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1 狂犬病防疫全球概況 From: straysanatomy.com 台灣大學獸醫專業學院費昌勇教授攻擊性行為是因為病毒感染後造成 :(1) 腦神經功能不全 (neuronal dysfunction) (2) 低血清素行動 (low CNS serotonergic activity), 與 (3) 高睪固酮症所致血清素管理生命現象諸如 : 睡眠甦醒記憶痛覺等, 屬於 limbic system 1 4 內容綱要病原性免疫性新治療法已開發與開發中國家疫情特徵世界衛生組織推薦之防疫措施美國犬貓狂犬病社會狀況中國狂犬病概況 Lyssavirus 之分類基因型特徵發生地區 I Rabies virus (RABV) 全世界肉食獸蝙蝠 ( 美國 ) II Lagos bat virus (LBV) 非洲蝙蝠 III Mokola virus (MOKV) 非洲鼠類 IV Duvenhage virus (DUVV) 非洲蝙蝠 V European bat lyssavirus type I (EBLV-1) 歐洲蝙蝠 I 型 VI European bat lyssavirus type II (EBLV-2) 歐洲蝙蝠 II 型 2 VII Australian bat lyssavirus (ABLV) 澳洲蝙蝠 From: 病毒經過不定時間, 在背根神經節複製後循脊髓神經繼續上行到腦 1. 動物咬感染 5. 感染腦部位 6. 病毒從腦透過神經散播到所有器官, 主要是眼腎唾液等處 3. 病毒感染被咬部位附近的周圍神經向上逆行 retrograde movement 人畜幾乎沒有免疫反應是死亡率高之主因造成 2005 美國四人器官移植感染本病 Negri body 2. 先在咬的肌肉繁殖無症狀 (binding to the neuromuscular junction) From: Microbiology and Immunology on-line, Chapter 20 Rabies University of South Carolina, School of Medicine Negri bodies, round eosinophilic cytoplasmic inclusions measuring 1-7 m, are pathognomonic of rabies (HE, high power). Hippocampal neurons are the preferential site of Negri body formation. From: US_CDC 3 6 1

睡眠甦醒記憶痛覺等, 屬於 limbic system 1 4 內容綱要病原性免疫性新治療法已開發與開發中國家疫情特徵世界衛生組織推薦之防疫措施美國犬貓狂犬病社會狀況中國狂犬病概況 Lyssavirus 之分類基因型特徵發生地區 I

2 狗狂暴型 (25%) 麻痺型 (75%) Furious rabies ( 狂暴型 ) causes the animal to foam ( 口吐白沫 ) and drool ( 從嘴滴下 ) at the mouth. Animals behave unpredictably and may become vicious, snap ( 猛咬 ) at imaginary objects and attack without warning. The animal becomes progressively unco-ordinated, paralysed and usually dies in 4-5 days. Dumb rabies ( 麻痺型 ) causes early paralysis, followed by drooling and death. Animals with dumb rabies remain quiet and only bite when provoked. They are unable to eat, but will frequently try to drink water. From: ; 感染方式咬舔 ( 動物吃動物 ) 吃反芻食物 ( 母狼餵小狼 ) 吃奶 ( 牛奶中排毒 --- 巴斯德滅菌法可滅毒 ) 呼吸道吸入胎盤感染黏膜接觸 7 10 應接受預防注射之高風險族群 Pre-exposure, prophylactic immunisation 1. Laboratory staff 傳染病實驗室員工 2. Quarantine stations 檢疫人員 3. Animal handlers 動物照顧者 4. Veterinary surgeons 獸醫師 5. Field workers 野外工作者 6. Port officials 港口工作者 7. Licensed handlers 發動物相關證照者 8. Health workers 衛生醫療人員 9. Travellers 旅客 A rabid dog, with saliva dropping out of the mouth. From Wikipedia 8 11 美國研發成功狂犬病治療新法世界第一例 : 美國 Wisconsin 州 Fond du Lac 郡的一位 15 歲女學生 Jeanna Giese 2004 年被蝙蝠咬後出現典型之狂犬病臨床症狀, 經 Dr. Rodney Willoughby Jr. 研發之 Milwaukee protocol 治療後痊癒原理是感染狂犬病後用 ketamine, phenobarbital 等藥物引導病人麻醉六天, 以避開狂犬病病毒之致害反應等病人的免疫系統啟動並殺死病毒後, 再讓病人甦醒結果陸續治癒多人後 Jeanna Giese 2011 年 Spring 從 Lakeland College, Dept. Biology 畢業 From: (1) Recovery of a Patient from Clinical Rabies --- Wisconsin, 2004, CDC Weekly December 24, 2004 / 53(50); (2) Wikipedia. 9 狂犬病流行之風險有病源之保毒者 ( 蝙蝠 / 浣熊 / 臭鼬 / 狐 / 豺狗 ) 狗群管理不好疫苗接種率低於 70% (WHO--- 含流浪狗 ) 民眾不了解 ( 社會教育不夠 ) 環境髒亂資料來源 1. WHO 2005 Technical Report Series 931, 2005 published. p Matter H C and Daniels T J 2000 Dog ecology and population biology, in dogs, zoonoeses and public health. In Macpherson C N L, Meslin F X and Wandeler A I (eds) Dogs, Zoonoses and Public Health, chap. 2, pp CABI Publication, USA. 12 2

The animal becomes progressively unco-ordinated, paralysed and usually dies in 4-5 days. Dumb rabies ( 麻痺型 ) causes early paralysis, followed by drooling and death.

3 開發中國家之特徵 ( 亞洲非洲等 ) : 狗貓感染率高美國狗貓狂犬病疫情與人口密度呈正相關 (2009 年數據 ) 家狗多, 管理不好疫苗接種率低疫苗品質不好民眾認知不足 ( 社會教育不足 ) 流浪狗多四處傳播疾病 13 已開發國家之特徵 ( 美國與西歐 ): 狗貓感染率低美國各州狗貓狂犬病法律不一致家狗家貓管理得很好, 感染率低流浪狗貓少, 疾病不會散布主要是蝙蝠等野生動物保毒與散布 14 美國人狗貓狂犬病疫情美國野生保毒動物 1. 狗 : 都市近郊之垃圾箱吸引帶原野生動物來吃垃圾時感染狗 2. 貓 : 貓因外出至家附近森林玩耍被帶原之野生動物感染 350 美國人狗貓狂犬病感染數目 ( 美國 CDC 資料 ) dogs cats humans

等野生動物保毒與散布 14 美國人狗貓狂犬病疫情 2002-2009 美國野生保毒動物 1. 狗 : 都市近郊之垃圾箱吸引帶原野生動物來吃垃圾時感染狗 2.

4 TNR 流浪貓聚落之狂犬病風險 By LIZ MUGAVERO Norwich Bulletin (Feb. 11, 2007) GRISWOLD -- A feral cat colony is in danger of extermination after one of the kittens was discovered to be rabid. The colony is living behind a home on Voluntown Road and has a caregiver, according to Mark Wickerd, president of Forgotten Angels Animal Sanctuary. Wickerd was assisting in a trap-neuter-return program (TNR) with the cats in the colony when the kitten was discovered to have a bite wound and apparent neurological problems. He brought the kitten to a veterinarian, where it was euthanized and sent out for rabies testing 十九世紀歐洲都市狂犬病防疫通告 ( 標準都市型防疫措施 ) 11th, June 1829 Bologna, Italy 公告昨天一隻無主兇狗進城, 被咬的人均已送醫茲規定如下 : 1. 所有家狗禁止外出, 且注意在家中不得咬訪客 2. 家狗出門一律繫頸鍊, 否則以無主狗論處 3. 警察將撲殺所有室外無主狗, 即使帶狗鍊亦要撲殺 4. 所有狗咬人事件均需報告市公所公共衛生部門 5. 凡家狗被其他狗咬, 或出現疑似狂犬病症狀都要報告 6. 註 : 當時沒有 [ 戴口罩 ] 之規定 22 收容所疑似狂犬病檢疫狗被偷 ABC News (Feb, 12, 2007) Little River man who was bitten by a pit bull may have to get several shots unless the stolen dog is found. Bill Rosallino got bitten in the leg when he tried to break up a fight between a pit bull and his dog. Animal control officers picked up the pit bull, but it and another dog were stolen from the county's animal shelter Friday night. The Department of Health says they were holding the animal for 10 days to check it for rabies. Both dogs had been strays that were found in the Little River area 中國狂犬病近半世紀流行狀況 No of human rabies cases 第一次第二次第三次 From: Zhang YZ et. al. ( 張永振等贈圖檔 ). Human rabies in China. Emerg. Infect Dis, 2005, 11: 容易被狗咬的年齡 From: (Indiana State Dept. Health) 21 中國之狂犬病疫情中國狂犬病屬基因 I 型 (Virus Research 121 (2006) pp ); 狗咬發生率佔總感染率之 96~98%, 貓咬佔 2~3% 狗肉師傅傷口接觸狂犬狗屠體之腦與唾液感染早期感染尚未出現症狀之狂犬狗舔人類傷口感染中國之國產疫苗是用減毒 ERA 株 /SAD 株, 與市街毒之 DNA 高度同源 (WHO 僅推薦 SAG2 與 VRG 減毒株作狂犬病疫苗 ) 未做狗數調查, 寵物登記不清楚, 未做狗族群研究疫苗供應量不足, 防疫不足狂犬病死亡病例 :34% 患者未清洗傷口 72% 患者未接受 ( 或未及時接受 ) 疫苗治療 <1% 之患者曾接受抗血清治療 24 4

Wickerd was assisting in a trap-neuter-return program (TNR) with the cats in the colony when the kitten was discovered to have a bite wound and apparent neurological problems.

5 WHO 狂犬病控制之標準做法 1. Epidemiological Surveillance ( 疫情調查 ) 2. Mass vaccination ( 疫苗注射須高於 >70%--- 含流浪狗 ) 3. Dog population control ( 狗口控制 --- 寵物登記流浪狗控制 ) Kansas 大學獸醫學院狂犬病診斷中心蝙蝠病例資料來源 From: a. WHO No. 931 Technical Report (2005). p. 30 b. Rabies surveillance in the United States during 2005 (CDC). c th July 2005 費昌勇受邀參訪時攝 28 中國國產之活毒疫苗毒株 Rabies Quarantine at George Lee Dunn Animal Shelter, Kansas City, KS 目前 WHO 僅承認 SAG2 株或基因重組之 VRG 株是安全的減毒疫苗中國犬貓用疫苗未使用 WHO 推薦之安全毒株中國狂犬病疫苗有 :(1) Vero 細胞組織培養之狂犬病 ERA 株, 包含在五合一疫苗內 ( 狂犬犬瘟副流感腺病毒犬小病毒 ) (2) BHK21 細胞培養之 Flury LEP 減毒株中國藥品生物製品檢定所董關木教授與衛生部張永振博士等均發現 : 狂犬病臨床市街毒株之 DNA 序列與國產活疫苗 ERA 毒株相似性達 99.1% WHO 的活毒疫苗剪毒標準 :(1) 對野生囓齒類經口肌肉與腦內注射都必須無病原性,(2) 疫苗施打後 3~4 天內唾液內不能有任何病毒出現 26 20th July 2005 費昌勇攝 29 Kansas 大學獸醫學院狂犬病診斷中心收件室 George Lee Dunn Animal Shelter, Kansas City, KS. 26th July 2005 費昌勇受邀參訪時攝 th July 2005 費昌勇攝 5

Rabies surveillance in the United States during 2005 (CDC). c. http://www.who.int/rabies/relevant_documents/en/index.

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