Year-Round Readiness Can Help Conquer the Unexpected

By Elizabeth Srejic

Throughout human history, pandemics responsible for the deaths of millions have plagued mankind. Unfortunately, experts believe occurrence of another pandemic is not so much a question of “if” as a question of “when.”

Although infectious disease disasters involve limited resources, difficulty maintaining operations and other crises, a healthcare facility is favorably positioned to soldier through these eventualities by developing a preparedness plan, or a “detailed operational blueprint of the best way to get through 12 to 24 months of a pandemic,”1  before disaster strikes. Although the process is complicated and expensive, prior planning increases the likelihood of a rapid, efficient and successful response to an outbreak and is critical for reducing human suffering and negative effects on the economy and society.2

The World Health Organization (WHO) in its 2005 checklist for preparedness planning cautioned healthcare facilities against not having preparedness plans: “Hospitals play a critical role within the health system in providing essential medical care to the community, particularly during a crisis such as an epidemic or a pandemic. Prolonged and combined outbreaks can lead to the progressive spread of disease with rapidly increasing service demands that can potentially overwhelm the capacity of hospitals and the health system at large. To enhance the readiness of the health facilities to cope with the challenges of an epidemic, a pandemic or any other emergency or disaster, hospital managers need to ensure the initiation of relevant generic priority action.”3

Although experts agree that preparedness plans may mitigate chaos during an infectious disease disaster, development of these strategic frameworks presents significant challenges. As such, many healthcare facilities are still struggling to create preparedness plans.

Perhaps the best-known cause of pandemics, influenza, every year causes millions of illnesses, hundreds of thousands of hospitalizations, 30,000 to 50,000 deaths in the United States, and a death rate 20 to 30 times that globally.4-6 Of the pandemics that occurred over the last 500 years, the influenza pandemic of 1918 is considered the worst, killing approximately 546,000 people in the United States and 50 million to 100 million people worldwide,7 although the influenza pandemic of 1830 was actually comparable in severity as the world’s population was smaller.8 With today’s world population of 6.5 billion, which is three times that of 1918, even a relatively mild pandemic could kill many millions of people.9 What’s worse, current worldwide trends such as the growing human population, increasingly crowded living conditions and air travel further increase the likelihood of a pandemic or other biological disaster.10-11

The contagion of the influenza virus arises in large part from its easy transmissibility through respiratory droplets.12 Presenting in both humans and animals, the influenza virus constantly undergoes change,13 which makes it particularly difficult to treat. In particular, influenza in animals is especially likely to mutate or recombine, forming new strains that may cross over to the human population and eventually be transmitted from human to human.14-19 For example, a 2009 pandemic was caused by H1N1, an influenza virus that originated in swine and eventually became a human seasonal influenza virus, and experts say the next zoonotic (animal-to-human) influenza virus that could cause a pandemic could be H5N1, a highly pathogenic avian influenza virus found in domestic poultry in parts of Asia and the Middle East.20-21 

The likelihood that viral strains will mutate or recombine is further increased by unhealthy living conditions among the rapidly growing, overcrowded populations of people, pigs and poultry in Asia.22-23 The prodigious increase of these populations, which measured at 790 million, 5.2 million and 12.3 million, respectively, during the influenza pandemic in China in 1968, and now measure 1.3 billion, 508 million and 13 billion, respectively, heightens the risk of a pandemic.24
Influenza subtype is only one of the currently unknown characteristics that will define the next pandemic. Public health experts and infectious-disease scientists say other unknowns include when the pandemic will occur, where it will arise and how severe it will be.25 However, research proposes that pandemics seem to occur every 40 years(26) and the next pandemic is likely to arise out of Asia or Africa;27-29 furthermore, it could kill an estimated 350 million people, disrupting healthcare systems, society and the world’s economy.30

It is important to note that not all pandemics are caused by influenza nor are all biological disasters the result of viruses. Currently joining influenza as a possible cause of a future pandemic is a bevy of new, potentially irrepressible “pandemics-in-waiting” such as human immunodeficiency virus (HIV) which affects the immune system, Ebola and Lassa viruses which cause hemorrhagic fever, rotaviruses causing acute intestinal diseases, coronaviruses such as that responsible for SARS (severe acute respiratory syndrome) and flaviviruses such as the causative pathogen in West Nile encephalitis. Other equally potent sources of biological disaster that may necessitate preparedness plans are agents used in biological warfare such as anthrax and other bacteria, as well as viruses, fungi and toxins.31-32

Infectious disaster preparedness plans may be based upon several categories of concern. Two of these are pharmacological interventions such as vaccines, antiviral agents, adjuvants and antibiotics,33 and non-pharmaceutical interventions including quarantine, isolation, social distancing and hand hygiene.34 Cost, infrastructure and healthcare worker (HCW) considerations represent other relevant issues35-37 as does procuring essential medical equipment and supplies such as personal protective equipment (PPE), respirators, syringes and gloves.38

Unfortunately, developing an infectious disease disaster preparedness plan is not an easy undertaking, mainly because resources are limited and the costs of planning are typically high. Victoria Davey, MPH, RN, wrote in the American Journal of Nursing in 2007: “Preparations are costly and complicated. If you’ve served in a hospital or community planning group, you may have estimated how many N95 respirators or doses of antiviral medications might be needed in a severe influenza pandemic – and been daunted by the cost and storage requirements. Or perhaps you’ve faced the administrative conundrum of how to quickly train retired nurses to replace those absent because of illness. And you may have questioned the worth of planning and the cost of stockpiling resources, when your facility has so many present needs.”39

Inability to stockpile resources is a particularly problematic aspect of preparedness plans that often results in shortage during disasters. Typically, pre-disaster stockpiling efforts are stymied by limited availability, inadequate manufacturing capacity and high cost of equipment and supplies. In 2005, only 105,000 mechanical ventilators existed in the United States; of these, 75,000 to 80,000 ventilators were in use at any given time for everyday medical care; but during a typical influenza season more than 100,000 ventilators would be required, leaving most patients without access to ventilation.40-41

On manufacturing capacity, Terri Rebmann, PhD, RN, CIC, associate professor of environmental and occupational health, and director of the Institute for Biosecurity at Saint Louis University, says, “Having enough medical supplies and equipment is critical - and often not possible - to create that large of a stockpile even if a healthcare facility can afford the cost of those supplies because manufacturers may not have the capacity themselves to provide those items.”
In many cases, vaccination is the foundation of an infectious disease preparedness plan and, as with other resources, availability, cost and production capacity are likely barriers.42-43 Following identification and isolation of the causative strain, production of an influenza vaccine takes a minimum of six months during which supplies are limited to fewer than a billion monovalent doses.44 Furthermore, since two doses may be required for protection, the available quantity of vaccines would cover fewer than 500 million people or approximately 14 percent of the world’s population, making allocation difficult.45 National and even international consensus on prioritizing distribution should therefore be reached well in advance of a pandemic.46

The need to create a new vaccine for each influenza outbreak is mainly consequent of antigenic drift, or accumulation of minor genetic changes in the virus which necessitates vaccine reformulation.47 Accordingly, an influenza vaccine cannot be manufactured in advance of a pandemic48-49 and research and development in “universal” vaccines capable of inducing heterotypic immunity and administration before an outbreak have therefore become important.50 Ideally, such universal vaccines would be cell-culture-based and not require reformulation from year to year yet be still maintain efficacy against all influenza virus subtypes.51

“The goal would be a safe and effective vaccine that works against all strains and would be available for pre-emptive vaccination to everyone,” says Rebmann. “Unfortunately, making a vaccine against one strain is not an easy task and making a universal vaccine is even more complex. It would be very difficult to accomplish that.”

Also, experts advise that the fragile and limited egg-based manufacturing technologies currently used to manufacture vaccines be replaced as they require more than 350 million chicken eggs and at least six months for production and are unable to produce the large quantities of product needed in a pandemic.52 Replacing current technologies with more advanced methods such as cell culturing and increasing industrial capacity could potentially yield larger quantities of vaccine in less time.54-56

In anticipation of limited supply, preparedness plans should specify which demographic groups would be prioritized to receive vaccination, deferring to legislation if it exists.(57) For example, policymakers may appropriate currently available vaccines for novel influenza strains such as H1N1 for use in individuals or communities potentially at greatest risk of infection in a pandemic.58

“The Centers for Disease Control and Prevention (CDC) released prioritization schedules when an inadequate amount of H1N1 vaccines were released in the United States,” says Rebmann. “These schedules identified which demographic groups were at highest risk during the H1N1 outbreak and prioritized them to receive the vaccine first. Prioritization is important in each pandemic because the highest-risk groups may change. The young and the old aren’t always the most affected. If you look at the 1918 influenza pandemic, young adults were unusually and disproportionately affected. Or, with H1N1, the elderly, who are generally one of the highest-risk groups for seasonal influenza in terms of morbidity and mortality, seemed to show protective, residual immunity either from past vaccinations or from past exposure to other influenza strains, in comparison to younger individuals and the pediatric risk of morbidity and mortality was highest - three times that of children in seasonal influenza. We really don’t know which groups will be at highest risk with the next pandemic.”

Antiviral agents are another prophylaxis of importance in influenza pandemics and other viral outbreaks, particularly due to their utility in vaccine shortages, and are being stockpiled in many industrialized countries.59-61 However, antiviral drugs are not an ideal weapon against influenza as resistant strains of the virus eventually emerge.62 Adjuvants may also be important in vaccine shortages as they can bolster immune response,63-64 as are antibiotics which can treat secondary infections following viruses such as bacterial pneumonia arising from influenza.65 Unfortunately, antibiotics are already in short supply despite relatively stable operating conditions and increasing production of antibiotics to for pre-emptive stockpiling is unlikely due to manufacturing shortfalls.66
Another element for consideration in preparedness plans is personnel. HCWs should receive basic training on infection control practices such as using PPE and performing hand hygiene correctly.67 Preparedness plans should also devise strategies to mitigate HCW absenteeism which is common in infectious disease outbreaks.68-70

“Staff absenteeism is an interesting concept,” says Rebmann. “Overall, research indicates that the higher-risk the scenario, the less likely staff are going to be to come to work. However, HCWs are much more likely and willing to come to work during a pandemic if they are provided PPE and they and their families are prioritized to receive vaccine or other anti-infective therapies. Unfortunately, for diseases lacking vaccines like MERS (Middle Eastern respiratory syndrome) and SARS (sudden acute respiratory syndrome), we don’t even have a vaccine to offer to HCWs to protect themselves.”

Preparedness plans should examine an institution’s surge capacity, or capability to meet a sudden increase in need for resources like staff, supplies and infrastructure, in an infectious disease outbreak. Since resources are commonly inadequate among healthcare institutions even during normal circumstances, they would almost certainly be lacking during an infectious disease disaster. Stockpiling may seem like a pre-emptive solution to a future shortage of resources but can siphon funding away from present needs.71 

“Surge capacity is an issue in any type of disaster because a sudden major influx of patients necessitates more HCWs, equipment, supplies and space. Manufacturers may be incapable of producing extra goods within the necessary timeframe. And many HCWs may not be trained in using the necessary equipment, such as ventilators. Regarding extra space, companies have been developing new portable temporary isolation areas to increase patient isolation surge capacity in a pandemic but obviously there is a cost associated with procurement of these and other resources and in many cases the cost is a significant barrier. Overall, it’s very expensive to engage in disaster planning. It’s an investment put up front for something that may never be needed, which is why some facilities and organizations seem to make it a lower priority. When a biological event does occur, awareness grows temporarily and healthcare facilities and organizations spend a lot of time and money responding to the event; but when the event is over complacency gradually ensues.”

Seib, et al. (2014) conducted a survey of immunization program managers regarding budgetary and proposed changes in emergency preparedness programs during the H1N1 vaccination campaign; according to the results, respondents said a primary budget-related challenge faced during H1N1 was inability to hire extra HCW or pay regular staff overtime resulting in overworked regular staff.72 They also described operational budget shortfalls and vaccine procurement delays which they tried to overcome by increasing staff where possible, using executive order or other high-level support by officials to access emergency funds, make policy changes and  expedite hiring and spending processes according to their pandemic influenza plan or by direction from leadership. Planned changes included tailoring vaccine allocation strategies to the event by taking disease virulence, vaccine production rates and public demand into account; keeping vaccine allocation strategies flexible; clarifying vaccine prioritization to providers and the public; and setting up targeted clinics in places such as pharmacies and schools. And implemented changes included improving internal and external communication, improving vaccine allocation efficiency and planning for specific scenarios. The authors concluded that pandemic preparedness programs should focus on defining roles, collaborating during non-emergency situations, funding and improving technologies.

Clearly, the confounding problems in disaster preparedness planning make it a complex challenge. However, healthcare institutions should still put preparedness planning on their agendas to potentially minimize the impact of a pandemic or other biological disaster. Michael Osterholm, PhD, MPH, wrote in the New England Journal of Medicine (2005): “Planning for a pandemic must be on the agenda of every public health agency, school board, manufacturing plant, investment firm, mortuary, state legislature and food distributor. Health professionals must become much more proficient in ‘risk communication,’ so that they can effectively provide the facts - and acknowledge the unknowns - to a frightened population. … [Infectious disease disaster planning] depends on how everyone, from world leaders to local elected officials, decides to respond. We need bold and timely leadership at the highest levels of the governments in the developed world; these governments must recognize the economic, security and health threats posed by the next influenza pandemic and invest accordingly. The resources needed must be considered in the light of the eventual costs of failing to invest in such an effort. The loss of human life even in a mild pandemic will be devastating and the cost of a world economy in shambles for several years can only be imagined.”73 

Elizabeth Srejic is a freelance writer.

References:
1. Osterholm MT. Preparing for the next pandemic. N Engl J Med. 2005 May 5;352(18):1839-42.
2. Gerberding JL. Pandemic preparedness: pigs, poultry, and people versus plans, products, and practice. J Infect Dis. 2006 Nov 1;194 Suppl 2:S77-81.
3. “WHO Checklist for Influenza Pandemic Preparedness Planning.” 2005. Accessed November 15, 2015.
4. http://www.flu.gov/about_the_flu/h5n1/index.html
5. Taubenberger JK, Morens DM. Influenza: The Once and Future Pandemic. Public Health Reports. 2010;125(Suppl 3):16-26.
6. N Engl J Med. 2005 May 5;352(18):1839-42. Preparing for the next pandemic. Osterholm MT.
7. Ibid.
8. Ibid.
9. Ibid.
10. Davey VJ. Striking a balance between risk and preparedness. Am J Nurs. 2007 Jul;107(7):50-6; quiz 57. Disaster care: questions and answers on pandemic influenza.
11. Askling HH, Rombo L. Influenza in travellers. Curr Opin Infect Dis. 2010 Oct;23(5):421-5. doi: 10.1097/QCO.0b013e32833c6863.
12. Graman PS, Hall CB. Nosocomial viral respiratory infections. Semin Respir Infect. 1989 Dec;4(4):253-60.
13. Chen J, Deng YM. Influenza virus antigenic variation, host antibody production and new approach to control epidemics. Virol J. 2009 Mar 13;6:30. doi: 10.1186/1743-422X-6-30.
14. http://www.flu.gov/about_the_flu/h5n1/index.html
15. Gerberding JL. Pandemic preparedness: pigs, poultry, and people versus plans, products, and practice. J Infect Dis. 2006 Nov 1;194 Suppl 2:S77-81.
16. Davey VJ. Striking a balance between risk and preparedness. Am J Nurs. 2007 Jul;107(7):50-6; quiz 57. Disaster care: questions and answers on pandemic influenza.
17. Osterholm MT. Preparing for the next pandemic. N Engl J Med. 2005 May 5;352(18):1839-42.
18. Grebe KM, Yewdell JW, Bennink JR. Heterosubtypic immunity to influenza A virus: where do we stand? Microbes Infect. 2008 Jul;10(9):1024-9. doi: 10.1016/j.micinf.2008.07.002.
19. Pappaioanou M. Highly pathogenic H5N1 avian influenza virus: cause of the next pandemic? Comp Immunol Microbiol Infect Dis. 2009 Jul;32(4):287-300. doi: 10.1016/j.cimid.2008.01.003.
20.http://www.flu.gov/about_the_flu/h5n1/index.html
21. Osterholm MT. Preparing for the next pandemic. N Engl J Med. 2005 May 5;352(18):1839-42.
22. Gerberding JL. Pandemic preparedness: pigs, poultry, and people versus plans, products, and practice. J Infect Dis. 2006 Nov 1;194 Suppl 2:S77-81.
23. Ibid.
24. Gerberding JL. Pandemic preparedness: pigs, poultry, and people versus plans, products, and practice. J Infect Dis. 2006 Nov 1;194 Suppl 2:S77-81.
25. Taubenberger JK, Morens DM. Pandemic influenza-including a risk assessment of H5N1. Rev Sci Tech. 2009 Apr;28(1):187-202.
26. Taubenberger JK, Morens DM. Influenza: The Once and Future Pandemic. Public Health Reports. 2010;125(Suppl 3):16-26.
27. Pascua PN, Choi YK. Zoonotic infections with avian influenza A viruses and vaccine preparedness: a game of “mix and match”. Clin Exp Vaccine Res. 2014 Jul;3(2):140-8. doi: 10.7774/cevr.2014.3.2.140. Epub 2014 Jun 20.
28. McCullers JA. Preparing for the next influenza pandemic.Pediatr Infect Dis J. 2008 Oct;27(10 Suppl):S57-9. doi: 10.1097/INF.0b013e3181684d41.
29. Abdelwhab EM, Abdel-Moneim AS.Epidemiology, ecology and gene pool of influenza A virus in Egypt: will Egypt be the epicentre of the next influenza pandemic? Virulence. 2015;6(1):6-18. doi: 10.4161/21505594.2014.992662.
30. Jennings LC, Monto AS, Chan PK, Szucs TD, Nicholson KG. Stockpiling prepandemic influenza vaccines: a new cornerstone of pandemic preparedness plans. Lancet Infect Dis. 2008 Oct;8(10):650-8. doi: 10.1016/S1473-3099(08)70232-9.
31. Onishchenko GG. [Important issues of biological safety]. [Article in Russian]. Vestn Ross Akad Med Nauk. 2007;(12):40-4.
32. Montero A. [Chikungunya fever - A new global threat]. [Article in Spanish]. Med Clin (Barc). 2015 Aug 7;145(3):118-23. doi: 10.1016/j.medcli.2014.05.031. Epub 2014 Jul 30.
33. Collin N, Dubois PM. The Vaccine Formulation Laboratory: a platform for access to adjuvants. Vaccine. 2011 Jul 1;29 Suppl 1:A37-9. doi: 10.1016/j.vaccine.2011.04.125.
34. http://wwwnc.cdc.gov/eid/article/12/1/05-1370_article
35. Daems R, Del Giudice G, Rappuoli R. Anticipating crisis: towards a pandemic flu vaccination strategy through alignment of public health and industrial policy. Vaccine. 2005 Dec 30;23(50):5732-42.
36. Chunsuttiwat S. Response to avian influenza and preparedness for pandemic influenza: Thailand’s experience. Respirology. 2008 Mar;13 Suppl 1:S36-40.
37. Russo RM, Galante JM, Jacoby RC, Shatz DV. Mass casualty disasters: who should run the show? J Emerg Med. 2015 Jun;48(6):685-92. doi: 10.1016/j.jemermed.2014.12.069.
38. Oshitani H, Kamigaki T, Suzuki A. Major Issues and Challenges of Influenza Pandemic Preparedness in Developing Countries. Emerging Infectious Diseases. 2008;14(6):875-880. doi:10.3201/eid1406.070839.
39. Davey VJ. Striking a balance between risk and preparedness. Am J Nurs. 2007 Jul;107(7):50-6; quiz 57. Disaster care: questions and answers on pandemic influenza.
40. Osterholm MT. Preparing for the next pandemic. N Engl J Med. 2005 May 5;352(18):1839-42.
41. Jennings LC, Monto AS, Chan PK, Szucs TD, Nicholson KG. Stockpiling prepandemic influenza vaccines: a new cornerstone of pandemic preparedness plans. Lancet Infect Dis. 2008 Oct;8(10):650-8. doi: 10.1016/S1473-3099(08)70232-9.
42. Yen C, Hyde TB, Costa AJ, Fernandez K, Tam JS, Hugonnet S, Huvos AM, Duclos P, Dietz VJ, Burkholder BT. The development of global vaccine stockpiles. Lancet Infect Dis. 2015 Mar;15(3):340-7. doi: 10.1016/S1473-3099(14)70999-5.
43. Oshitani H, Kamigaki T, Suzuki A. Major Issues and Challenges of Influenza Pandemic Preparedness in Developing Countries. Emerging Infectious Diseases. 2008;14(6):875-880. doi:10.3201/eid1406.070839.
44. Osterholm MT. Preparing for the next pandemic. N Engl J Med. 2005 May 5;352(18):1839-42.
45. Ibid.
46. Ibid.
47. Davey VJ. Striking a balance between risk and preparedness. Am J Nurs. 2007 Jul;107(7):50-6; quiz 57. Disaster care: questions and answers on pandemic influenza.
48. Jennings LC, Monto AS, Chan PK, Szucs TD, Nicholson KG. Stockpiling prepandemic influenza vaccines: a new cornerstone of pandemic preparedness plans. Lancet Infect Dis. 2008 Oct;8(10):650-8. doi: 10.1016/S1473-3099(08)70232-9.
49. Oshitani H, Kamigaki T, Suzuki A. Major Issues and Challenges of Influenza Pandemic Preparedness in Developing Countries. Emerging Infectious Diseases. 2008;14(6):875-880. doi:10.3201/eid1406.070839.
50. Ibid.
51. Osterholm MT. Preparing for the next pandemic. N Engl J Med. 2005 May 5;352(18):1839-42.
52. Ibid.
53. Ibid.
54. Ibid.
55. Milián E, Kamen AA. Current and emerging cell culture manufacturing technologies for influenza vaccines. Biomed Res Int. 2015;2015:504831. doi: 10.1155/2015/504831. Epub 2015 Mar 1.Ibid.
56. Cox MM, Izikson R, Post P, Dunkle L. Safety, efficacy, and immunogenicity of Flublok in the prevention of seasonal influenza in adults. Ther Adv Vaccines. 2015 Jul;3(4):97-108. doi: 10.1177/2051013615595595.
57. Oshitani H, Kamigaki T, Suzuki A. Major Issues and Challenges of Influenza Pandemic Preparedness in Developing Countries. Emerging Infectious Diseases. 2008;14(6):875-880. doi:10.3201/eid1406.070839.
58. Jennings LC, Monto AS, Chan PK, Szucs TD, Nicholson KG. Stockpiling prepandemic influenza vaccines: a new cornerstone of pandemic preparedness plans. Lancet Infect Dis. 2008 Oct;8(10):650-8. doi: 10.1016/S1473-3099(08)70232-9.
59. Oshitani H, Kamigaki T, Suzuki A. Major Issues and Challenges of Influenza Pandemic Preparedness in Developing Countries. Emerging Infectious Diseases. 2008;14(6):875-880. doi:10.3201/eid1406.070839.
60. Reddy D. Responding to pandemic (H1N1) 2009 influenza: the role of oseltamivir. J Antimicrob Chemother. 2010 Apr;65 Suppl 2:ii35-ii40. doi: 10.1093/jac/dkq014.
61. Meltzer MI, Gambhir M, Atkins CY, Swerdlow DL. Standardizing scenarios to assess the need to respond to an influenza pandemic. Clin Infect Dis. 2015 May 1;60 Suppl 1:S1-8. doi: 10.1093/cid/civ088.
62. Oshitani H, Kamigaki T, Suzuki A. Major Issues and Challenges of Influenza Pandemic Preparedness in Developing Countries. Emerging Infectious Diseases. 2008;14(6):875-880. doi:10.3201/eid1406.070839.
63. http://wwwnc.cdc.gov/eid/article/12/1/pdfs/05-1068.pdf
64. Pasquale AD, Preiss S, Silva FT, Garçon N. Vaccine Adjuvants: from 1920 to 2015 and Beyond. Vaccines (Basel). 2015 Apr 16;3(2):320-43. doi: 10.3390/vaccines3020320.
65. Morens DM, Taubenberger JK, Fauci AS. Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. J Infect Dis. 2008 Oct 1;198(7):962-70. doi: 10.1086/591708.
66. Osterholm MT. Preparing for the next pandemic. N Engl J Med. 2005 May 5;352(18):1839-42.
67. Oshitani H, Kamigaki T, Suzuki A. Major Issues and Challenges of Influenza Pandemic Preparedness in Developing Countries. Emerging Infectious Diseases. 2008;14(6):875-880. doi:10.3201/eid1406.070839.
68. Bhadelia N, Sonti R, McCarthy JW, Vorenkamp J, Jia H, Saiman L, Furuya EY. Impact of the 2009 influenza A (H1N1) pandemic on healthcare workers at a tertiary care center in New York City. Infect Control Hosp Epidemiol. 2013 Aug;34(8):825-31. doi: 10.1086/671271. Epub 2013 Jun 25.
69. May L, Katz R, Johnston L, Sanza M, Petinaux B. Assessing physicians’ in training attitudes and behaviors during the 2009 H1N1 influenza season: a cross-sectional survey of medical students and residents in an urban academic setting. Influenza Other Respir Viruses. 2010 Sep;4(5):267-75.
70. Park YS, Behrouz-Ghayebi L2, Sury JJ3. Do shared barriers when reporting to work during an influenza pandemic influence hospital workers’ willingness to work? A multilevel framework. Disaster Med Public Health Prep. 2015 Apr;9(2):175-85. doi: 10.1017/dmp.2015.4.
71. Drake T, Chalabi Z, Coker R. Buy now, saved later? The critical impact of time-to-pandemic uncertainty on pandemic cost-effectiveness analyses. Health Policy Plan. 2015 Feb;30(1):100-10. doi: 10.1093/heapol/czt101. Epub 2013 Dec 24.
72. Seib K, Chamberlain A, Wells K, Curran E, Whitney EA, Orenstein WA, Hinman AR, Omer SB. Challenges and changes: immunization program managers share perspectives in a 2012 national survey about the US immunization system since the H1N1 pandemic response. Hum Vaccin Immunother. 2014;10(10):2915-21. doi: 10.4161/21645515.2014.972798.
73. Osterholm MT. Preparing for the next pandemic. N Engl J Med. 2005 May 5;352(18):1839-42.