辉瑞疾病防控

1

PIG

DISEASE

PREVENTION

ANDCONTROL

TECHNOLOGY

IN

CHINA中国猪病的预防与控制技术SHUCHENG

ZHANG

张树成DVM,

PhD

博士Pfizer

Animal

Health

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(27%ROW)(48%)FeMInexddiPoica(2lao(2%nd(2%N)am%)(2)%Sp(2)ai%Gn)er(3m%an)y(3%Bra)zil(3%)RussianVietUSA(6%)China2World

Pig

Population

全球猪的分布ChinaUSABrazilGermanySpainViet

NamPolandMexicoIndiaRussian

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3Pig

Farms

猪场类型PDF

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Major

Swine

Infectious

Diseases

in

China

中国重要的猪病(1)Major

Viral

Pathogens•

Porcine

Respiratory

and

Reproductive

Syndrome

(PRRS)•••••••Classical

Swine

feverFoot

and

Month

DiseaseCircovirus

type

2PseudorabiesTransmissible

gastroenteritisPorcine

parvovirusSwine

Influenza主要病毒性病原•

篮耳病

（猪繁殖与呼吸综合症）•

猪瘟••••••口蹄疫圆环病毒2型猪伪狂犬病传染性胃肠炎猪细小病毒猪流感

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5Major

Swine

Infectious

Diseases

in

China

中国重要的猪病

(2)•Major

Bacterial

Pathogens

–

Mycoplasma

hyopneumoniae

–

Actinobacillus

pleuropheumoniae

–

Haemophilus

parasuis

–

Pasteurella

multocida

–

Streptococcus

suis

–

Pasteurella

haemolytica

–

Bordetella

Bronchiseptica

–

Escherichia

coli

–

Salmonella

Spp

–

Erysipelothrixrhusionpathiae•主要的细菌性病原

–

肺炎支原体

–

胸膜肺炎放线杆菌

–

副猪嗜血杆菌

–

多杀性巴氏杆菌

–

猪链球菌

–

溶血性巴氏杆菌

–

支气管败血波氏杆菌

–

大肠杆菌

–

沙门氏菌

–

丹毒丝菌

–

钩端螺旋体

–

Leptospira

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Virus

Isolations

in

32

Farms

of

3

Provinces

3省32个猪场病毒分离调查（2007.9）

PRRSV

-29%

CSFV

-

9%

PRV

-3%Unknown-

9%PRRSV+CSFV

-

26%

PRRSV+PCV2

-

9%

PRRSV+SIV

-

3%

PCV2+PRV

-3%总结

(Summary)篮耳病病毒(PRRSV)

75%猪瘟病毒(CSFV)

44%圆环病毒2型(PCV2)

22%伪狂犬病毒

(PRV)

6%

PRRSV+CSFV+

PCV2

-9%

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7PRRS

-

Clinical

Pictures

蓝耳病临床图片Characteristics

of

PRRS蓝耳病特征•

Abortions

and

infertility

ofsudden

onset流产和不孕•

Weak

birth

or

dead

piglets弱仔和死产•

High

mortality

of

young

piglets仔猪高死亡率•

Poor

response

to

treatment治疗效果差•

Clinical

signs

last

2-4

months临床症状持续2-4月•

Multiple

systems

are

affected多系统损伤PDF

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Historical

Review

of

PRRS

Virus

蓝耳病病毒回顾•

Virus

Isolation

病毒分离

–

In

1991,

a

RNA

virus

was

identified

as

Lelystad

virus

(LV)

inEurope1991年欧洲首次分离病原并鉴定为RNA病毒，命名为

Lelystad病毒–

In

1991,

PRRS

virus

was

identified

in

US

1991年美国也分离到

PRRS病毒–

In

1996,

PRRS

virus

was

isolated

in

China

by

Harbin

Vet.

Res.Inst.1996年哈尔滨兽医研究所在中国首次分离到篮耳病病毒•

Virus

Characterization

病毒特性

–

A

member

of

Arteriviridae,

RNA

virus,

virus

genome

ranges

from

15

to

15.5

kb

动脉炎病毒科成,

员RNA病毒，基因组大小为

15到15.5

kb

–

Genotypes

基因型•

European

type

-Type

I欧洲型

-

I型

•

North

American

type

-

type

II

北美型

-

II型

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PRRS

Epidemiology

蓝耳病流行病学•••

It

is

not

very

clear

where

the

virus

originated，but

virus

is

found

nearly

all

area

of

the

world

where

pigs

are

located关于病毒来源还不十分清楚,

全球凡有养猪地区均能找到病毒

Highly

infectious

and

high

prevalence

高度传染性和高流行率

Transmission传播方式

–

Transmitted

vertically

during

gestation

known

as

“

in

utero”

infection,

also

through

milk

怀孕期间的垂直传播被称为“子宫内感染”，也可通过

乳汁传播

–

Horizontal

infection

-

possible

via

body

fluids

(semen,

blood,

oral

and

nasal

secretions)

faces,

contaminated

surface,

or

through

air

水平感染-可能通过体液（精液，血液，口鼻分泌物）粪便，污染物，或

者空气传播

–

Vectors

for

virus

transmission

-

syringe,

insects,

clothing

and

outerware

病毒传播媒介-注射器，昆虫，衣服和外部器械

–

Pig

movement

and

swine

semen

facilitated

the

spread

of

disease

between

countries

猪群流动和人工授精推动此病在各国之间的传播

–

Virus

can

be

found

in

pork

meet,

but

the

ingestion

of

pork

meat

is

not

thought

to

be

important

in

virus

transmission

尽管猪肉中也可以发现病

毒，但是普遍认食猪肉对于病毒传播并不重要

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10High

Pathogenic

PRRS

in

China

中国的高致病性蓝耳病

•

First

outbreak

in

2006

in

Jiangxi,

China

2006年,

中国江西首先爆发

•

Spread

to

most

parts

of

China

in

6

months

6个月后传遍中国大部分地区

•

High

fever

(41℃

last

for

up

to

10

days)

高热（41

℃），可持续长达10天

•

Hyperemia

of

the

ears

and

bodies

耳部和全身郁血

•

Anorexia

食欲减退/厌食

•

High

morbidity

高发病率

(50

-100%)

•

High

mortality

高死亡率

(20

-100%)

•

Co-infected

or

secondarily

infected

with

other

viruses,

e.g.

CSFV,

PCV-

-2,

PRV,

SIV

混合感染或者继发感染猪瘟，圆环病毒2型，猪伪狂

犬病，猪流感

•

Secondary

infections

with

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11PRRS

Vaccines

蓝耳病疫苗•

Inactivated

Vaccines

灭活疫苗–

CH-1a

,

Harbin

Vet.

Res.

Inst

(哈兽研）–

SD1

（山东？）–

High

pathogenic

(JXA1)•

Live

attenuated

vaccines

弱毒活疫苗–

INGELVAC

PRRS

MLV

(Boehringer

Ingelheim)–

INGELVAC

PRRS

弱毒苗–

CH-1R,

(classical

PRRS)CH-1R（传统PRRS）–

High

pathogenic

PRRS

(JXA1-R)?

高致病性PRRS疫苗（

JXA1-R）？–

More

live

high

pathogenic

PRRS

vaccines

under

development更多高致病性蓝耳病弱毒活疫苗正在研发之中PDF

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Classical

Swine

Fever

(CSF)

猪瘟•••Diseases

in

China

中国的猪瘟

–

Major

problems

in

60

and

70s

上世纪60和70年代,

最主要的猪的疾病

–

Currently,

sporadically,

small

scale

outbreak

were

reported

现在是零星和

小规模的爆发Prevention

and

Control

预防和控制

–

Mandatory

immunization

and

culling

强制计划免疫与宰杀

–

Vaccine

疫苗

•

Attenuated

vaccine

(CSF

virus

C

strain

adapted

in

rabbits)

猪瘟兔化弱毒疫苗

•

The

vaccine

has

been

used

in

China

for

50

years

中国使用该疫苗有50年

•

CSF

vaccine

C

strain

protects

against

heterologous

wild

viruses

C株猪瘟疫苗可以有效预防异源野毒的感染发病Major

Issues

主要问题

–

Atypical

infection

in

piglets

仔猪的非典型猪瘟

–

Persistent

infection

even

after

vaccination

免疫后,存在持续感染

–

Differentiation

between

vaccinated

and

infected

pigs

干扰感染猪和免疫猪

的鉴别诊断

–

Quality

of

vaccine

疫苗的质量

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Foot

and

Month

Disease

(FMD)

口蹄疫•

FMD

virus

in

China

中国的口蹄疫病毒

–

Before

1990;

Type

A

1990年以前；A型–

1999

-

Type

O1999年-O型

–

2005

–

2008:

Type

Asia

I

2005-2008年亚洲

I

型•

Prevention

and

Control

预防控制

–

Mandatory

Vaccination

program

for

pig,

cattle,

and

sheep/goat

对

猪、牛、羊（绵羊/山羊）进行强制免疫

–

Vaccine

types

疫苗类型

•

Killed

whole

virus

vaccine

全病毒灭活疫苗•

Synthesized

peptide•

Subunit

vaccine合成肽疫苗亚单位疫苗

–

Major

Issues

主要问题

•

Vaccine

production

techniques

疫苗生产技术须改进

•

Local

reactions

and

low

efficacy

of

vaccine

疫苗的保护效果不好，

局部反应严重

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Major

Swine

Respiratory

Diseases

主要的呼吸道病•

Bacteria

–

Mycoplasma

hyopneumoniae

–

Actinobacillus

pleuropheumoniae

–

Haemophilus

parasuis

–

Pasteurella

multocida

–

Streptococcus

suis––Pasteurella

haemolyticaBordetella

Bronchiseptica•

Viruses

病毒

–

PRRS

蓝耳病

–

Swine

Influenza

猪流感

–

Porcine

circovirus

2

圆环病毒2•Helminths

寄生虫细菌•

肺炎支原体•

胸膜肺炎放线杆菌•

副猪嗜血杆菌•

多杀性巴氏杆菌•

链球菌•

溶血性巴氏杆菌•

支气管败血波氏杆菌

–

Ascarid

larval

migration

蛔虫幼虫的移行

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15Factors

Contributing

to

PRDC

猪呼吸道综合症的发病因素PRDC

=

M

hyo

+

bacteria

+

viruses

+other

factors防御机制

薄弱细菌病原

病毒病原

环境因素引起的应激

PRDC

=

肺炎支原体

+

细菌

+

病毒

+其他因素PDF

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Survey

of

PRDC

Pathogens

in

48

Farms

(2005）

48

个猪场猪呼吸道综合症的病因调查Pathogen

病原PRRSV

+

Bacteria篮耳病病毒+细菌感染PRRSV

+

PRV篮耳病病毒+

伪狂犬病病毒PRRSV

+

PRV+PCV2篮耳病病毒+伪狂犬病病毒+圆环病毒2型PRRSV+PCV2篮耳病病毒+圆环病毒2型PRRSV+CSFV篮耳病病毒+猪瘟病毒PRV+PCV2

No

of

PositiveFarms

阳性猪场

45

10

8

5

6

3Positive

(%)

阳性率

94

21

17

10

13

6

伪狂犬病病毒+圆环病毒2型

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17PRDC

猪呼吸道综合症Mh/Pm/PRRS/Other

viralinfection肺炎支原体/多杀性巴氏杆菌/篮耳病/其它病毒感染Severe

depression,high

fever,

anorexiaExpiratory

dyspnea

Rapidloss

of

conditionMedication

less

efficaciousHigh

morbidity

and

highmortality严重的精神沉郁，高烧，厌食，呼吸困难，体重快速损失，药物疗效差，发病率和死亡率高PDF

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18M.

hyopneumoniae

Infection肺炎支原体感染PDF

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M.

hyopneumoniae

Infection

肺炎支原体感染•Common,

not

easily

eliminated,

persists

for

months

流行普遍，不易根除，持续数月•Moderate

morbidity/no

mortality发病率中等/无死亡•Affect

growth

performance影响猪的增重••Damage

of

respiratory

track

and

immune

system损坏呼吸道和免疫系统Clinical

signs

临床症状––No

fever

不发烧Cough:

dry,

nonproductive/chronic

咳嗽：干咳，非生产性/慢性–Labored

breathing呼吸困难–Slow

growth生长缓慢•Lesions

病变–

Starting

7

days

post

infection感染后7天开始出现–

Peak:

2

weeks

post

infection感染2周后为高峰期单纯感染–

May

be

resolved

by

10

weeks

in

uncomplicated

infections

10周后也可以自我恢复

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••••Horizontal

transmission

水平传播Nose-to-nose

contact;

sneezing/coughing

鼻对鼻接触；喷嚏/咳嗽Infected

pig

to

its

pen

mates!

感染猪的转栏Farrow-to-finish

continuously

M.

hyopneumoniae

Infection

肺炎支原体感染•

Transmission

传播

–

From

infected

farms

to

adjacent

farms

within

4

km

病菌可以从污染场传至4公里外的洁净场

–

From

the

sow/gilt

to

piglets

-

Vertical

transmission

从母猪/后备母猪垂直传播给仔猪

–

Spread

among

pen

mates

栏舍之间传播

分娩到育肥的持续性发生

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21A.

pleuropneumniae

Infection

APP感染Agent:

Actinobacillus(Haemophilus)pleuropneumoniae病原：胸膜肺炎放线杆菌Acute

Disease:

急性发病Affect

8-16

wks

old

pigs,

suddendeath,

high

fever,

short

cough,severe

breathing

difficulties,

blueears.

severe

depression.8—16周猪易感，突然死亡，高烧，短咳嗽，严重的呼吸困难，耳朵发紫，严重沉郁Sub-acute

disease

亚急性发病Abdominal

breathing,

shortcoughing

腹式呼吸、短咳PDF

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22Atrophic

Rhinitis

萎缩性鼻炎

Agent:

B.

bronchiseptica

P.

multocida

Type

D

病原：支气管败血波氏杆菌

D型多杀性巴氏杆菌

Disease:

Affect

young

pigs,

coughing,

low

growth

rate

and

feed

efficiency

发病：青年猪为主，咳嗽，生长缓慢和饲料效率低PDF

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23Disease:

Usually

acute

form

Lethargy

Persistent

cough

(barking)

Labored

breath

FeverSwine

Influenza

猪流感

Influenza

viruses:

H1N1,

Swine-

-origin

H1N1,

Human-

-origin

H3N2,

Human-

-origin

H3N2,

Triple-

-reassortant

猪流感病毒:

H1N1,猪源

H1N1,

人源

H3N2,

人源

H3N2,

三源重组发病：通常急性发病，发烧，精神委靡，持续咳嗽，呼吸困难，3-5天快速恢复，严重影响猪的生长

Recover

quickly

3-5d

Affect

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甲型

H1N1

流感病毒24Novel

Swine-Origin

Influenza

A

(H1N1)

Virus

Investigation

Team.

N

Engl

J

Med2009;10.1056/NEJMoa0903810Comparison

of

H1N1

Swine

Genotypes

in

Recent

Cases

in

the

United

StatesType

A

H1N1

Influenza

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25

Swine

Flu

Bivalent

(H1N1

and

H3N2)

Vaccine猪流感双价苗（H1N1

和H3N2)

Vaccination:

2

doses

at

minimum

age

of

3

week

old

in

3

week

interval

免疫：两次注射，间隔3周

Effective

against

heterologous

H1N1

or

H3N2

对不同的H1N1和H3N2

型攻击有效

Reduce

clinical

signs/

lung

lesion/

virus

shedding

减少临床症状/肺病变/病毒扩散

Safe

to

3-day

old

piglets

and

pregnant

sows

–

对3日令仔猪和怀孕母猪安全PDF

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26

Diagnosis

of

Respiratory

Diseases

呼吸道病诊断•

Clinical

diagnosis

–

Easy

and

clear

临床诊断—简单明了•

Differential

diagnosis

by

clinical

sign

is

difficult

依据临床症状很难鉴别诊断

–

Usually

multiple

agents

involved

常有多病因参与

–

Need

to

compare

clinical

signs,

history,

production

records

需要比较临床症状，病史和生产纪录

–

Compare

gross

lesions

and

microscopic

lesions

需要比较病理及组织学变化•

Confirmation

of

diagnosis

by

isolation

of

specific

agent

or

detection

of

specific

antigens

or

nucleic

acid

通过病原分离或检测病原核酸序列来确珍PDF

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Prevention

and

Control

of

Swine

Infectious

Diseases

猪传染性疾病的预防和控制•••••

Vaccination

-

Common

practice免疫接种-是最常用手段

Vaccination

and

culling

-

Only

apply

for

high

pathogenic

infectious

diseases

(HPAI,

FMD,

CSF)免疫和淘汰

-

仅对烈性传染病（高致病性禽流感，口蹄疫，猪瘟）

Eradication

-

Not

practical

all

the

diseases净化

–

只适合少数传染病

Antibiotics

-

Common

practice

for

prevention

and

treatment抗生素

-

常用于预防和治疗

Environmental

control

-

Good

animal

husbandry

practice

and

environment

control

环境控制

-

良好的饲养条件和环境控制

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28

Swine

Vaccines

in

China

中国猪用疫苗•

Success

of

vaccination

program

疫苗应用的功绩

–

Major

Swine

Infectious

Diseases

are

under

control

主要的猪传染

病都得到控制–

Reduced

incidence

of

diseases降低发病频率减轻临床症状和经济–

Reduce

clinical

signs

and

economic

loss

损失•

Issues

and

concerns

with

vaccine

and

vaccination

疫苗

及应用中存在的问题

–

Efficacy:

效果

•

Provide

incomplete

protection

不能提供完全的保护

•

Can

not

follow

the

variation

of

filed

isolates

and

antigenic

mutations

跟不上田间分离株的变化和抗原性变异

–

Safety:

安全性

•

Local

reaction/Systemic

reaction

局部反应/全身反应

•

Safety

for

food

and

environment

影响环境和食品安全

–

Interference

of

diagnosis

干扰鉴别诊断

•

Could

not

differentiate

between

vaccinated

animals

and

infected

animal

不能区分免疫猪和感染猪PDF

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Recent

Improvement

in

Vaccines

疫苗的研究进展•Antigen

improvement抗原的改进

–

More

multivalent

vaccines

更多的多价疫苗

•

Multiple

organisms,

or

multiple

serotypes,

or

multiple

antigens

多种病原，或者多个血

清型，或者多种抗原

–

Subunit

vaccine

亚单位疫苗

•

Antigen

expressed

in

E.

coli,

Yeast,

Insect

cells

用大肠杆菌，酵母，昆虫细胞表达抗原

•

Synthesized

peptide

vaccine,

e.g.,

FMD

vaccines

合成多肽疫苗，如口蹄疫疫苗–

DNA

vaccineDNA疫苗

•

Deliver

nucleic

acid

(DNA)

by

a

plasmid

通过质粒或病毒载体转运核酸–

Marked

vaccines

标记疫苗

•

Negative

marker

-

阴性标记

•

Positive

marker

-

阳性标记•••Adjuvant

improvement

-

new

and

safe

adjuvants佐剂的改进

–

高效和安全Stabilizer

improvement

-

stable

at

different

temperatures稳定剂的改进–

使疫苗抗原在室温长期稳定Improvement

Formulation/Manufacture

process

配方及制造工艺的改进

–

安全及方便使用

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30RespisureRespiSure®

-

瑞倍适®瑞倍适对支原体肺炎的免疫保护长达5个半月PDF

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31

RespiSure-One®

-

瑞倍适-旺®Respisure

One

瑞倍适-旺

对支原体肺炎的免疫保护长达6个半月PDF

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32Adjuvant:

AmphigenTM

佐剂：爱菲金•

Uniquestructure:

独特结构–

Micelles:

tiny

oil

droplets

coated

withlecithin微囊：由卵磷脂包被的小油滴•

Lecithin

–

tissue-friendly;

less

injectionsite

irritation

卵磷脂

-

组织亲和性好，对注射部位无损伤•

Increased

surface

area

of

antigen

bindingsites增加抗原结合的表面积–

More

antigens

presented

to

pig’s

immunesystem

to

enhance

immune

response更多的抗原进入免疫系统

-增强免疫反应–

But

excellent

syringe

ability!容易注射PDF

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Amphigen33•

Enhanced

immune

response:

增强免疫反应

–

Attraction

of

macrophages

on

the

antigen

sites

吸引巨噬细胞到注射部位

–

Helps

exposure

and

uptake

of

antigen

by

the

APCs

(antigen

presenting

cells)

使免疫系统接受和吸收更多的抗原

Enhances

proactive

formation

of

memory

cells

and

activated

macrophages

激活记忆细胞和巨噬细胞

–

Enhances

the

launch

of

a

cellular

immune

response

in

pigs

exposed

to

M.

hyopneumoniae

强化对肺炎支原体的细胞

免疫反应•

Long

duration

of

immunity

延长免疫保护期–

Ag

slow

release

抗原缓作用Adjuvant:

AmphigenTM佐剂：爱菲金

T

M4.5%

Mineral

Oil

0.5%

Lecithin

(phospholipids

&

glycolipids)

Water

4.5%矿物油

0.5%卵磷脂(磷脂和糖脂)

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34Use

of

Antibiotics

抗生素应用•

Advantages

of

using

antibiotics抗生素的优势–

Use

in

feed

additives

(19

antibiotics

in

US)饲料添加（在美国有19种）•

Improve

growth

rate

(4-15%)

and

feed

efficiency

(2-6%)

促生长（4-15%）和提供饲料效率(2-6%)•

Improve

conception

rate

and

litter

size提高受胎率和增加窝重–

Use

for

treatment

of

infectious

diseases治疗传染病•

Reduce

mortality

and

economic

loss降低死亡和减少经济损失PDF

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35Use

of

Antibiotics

抗生素应用•

Concerns

with

using

antibiotics应用抗生素的顾虑–

Development

of

antibiotics-resistance

organisms使病原产生耐药性–

Potential

threat

to

human

health

by

transmitting

resistanceorganism

to

human耐药菌株可传递给人，

对人类健康有潜在威胁–

Over

use

of

antibiotics

would

affect

the

export

of

pork

to

certaincountries

(some

EU

countries)滥用抗生素影响猪肉出口（某些欧盟国家）–

Food

safety

食品安全•

Future

of

using

antibiotics

抗生素应用趋势–

Development

of

antibiotics

replacement

寻找替代品–

Reducing

antibiotics

use

by

developing

effective

and

long-lastingantibiotics

product研发高效及长效抗生素，减少抗生素用量PDF

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36EXCEDE®

易速达®•

Indication:

For

thetreatment

of

SRDassociated

with:适应症：治疗呼吸道病综合症–

Actinobacilluspleuropneumoniae–

Pasteurella

multocida–

Haemophilus

parasuis–

Streptococcus

suisPDF

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EXCEDE

®

易速达®•

Ready

to

use

Sterile

Suspension混悬注射液

•

Contents：

Ceftiofur

as

a

free

acid

主要成份：头孢噻

呋晶体游离酸

•

True

single-dose

treatment

单针注射,

方便实用

•

Sustained

release,

at

least

seven

days

of

therapeutic

levels

against

label

pathogens

缓慢释放,

对于特效的

病原菌，药效期7-10天

•

Excellent

stability,

24

months

shelf-life

at

room

temperature

极好的稳定性,室温保存24个月以上

•

No

change

in

susceptibility

by

targeted

pathogens

(drug-resistance)

长期应用，病原不产生耐药性

•

Safe

and

environmentally

friendly

安全和环保

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A

Major

TherapeuticAdvancefor

Swine

Respiratory

Disease

猪呼吸道病治疗的革命性突破瑞可新®

NEW

SCIENCE

–

NEW

MEDICINE

–

NEW

OPPORTUNITIESPDF

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Draxxin®

瑞可新®Indication:

Major

respiratory

disease

pathogens

in

cattle

and

swine:适应症：猪的主要呼吸道细菌病原

–

Mannheimia

(Pasteurella)

haemolytica

溶血性巴氏杆菌–

Pasteurella

multocida–

Haemophilus

somnus–

Actinobacillus

pleuropneumoniae–

Mycoplasma

hyopneumoniae

多杀性巴氏杆菌

副嗜血杆菌

胸膜肺炎放线杆菌猪肺炎支原体Efficacy

效果

–

Extraordinarily

high

efficacy

against

respiratory

pathogens

对呼吸道病格外高效

–

Fast

responses

to

treatment

疗效神速

–

One

single

dose,

min