transplacentally?

A

yes!

if fetus infected:

early in gestation- fetal death, reabsorption, infertility
mid gestation- abortion/birth of mummified fetus
late in gestation- cerebellar hypoplasia and optic nerve atrophy

121
Q

What kind of disease is seen with Panleukopenia in kittens vs older cats?

A

Kittens: acute and lethal infections if kittens have no immune protection

in cats, there is partial protection by Ab, so milder disease

122
Q

what plays a rold in pathogenesis of Panleukopenia?

A

secondary bacterial infection

123
Q

what type of disease is seen in older cats with panleukopenia?

A

mild, subclinical or asymptomatic disease unless the cats are immunosuppressed/FIV positive

124
Q

Stages of Panleukopenia disease

A

Peracute- young kittens
-overwhelming infection… no clinical signs, death within 1 day

Acute disease

  • fever, depression, anorexia, vomiting
  • EXTREME dehydration
  • characteristic posture: hunching over water bowl with head between paws
  • 25-90% case fatality

Cerebellar hypoplasia

  • seen in kittens born to dams infected late in pregnancy
  • incoordination, hypermetria, ataxia
125
Q

Diagnosis of Panleukopenia

A

History (young cat, anorexia, vomiting, dehydration)

clinical patho

  • LEUKOPENIA (<4000 cells/uL)
  • neutropenia, sometimes anemia

pathology:

  • at necropsy, dehydration with dilated SI (turgid hose-like appearance); edematous LN; petechial hemorrhages
  • Histopath: ballooned crypts, shortened villi, IN inclusions in jejunum and ileum
Virus isolation (not frequently done because FA faster)
-easily isolated on feline tissue culture cells

Detection of viral Ag
-FA test or immunohistochemistry or ELISA

Detection of Virus/Viral Nucleic acid

  • can be done by electron microscopy (not done usually)
  • PCR

Detection of Ab
-serology

126
Q

Prevention of Panleukopenia

A
  • kittens receive maternal antibodies via colostrum (half-life 8 days)… vaccinate at 9-10 weeks and again in 2 wks
  • can give hyperimmune serum prophylactically
  • disinfect premises with parvo scrub
  • vaccine
127
Q

treatment of panleukopenia

A

withold food, give fluids and antibiotics

128
Q

what age felines will we give MLV to?

A

NOT IN YOUNG KITTENS (<3wk) OR PREGNANT QUEENS

-for these, you will give inactivated vaccine

129
Q

by when will all kittens respond successfully to vaccination for panleukopenia

A

12 weeks of age (before 12 weeks, 70% of kittens will respond…maternal Ab interfere)

virology (5 decks)

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