獸醫(yī)師貓傳染病專題等多個文件-015esavs-貓病ii1貓口炎feline stomatitis katrin

Katrin

HartmannProf.,

Dr.

med.

vet.,

Dr.

habil.,

Dipl.

ECVIM-CAFeline

Stomatitis貓的口炎?Mister

Q“Siamese

暹羅貓9

years

9歲male

neutered雄性已絕育lives

in

Munich住在慕尼黑single-cat

household,only

indoors獨養(yǎng)，室內(nèi)referred

for

stomatitis因口炎轉(zhuǎn)診FIV

infection

known

since

6

years

6年前查出

FIVbiopsy:

lymphoplasmocytic

stomatitis活檢：淋巴漿細胞性口炎?Mister

Q“Stomatitis口炎=

inflammation

ofthe

mucous

membranes

of

themouth=口腔黏膜的炎癥very

common很常見often

young

cats常見于青年貓often

chronic通常是慢性的often

without通常沒有牙stomatogingivitis,

gingivostomatitis,faucitis，lymphoplasmocytic

stomatitis口腔牙齦炎，齦口炎，咽喉炎淋巴漿細胞性口炎Etiology

病因primary

pathogenes?oral

microbial

flora/病原體？?口腔菌群/牙chronic timulation?抗原慢性刺激immune-mediated

processes?免疫介導(dǎo)過程immune

dysregulation?免疫失調(diào)Etiology病因histology

組織學(xué):mainly

plasma

cells

and

lymphocyteswith

possible

neutrophilic

and

eosinophilicinflammation

(different

degrees)主要是漿細胞和淋巴細胞性炎癥，可能有中性粒細胞和嗜酸性粒細胞性炎癥（不同程度）circulating

lymphocytes

外周淋巴細胞?expression

von

inflammatory

cytokines炎性細胞因子表達增高=>

chronic timulation

and/ordysregulation

of

the

immune

system慢性抗原刺激和/或免疫系統(tǒng)調(diào)節(jié)異常Potential

Pathogenes

Involved潛在的病原體feline

calici貓杯狀

feline

herpes貓皰疹(FCV)(FHV)feline

immunodeficiency貓免疫缺陷(FIV)felines

leukemia

(FeLV)貓白血病Bartonella

(mainly

Bartonella

henselae)氏體（主要是漢氏氏體）other

bacteria

(e.g.,Bacteroides

spp.)其它細菌如，擬桿菌屬）Study:

Relevance

of

Pathogenes研究：相關(guān)病原體52

cats

with

chronic

stomatitis

52只慢性口炎貓stomatitis>3

weeks

口炎>3周no沒有牙or

other

dental

changes或其它口腔病變50

age-matched

control

cats50只

一致的對照貓clinically

healthy

臨床健康no

history

ofstomatitis

無口炎病史examinations

檢查生化history,

incl.

accurate

vaccination

history病史，包括精確的免疫史physical

examination

體檢blood

tests

血檢CBC

and

serum

biochemistry

血常規(guī)和antibodies

(FIV,

FCV,

Bartonella

henselae),漢氏巴）氏體)抗體檢測（貓免疫缺陷 ,

貓杯狀爾通氏體）(FeLV)

抗原檢測

（貓白血病RNA/DNA(Bartonella

henselae漢氏swabs

oftheoral

口腔拭子RNA/DNA

(FCV,

FHV,

Bartonella

henselae)Study:

Relevance

of

Pathogenes研究：相關(guān)病原體stomatitis口炎組

n=52controls對照組

n=50p*標(biāo)準(zhǔn)差FCV

swab

FCV拭子53.8

%14.0

%<

0.001FCV

AB

FCV抗體78.8%58.0

%0.024FHV

swab

FHV拭子13.5%6.0%0.320FIV

blood

FIV血液5.8%0

%0.121FeLV

blood

FeLV血9.6%0

%0.060B.

henselae

swab漢氏 氏體拭子19.2%12.0

%0.320B.

henselae

blood漢氏 氏體血液17.3%8.0%0.161B.

henselae

AB漢氏 氏體抗體9.6

%10.0

%1.000*Chi-square/‘s

exact

testStudy:

Relevance

of

Pathogenes研究：相關(guān)病原體stomatitis口炎組n

=

52controls對照組n

=

50p*標(biāo)準(zhǔn)差FCV

swab

FCV拭子53.8

%14.0

%<

0.001FCV

AB

FCV抗體78.8

%58.0

%0.024FHV

swab

FHV拭子13.5

%6.0%0.320FIV

blood

FIV血液5.8

%0

%0.121FeLV

blood

FeLV血9.6

%0

%0.060B.

henselae

swab漢氏 氏體拭子19.2

%12.0

%0.320B.

henselae

blood漢氏 氏體血液17.3

%8.0%0.161B.henselae

AB漢氏 氏體抗體9.6

%10.0

%1.000*Chi-square/‘s

exact

testStudy:

Relevance

of

Pathogenes研究：相關(guān)病原體stomatitis口炎組n

=

52controls對照組n

=

50p*標(biāo)準(zhǔn)差FCV

swab

FCV拭子53.8

%14.0%<0,001ODDs

ratio比值比（OR）confidence

interval置信區(qū)間7,12.5

<

OR

<

21.3FCV

AB

FCV抗體78.8

%58.0%0,024ODDs

ratio比值比confidence

interval置信區(qū)間2,71.0

<

OR

<

7.1*Chi-square/‘s

exact

testStudy:

Relevance

of

Pathogenes研究：相關(guān)病原體stomatitis口炎組n

=

52controls

對照組n

=

50p*標(biāo)準(zhǔn)差roam

outside

流浪貓42,3

%56,0

%0,173multi-cat

househ.家里飼養(yǎng)多只貓56,3

%63,4

%0,491%male

%雄性59,6

%58,0

%0,870%DSH

%本地短毛貓78,8

%92,0

%0,063vaccination

免疫48,1

%44,0

%0,784agemedian

中值mean

平均值5,0

years6,0

years5,0

years6,1

years0,911*Chi-square/‘s

exact

testStudy:

Relevance

of

Pathogenes研究：相關(guān)病原體Potential

Pathogenes

Involved潛在的相關(guān)病原體pfeline

calicifeline

herpes(FCV)

貓杯狀

（FCV）(FHV)

貓皰疹feline

immunodeficiency

(FIV)貓免疫缺陷felines

leukemia (FeLV)貓白血病Bartonella

(mainly

Bartonella

henselae)氏體（主要是漢氏

氏體）other

bacteria

(e.g.,

Bacteroides

s其它細菌（如，擬桿菌屬）Feline

Calici貓杯狀(FCV)(FCV)Etiology

病因

Symptoms

癥狀

DiagnosisTreatment

治療

Prophylaxis

預(yù)防Feline

Calici貓杯狀(FCV)(FCV)Etiology

病因

Symptoms

癥狀

DiagnosisTreatment

治療

Prophylaxis

預(yù)防Feline

Calici貓杯狀(FCV)(FCV)Etiology

病因clinical

signs

臨床癥狀DiagnosisTreatment

治療

Prophylaxis

預(yù)防Feline

Calici貓杯狀(FCV)(FCV)small,

unenveloped

RNA-with

cup-like

impressions小的，似杯狀的無衣殼RNAhighly

contagious

傳染性強infectious

up

to

3

weeks

in

the

environment在環(huán)境中3周仍有

性high

variability=>變異性強strains

with

high

pathogenicity

高致病性菌株ABCDEORF

15’3’ORF

35’HVRCons3’HVRFelineCalici貓杯狀(FCV)(FCV)ORF

2Excretion

排毒TransmissionTenacity穩(wěn)定性carrier

state帶毒狀態(tài)下by

oral

and

nasal

discharge,

saliva(few

days

up

to

life-long

period)從口腔和鼻

物，唾液（幾天到

）generally

direct,通常直接indirect

transmission

possible可能發(fā)生間接relatively

stable

in

theenvironment在環(huán)境中相對穩(wěn)定（可達3周）(up

to

3

weeks)replication

in

tonsills

andlymphoepithelial

tissuecontinuous

shedding在扁桃體和淋巴上皮組織中

不斷脫殼FCV

–

Epidemiology貓杯狀

-流行病學(xué)Carrierstatus

FCV貓杯狀

帶毒狀態(tài)elimination排毒chronic

shedder

慢性脫殼+susceptible

cat疑似病例40%colony

cats

40%群居貓

25%show

cats

25%純種貓

8%household

pets

8%家養(yǎng)貓

20%practice

cases

實踐案例cat

with

acute

FCV

infection急性FCV

的貓chronicSequelae慢性后遺癥clinicalRecovery臨床康復(fù)許many

cats

stillshedding30days

after

infection多貓30天后仍然排毒50%

cats

still

shedding75

days

post

infection50%的貓

后75天仍然排毒eliminatednon-carriers排毒后成為非攜帶者self-limiting自限性的or

life-long帶毒Carriers攜帶者Gaskell

&

Bennett,1996FCV

-carrierstateFeline

Calici貓杯狀(FCV)(FCV)Etiology

病因clinical

signs

臨床癥狀DiagnosisTreatment

治療

Prophylaxis

預(yù)防incubation

period潛伏期Signs

癥狀Nose

鼻Eyes

眼oral

口腔respiratory

tract呼吸道chronic

infections慢

染有時打噴嚏，

物+2-4

days

2-4天generally

milder

than

with

FHV通常比同時

FHV要輕sometimes

sneezing,

discharge

+usually

no

ocular

signs

通常沒有眼部癥狀big

vesicles,ulcers

大水泡，潰瘍rarely

p onia

罕見chronic

proliferative

stomatitis慢性增生性口炎Clinical

Signs臨床癥狀Clinical

Signs臨床癥狀Clinical

Signs臨床癥狀

/cpdvets/LimKitten

Syndrome

Pedersen

et

al.,

1983幼貓跛行綜合征Lmainly

in

kittens

of

6

-

12weeks主要在6-12周的幼貓Loften

after

vaccinations

常在免疫之后Lusually

intermittent,

often

with

fever一般是間歇性的，常伴發(fā)熱Lmostly

self-limiting

大多數(shù)是自限性的Lcertain

antigenic

variant?

確定有抗原變異？Lrelated

to

vaccine?免疫相關(guān)？L replication

in

joints?在關(guān)節(jié)嗎Limmune-mediated?免疫介導(dǎo)的？Lincreased

in

1-acid

glycoprotein?

-酸性糖蛋白升高Chronic

Proliferative

Stomatitis慢性增生性口炎Lchronic

慢性Lrecurrent

復(fù)發(fā)Lproliferative

增生Lulcerative

潰瘍Llymphocytic/plasmocytic淋巴細胞/漿細胞Limmune-mediated

reaction

to

chronicFCV

infection慢性FCV

的免疫介導(dǎo)效應(yīng)Lrole

of

chronic

carriers?慢性攜帶Lrole

of

FIV

and

FeLV?貓免疫缺陷者的作用和貓白血病

的作用in

some

studies

75

%

of

cases

of

chronic

stomatitis在某些研究結(jié)果中慢性口炎病例的75%hemorrhagic

syndrome(generalized

systemic

calicisyndrome)性綜合征（系統(tǒng)性杯狀

綜合征）Pedersen

et

al.,2000recently

described

syndrome最近此綜合征有被描述severe

?systemic

hemorrhagic

fever”嚴重的“系統(tǒng)性

熱”high

mortality,

mainly

older

cats率高，主要發(fā)生于老年貓no

protection

by

common

vaccines沒有常規(guī) 保護GSCVS系統(tǒng)性杯狀

綜合征LDSH

本地短毛貓L3

years

old

3歲Lmale

neutered

絕育公貓L

single

cat

household,

indoor

only家里只養(yǎng)了一只，室內(nèi)Lregularly

vaccinated,常規(guī)免疫complete

primo-vaccination,首次免疫完全last

vaccination

(HCP)最后一次免疫（貓三聯(lián)）4months

ago4個月前“Moritz”“Moritz”History

病史Lsince

1

day

problems

to

urinate

1天前排尿有問題

L

stranguria

痛性尿淋漓Ltoday

anorectic

今天開始厭食physical

examination

體檢Llarge

and

tense

bladder大且緊張DiagnosisFLUTD

貓下泌綜合征“Moritz”Treatment

治療Lindwelling

catheter

內(nèi)置導(dǎo)尿管Lemptying

ofthe

bladder排空Lfluid

therapy

(incl.

electrolyte

replacement)輸液治療（包括，補充電解質(zhì)）Lpain

medication

止痛藥follow-up

回訪L ng

better

shortlyafter

treatment治療后很快好轉(zhuǎn)

Lstarted

eating

開始進食

Lcatheter

left

in

placefor

24

hours導(dǎo)尿管留置24小時“Moritz”the

next

day

…第二天...“Moritz”物物new

problems

新問題Lfever

發(fā)熱Locular

discharge

眼Lnasal

discharge

鼻Lsneezing

噴嚏Lulcerations

on

the

tongue舌潰瘍Lulcerations

on

the

paws爪子上潰瘍?Moritz“Foto:

S.Unterer,

München?Moritz“Foto:

S.Unterer,

München“Tiger”“B?24

Hours

Later24小時之后“Tiger”“Moritz”???“B?rli”72

Hours

Later

…72小時后Feline

Calici貓杯狀(FCV)(FCV)Etiology

病因clinical

signs

臨床癥狀DiagnosisTreatment

治療

Prophylaxis

預(yù)防FCV

–

DiagnosisFCV-detection

of

antibodies抗體檢測-

PCR聚合酶鏈反應(yīng)detection

of

檢測- isolation

(cell

culture)分離（細胞培養(yǎng)）not

useful

無效vaccination

免疫antigenic

variability抗原變異性sensitive

and

specific敏感且特異Specific

特異

sensitive?敏感？strain

differentiation亞型鑒別Feline

Calici貓杯狀(FCV)(FCV)Etiology

病因clinical

signs

臨床癥狀DiagnosisTreatment

治療

Prophylaxis

預(yù)防Supportive

Treatment支持療法fluid

therapy

輸液治療=>Rehydration

再水合(=>

amelioration

of

the

mukociliary

clearance)（改善粘液纖毛清除率）gesia

if

necessary需要時進行鎮(zhèn)痛Lvitamin

A維生素ALvitamin

C維生素CLvitamin

B

complex復(fù)合維生素B5000

IU/kg

PO

q

24

h5000IU/kg

口服每24h一次80

mg/kg

PO

q

8

h80mg/kg

口服每8h一次SC

q

48

h皮下每48h一次Supportive

Treatment支持療法vitamins

(mucosal

regeneration)維生素（黏膜再生）Supportive

Treatment支持療法nutritional

management

營養(yǎng)管理purée

and

warmed

food(microwave)果泥和熱水（微波）appetite

stimulation

刺激食欲diazepam

(Valium?)

0.05

-

0.25

mg/kg

IV(immediate

effect)

0.05-0.25mg/kg

靜注（即時效應(yīng)）cyproheptadin

(Peritol?)

0.5

-

1

mg/kg

q

12

h

PO賽庚啶(Peritol

?)0.5-1mg/kg每12小時一次口服mirtazapine

3

mg/cat

PO

米氮平3mg/貓口服tube

feeding

if

necessary必要時可用飼喂管喂食Nasal

Tube鼻飼管Esophagal

Tube食道飼喂管effective

invitro體外作用controlledstudy

in

vivo體內(nèi)對照組effective

invivo體內(nèi)作用assessment

of

effectiveness(1

–

4)效果評估Immunglobulins免疫球蛋白Yes

有No

無Unknown未知possibly

effective

(4)有效率（4）Ribavirin

利巴韋林Yes

有jaNo

無too

toxic

systemically

(2),全身毒性強（2）possibly

as

aerosol(4)氣霧劑有效率（4）humaninterferon-α人用α-干擾素s.c.

high

dose皮下高劑量p.o.

low

dose口服低劑量Yes

有No

無Unknown未知Unknown未知possibly

effective

(4)有效率（4）Yes

有No

無probably

not

effective

(4)無效率（4）felineinterferon-ω貓ω-干擾素Yes

有No

無Unknown未知possibly

effective

(3)有效率（3）Antiviral

Chemotherapy抗

化療effective

invitro體外作用controlledstudy

in

vivo體內(nèi)對照組effective

invivo體內(nèi)作用assessment

of

effectiveness(1

–

4)效果評估Immunglobulins免疫球蛋白Yes

有No

無Unknown未知possibly

effective

(4)有效率（4）Ribavirin

利巴韋林Yes

有jaNo

無too

toxic

systemically

(2),全身毒性強（2）possibly

as

aerosol(4)氣霧劑有效率（4）humaninterferon-α人用α-干擾素s.c.

high

dose皮下高劑量p.o.

low

dose口服低劑量Yes

有No

無Unknown未知Unknown未知possibly

effective

(4)有效率（4）Yes

有No

無probably

not

effective

(4)無效率（4）felineinterferon-ω貓ω-干擾素Yes

有No

無Unknown未知possibly

effective

(3)有效率（3）Antiviral

Chemotherapy抗

化療Ribavirin利巴韋林commercially

available

e.g.

Ribazole?有商品化藥物，如Ribazole?antiviral

effects

抗

nucleoside效果ogue

(guanosine

derivative)核苷類似物（鳥苷衍生物）

interferes

with

DNA

and

mRNA

synthesis干擾DNA和mRNA的Dosage

劑量

11

mg/kg

q

24

h

PO

or

IV

(max.

7

days)11mg/kg

24h一 次

口服或靜注（最長7天）

only

in

combination

with

interferon-

orinliposomes?只能與a/w-干擾素或脂質(zhì)聯(lián)合使用side

effects

(already

in

therapeutic

dosage!)副作用（已經(jīng)在治療劑量中出現(xiàn)）

myelosuppression,

hepatotoxicity骨髓抑制，肝毒性

diarrhea,

gastro-intestinal

ulcera腹瀉，胃腸道潰瘍Ribavirin:

Experimental

Study

(2)利巴韋林：實驗報告(2)ribavirin

(25

mg/kg

q

8

h

PO

for

10

days)利巴韋林（25mg/kg

每8h一次口服服用10天）1

day

or

4

days

after

exposition

(aerosol)

to

FCV在FCV中1到4天后（氣霧劑）=>clinical

signsmore

severe

臨床癥狀更嚴重=>severe

side

effects

副作用越劇烈Povey,

1978Immunglobulins免疫球蛋白commercially

available

in

Europe

(Feliserin?)在歐洲有商品化藥物(Feliserin?)antiviral

effects

effect

against

FCV?抗作用

抗FCV的效果neutralizing

antibodiesagainst

FCV,

FHV,

FPV中和FCV,FHC,FPV抗體Dosage

劑量

for

prophylaxis

1

injection

SC

(1

ml)皮下注射1次（1ml）預(yù)防

for

treatment

3

injektionen

SC

(1

ml)

q

24

hlokal

application?治療每24h一次皮下注射3支外用？side

effects

副作用

anaphylaktic

reaction

in

cats

(repeated

application)貓的過敏反應(yīng)（重復(fù)應(yīng)用時）human

interferon-,

feline

interferon-人用a-干擾素，貓w-干擾素antiviral

effects

抗

作用

inhibits抑制assemly

and

budding裝配和芽孢

cytokine,

immunomodulatory

effect細胞因子，免疫調(diào)節(jié)作用Dosage

劑量

huIFN-

high

dose

105

IU/kg

q

24

h

SQ

(short

term)人a-干擾素高劑量105

IU/kg

每24h

皮下（短期）

huIFN-

low

dose

1

(-50)

IU

q

24

h

PO

(long

term)人a-干擾素低劑量1(-50)IU

每24h

口服（長期）

feIFN-

106

IU/kg

S 24

h

on

5

consecutive

days貓w-干擾素

106

IU/kg

皮下每24h

連用5天side

effects

副作用

rarely

allergic

reactions

(huIFN-)少見過敏反應(yīng)（人a-干擾素）Interferon-ωΩ-干擾素Interferon-ωΩ-干擾素L

in

vitro

strain-dependent

efficacyTaira

et

al.,

2005,

Kyoko

et

al.,2008品種依賴型體外有效性no

controlled

clinical

studies沒有對照的臨床研究----multi-center

study

多中心研究no

FCV

diagnostics

沒有

FCVno

controls

沒有對照not

controlled,

all

cats

received

symptomatic

treatment所有貓接受對癥治療felines

interferon-ω

2.5

or

5

x

106

IU/kg

IV

q

24

h

for

3

daysimprovement

<

4

days

after

signs

had

appeared貓ω-干擾素

2.5

or

5

x

106

IU/kg

靜注每24h一次

3天出現(xiàn)臨床癥狀后4天之內(nèi)得到改善efficacy?有效？Interferon-ω

in

Acute

FCV

InfectionΩ-干擾素在急性FCV

中的應(yīng)用field

study(Japan)領(lǐng)域研究（Uhino

et

al.,

1997160

cats

with

URTD

or

stomatitis160只貓，上呼吸道疾病或口炎）Experimental

Drugs實驗性藥物-specific

antiviral

抗特異

藥物phosphorodiamidate

morpholino

oligomer磷酰二胺嗎啉代低聚物experimental

infection

實驗

染=>improved

survival

rate

提高存活率Smith

et

al.,

2008not

commercially

available

沒有商品化藥物Treatment

of

Chronic

Stomatitis慢性口炎的治療Interferon-ω

in

Chronic

Stomatitisω-干擾素在慢性口炎中的應(yīng)用lokale

treatment

with

interferon-Mihaljevic,

2003局部使用-干擾素sofar

no

placebo-controlled

studies(!)至今沒有可靠的對照研究feline

interferon-

2.5

x

106

IU/kginjection

of

several

depots

of

0.1

ml

(gingiva)

+

left

over

SQ貓w-干擾素2.5x106

IU/kg

0.1ml多點注射（牙齦）+剩余皮下treatment

repeated

if

necessary

必要時重復(fù)important:

proper

dental

surgeries

(!)重要的是：恰當(dāng)?shù)难揽剖中g(shù)efficacy

of

interferon-ω???ω-干擾素有效性？？？Treatment

of

Chronic

Stomatitis慢性口炎的治療prednisolone0,5

mg/kg

q

12

h

PO龍0.5mg/kg

每12h一次口服+cyclosporin

環(huán)孢菌素week

5

10

mg/kg

q

24

h

PO

for

5

days,

2-day

break,afterwards

5

mg/kg

q

12

h

PO

for

5

days,

2-day

break,after

that

5

mg/kg

q

12

h

PO

for

5

days,

2-day

break,etc.5周10mg/kg

每24h一次口服5天，停2天，之后5mg/kg

每12h一次口服5天，停2天，之后5mg/kg

每12h一次口服5天，停2天…Alternative

可選擇tooth

extraction

拔牙if

necessary

all

teeth!必要拔掉所有牙齒Treatment

of

Chronic

Stomatitis慢性口炎的治療Feline

Calici貓杯狀(FCV)(FCV)Etiology

病因clinical

signs

臨床癥狀DiagnosisTreatment

治療

Prophylaxis

預(yù)防Problems

with

Vaccination免疫帶來的問題no

complete

protection

against

disease對疾病沒有完全的保護性L only

against

developm