INTRODUCTION SUPPLEMENT ARTICLE Seasonal and Pandemic Influenza Preparedness: A Global Threat Downloaded from https://academic.oup.com/jid/article/194/Supplement_2/S65/851306 by guest on 01 October 2021 Richard J. Whitley1 and Arnold S. Monto2 1Departments of Pediatrics, Microbiology, Medicine, and Neurosurgery and Center for Biodefense and Emerging Infections, University of Alabama at Birmingham, Birmingham; 2Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor The increase in the incidence of avian influenza worldwide in both poultry and humans introduces the potential for another influenza A pandemic that could pose a significant threat to both human health and the global economy. The impact of the next influenza pandemic will be influenced, in part, by how well the medical, government, business, and lay communities are prepared. Despite the additional tools and resources that have become available since prior epidemics, there are limits to the quantity of antiviral drugs that can be manufactured and concerns over the current vaccine production systems. Despite these challenges, there is an opportunity to take action before the emergence of a pandemic influenza strain and, possibly, to prevent its spread or at least mitigate its impact on the world. In February 2006, a group of representatives from federal, state, and local governments; professional bodies; academia; and the pharmaceutical industry met to review the current state of preparedness in the United States for a potential influenza pandemic and its relationship to seasonal influenza. The goal of the meeting was to examine the recently revised US Department of Health and Human Services plan for preparedness and response to an influenza pandemic and to make recommendations to actualize this plan at the state and local levels. The worldwide increase in the incidence cant threats to human health, national and tion and marked pulmonary damage, in of influenza caused by avian influenza global economies, and, potentially, socie- part resulting from activation of a vigor- A(H5N1) virus, manifested in poultry out- ties. With the emergence of the H5N1 vi- ous proinflammatory cytokine cascade breaks and sporadic human infections, rus, the threat of a pandemic is higher now that may have contributed to acute respi- highlights the concern that another influ- than it has been since the last influenza A ratory distress syndrome [6]. Since the enza A pandemic is likely to occur soon. pandemic, in 1968. Three pandemics oc- 1918 pandemic, the population of the Should this happen, there will be signifi- curred during the past century. Of these, world has grown 3-fold; therefore, if a new the 1918 H1N1 influenza pandemic was influenza A virus is as lethal as the 1918 Presented in part: Seasonal and Pandemic Influenza 2006: by far the worst, resulting in 50–100 mil- virus, as many as 180–360 million people At the Crossroads, a Global Opportunity, Washington, DC, 1–2 lion deaths [1]. The H1N1 virus that caused could die [7]. Such a pandemic would February 2006 (for a list of sponsors and funding, see the the pandemic originated from an avian overwhelm the health care systems of the Acknowledgments). The authors were co-chairs of the independent committee that planned and coordinated the influenza virus, which adapted to humans world and have a devastating socioeco- conference. by mutation [2]. Unlike seasonal influ- nomic impact. The 1957 H2N2 and 1968 Potential conflicts of interest: A.S.M. has received grant support from Roche and Sanofi Pasteur and the National enza, which causes most of its estimated H3N2 pandemics also involved new influ- Institutes of Health (grant U01 AI057853) and has served as an 36,000 annual US deaths among the el- enza viruses generated by reassortment ad hoc consultant to Roche, MedImmune, and Chiron. R.J.W. 1 is on the Scientific Advisory Board for Gilead Sciences and is derly [3], 90% of the deaths caused by events, and, although they were less vir- a member of the GlaxoSmithKline and Novartis Speakers pandemic influenza have occurred in ulent than the 1918 H1N1 virus, they still Bureaus. ! Financial support: supplement sponsorship is detailed in healthy people 65 years of age [4]. This caused significant morbidity and mortality. the Acknowledgments. H1N1 virus was particularly virulent and Recently, several avian influenza A virus Reprints or correspondence: Dr. Richard J. Whitley, University showed extraordinarily high levels of rep- subtypes, including H5N1, H9N2, H7N3, of Alabama at Birmingham, CHB 303, 1600 7th Ave. S, Birmingham, AL 35233-1711 ([email protected]). lication in the lungs of experimentally in- and H7N7, have been shown to cross the The Journal of Infectious Diseases 2006;194:S65–9 fected animals [5]. Indeed, a conventional species barrier from poultry or wild mi- ᮊ 2006 by the Infectious Diseases Society of America. All rights reserved. human virus containing only the 1918 gratory birds to infect humans. The H7N7 0022-1899/2006/19409S2-0001$15.00 hemagglutinin caused high viral replica- and H9N2 viruses largely resulted in mild Seasonal and Pandemic Influenza: Introduction • JID 2006:194 (Suppl 2) • S65 self-limiting disease or asymptomatic in- transmission efficient. Although genotype whelmed state and local public health in- fection, although 1 lethal infection asso- Z appears to be dominant in most parts frastructures in Louisiana and Mississippi, ciated with a mutated H7N7 virus was rec- of Asia, there are 2 major clades circulat- required an unprecedented federal re- ognized in a Dutch veterinarian [8]. In ing, as well as a diversity of genotypes in sponse, and led to international offers of addition, since the emergence of H5N1 parts of southern China, with observations assistance. Although this response was in Hong Kong in 1997, clinically doc- indicating that the virus continues to successful in some areas, several important umented H5N1 infections have been as- evolve. Because different viruses may have weaknesses were identified [18]. The most sociated with a high mortality rate in altered antigenicity, it would be unwise to concerning, in terms of a potential re- humans [9–11]. Since 2003, 241 labora- rely on a single target virus for vaccine sponse to pandemic influenza, was the tory-confirmed cases have been reported development [16]. Indeed, in the United poor coordination of federal assets, within in 10 countries (Azerbaijan, Cambodia, States, the Department of Health and Hu- and across agencies, resulting from a frag- Downloaded from https://academic.oup.com/jid/article/194/Supplement_2/S65/851306 by guest on 01 October 2021 China, Egypt, Indonesia, Iraq, Thailand, man Services (HHS) has recently an- mented command and response structure. Turkey, Vietnam, and Djibouti); as of 23 nounced its intention to proceed with de- This caused substantial delays in the de- August 2006, 141 (59%) of these cases velopment of a candidate vaccine based ployment of federal assets in critical areas. have resulted in death [11]. Typically, on clade 2 H5N1 virus [17]. In other cases, assets were deployed in- death after infection with the H5N1 virus The impact of the next influenza pan- appropriately and were subsequently un- occurred, on average, 9–10 days after the demic on the world’s populations will be derutilized. In addition, communication onset of illness and was usually the result influenced, in part, by how well the med- to the public was poorly coordinated of progressive respiratory failure [12]. The ical, government, business, and lay com- among federal, state, and local agencies, high mortality rates may be an overesti- munities are prepared. Additional tools which resulted in contradictory and con- mate, because limited surveillance studies and resources are available, such as anti- fusing messages being issued [18]. in Vietnam have reported that several con- viral drugs, diagnostics, and vaccines, that Background. In February 2006, a tacts of patients may have developed mild did not exist during prior pandemics. group of representatives from federal, or asymptomatic infection with H5N1 However, there are limits to the quantity state, and local governments; professional [13]. However, recent serologic studies of antiviral drugs that can be manufac- bodies; academia; and the pharmaceutical in Southeast Asia have found infrequent tured and effectively deployed, as well as industry met to review the current state H5N1 antibody positivity in apparently uncertainties regarding vaccine effective- of preparedness in the United States for a healthy contacts, indicating that most in- ness and concerns regarding the current potential influenza pandemic and its re- lationship to seasonal influenza. The goal fections are clinically manifest. By any vaccine production systems. In addition, of the meeting was to examine the recently standard, H5N1 infection is highly viru- new challenges exist, such as rapid inter- revised HHS plan for preparedness and lent in humans. continental transportation and a larger response to an influenza pandemic [17] The final step required for a pandemic global population. Despite these chal- and to make recommendations to actu- is efficient human-to-human transmission lenges, there is an opportunity to take ac- alize this plan at the state and local levels. of the virus. The H5N1 virus is now en- tion before the emergence of a pandemic In addition, the group identified areas for demic in poultry in Asia and parts of Af- influenza strain and, possibly, to prevent further research and consideration. rica and is spreading globally despite active or delay its spread or at least mitigate its The revised HHS plan was designed to control measures. The greatest current impact on the world. In part, this can be provide guidance to national, state, and concern is that the H5N1 virus may be- achieved by improving the current infra- local policy makers and health depart- come more transmissible in humans, ei- structure for managing seasonal influenza, ments, to enable them to prepare for the ther through mutation or through genet- an action that would have the additional management of an influenza pandemic.