PIG DISEASE PREVENTION AND CONTROL 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 辉瑞动物保健 1
World Pig Population 全球猪的分布 ROW (27%) China USA Brazil Russian Fed (2%) India (2%) Mexico (2%) Poland (2%) Viet Nam (2%) Spain (3%) Germany (3%) Brazil (3%) USA (6%) China (48%) Germany Spain Viet Nam Poland Mexico India Russian Fed ROW 2
Pig Farms 猪场类型 3
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 fever Foot and Month Disease Circovirus type 2 Pseudorabies Transmissible gastroenteritis Porcine parvovirus Swine 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 4
Major 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 Erysipelothrix rhusionpathiae Leptospira interrogans 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 5
Virus Isolations in 32 Farms of 3 Provinces 3 省 32 个猪场病毒分离调查 (2007.9) PRRSV+CSFV - 26% PRRSV+PCV2-9% PRRSV+SIV - 3% PCV2+PRV -3% PRRSV+CSFV+ PCV2-9% PRRSV -29% CSFV - 9% PRV -3% Unknown- 9% 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% 6
PRRS - Clinical Pictures 蓝耳病临床图片 Characteristics of PRRS 蓝耳病特征 Abortions and infertility of sudden 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 7
Virus Isolation 病毒分离 Historical Review of PRRS Virus 蓝耳病病毒回顾 In 1991, a RNA virus was identified as Lelystad virus (LV) in Europe 1991 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 8
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 9
High 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 bacteria 细菌性继发感染 10
PRRS 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 11
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 12
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 O 1999 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 合成肽疫苗 Subunit vaccine 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 13
Major Swine Respiratory Diseases 主要的呼吸道病 Bacteria Mycoplasma hyopneumoniae Actinobacillus pleuropheumoniae Haemophilus parasuis Pasteurella multocida Streptococcus suis Pasteurella haemolytica Bordetella 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 Ascarid larval migration 蛔虫幼虫的移行 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 14
Factors Contributing to PRDC 猪呼吸道综合症的发病因素 防御机制薄弱 病毒病原 细菌病原 环境因素引起的应激 PRDC = M hyo + bacteria + viruses +other factors PRDC = 肺炎支原体 + 细菌 + 病毒 + 其他因素 15
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 伪狂犬病病毒 + 圆环病毒 2 型 No of Positive Farms 阳性猪场 45 10 8 5 6 3 Positive (%) 阳性率 94 21 17 10 13 6 16
PRDC 猪呼吸道综合症 Mh/Pm/PRRS/Other viral infection 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, anorexia Expiratory dyspnea Rapid loss of condition Medication less efficacious High morbidity and high mortality 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 17
M. hyopneumoniae Infection 肺炎支原体感染 18
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 May be resolved by 10 weeks in uncomplicated infections 单纯感染 10 周后也可以自我恢复 19
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 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 分娩到育肥的持续性发生 20
A. 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, sudden death, high fever, short cough, severe breathing difficulties, blue ears. 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, short coughing 腹式呼吸 短咳 21
Atrophic 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 22 和饲料效率低
Swine Influenza 猪流感 Influenza viruses: H1N1, Swine-origin H1N1, Human-origin H3N2, Human-origin H3N2, Triple-reassortant reassortant Disease: Usually acute form Lethargy Persistent cough (barking) Labored breath Fever Recover quickly 3-5d Affect growth rate 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 23
Type A H1N1 Influenza Virus Comparison of H1N1 Swine Genotypes in Recent Cases in the United States 甲型 H1N1 流感病毒 Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. N Engl J Med 2009;10.1056/NEJMoa0903810 24
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 25
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 26
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 27
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 Reduce clinical signs and economic loss 减轻临床症状和经济损失 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 28
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 vaccine DNA 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 29
RespiSure - 瑞倍适 Respisure 瑞倍适对支原体肺炎的免疫保护长达 5 个半月 30
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 31
Adjuvant: Amphigen TM 佐剂 : 爱菲金 Unique structure: 独特结构 Micelles: tiny oil droplets coated with lecithin 微囊 : 由卵磷脂包被的小油滴 Lecithin tissue-friendly; less injection site irritation 卵磷脂 - 组织亲和性好, 对注射部位无损伤 Increased surface area of antigen binding sites 增加抗原结合的表面积 More antigens presented to pig s immune system 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 32
Adjuvant: Amphigen TM 佐剂 : 爱菲金 Amphigen T M 4.5% Mineral Oil 0.5% Lecithin (phospholipids & glycolipids) Water 4.5% 矿物油 0.5% 卵磷脂 ( 磷脂和糖脂 ) 水 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 33
Use 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 34
Use 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 resistance organism 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 certain countries (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-lasting antibiotics product 研发高效及长效抗生素, 减少抗生素用量 35
EXCEDE 易速达 Indication: For the treatment of SRD associated with: 适应症 : 治疗呼吸道病综合症 Actinobacillus pleuropneumoniae Pasteurella multocida Haemophilus parasuis Streptococcus suis 36
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 37
瑞可新 A Major Therapeutic Advance for Swine Respiratory Disease 猪呼吸道病治疗的革命性突破 NEW SCIENCE NEW MEDICINE NEW OPPORTUNITIES 38
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 多杀性巴氏杆菌 Haemophilus somnus 副嗜血杆菌 Actinobacillus pleuropneumoniae 胸膜肺炎放线杆菌 Mycoplasma hyopneumoniae 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, minimizing labor and handling stress 单针注射全程疗效, 节约 劳力, 减少应激 Disease prevention in healthy, in-contact, at-risk animals 对于健康群, 受威 胁猪群, 高风险猪群均有良好的预防保护 Safety 安全性 10X recommended dose-no serious adverse effects 10 倍剂量注射无不良反应 Confirmed safety under field-use conditions 现地应用安全性好 39
Draxxin -Chemistry and Mode of Action 瑞可新 化学结构和作用机理 First triamilide antimicrobial agent 首次合成的三氨基的大环内脂类抗生素 New unique macrolide class 新型大环内脂 Exceptional pharmacokinetics 卓越的药物代谢动力学 Tribasic triamilide molecule is highly charged and readily penetrates Gramnegative bacteria 带电丰富的三氨基分子有利于药物快速穿透革兰氏阴性菌 Reduced affinity for bacterial efflux pump, so antibiotic accumulates in bacteria, enhancing antibacterial activity 降低对细菌排除泵的亲和力, 便于渗入细菌体内, 增强抗菌活性 Rapid absorption from injection site and distribution to lungs, followed by slow elimination from body 注射部位的快速吸收和高浓度药物的肺脏分布, 在体内缓慢消除 Concentrations in swine lungs 60-times greater than in plasma 肺组织药物浓度是组织液的 60 倍 Lung concentrations remain at effective levels for up to 15 days after a single dose 单次注射针对肺炎支原体的药效期长达 15 天 40
SRD Control program 猪呼吸道病综合症控制计划 易速达 / 瑞可新 Swine Excede & Draxxin program 断奶 weaning 转入育肥舍 Transfer to fattening 周龄 Age of week 1 2 3 4 5 6 7 8 9 10 EXCEDE Draxxin EXCEDE or Draxxin (depend on diseases) 41
SRD Control Program 猪呼吸道病综合症控制计划 瑞倍适 / 易速达 / 瑞可新 /-- Respisure + Excede + Draxxin + Lincospectin 瑞倍适 + 易速达 + 瑞可新 + 利高 44 Total solution program to increase economic profit 全面解决方案, 增加经济效益 Respisure 断奶 weaning 转入育肥舍 Transfer to fattening week 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Lincospectin EXCEDE Draxxin EXCEDE or Draxxin (Depend on infection pressure) 42
Thank You 43