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1、Avian and Human Influenza 禽流感與人類流感病毒,新光醫院感染科 張藏能,Influenza: A Historical Perspective,First well-recorded pandemic occurred in 1580 Originated in Asia and subsequently spread to Africa, Europe, and America. In 1932, influenza virus was first identified in the laboratory as the causative agent respons
2、ible for these periodic outbreaks of respiratory illness.,Organism or Infection Total no. of patients N=200 (%) Rinovirus 105 (53) Coronavirus 14 (7.0) Influenza 12 (6.0) Parainfluenza 7 (4.0) RSV 4 (2.0) Adenovirus 2 (1.0) Enterovirus 1 (0.5) C. pneumoniae 1 (0.5) M. pneumoniae 1 (0.5) S. pneumonia
3、e 1 (0.5) Double virus infection 10 (5.0) Viral and bacterial infection 6 (3.0),Etiology of the Common Cold prospective study during 10 months,Makela MJ. J Clin Micro 1998,流感(Influenza)的真面目,流感 (Influenza)與感冒(cold)是完全不同的疾病。 流感是一種可怕的疾病，它曾在1918年度造成全球超過2000萬人死亡。 流感是一種年年發生的疾病。 流感造成的社會成本是其他疾病無法比擬的。,Pathog
4、en Total (%) N=267 Bacterial pathogens 144 (54) S. pneumonia 129 (48) H. influenza 20 (7) Atypical pathogens 60 (22) C. pnuemoniae 35 (13) M. pnuemonia 9 (3) Legionella 9 (3) Virus 62 (23) Influenza A 50 (19) Influenza B 2 (1) RSV 11 (4),Community acquired pnuemonia in adults admitted to hospital,Li
5、m WS Thorax 2001,流行感冒,病毒依其基因分為A型、B型及C型 A型流行感冒病毒主要流行於人類、家禽、豬、馬等 B型及C型流行感冒病毒則迄今只發現於人類間流行,Type A 通常造成較強的病症徵狀 可造成區域性流行(Epidemics) and 全面 性行(Pandemics)病毒變異快速 Type B 通常不會造成強的病症徵狀 大多造成區域性流行(Epidemics),相較於 A型病毒而言較為單純不易有大變化 Type C 通常造成相當輕甚至是可忽略的病症徵 對公眾健康的衝擊輕微,流感病毒的分類,Influenzae virus: epidemiology,Ag variati
6、on: Hemagglutinin, Neuraminidase. Ag drift (抗原飄變): minor change & occur every year. Type A and B Ag shift (抗原移變): new virus, herald pandemic (全面流行)influenzae. 1918 H1N1 - 1957 H2N2. Only Type A,Influenza Viruses: Structure,Envelope proteins Hemagglutinin (HA): functions in attachment and penetration
7、 Neuraminidase (NA): cleaves sialic acid from glycoconjugates; facilitates elution of progeny virions from infected cells M2: functions in uncoating and virus maturation,The Influenza A Virus,Primary Ag determinant- glcoprotein Hemagglutinin: H1-15 Neuraminidase : N1-9.,Influenza Pandemic: origin ?,
8、1918 pandemic was associated with an unusually high case-fatality rate in young healthy adults. The origin of the 1918 Spanish influenza virusis still a work in progress. Gradual adaptation of avian influenza viruses to human transmission. There is some evidence that this occurred in the 1918 H1N1 p
9、andemic. Sequence and phylogenetic analysis of the HA, NA, and gene segments of these samples suggests that an avian influenza virus was transmitted to humans and pigs, developing separate lineages sometime before 1918. It seems to be more akin to the “bird flu“ that emerged in Hong Kong in 1997.,We
10、bster, Robert G. Science. 293(5536):1773, 2001,Persons with Increased Risk for Complications from Influenza, 50 years of age Chronic pulmonary or cardiovascular disease Chronic metabolic disease, renal dysfunction, hemoglobinopathies, immunosuppression Children & teens (6 mo.-18 yr.) taking aspirin
11、Women in the 2nd or 3rd trimesters of pregnancy,Influenza B Predominant,Influenza A Predominant,Distribution of Influenza Isolates by Subtype September 29, 2002 June 13, 2003,A: 78% B: 22%,A: 77% B: 23%,A: 49% B: 51%,A: 42% B: 58%*,A: 22% B: 78%,A: 72% B: 28%,A: 41% B: 59%,A: 86% B: 14%,A: 57% B: 43
12、%,Influenza Viruses Isolated by WHO/NREVSS Collaborating Laboratories 2002-03,58% A 42% B,73% A (H1) 27% A (H3N2),Influenzae virus,Incubation: 1-3 days depending on the initial viral inoculum. Major focus of infection: ciliated respiratory epithelium.,Sinusitis(鼻竇炎)， Otitis Media (中耳炎),Bronchitis (支
13、氣管炎)，Pneumonia (肺炎)， 有下列疾病時會更加重症狀: Asthma (哮喘病)， COPD (慢性阻塞性肺病),流感感染的併發症,Systemic Complications Myositis(肌炎), Myocarditis (心肌炎)， Encephalitis (腦炎),胸部併發症,Laboratory Diagnosis,Detection of Antigen - a rapid diagnosis can be made by the detection of influenza antigen from nasopharyngeal aspirates and t
14、hroat washings by IFT and ELISA Virus Isolation - virus may be readily isolated from nasopharyngeal aspirates and throat swabs. Serology - a retrospective diagnosis may be made by serology. CFT most widely used. HAI and EIA may be used to give a type-specific diagnosis RT-PCR,禽流感 avian influenza vir
15、us bird-flu (Fowl Plague) 雞瘟,Transmission of the disease to humans remains a major concern,Avian Influenza,Caused by Orthomyxoviridae, type A (multiple stranded RNA virus) Multiple spike glycoproteins Hemagglutinin (15) Neuraminidase (9) Viruses classified on combination of H and N types (eg. H5N2)
16、Recombination occurs very commonly by “shift and drift”,Subdivisions of virus types on basis of pathogenicity: Low pathogenicity High pathogenicity Pathogenicity determined by live bird inoculations or viral genomic sequencing analysis Establishing viral H&N / pathotype very important in outbreak re
17、sponse Birds can get all 15 H and 9 N types of type A Influenza High pathogenicity : always of the H5 or H7 subtypes, but not all H5 and H7 viruses are highly pathogenic,Pathogenesis,Incubation Period: 3-14 days Highly contagious (100%) Low Path low mortality, recover in 3 weeks High Path 95% mortal
18、ity within 24 hrs,HPAI-clinical signs,Clinical signs Disease in most species of birds-in US, most in chickens and turkeys Repiratory diseasesnicking, sneezing, lacrimation, sinusitis, etc. edema, hemorrhages, cyanosis of combs and wattles High mortality Neurologic disease (in some cases) May be sudd
19、en mortality without significant clinical signs Change in eggshell pigmentation, shell-less eggs produced,Edematous, cyanotic comb and wattles of a chicken,禽流感 Avian Influenza,目前禽流感停留在禽鳥傳染病的階段，偶有人類因為密切接觸禽鳥，遭大量病毒感染，但人和人之間不會互相傳染。,Avian Influenza in Hong Kong 1997: case present,On 9 May 1997, a previou
20、sly healthy 3-year-old boy, who was a resident of Hong Kong, often played with pet ducks, developed a sore throat, dry cough, and fever. Hospitalized on 15 May- remarkable for leukopenia (WBC: 2000) -next day, he developed progressive respiratory distress associated with hypoxemia.-died on 21 May wi
21、th several complications, including respiratory failure, renal failure, and disseminated intravascular coagulopathy,Avian Influenza in Hong Kong 1997: case present,Final diagnosis: Reye syndrome, acute influenza pneumonia, and respiratory distress syndrome Influenza A(H5N1) virus was isolated from a
22、 tracheal aspirate collected on May 19.,Avian Influenza in Hong Kong 1997 A型流行性感冒H5N1,香港一九九七年出現十八個病例，其中六例死亡，死亡率為33.3 病徵及發病初期，與一般流感類似，但發燒可高至 41C ，且較一般流感容易影響肝功能，也較易引致 淋巴細胞減少及呼吸衰竭，甚至多器官功能衰竭而 死亡。 死者多是平時身體頗健康的成年人。,Avian Influenza in Hong Kong 1999 H9N2,Several cases of human infection with avian H9N2 vir
23、us occurred in Hong Kong and Southern China in 1999. The disease was mild and all patients made a complete recovery Again, there was no evidence of reassortment,南韓爆發禽流感 (H5N1) 上萬雞隻暴斃 2003-12-16,南韓最近爆發禽流感疫情，造成至少有數萬隻雞暴斃死亡，由於擔心消費者遭到感染，南韓官方除了緊急關閉相關養殖場，也暫時停止雞肉的出口。 南韓正式證實發生H5NI病毒型禽流感。,日本證實自1925年以來首度爆發禽流感疫
24、情 2004-1-12,西部的山口縣官員周一表示，當地一家禽農場約有6,000雞隻已因感染禽流感而病死。,越南禽流感嚴重 2004-1-15,越南已經有十五個省分爆發疫情，南部疫情尤其嚴重，大約有兩百萬隻雞被撲殺或死亡。,WHO Confirms Fifth Death from Bird Flu in Vietnam 1/18, 2004,The World Health Organization confirmed Monday that a fifth person in Vietnam has died after contracting a bird flu that is rava
25、ging chicken farms throughout Asia.,彰化禽流感 撲殺2萬蛋雞 2004/01/16,防疫單位最近在彰化縣芳苑鄉一處蛋雞場檢出禽流感病毒，所幸是弱毒株，不會傳染給人。農委會為了避免病毒變異為強毒株，昨晚十一時開始撲殺該雞場兩萬多隻雞。,陳建仁：台灣發生禽流感是必然,亞洲多國爆發禽流感，衛生署署長陳建仁昨天表示，台灣發生禽流感是必然的事，衛署會加強追蹤養雞場負責人、工作與消毒人員的健康情況。 2004/01/16,嘉義縣也傳禽流感 三萬隻雞下午撲殺 2004-1-17,繼彰化縣芳苑鄉爆發禽流感病毒之後，嘉義縣新港鄉菜公村一家養雞場，也檢驗出雞隻感染禽流感病毒，行
26、政院農委會動植物防疫檢疫局為了避免疫情擴大，將比照彰化縣的模式，從今天下午起撲殺養雞場內三萬隻雞。,彰嘉禽流感 疫苗惹的禍 2004-01-19,彰化與嘉義養雞場陸續檢測出禽流感弱毒株，養雞業者私下流傳，指染病雞場可能是私自注射來路不明禽流感疫苗肇禍。農委會防檢局準備派人前往香港、墨西哥等地蒐集禽流感疫苗，與本次發現的病毒株進行核酸序列比對，釐清感染來源。 禽流感疫苗為不活化疫苗，毒性已降低，但全球只有香港、墨西哥與義大利使用，雞隻施打疫苗雖可降低死亡率與減緩症狀，卻無法完全抑制病毒在體內複製，病毒仍可藉由糞便或分泌物排出體外。,WHO警告 全球性流感迫在眉睫 2004-1-16,面對禽流感在亞洲地區蔓延，世界衛生組織 (WHO)警告，專家認為全球性流行性感冒不但無法避免，可能已是迫在眉睫。 世界衛生組織指出，亞洲爆發的禽流感問題，情況可能比SARS還大。如果禽流感和其他感冒病毒結合，在人類之間傳播的話，那後果不堪想像。,世衛禽流感疫苗研製需時4月,禽流感來勢洶洶，為了預防疫情擴大，世衛組織西太平洋區發言人（科丁尼）說，世衛已經在多人染病的越南抽取禽流感樣本，送往其他實驗室研製禽流感疫苗，但需要4個月才會有結果。,