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新型流感 A (H1N1) influenza A (H1N1)

新型流感 A (H1N1) influenza A (H1N1). 傳染病防治醫療網東區疫情指揮中心 李仁智指揮官. 人類 A 型流行性感冒病毒的流行. 歷史上，最早可以追溯至西元前 412 年希伯來文明（ Hippocrates ）有人類感染類似流行性感冒的相關紀錄的紀錄。 1933 : 第一株人類流感病毒被分離 [Smith et al., 1933] 之後，人們因而能證實並瞭解 1933 年之後的流行是由何種的流行性感冒病毒所造成的。. 二十世紀歷史上流感流行 所造成的死亡人數 1. “ Spanish flu” (H1N1). 1918–19.

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新型流感 A (H1N1) influenza A (H1N1)

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  1. 新型流感A (H1N1)influenza A (H1N1) 傳染病防治醫療網東區疫情指揮中心 李仁智指揮官

  2. 人類A型流行性感冒病毒的流行 歷史上，最早可以追溯至西元前412年希伯來文明（Hippocrates）有人類感染類似流行性感冒的相關紀錄的紀錄。 1933:第一株人類流感病毒被分離 [Smith et al., 1933] 之後，人們因而能證實並瞭解1933年之後的流行是由何種的流行性感冒病毒所造成的。

  3. 二十世紀歷史上流感流行所造成的死亡人數 1 “Spanish flu” (H1N1) 1918–19 全球近4000萬人死亡 1957–58 “Asian flu” (H2N2) 全球近400萬人死亡 1968–69 “Hong Kong flu” (H3N2) 全球近200萬人死亡 二十世紀歷史上流感的大流行 (Influenza pandemics) 1Oxford JS. Rev Med Virol 2000;10:119–33

  4. Initial Genetic Characterization of the 1918 “Spanish” Influenza Virus Jeffery K. Taubenberger,*† Ann H. Reid,† Amy E. Krafft, Karen E. Bijwaard, Thomas G. Fanning SCIENCE 1997:275;1793-1796

  5. 28% of the U.S. population is estimated to have been infected. The disease was also exceptionally severe, with mortality rates among the infected of over 2.5%, as compared with less than 0.1% in other influenza epidemics. 流感發病率為美國人口的28%, 病人的致死率為2.5% SCIENCE 1997:275;1793-1796

  6. 1918 Vs. average annual mortality of 1913–1917 1957 Vs, 1952–1956 1968 Vs. 1963–1967 Source: CID 2001:33:1375-8 (15 October)

  7. Gustau Klimt 1862-1918 The kiss

  8. Images from the 1918 Influenza Epidemic

  9. 陶賓柏格 (Jeffery K. Taubenberger ) 維吉尼亞州醫學院醫學博士1995年3月19日 PCR 1997年3月 “ 科學 ” 期刊

  10. 陶賓柏格和蕾德在華盛頓特區的美國陸軍病理研究院，檢視DNA序列的實驗結果。他們希望能從1918流行性感冒患者的組織樣本中，找出為什麼病毒如此致命的原因（艾瑞克，赫斯Eric Haase提供）。

  11. 石蠟塊中的肺部組織樣本，取自1918流行性感冒受害者。這些樣本儲存在陸軍病理研究院的國家組織儲藏庫中石蠟塊中的肺部組織樣本，取自1918流行性感冒受害者。這些樣本儲存在陸軍病理研究院的國家組織儲藏庫中

  12. 約翰．哈爾汀(Johan V. Hultin) 瑞典病理學家 1951年六月 第一次挖掘 1997年八月 第二次挖掘-露西(Lucy) 阿拉斯加的泰勒路德傳教區 Teller Lutheran mission 現在稱為貝立格Brevig

  13. 一九五一年六月，哈爾汀和他的同事在阿拉斯加的貝立格合影。他們站在1918流行性感冒受難者的集體墳墓前，這些屍體原封不動地被保存在凍土層中。圖中由左而右為哈爾汀、吉斯特、雷頓、麥基 (哈爾汀提供) 。

  14. 一九九七年八月，哈爾汀重返阿拉斯加貝立格的集體墳墓尋找完整的肺部組織。他發現一具女性屍體的肺臟仍然保存完好。圖中他蹲在那位女性骸骨旁（哈爾汀提供）。一九九七年八月，哈爾汀重返阿拉斯加貝立格的集體墳墓尋找完整的肺部組織。他發現一具女性屍體的肺臟仍然保存完好。圖中他蹲在那位女性骸骨旁（哈爾汀提供）。

  15. Dr. Terrence Tumpey, a U.S. Centers for Disease Control microbiologist for the National Center for Infectious Diseases, examines specimens of the 1918 pandemic influenza virus, a virus that he reconstructed to identify and research the characteristics that made it so harmful in this 2005 handout photo acquired from the CDC on April 24, 2009.

  16. 流感病毒 • 流感病毒可以分為 A、B、C三型，其中只有A型與B型可以引起大規模的流行，C型流感則在臨床上不太重 要。 • 流感病毒是一種RNA病毒，它的RNA分成八個節段而分別製造不同的十種蛋白質。 • 病毒的外表有兩種重要的抗原： • 血球凝集素 (hemagglutinin, H抗原) • 神經胺酸酵素 (neuraminidase, N抗原)

  17. 新型流感A (H1N1)病毒影像

  18. 神經胺酸脢 (Neuraminidase) (N1-N9), (N1, N2) 血球凝集素 (Hemagglutinin) (H1-H15), (H1, H2, H3) RNA M2蛋白 (僅 A型流感病毒才有) 流感病毒的表面蛋白

  19. Haemagglutinin (H) RNA (8 segments) Nucleoprotein (A,B & C types) Envelope Neuraminidase (N) Typing and Sub-typing of Influenza Virus MAN PIG HORSE BIRD H types H1 √√√ H2 √  √ H3 √ √√ H4 √ H5 √√ H6 √ H7 √√√ H8 √ H9 √√ H10-H15 √ N types N1 √√√ N2 √√√ N3 √ N4 √ N5 √ N6 √ N7 √√ N8 √√ N9 √

  20. 1. 抗原飄變(antigenic drift)：病毒遺傳基因有易變性（labile），主因RNA病毒複製過程中若產生錯誤而缺少校對（proof-reading）與修補的機制，所以突變的新病毒株足以取代原有的病毒株，即病毒的胺基酸之「小」的變異，如此因而極易適應於宿主防禦體系。 2. 抗原移變（antigenic shift）：即來自兩各不同來源的流感病毒基因重組而致生「新」的病毒，此是幾次世界性大流行有眾多死亡人數的主因。

  21. RNA Hemagglutinin Neuraminidase Antibodies Sialic acid 血球凝集素 (Hemagglutinin) 神經胺酸脢 (Neuraminidase) 抗體 (Antibody) Antigenic Drift

  22. Antigenic Shift

  23. 了解流感的傳播途徑 • 傳播途徑: • 流感透過咳嗽和噴嚏形成的飛沫傳播。它通常由一人傳染給另一人，某人偶然接觸帶有病毒的物件後再接觸口鼻，就可能被感染。 • 潛伏期: 1~3天 • 傳染力: • 成年人出現症狀前一天和患病後七天內都能夠傳染他人。因此，您得知患病之前和患病時，都可能將流感傳染他人。

  24. Emergence of a Novel Swine-Origin Influenza A (H1N1)Virus in Humans Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team* N Engl J Med 2009;361

  25. RESULTS From April 15 through May 5, a total of 642 confirmed cases of S-OIV infection were identified in 41 states. The ages of patients ranged from 3 months to 81 years; 60% of patients were 18 years of age or younger. 25% of patients had diarrhea, 36 (9%) required hospitalization. 8 required admission to an intensive care unit, 4 had respiratory failure, and 2 died. The S-OIV was determined to have a unique genome composition that had not been identified previously. N Engl J Med 2009;361

  26. N Engl J Med 2009;361

  27. N Engl J Med 2009;361

  28. CONCLUSIONS A novel swine-origin influenza A virus was identified as the cause of outbreaks of febrile respiratory infection ranging from self-limited to severe illness. It is likely that the number of confirmed cases underestimates the number of cases that have occurred. 一種全新的A型流感病毒已經出現，可以造成輕症和重症。 N Engl J Med 2009;361

  29. PATIENTS IN OUTBREAK On March 30, 2009, in San Diego County, California,a 10-year-old boy with asthma (Patient 1) hadan onset of fever, cough, and vomiting. On April 1,he was evaluated in an urgent care clinic. He recoveredfrom the illness within approximately 1 week. Aninfluenza A virus that could not be sub-typedwas identified from a nasopharyngeal specimenthat was collected from Patient 1 as part of aclinical trial to evaluate an experimental diagnostictest. As specified by the study protocol,the specimen was then sent to a reference laboratoryfor further testing and was found to be positivefor influenza A virus but negative for bothhuman H1 and H3 subtypes. N Engl J Med 2009;361

  30. PATIENTS IN OUTBREAK On April 15, the CDCreceived the clinical specimen and identified a novel influenza A (H1N1) virus of swine origin. A viral isolate was found to contain genes from triple-reassortant swine influenza viruses that were known to circulate among swine herds in North America and two genes encoding the neuraminidase and matrix proteins that were most closely related to genes of viruses obtained from ill pigs in Eurasia, according to results available in GenBank. N Engl J Med 2009;361

  31. Viral Gene Sequences to Assist Update Diagnostics for Swine Influenza A(H1N1) - GenBank Accession Numbers 28 April 2009 The WHO Collaborating Centre for influenza in CDC Atlanta USA has posted the full genome sequences of swine influenza A/California/04/2009 (H1N1) influenza virus on the GenBank sequence database. To access, go to: http://www.ncbi.nlm.nih.gov/sites/entrez?db=nuccore&itool=toolbar, then enter the accession number as shown below: • PB2 gene accession number is: FJ966079 • PB1 gene accession number is: FJ966080 • PA gene accession number is: FJ966081 • HA gene accession number is: FJ966082 • NP gene accession number is: FJ966083 • NA gene accession number is: FJ966084 • M gene accession number is: FJ966085 • NS gene accession number is: FJ966086

  32. Science 8 May 2009;342;700-703

  33. Comparison of H1N1 Swine Genotypes in Recent Cases in the United States. N Engl J Med 2009;361

  34. All S-OIVs that havebeen examined are susceptible to both oseltamivirand zanamivir, two antiviral medications approvedfor the prevention and treatment of influenzain the United States. N Engl J Med 2009;361

  35. Transmission modes The modes of transmission of influenzaviruses in humans, including S-OIV, arenot known but are thought to occur mainlythrough the dissemination of large droplets andpossibly small-particle droplet nuclei expelledwhen an infected person coughs. There is alsopotential for transmission through contact withfomites that are contaminated with respiratoryor gastrointestinal material.Since many patientswith S-OIV infection have had diarrhea,the potential for fecal viral shedding and subsequentfecal–oral transmission should be consideredand investigated. N Engl J Med 2009;361

  36. Incubation period The incubation period for S-OIV infection appearsto range from 2 to 7 days; however, additionalinformation is needed. N Engl J Med 2009;361

  37. As of May 5, 2009, the CDC hasrecommended that health care workers who providedirect care for patients with known or suspectedS-OIV infection should observe contact anddroplet precautions, including the use of gowns,gloves, eye protection, face masks, and fit-tested,disposable N95 respirators. 醫護人員照顧流感病人時應注意接觸和飛沫傳染，包括使用防護衣、手套、眼罩、口罩和N95口罩。 N Engl J Med 2009;361

  38. Patientswith confirmed or suspected S-OIV infectionshould be placed in a single-patient room with thedoor kept closed, and airborne-infection isolationrooms with negative-pressure handling should beused whenever an aerosol-generating procedureis being performed. Frequent hand washing withsoap and water may reduce the risk of infectionand transmission. N Engl J Med 2009;361

  39. Science 8 May 2009;342;700-703

  40. MMWR Dispatch Vol.58/April 30, 2009

  41. NYC Department of Health and Mental Hygiene (DOHMH) House Quarantine • Persons with mild (uncomplicated) ILI are being advised to stay home for 7 days after symptom onset or 24–48 hours after symptom resolution, whichever is longer, and to cover their coughs and sneezes and wash their hands frequently • 流感病人應當在家休養七天（症狀開始日起算）或症狀消失48小時後才可以上班上學。病人應常洗手，咳嗽時請掩蓋口鼻。 MMWR Dispatch 2009;58:April 30.

  42. Case fatality ratio Our estimates suggestthat 23,000 (range 6,000-32,000) individuals had beeninfected in Mexico by late April, giving anestimated casefatality ratio (CFR) of0.4% (range 0.3% to 1.5%) basedon confirmed and suspect deaths reportedto that time. Clinical severity appears less than that seen in 1918 but comparable with that seen in 1957. 病人的致死率估計為0.4% Science 11 May 2009

  43. 30 April 2009 -- From today, WHO will refer to the new influenza virus as influenza A (H1N1) H1N1 Flu (Swine Flu)

  44. Medical staff work near a quarantine area where a man is held for having the H1N1 flu at Taoyuan General Hospital, northern Taiwan, May 20, 2009.

  45. A nurse works inside a quarantine area where a man is held for having the H1N1 flu at Taoyuan General Hospital, northern Taiwan, May 20, 2009. Taiwan on Wednesday reported its first case of H1N1 flu case, a foreign national who entered Taiwan from the U.S. The man is a 52-year-old doctor who arrived by air in Taipei on Tuesday night

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