J R Soc Med. 2003 Jul; 96(7): 345–346. PMCID: PMC539539
Influenza as a bioweapon / (Traduction EN FRANÇAIS en italiques)
Mohammad Madjid, MD,3,4Scott Lillibridge, MD,1Parsa Mirhaji, MD,2 and Ward Casscells, MD2,3,4Author information ►Copyright and License information ► This article has been cited by other articles in PMC.
Two years ago, we published a case–control study with the surprising finding that influenza immunization reduced the risk of recurrent myocardial infarction by 66%.1 Simultaneously, Siscovick and colleagues reported that influenza immunization was associated with a 49% reduction in the risk of sudden cardiac death.2 A subsequent report described a 50% reduction in risk of stroke in association with influenza immunization,3 and later a randomized control trial pointed to a 50–75% reduction in the risk of adverse endpoints and cardiovascular death.4 Furthermore, an ecological study suggests that the 1918 influenza pandemic may have contributed to the epidemic of coronary heart disease mortality registered in the 20th century.5
Il y a deux ans, nous avons publié une étude cas-témoins avec la découverte surprenante que la vaccination antigrippale réduisait le risque d’infarctus du myocarde récurrent de 66 %. mort subite d’origine cardiaque.2 Un rapport ultérieur a décrit une réduction de 50 % du risque d’accident vasculaire cérébral en association avec la vaccination contre la grippe,3 et plus tard un essai contrôlé randomisé a indiqué une réduction de 50 à 75 % du risque d’effets indésirables et de décès d’origine cardiovasculaire.4 En outre , une étude écologique suggère que la pandémie de grippe de 1918 pourrait avoir contribué à l’épidémie de mortalité par maladie coronarienne enregistrée au 20e siècle.5
These data caused us to re-examine the usual estimate that, in the USA, influenza kills 20 000 a year.6 From more recent studies of all-cause mortality, we suspect that the total is closer to 90 000. The Spanish flu epidemic in 1918 killed 20–40 million people.7 Less severe epidemics were the Asian flu in 1957, Russian flu in 1977, and Hong Kong flu in 1978.7 In addition to such spontaneous mutations, we must, since the terrorist attacks of September and October 2001, consider the possibility of malicious genetic engineering to create more virulent strains. Sequencing of the genome of the 1918 Spanish influenza virus is nearly complete; once it is published, unscrupulous scientists could presumably utilize candidate virulence sequences.8,9 Recently, the possibility of synthesizing an infectious agent solely by following instructions from a written sequence has moved from theory to practice.10
Ces données nous ont amenés à réexaminer l’estimation habituelle selon laquelle, aux États-Unis, la grippe tue 20 000 par an.6 D’après des études plus récentes de mortalité toutes causes confondues, nous soupçonnons que le total est plus proche de 90 000. L’épidémie de grippe espagnole en 1918 a tué 20 à 40 millions de personnes7. Des épidémies moins graves ont été la grippe asiatique en 1957, la grippe russe en 1977 et la grippe de Hong Kong en 19787. En plus de ces mutations spontanées, nous devons, depuis les attentats terroristes de septembre et octobre 2001 , envisagez la possibilité d’un génie génétique malveillant pour créer des souches plus virulentes. Le séquençage du génome du virus de la grippe espagnole de 1918 est presque terminé ; une fois publiée, des scientifiques peu scrupuleux pourraient vraisemblablement utiliser des séquences de virulence candidates8,9. Récemment, la possibilité de synthétiser un agent infectieux uniquement en suivant les instructions d’une séquence écrite est passée de la théorie à la pratique.10
FLASHBACK
Influenza is usually transmitted by direct contact but can also be transmitted by aerosol (e.g. on a passenger plane).11 Indeed, international transmission is increasingly frequent. Notably, aerosol transmission of influenza requires up to 27 000 times fewer virions to induce equivalent disease.12 Taken together with the fact that influenza virus is readily accessible and may be causing more deaths than previously suspected, the possibility for genetic engineering and aerosol transmission suggests an enormous potential for bioterrorism.
La grippe se transmet généralement par contact direct mais peut également se transmettre par aérosol (par exemple dans un avion de ligne).11 En effet, la transmission internationale est de plus en plus fréquente. Notamment, la transmission de la grippe par aérosol nécessite jusqu’à 27 000 fois moins de virions pour induire une maladie équivalente.12 Conjuguée au fait que le virus de la grippe est facilement accessible et peut causer plus de décès qu’on ne le pensait auparavant, la possibilité de génie génétique et de transmission par aérosol suggère un énorme potentiel de bioterrorisme.
Influenza is a very different virus from smallpox, and the public health implications of influenza as a bioweapon differ from those for smallpox: influenza is readily available, whereas known stocks of smallpox are secured at the Centers for Disease Control and Prevention in Atlanta and at a facility in Russia (though there is reason to suspect its leakage to weapons programmes elsewhere). Secondly, because influenza occurs naturally, a cluster of cases would not prompt an investigation, and an epidemic would have a considerable head start on public health authorities. A third difference is that the incubation period for influenza is short (1–4 days) versus 10–14 days for smallpox. Immunization after exposure to influenza is therefore not protective, and even the neuraminidase inhibitors such as oseltamivir must be administered before symptoms develop or within the first 48 hours after their appearance. Fourth, influenza is harder to eradicate, because of avian, murine, and swine reservoirs. Fifth, influenza outside of pandemics, has lower case-fatality (2.5% versus 25%, though the newly recognized triggering of cardiovascular events suggests that the true mortality may be much higher in ill or elderly persons). Finally, influenza poses a greater threat to world leaders than does smallpox, because they are older and prone to influenza and its cardiovascular complications, have some residual immunity to smallpox (whereas unvaccinated youth have none), and are often in public places.
La grippe est un virus très différent de la variole, et les implications pour la santé publique de la grippe en tant qu’arme biologique diffèrent de celles de la variole : la grippe est facilement disponible, tandis que les stocks connus de variole sont sécurisés aux Centers for Disease Control and Prevention à Atlanta et à un installation en Russie (bien qu’il y ait des raisons de suspecter sa fuite vers des programmes d’armement ailleurs). Deuxièmement, parce que la grippe se produit naturellement, un groupe de cas ne déclencherait pas d’enquête et une épidémie aurait une longueur d’avance considérable sur les autorités de santé publique. Une troisième différence est que la période d’incubation de la grippe est courte (1 à 4 jours) contre 10 à 14 jours pour la variole. La vaccination après exposition à la grippe n’est donc pas protectrice et même les inhibiteurs de la neuraminidase tels que l’oseltamivir doivent être administrés avant l’apparition des symptômes ou dans les 48 heures suivant leur apparition. Quatrièmement, la grippe est plus difficile à éradiquer en raison des réservoirs aviaires, murins et porcins. Cinquièmement, la grippe en dehors des pandémies a une létalité plus faible (2,5% contre 25%, bien que le déclenchement nouvellement reconnu d’événements cardiovasculaires suggère que la mortalité réelle puisse être beaucoup plus élevée chez les personnes malades ou âgées). Enfin, la grippe représente une plus grande menace pour les dirigeants mondiaux que la variole, car ils sont plus âgés et sujets à la grippe et à ses complications cardiovasculaires, ont une certaine immunité résiduelle contre la variole (alors que les jeunes non vaccinés n’en ont pas) et se trouvent souvent dans les lieux publics.
Even a natural epidemic of influenza can devastate our healthcare system and render society vulnerable to terrorist attacks of any kind.13 In addition, because of the similarity between early symptoms of influenza and other bioterror agents (such as anthrax), clinicians need to understand the differences in symptoms and signs and be aware of the initial screening tests for anthrax and influenza. Since the two diseases could coexist it is unfortunate that there are, to date, no point-of-care tests to diagnose both and thus minimize confusion and panic. We have seven proposals to address these issues.
- The World Health Organization and the Centers for Disease Control and Prevention (CDC) should bring together experts in influenza, bioterrorism, health policy, international law, and ethics to study this matter. Authorities should recognize that smallpox-based lessons drawn from exercises such as Dark Winter are not all applicable to weaponized influenza. Depending on their other public health needs and resources and their likelihood of being targeted, countries might consider only some of the steps listed below, which are suggested in particular for the USA. CDC should advance influenza as a critical agent in priority as a bioterrorism threat.
- Physicians, nurses and their organizations, insurers, and health officials should increase efforts to immunize those for whom immunization is currently recommended. The policy might be extended to mandatory immunization of medical personnel, or even universal immunization.
- Increase the security of laboratories conducting influenza research, and of manufacturers and distributors of vaccines and antivirals.
- Stockpile antiviral drugs and increase capacity to develop and produce vaccine. These might also be added to the ‘push-packs’ for urgent distribution by the US Department of Health and Human Services.
- Consider a Federal influenza gene-sequencing and vaccine development programme, based at high-security government, pharmaceutical and university laboratories.
- Expand active sero-epidemiological surveillance and offer incentives to reporting of clinical cases. The recently developed influenza assays make serological surveillance simple and fast, yet are little used by clinicians. New syndromic surveillance systems are required, capable of detecting incipient epidemics.
- Consider Federal programmes to develop antiviral filters, biosensors, and inactivation systems (e.g. ultraviolet) for ventilation systems. Such efforts could be part of a broader viral protection programme.
Go to:
Acknowledgments
This work is supported in part by the US Army’s Disaster Relief and Emergency Medical Services (DREAMS) grant #DAMD 17-98-1-8002.Go to:
References
1. Naghavi M, Barlas Z, Siadaty S, Naguib S, Madjid M, Casscells W. Association of influenza vaccination and reduced risk of recurrent myocardial infarction. Circulation 2000;102: 3039-45 [PubMed] 2. Siscovick DS, Raghunathan TE, Lin D, et al. Influenza vaccination and the risk of primary cardiac arrest. Am J Epidemiol 2000;152: 674-7 [PubMed] 3. Lavallee P, Perchaud V, Gautier-Bertrand M, Grabli D, Amarenco P. Association between influenza vaccination and reduced risk of brain infarction. Stroke 2002;33: 513-18 [PubMed] 4. Gurfinkel EP, de la Fuente RL, Mendiz O, Mautner B. Influenza vaccine pilot study in acute coronary syndromes and planned percutaneous coronary interventions: the FLU Vaccination Acute Coronary Syndrome (FLUVACS) Study. Circulation 2002;105: 2143-7 [PubMed] 5. Azambuja MI, Duncan BB. Similarities in mortality patterns from influenza in the first half of the 20th century and the rise and fall of ischemic heart disease in the United States: a new hypothesis concerning the coronary heart disease epidemic. Cad Saude Publica 2002;18: 557-77 [PubMed] 6. Simonsen L, Clarke MJ, Williamson GD, Stroup DF, Arden NH, Schonberger LB. The impact of influenza epidemics on mortality: introducing a severity index. Am J Publ Health 1997;87: 1944-50 [PMC free article] [PubMed] 7. Laver WG, Bischofberger N, Webster RG. Disarming flu viruses. Sci Am 1999;280: 78-87 [PubMed] 8. Webster RG. Virology. A molecular whodunit. Science 2001;293: 1773-5 [PubMed] 9. Basler CF, Reid AH, Dybing JK, et al. Sequence of the 1918 pandemic influenza virus nonstructural gene (NS) segment and characterization of recombinant viruses bearing the 1918 NS genes. Proc Natl Acad Sci USA 2001;98: 2746-51 [PMC free article] [PubMed] 10. Cello J, Paul AV, Wimmer E. Chemical synthesis of poliovirus cDNA: generation of infectious virus in the absence of natural template. Science 2002;297: 1016-18 [PubMed] 11. Hammond GW, Raddatz RL, Gelskey DE. Impact of atmospheric dispersion and transport of viral aerosols on the epidemiology of influenza. Rev Infect Dis 1989;11: 494-7 [PubMed] 12. Alford RH, Kasel JA, Gerone PJ, Knight V. Human influenza resulting from aerosol inhalation. Proc Soc Exp Biol Med 1966;122: 800-4 [PubMed] 13. Schoch-Spana M. Implications of pandemic influenza for bioterrorism response. Clin Infect Dis 2000;31: 1409-13 [PubMed]
Articles from Journal of the Royal Society of Medicine are provided here courtesy of Royal Society of Medicine Press