Influenza. Christoph Wenisch 4.Medizinische Abteilung SMZ-Süd KFJ Spital

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1 Influenza 2009 Christoph Wenisch 4.Medizinische Abteilung SMZ-Süd KFJ Spital

2 Übertragen Tröpfcheninfektion Schmierinfektion (Schneuzen, Nasenbohren) Viren auf Gegenständen, Körperoberflächen, Kot mechanisch auf Haaren, Haut Tage nach Ansteckung wird man krank Longini 2009, Fergurson 2008 Influenza und Reise Respiratory viruses were detected in 44 out of 118 (37%) travelers included in the study, representing 56% of the patients with respiratory symptoms. The most frequently viruses detected were influenza virus (38%), rhinovirus (23%), adenovirus (9%), and respiratory syncytial virus (9%). J Med Virol Apr;80(4): Incidence of respiratory viruses among travelers with a febrile syndrome returning from tropical and subtropical areas. Camps M, Vilella A, Marcos MA, Letang E, Muñoz J, Salvadó E, González A, Gascón J, Jiménez de Anta MT, Pumarola T.

3 Influenza beim Pilgern Fifty-four patients (10.8%) had positive viral throat cultures. Of these, 27 (50%) were influenza B, 13 (24.1%) were HSV, 7 (12.9%) were RSV, 4 (7.4%) were parainfluenza, and 3 (5.6%) were influenza A. No enteroviruses or adenoviruses were detected, and no multiple infections were detected. Only 22 (4.7%) pilgrims received the influenza vaccine. When the results are applied to the total number of pilgrims in 2003, an estimate of 24,000 cases of influenza is obtained. J Travel Med Mar-Apr;11(2):82-6. Influenza a common viral infection among Hajj pilgrims: time for routine surveillance and vaccination. Balkhy HH, Memish ZA, Bafaqeer S, Almuneef MA.

4 Influenza und HIV Fifty patients (median CD4(+) T cell count, 325 cells/microl; median HIV RNA level, <50 copies/ml). A causative pathogen was identified in 25 patients (50%). Even though 76% of subjects had received influenza vaccine, viral infections were diagnosed in 21 patients (42%), as follows: influenza A, 10 patients; influenza B, 10; and parainfluenza virus type 3 infection, 1. Antibiotic prescriptions were common: 70% of patients received antibiotics. No patients with influenza required hospitalization, compared with 21% of other patients (P=.03). Clin Infect Dis Jul 15;45(2): Epub 2007 Jun 12. Influenzavirus infection is a primary cause of febrile respiratory illness in HIV-infected adults, despite vaccination. Klein MB, Lu Y, DelBalso L, Coté S, Boivin

5 Letalität Alter Tot durch Influenza < > Total/Jahr Thompson, JAMA 2003; 289:179 Österreich 10 Fälle/Jahr

6 Influenza Surface Proteins Neuraminidase Hemagglutinin RNA M 2 protein (only on type A) Influenza und Herz Eur Heart J May;28(10): Epub 2007 Apr 17. Influenza epidemics and acute respiratory disease activity are associated with a surge in autopsyconfirmed coronary heart disease death: results from 8 years of autopsies in 34,892 subjects Madjid M, Miller CC, Zarubaev VV, Marinich IG, Kiselev OI, Lobzin YV, Filippov AE, Casscells SW 3rd. Median age was 75 for women and 65 for men. When comparing the average influenza epidemic weeks to average off-season weeks, the odds for AMI and chronic IHD death increased by 1.30 (95% confidence interval (CI): ) and 1.10 (95% CI: ), respectively.

7 Influenza, respiratorische Erkrankungen und KHK-Todesfälle Fälle pro Woche Autopsieresultate über 8 Jahre in St. Petersburg; Autopsien 60 Infarktmortalität Atemwegserkrankungen Influenzaepidemien sind mit einer Erhöhung der autopsiegesicherten koronaren Todesfälle assoziiert Influenzaepidemie Madjid M et al. Eur Heart J 2007;28: Atemwegskomplikationen Sekundäre bakterielle Pneumonie Betrifft ca. 75% der Patienten mit Influenza- Pneumonien Erreger: S. aureus (ca. 70%) in Pandemie. S. aureus mit 28 % Letalität, andere Erreger 12% Letalität 2-3 Tage nach Influenzabeginn akut Husten, Thoraxschmerzen und Dyspnoe. Klinisch Rasselgeräusche, selten Dämpfung. >> Dyspnoe, Tachypnoe, Zyanose und Hämoptoe schlechte Prognose: Tod nach 4-5 Tagen. Pathologie: Hämorrhagien, keine Konsolidation. Hyperämie der Mucosa

8 Influenzapneumonie mit S.aureus Superinfektion Influenza und Pneumokokken Asymptomatische Kolonisation Epithelschaden durch Influenza Adhärenz/Invasion von. S. pneumoniae erleichtert Verschlechterte anti-streptokokken Immunantwort Amplifikation der inflammatorischen Kaskade durch Koinfektion McKuller JA, Clin Microbiol Rev 2006;19:571

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11 Klinik der Influenza Untersuchung bei 520 Erwachsenen Husten Abgeschlagenheit Fiebergefühl plötzliches Auftreten Schüttelfrost Kopfschmerz Appetitlosigkeit Myalgien Halsweh Sputum Schwindelgefühl Heiserkeit Thoraxschmerzen Nausea Fieber >37.8 ºC % Influenza Fälle mit dem entsprechenden Symptom K.G. Nicholson: Managing Influenza in Primary Care. Blackwell Science,19 Differentialdiagnose Influenza versus grippaler Infekt Influenza Grippaler Infekt Erreger: Influenzavirus A,B Rhinoviren, Adenoviren, RS-viren, Coronaviren Klinisches systemisch lokalisiert Spektrum: Krankheitsbeginn: abrupt schrittweise Fieber: C subfebril Typische Symptome: Schüttelfrost, Myalgien, Husten, Halsschmerzen, Niesen, Rhinorrhoe, trockener kratzender Hals Appetitlosigkeit Krankheitsgefühl: ausgeprägt mild Krankheitsdauer: 1-2 Wochen (ev. rasche Erholung Postinfluenza-Asthenie) Komplikationen: hoch, incl. Mortalität gering Auftreten: Nördliche Hemisphäre: Nov.- April Südl. Hemisphäre: Mai-Okt. ganzjährig Das Lehrbuch, nicht die moderne PatientIn

12 Influenza und Lebensalter >65 Jahre vs. < 65 Jahre Krankheitsgefühl in 76.4% vs 92.6%, p = 0.07 Muskelschmerzen: 56.9% vs 77.8%, p = 0.06 Fieber: 54.2% vs 70.4%, p = 0.08 Kopfschmerzen: 35.2% vs 66.7%, p = Leistungsknick: 47.2% vs 66.7%, p = 0.08 Husten: 94.4% vs 77.8%, p = 0.02 Spitalsaufnahme 65.3% vs 40.7%, p = 0.03 Antibiotika: 81.9% vs 63.0%, p = Spitalsaufnahme korreliert mit Begleiterkrankungen und fehlender Impfung OR = 4.5, 95% IC , p = 0.02 Infection Apr;32(2): Unmasking influenza virus infection in patients attended to in the emergency department. Monmany J, Rabella N, Margall N, Domingo P Gich I Vázquez G

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22 Dr.Wenisch, Seuchenkurs, Würzburg

23 The World Needs to Prepare for a Potential Influenza Pandemic The virus (H5N1) could ignite the next human flu pandemic. I do not need to tell you of the terrible consequences that could bring to all nations and all people. To be truly prepared we will need to mount a massive effort Kofi Annan, Former Secretary General of the United Nations Global Preparedness plan (2005) Recommendations on global and regional preparedness Recommendations on stockpiling and use of antivirals and vaccines Community influenza preparedness and response planning (November 2005) 20th Century Pandemics Have Caused Substantial Mortality and Morbidity Credit: US National Museum of Health and Medicine 1918: 1957: 1968: Spanish Flu Asian Flu Hong Kong Flu A(H1N1) A(H2N2) A(H3N2) million deaths 1-4 million deaths 1-4 million deaths

24 Status Could Progress from Current Alert to Full Pandemic h5n1 in a Few Months How long is phase likely to last? Decades Years Months Weeks 1-2 years What Will a Pandemic Mean for Society? Pandemic life life cycle: 6 6 weeks to 3 to 3 months months Outbreak Peak impact Recovery Societal impact Increasing absentee rates ( 20%) Peak absentee rates ( 40 50%) Falling absentee rates Estimated: billion people will require medical care 7-28 million hospitalizations million deaths Late deliveries Operations/offices shut down where critical employees affected Stressed infrastructure (e.g. call centre) Cancellation of events/meetings No deliveries Stores / offices / schools close Trade (food etc) markedly reduced Hospitals full Operations resume Lower staff levels Consumer demand remains depressed Ongoing supply outages Repair costs

25 And Avian H5N1 is Spreading Around the World Human Cases of H5N1 Already Reported Around the World

26 Status Could Progress from Current Alert to Full Pandemic h5n1 in a Few Months h1n1 How long is phase likely to last? Decades Years Months Weeks 1-2 years An Influenza Pandemic Could Cross the World in a Few Months Example timings from 1957 Influenza Pandemic Dunn, J Am Med Assoc Mar 8;166(10):1140-8

27 Wer wurde krank?

28 WHO Has Recommended Antivirals for Use in case of an Influenza Pandemic Antiviral treatment in patients with confirmed or strongly suspected H5N1 infection Applies to adults (including pregnant women) and children Regimen for H5N1 is as recommended for seasonal influenza Antiviral chemoprophylaxis in management of avian (H5N1) influenza In high risk exposure groups oseltamivir / zanamivir (alternative) should be administered (strong recommendation) In moderate risk exposure groups oseltamivir / zanamivir might be administered (weak recommendation) Continuing for 7-10 days after the last known exposure The Favourable Resistance Profile of Relenza is Important in Choice of Antivirals for Stockpiling in case of an influenza pandemic..although both (Relenza zanamivir and Tamiflu oseltamivir) have similar efficacy, Relenza..a favorable resistance profile. The resistance factor would be an important consideration in a pandemic situation Tsang KW et al.lancet 2005;366; If this frequent emergence of resistant mutants is found to be a general occurrence in children, it is a serious concern, especially since children are an important source of the spread of infection in the community. Moscona A. NEJM, Sept 2005; 353:

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31 Triage Nicholoson Kriterien* erfüllt Schweregrad VAB-65** <2 Punkte Schweregrad VAB-65 >1 Punkte Zanamivir 2x10mg oder Oseltamivir 2x75mg/d nach Hause Kontrolle bei Bedarf Zanamivir 2x10mg oder Oseltamivir 2x75 mg/d Aufnahme/KH-Hygiene Supportive Therapie

32 Therapie-Anekdoten Rascher Therapiebeginn Oseltamivir 2x150mg Oseltamivir 2x150mg plus Amantadin 3x100mg Kein Steroid Oseltamivir plus Zanamivir 2009 Christoph Wenisch 4.Medizinische Abteilung SMZ-Süd KFJ Spital