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Avian Flu and H1N1 - Reductionism + Speculation = Big Waste

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Avian Flu and H1N1 - Reductionism + Speculation = Big Waste Does modelling help to predict outbreaks? LONDON « Ignorance and blindness » 03.04.2012 WHY SHOULD WE FIGHT THIS? France based on the fear of H5NI Prevision of 700 beds devoted to flu H1N1 for Marseilles (1M inhibition) we needed 20! Vaccination using cells (no eggs), double injection, with adjuvant (90 M doses!) Proposing of vaccination© byby authority author Vs doctors Lower vacination in our hospital personnel ever! ESCMIDFalse prediction Online => Lecture mismanagement Library IGNORANCE AND BLINDNESS 1- Rationale of modelling when we are ignorant 2- Future outbreaks Avian flu and H1N1 - Reductionism + speculation = big waste Bioterrorism and smallpox 3- Is it science or religion© by ?author ESCMID Online Lecture Library IGNORANCE Autopsy series of 68 cases dying before and during We ignore the cause of death Measle, flu kills by super the 1918 influenza pandemic peak. Sheng ZM, et al. Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):16416- infection 21. Microbiota regulates immune defense against We ignore the role of environment respiratory tract influenza A virus infection. Ichinohe (role of microbiota, temperature, sun, T, et al. Proc Natl Acad Sci USA. 2011 Mar 29;108(13):5354-9 reservoirs) Microbe interactions undermine predictions. Raoult D. Science. 2011 Jan 14;331(6014):144-5 Molecular, epidemiological, and clinical complexities Raoult of predicting patterns of infectious diseases. D. Front Microbiol. 2011;2:25 We ignore the « learning » capabilities Malaria morbidity and pyrethroid resistance after the - societies introduction of insecticide-treated bednets and artemisinin-based combination therapies: a - individuals longitudinal study.Trape JF, et al. Lancet Infect Dis. - Animals (anopheles gambiae) 2011 Dec;11(12):925-32 - infectious agents We ignore the transmission ways © by author ESCMID Online Lecture Library The 1918 to 1919 “Spanish” influenza pandemic virus killed up to 50 million people. We report here clinical, pathological, bacteriological, and virological findings in 68 fatal American influenza/pneumonia military patients dying between May and October of 1918, a period that includes 4 mo before the 1918 pandemic was recognized, and 2 mo (September–October 1918) ∼ Several variable during which it appeared and peaked. The lung tissues of 37 of these cases were positive for influenza viral antigens or viral RNA, including four from the prepandemic period (May–August). The prepandemic and pandemic peak cases were indistinguishable clinically and pathologically. All 68 cases Not different had histological evidence of bacterial pneumonia, and 94% showed from the other abundant bacteria on Gram stain. Sequence analysis of the viral hemagglutinin receptor-binding domain performed on RNA from 13 cases influenzas suggested a trend from a more “avian-like” viral receptor specificity with G222 in prepandemic cases to a more “human-like” specificity associated with D222 in pandemic peak cases. Viral antigen distribution in the Bacterial respiratory tree, however, was not apparently© by different author between prepandemic and pandemic peak cases, or between infections with viruses pneumonias! bearing different receptor-binding polymorphisms. The 1918 pandemic virus was circulating for at least 4 mo in the United States before it was recognized epidemiologically in September 1918. The causes of the unusually high mortality in the 1918 pandemic were not explained by the pathological and virological parameters examined. These findings have important implicationsESCMID for understanding Online the origins Lectureand evolution of Library pandemic influenza viruses. © by author ESCMID Online Lecture Library AGE-RELATED COMPLICATIONS OF PNEUMONIA AND DEATH, AND CASE FATALITY RATE, 1918–1919 PANDEMIC 100 10 1 Pneumonia case-fatality Complicated by pneumonia Percentage of cases(Log scale) © by author Total case-fatality 0 0 10 20 30 40 50 60 70 80 Age (years) ESCMID Online Lecture Library Nicholson, Human Influenza, In Nicholson, Webster, Hay, Textbook of Influenza, Blackwell; Oxford 1998:p237 TIMELINE POST-INFECTION OF INFLUENZA DEATHS: 1918 EPIDEMIC 0,1 0,08 0,06 Proportion 0,04 0,02 © by author 0 7 14 21 28 Days since infection ESCMID Online Lecture Library Mills et al. Nature 2004;432:904–6, Supplementary fig 2 1918 PNEUMONIA DEATHS DUE TO BACTERIAL INFECTION – 58 AUTOPSIES REVIEWED IN 2008 A B A: Typical picture of severe, widespread bacterial bronchopneumonia B: Massive infiltration of neutrophils in the airspaces of alveoli associated with bacterial C D bronchopneumonia C: Bronchopneumonia with intra-alveolar edema and © by authorhemorrhage D: Bronchopneumonia with evidence of pulmonary repair ESCMID Online Lecture Library Morens et al. JID 2008;198:962–70 POSITIVE BLOOD CULTURES IN PNEUMONIA CASES DURING 1918 PANDEMIC It will never be the same! © by author ESCMID Online Lecture Library Chien, Klugman, Morens, NEJM, 2009, 361,2582-3 9 Association between use of statins and mortality among patients hospitalized with laboratory- confirmed influenza virus infections: a multistate study. Vandermeer ML, Thomas AR, Kamimoto L, Reingold A, Gershman K, Meek J, Farley MM, Ryan P, Lynfield R, Baumbach J, Schaffner W, Bennett N, Zansky S. J Infect Dis. 2012 Jan;205(1):13-9. Abstract BACKGROUND: Statins may have anti-inflammatory and immunomodulatory effects that could reduce the risk of mortality from influenza virus infections. METHODS: The Centers for Disease Control and Prevention's Emerging Infections Program conducts active surveillance for persons hospitalized with laboratory-confirmed influenza in 59 counties in 10 states. We analyzed data for hospitalized adults during the 2007-2008 influenza season to evaluate the association between receiving statins and influenza-related death. RESULTS: We identified 3043 patients hospitalized with laboratory-confirmed influenza, of whom 1013 (33.3%) received statins and 151 (5.0%) died within 30 days of their influenza test. Patients who received statins were more likely to be older, male, and white; to suffer from cardiovascular, metabolic, renal, and chronic lung disease; and to have been vaccinated against influenza that season. In a multivariable logistic regression model, administration of© statins by prior author to or during hospitalization was associated with a protective odds of death (adjusted odds ratio, 0.59 [95% confidence interval, .38-.92]) when adjusting for age; race; cardiovascular, lung, and renal disease; influenza vaccination; and antiviral administration. CONCLUSIONS: Statin use mayESCMID be associated with reduced Online mortality Lecturein patients hospitalized Library with influenza . IGNORANCE Autopsy series of 68 cases dying before and during the 1918 We ignore the cause of death Measle, flu kills by super influenza pandemic peak. Sheng ZM, et al. infection Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):16416-21. Microbiota regulates immune defense against respiratory We ignore the role of environment tract influenza A virus infection. Ichinohe T, et al. Proc Natl (role of microbiota, temperature, sun, Acad Sci USA. 2011 Mar 29;108(13):5354-9 Microbe interactions undermine predictions. reservoirs) Raoult D. Science. 2011 Jan 14;331(6014):144-5 Molecular, epidemiological, and clinical complexities of predicting patterns of infectious diseases. Raoult D. Front Microbiol. 2011;2:25 We ignore the « learning » capabilities Malaria morbidity and pyrethroid resistance after the - societies introduction of insecticide-treated bednets and artemisinin- based combination therapies: a longitudinal study.Trape JF, - individuals et al. Lancet Infect Dis. 2011 Dec;11(12):925-32 - Animals (anopheles gambiae) - infectious agents We ignore the transmission ways © by author ESCMID Online Lecture Library Microbiota regulates immune defense against respiratory tract influenza A virus infection. Ichinohe T, Pang IK, Kumamoto Y, Peaper DR, Ho JH, Murray TS, Iwasaki A. Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5354-9. Although commensal bacteria are crucial in maintaining immune homeostasis of the intestine, the role of commensal bacteria in immune responses at other mucosal surfaces remains less clear. Here, we show that commensal microbiota composition critically regulates the generation of virus-specific CD4 and CD8 T cells and antibody responses following respiratory influenza virus infection . By using various antibiotic treatments, we found that neomycin-sensitive bacteria are associated with the induction of productive immune responses in the lung. Local or distal injection of Toll-like receptor (TLR) ligands could rescue the immune impairment in the antibiotic-treated mice. Intact microbiota provided signals leading to the expression of mRNA for pro-IL-1β and pro-IL-18 at steady state. Following influenza virus infection, inflammasome activation led to migration of dendritic cells (DCs) from the lung to the draining lymph node and T-cell priming. Our results reveal the importance of commensal microbiota in regulating immunity in the respiratory mucosa through the proper© activation by authorof inflammasomes . ESCMID Online Lecture Library Rhinoviruses delayed the circulation of the pandemic influenza A (H1N1) 2009 virus in France. Casalegno JS, Ottmann M, Duchamp MB, Escuret V, Billaud G, Frobert E, Morfin F, Lina B. Clin Microbiol Infect. 2010 Apr;16(4):326-9 In contrast to the experience in other European countries, the onset of the A(H1N1)2009 influenza virus epidemic was unexpectedly slow in France during the first part of autumn 2009. Our objective
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