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Präsentation W. Preiser, Frankfurt/Main Jahrestagung der Paul-Ehrlich-Gesellschaft für Chemotherapie e. V. – Bonn, 25.9.2004 SARS & Co.: Lehren für neue Erkrankungen Wolfgang Preiser Institut für Medizinische Virologie, Klinikum der J. W. Goethe-Universität Frankfurt a.M. Communicable Disease Surveillance & Response (CSR) - Disease Outbreak News http://www.who.int/csr/don/2003_02_11/en/ Acute respiratory syndrome in China 11 February 2003 Disease Outbreak Reported WHO has received reports from the Chinese Ministry of Health of an outbreak of acute respiratory syndrome with 300 cases and 5 deaths in Guangdong Province. 2 Communicable Disease Surveillance & Response (CSR) - Disease Outbreak News http://www.who.int/csr/don/2003_2_19/en/ Influenza A(H5N1) in Hong Kong Special Administrative Region of China - 19 February 2003 As of 19 February results from two laboratories have confirmed the presence of an avian influenza virus in a child in Hong Kong SAR. Tests conducted in two samples from this single patient have identified the virus as the strain of influenza A(H5N1). A similar virus caused an outbreak in Hong Kong SAR in 1997, with 18 cases detected and six deaths. In the current outbreak, a 9-year-old boy who travelled to Fujian Province (China) in January with his mother and his two sisters became ill on February 9 and was admitted to a Hong Kong hospital on February 12. He has recovered and is in a stable condition. Other members of his family presented with a similar illness. The child’s sister and father have died. The boy’s mother was ill but has recovered. ... 3 Communicable Disease Surveillance & Response (CSR) - Disease Outbreak News http://www.who.int/csr/don/2003_2_20/en/ Acute respiratory syndrome in China - Update 3 20 February 2003 The Ministry of Health, China has reported that the causal agent for the atypical pneumonia outbreak in Guangdong Province, which affected a total of 305 cases including 5 deaths, was probably caused by Chlamydia pneumoniae. Further epidemiological investigations are underway coordinated by the Guangdong provincial health department. 4 Infektionsausbruch um das Hotel "M" in HongKong, Februar 2003 HCW = Kliniksmitarbeiter5 mod. nach MMWR 52(12), 28 Mar 2003 Ausbreitung von SARS: HongKong → Welt HongKong Vietnam Carlo Urbani ! 6 Communicable Disease Surveillance & Response (CSR) - Disease Outbreak News http://www.who.int/csr/don/2003_03_12/en/ Acute respiratory syndrome in Hong Kong Special Administrative Region of China / Viet Nam PRESS RELEASE ISSUED BY WHO - 12 March 2003 WHO issues a global alert about cases of atypical pneumonia Cases of severe respiratory illness may spread to hospital staff 12 March 2003 | GENEVA -- Since mid February, WHO has been actively working to confirm reports of outbreaks of a severe form of pneumonia in Viet Nam, Hong Kong Special Administrative Region (SAR), China, and Guangdong province in China. In Viet Nam the outbreak began with a single initial case who was hospitalized for treatment of severe, acute respiratory syndrome of unknown origin. He felt unwell during his journey and fell ill shortly after arrival in Hanoi from Shanghai and Hong Kong SAR, China. Following his admission to the .... 7 Ausbreitung von SARS: HongKong → Welt Irland Frankfurt Kanada USA HongKong Vietnam Singapur Frankfurt am Main, 15. März 2003 8 Communicable Disease Surveillance & Response (CSR) - Disease Outbreak News http://www.who.int/csr/don/2003_03_15/en/ PRESS RELEASE ISSUED BY WHO - 15 March 2003 World Health Organization issues emergency travel advisory Severe Acute Respiratory Syndrome (SARS) Spreads Worldwide 15 March 2003 | GENEVA -- During the past week, WHO has received reports of more than 150 new suspected cases of Severe Acute Respiratory Syndrome (SARS), an atypical pneumonia for which cause has not yet been determined. Reports to date have been received from Canada, China, Hong Kong Special Administrative Region of China, Indonesia, Philippines, Singapore, Thailand, and Viet Nam. Early today, an ill passenger and companions who travelled from New York, United States, and who landed in Frankfurt, Germany were removed from their flight and taken to hospital isolation. .... 9 WHO collaborative multi-centre research project on Severe Acute Respiratory Syndrome (SARS) diagnosis Winnipeg, CND Atlanta, USA London, UK Rotterdam, NL Tokyo, Japan Klaus Stöhr, WHO Paris, F Frankfurt, Marburg, Beijing, Guangzhou, SGH, CUHK, HKU, Hamburg, D China Singapore Hongkong, SAR WHO Expert Team at Guangdong Provincial CDC, Guangzhou, 3 -8 April 200311 " Zeitliche 400 "atypischerZeitliche s 350 se a 300 c 250 r of e 200 Verteilung b 150 Pneumonie num100 50 373 0 der 7 " in GuangzhouF ä Jan 1-10 13 älle 63 von Jan 11-20 224 Jan 21-31 Feb 1-10 95 Feb 11-20 110 Feb 21-28 94 Mar 1-10 Mar 11-20 22 Mar 21-31 12 AltersverteilungAltersverteilung derder FFäällelle vonvon ""atypischeratypischer PneumoniePneumonie"" inin GuangzhouGuangzhou 180 160 s 140 e s non-HCW HCW a 120 c 100 of r e 80 b 60 num 40 20 0 0 1 5 10152025303540455055606570758085 age group Insgesamt erkrankten 289 Krankenhausmitarbeiter (28,9 %) 13 Epidemiologische Charakteristika 60 aggregated cases 50 scattering cases total 40 30 20 10 0 1 5 9 1. 1. 7 13 1. 1 21 9 25 2 1. 1. 2 6 1. 0 1. 2. 4 1. 2. 1 8 1 1 6 2. 22 2 2 2. 6 Date 2. 2. 3. 4 2. 3. 10 8 1 2 1 6 3. 2 3. 2 3. 3. Figure 2. The number of AP cases in Guangzhou3. (the abscissa is the date when the patiets came down with the disease) 14 Guangdong super-spreader - epidemic curve of secondary cases Guangdong Province, Jan-Feb 2003 25 Secondary family Secondary HCW - Hosp 2 20 Tertiary HCW - Hosp 1 Secondary HCW - Hosp 1 Index case 15 s se ca f o . o N 10 5 Zh 0 n n n n n n n b b b b b b b a a an e e eb e eb e eb e eb e e eb J Ja . Ja J . Ja J . Ja Ja F F F F F F F F F 8. F . F . F 16. 1 20 22. 24 26. 28 30. 01. 03 05. 07 09. 11 13 15. 17. 19. 21 23. Date of onset 15 16 6000 Gemeldete "wahrscheinliche SARS-Fälle, kumulativ 5000 4000 China, 1. November 2002 bis 19. Juni 2003 3000 2000 1000 0 12.04.03 19.04.03 Guangdong H ebei 26.04.03 03.05.03 Beijing 10.05.03 Jilin 17.05.03 24.05.03 Shanx T 31.05.03 i anjin i 07.06.03 14.06.03 Inner M C h ina T o ngolia o ta l 17 27 March: WHO recommends exit screening of air passengers departing from areas where transmission is known to be occurring in local chains. No cases of suspected in-flight transmission are reported following this date. WHO Update 92 – 18 http://www.who.int/csr/don/2003_07_01/en/ Travel recommendations (postpone all but essential travel) 2 April: Issued for Hong Kong and Guangdong Province, China. 23 April: Issued for Beijing and Shanxi Province, China, and for Toronto, Canada. 30 April: Lifted for Toronto. 8 May: Issued for Tianjin and Inner Mongolia, China, and Taipei, Taiwan. 17 May: Issued for Hebei Province, China. 21 May: Issued for all of Taiwan. 23 May: Lifted for Hong Kong and Guangdong. 13 June: Lifted for Heibei, Inner Mongolia, Shanxi, and Tianjin provinces, China. 17 June: Lifted for Taiwan. 24 June: Lifted for Beijing – the last area on the list. 19 WHO Update 92 – http://www.who.int/csr/don/2003_07_01/en/ 20 21 Kumulative Anzahl der gemeldeten wahrscheinlichen Fälle von SARS 1. Nov. 2002 bis 31. Juli 2003 (Revision 21.4.2004) Quelle: http://www.who.int/csr/sars/ " Anzahl der Fälle weltweit : 8096 " Anzahl der Todesfälle weltweit: 774 " Letalität: 9.6 % " Anzahl der betroffenen Länder: 30 " Anzahl der Fälle in Dtl.: 9 22 Zusammenfassung und Fazit – I " SARS stammt aus Guangdong (Kanton) " wahrscheinlich Zusammenhang mit Wildtierhandel und -verzehr " Die erste SARS-Epidemie wurde relativ rasch unter Kontrolle gebracht, und zwar " durch strikt durchgesetzte, "traditionelle" Maßnahmen zur Verhinderung der Mensch-zu- Mensch-Übertragung " Totalitäre Regimes haben hierbei evtl. Vorteile, insgesamt jedoch hat mangelnde Offenheit intern wie extern zu enormen Problemen geführt 23 Zusammenfassung und Fazit – II " Auch industrialisierte Länder mit modernen Gesundheitssystemen sind nicht gefeit ⇒ stete Aufmerksamkeit erforderlich! " Erhebliches nosokomiales Potential " Massive wirtschaftliche und soziale Folgen " Risiko eines Wiederaufflackerns? " Überwachung von Laboren! " Zahlreiche Fragen weiterhin ungeklärt ⇒ dringend weitere wiss. Untersuchungen 24 WelcheWelche LehrenLehren sindsind ausaus demdem SARSSARS--AusbruchAusbruch zuzu ziehenziehen?? lokation Trans- Ex situ-Kontakt, Manipulation Menschliches Verstädterung Reisen, Verhalten, Eindringen, ökologische ("spill-over") und Zur Ökologische Wirts-Parasiten-Kontinua und Wildtier Wildtier Entstehen neuerInfektionskrankheiten Eindringen, Einführung, Über- Mensch ü Mensch ck"schwappen" ("spill-back") Haustier Haustier Ernährung Medizin, Technologie, Industrie Intensiv- haltung Daszak et al., Science 287, 2001 West Nil-Aktivität in den USA Stand: 07.04.2004 kumulativ: 9858 Erkrankungen, davon 2863 neuro-invasiv und 262 Todesfälle 27 http://www.frankfurt.de Kompetenzzentrum für hochkontagiöse, lebensbedrohliche Erkrankungen FRA 15. März 2003 http://www.kgu.de/zhyg/virologie/vhf-komp.html 28 Proben-Management im S3/L3-Hochsicherheits-Laboratorium ⇒ extensive Ausschlußdiagnostik 29 Zellkultur und Elektronenmikroskopie zur Isolierung und Visualisierung eines neuen Virus Cytopathischer Effekt (CPE) in Vero-Zellkultur 4 Tage nach Beimpfung mit Sputum des Frankfurter Indexpatienten 30 Identifizierung des neuen Agens mittels unspezifischer PCR • Zellkultur-Überstand der Frankfurter SARS-Patienten • RT-PCRs mit 15 "degenerierten" Primerpaaren ⇒ 20 verschiedene DNA-Fragmente • Sequenzierung: 2 dieser Amplicons (BNI-1, BNI-2) zeigten Homologie mit Coronaviren auf Proteinebene ⇒ kontinuierliches 3kb-Fragment CDC-BNI1 31 Drosten et al., NEJM • www.nejm.org • April 10, 2003 Phylogenetische Analyse des neu entdeckten Coronavirus SARS-assoziiertes Coronavirus basierend auf der BNI-1-Sequenz entsprechenden Fragmenten des Polymerase-Genes 32 Drosten et al., NEJM • www.nejm.org • April 10, 2003 Immunfluoreszenztest (IFT) zum Nachweis der Serokonversion Vero-Zellen 2 Tage p.i.
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