The ghost of pandemics past
Authors: Thomas M Mack
Journal: The Lancet (2005)

Prominent North American and European politicians convened recently for a table-top exercise designed to illustrate the international scope of bioterrorism.1D'Esopo M Exercise illuminates transatlantic leaders' reactions to bioterror attack. Center for Biosecurity, University of Pittsburgh Medical Center, 2005http://www.upmc-biosecurity.org/pages/center/press/atlantic_storm.htmlGoogle Scholar Participants were asked to respond to a hypothetical apocalyptic incident, in which the simultaneous release of lyophilised variola in six countries caused 74 000 cases in a single generation. Not surprisingly, such an attack, irrespective of the agent, defied easy control in the exercise. Issues about the manufacture and distribution of massive amounts of smallpox vaccine dominated the discussion. Three false lessons were conveyed to readers of the ensuing press release, and doubtless to the lay participants: a smallpox pandemic is likely; ordinary methods of public health cannot control person-to-person infections; and vaccine stores are the key to control. Poppycock, poppycock, poppycock! 3 years ago, the Bush policy of vaccination against smallpox on a large scale2Stevenson RW Stolberg SG Bush lays out plan on smallpox shots; military is first.New York Times. Dec 14, 2002; : A1PubMed Google Scholar, 3DeRugy V Pena C Responding to the threat of smallpox bioterrorism.Policy Anal. 2002; 434: 1-16Google Scholar was in part motivated by Dark Winter, a similar table-top exercise, also with questionable assumptions.4O'Toole T Mair M Inglesby T Shining light on "dark winter".Clin Infect Dis. 2002; 34: 972-983Crossref PubMed Scopus (127) Google Scholar Sceptics questioned the benefits of mass vaccination, and raised concerns about vaccine complications.5Mack T A different view of smallpox and vaccination.N Engl J Med. 2003; 348: 460-463Crossref PubMed Scopus (50) Google Scholar, 6Lane J Goldstein J Evaluation of 21st-century risks of smallpox vaccination and policy options.Ann Intern Med. 2003; 38: 488-493Crossref Scopus (68) Google Scholar Doubts about the net benefits of mass vaccination grew after reports of subsequent cardiovascular events,7Centers for Disease Control and PreventionUpdate: Adverse events following smallpox vaccination—United States, 2003.MMWR Morb Mortal Wkly Rep. 2003; 52: 278-282PubMed Google Scholar, 8Arness M Eckart R Love S et al.Myoperidarditis following smallpox vaccination.Am J Epidemiol. 2004; 160: 642-651Crossref PubMed Scopus (116) Google Scholar and only a few people have been vaccinated. In the meantime, a different global pandemic attracted attention. A culinary choice in south China led to a fatal infection in Hong Kong, and subsequently to 8000 cases of severe acute respiratory syndrome (SARS), and nearly 1000 deaths in 30 countries on six continents.9Tomlinson G Cockram C SARS: experience at Prince of Wales Hospital, Hong Kong.Lancet. 2003; 361: 1486-1487Summary Full Text Full Text PDF PubMed Scopus (133) Google Scholar, 10World Health OrganizationSARS: breaking the chains of transmission.http://www.who.int/features/2003/07/en/Date: 2003Google Scholar Despite rapid geographical dissemination and much economic angst, clinicians and epidemiologists proved up to the task, and SARS was controlled in all locations after about 3 months. Control was accomplished by well-informed managers11Riley S Fraser C Donnelly C et al.Transmission dynamics of the etiological agent of SARS in Hong Kong: impact of public health intervention.Science. 2003; 300: 1961-1966Crossref PubMed Scopus (885) Google Scholar using the same basic strategy of surveillance for cases and isolation of contacts that had eradicated smallpox 25 years before,10World Health OrganizationSARS: breaking the chains of transmission.http://www.who.int/features/2003/07/en/Date: 2003Google Scholar augmented only by high-tech record-keeping and communication.12Seto W Tsang D Yung R et al.Effectiveness of precautions against droplets and contact in prevention of nosocomial transmission of severe acute respiratory syndrome (SARS).Lancet. 2003; 361: 1519-1520Summary Full Text Full Text PDF PubMed Scopus (714) Google Scholar In fact, SARS presented a challenge far more difficult than smallpox. Like smallpox, SARS spread efficiently at the bedside to family members and caregivers5Mack T A different view of smallpox and vaccination.N Engl J Med. 2003; 348: 460-463Crossref PubMed Scopus (50) Google Scholar, 6Lane J Goldstein J Evaluation of 21st-century risks of smallpox vaccination and policy options.Ann Intern Med. 2003; 38: 488-493Crossref Scopus (68) Google Scholar by means of large droplets. Like smallpox, the coronavirus was capable of wide dissemination from only a small number of individual cases,13Donnelly C Ghani A Leung G et al.Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong.Lancet. 2003; 361: 1761-1766Summary Full Text Full Text PDF PubMed Scopus (785) Google Scholar with the help of favourable air currents and contaminated clothing or linens. However, neither vaccine prophylaxis nor sophisticated diagnostic methods were available to combat SARS. Whereas unvaccinated people with infectious smallpox have a characteristic vesicular rash, which is likely to keep potential contacts at a distance, SARS was disseminated in material or faeces from people with early non-specific symptoms.9Tomlinson G Cockram C SARS: experience at Prince of Wales Hospital, Hong Kong.Lancet. 2003; 361: 1486-1487Summary Full Text Full Text PDF PubMed Scopus (133) Google Scholar Control of smallpox, but not SARS, was facilitated by a 2-week period between exposure and infectiousness in which to identify and isolate contacts. Had the outbreak been of smallpox instead of SARS, control in Toronto, for example, would have been quickly established by the old-fashioned techniques of public health: surveillance and isolation, identifying the exposed for vaccination, and avoiding mass vaccination to the extent possible politically. On the basis of the early sequence of events in this largely nosocomial outbreak,14Poutenen S Low D Henry B et al.Identification of severe acute respiratory syndrome in Canada.N Engl J Med. 2003; 348: 1995-2005Crossref PubMed Scopus (1035) Google Scholar containment of smallpox probably would have occurred by the appearance of the third disease generation, much sooner than SARS was contained. SARS will probably reappear, and there is a remote chance that smallpox will be introduced by a terrorist act (but not with 74 000 first-generation cases). An outbreak of either disease would be costly, but experience suggests that control would again be quickly established. Of greater concern are the more virulent strains of influenza. Reconstruction of the DNA of the 1918 Spanish virus is not only possible, but also a reality,15Kobasa D Takada A Shinya K et al.Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus.Nature. 2004; 431: 703-707Crossref PubMed Scopus (410) Google Scholar and we can only hope it does not escape into the population. Moreover, the number of human cases of avian influenza in Asia has been increasing.16Monto A The threat of an avian influenza pandemic.N Engl J Med. 2005; 352: 323-325Crossref PubMed Scopus (121) Google Scholar The first clear person-to-person transmission of influenza A (H5N1) reported from Thailand17Ungchusak K Auewarakul P Dowell S et al.Probable person-to-person transmission of avian influenza A (H5N1).N Engl J Med. 2005; 352: 333-340Crossref PubMed Scopus (798) Google Scholar was even more limited to family members than smallpox or SARS, despite the H5N1 exposure of other family members and hospital staff. As yet there is no change in the host specificity of the viral receptor's binding preference, which would probably enable more efficient human-to-human transmission, but that might be only a matter of time.16Monto A The threat of an avian influenza pandemic.N Engl J Med. 2005; 352: 323-325Crossref PubMed Scopus (121) Google Scholar Whatever pandemic agent next appears (and smallpox is certainly not the most likely), each community must be prepared. Vaccines will doubtlessly evolve, although avian influenza will require a constant struggle,18Stohr K Avian influenza and pandemics—research needs and opportunities.N Engl J Med. 2005; 52: 405-407Crossref Scopus (87) Google Scholar prototype SARS vaccines now appear strain-specific,19Yang Z-Y Werner H Kong W-P et al.Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses.Proc Natl Acad Sci USA. 2005; 102: 797-801Crossref PubMed Scopus (216) Google Scholar and the qualities of any new smallpox vaccine can never be evaluated.20Greenberg R Kennedy J Clanton D et al.Safety and immunogenicity of new cell-cultured smallpox vaccine compared with calf-lymph derived vaccine: a blind single-centre, randomised controlled trial.Lancet. 2005; 265: 398-409Summary Full Text Full Text PDF Scopus (0) Google Scholar Even so, it is easy and politically safe to budget for vaccine production, with or without plans for mass vaccination as a pre-emptive strategy or as outbreak control. However, no weapon is effective without an appropriate delivery system. It is harder to budget for field personnel in public health, and justify them to the accountants, than it is to budget for vaccines, even if these people are absolutely essential. Identification of cases and of contacts eligible for prophylaxis requires active surveillance, and any isolation policy requires a detailed plan. Both actions will be needed to break a chain of person-to-person infection, and both require management skills that are grounded in biology, local sociology, and the medical-care system. History tells us that protection against a viral pandemic will always depend on the availability of a local cadre of skilled public-health workers. Although the return on an investment for the support of such personnel is hard to quantify, we assign it low priority at our peril. I declare that I have no conflict of interest.