Preparing for the threat of a bio-event

by Dr. Howard Levitin, MD, FACEP

More than eight years after the deadly 2001 anthrax attacks, the United States is still unprepared to respond to the threat of large-scale bioterrorism, according to a recent report from a congressionally appointed commission.¹ In the report the White House and Congress were given “F” grades for not building a rapid-response capability for dealing with disease outbreaks from bioterrorism, or providing adequate oversight of security and intelligence agencies.             According to the commission’s chairman, Senator Bob Graham, “it is more likely than not that a weapon of mass destruction (WMD) will be used in a terrorist attack somewhere in the world by the end of 2013. That weapon is more likely to be biological than nuclear.” In an earlier report by the same authors it was predicted that a bioterrorist attack will quite likely occur in the United States or at a U.S. facility in some other country. ²

This is unwelcome news for healthcare providers—particularly those who were heavily impacted by limited medical surge capability during the 2009 H1N1 Pandemic flu outbreak, an epidemic that was considered minor by many in terms of overall morbidity and mortality. A report released in December 2009 by the Trust of America’s Health and the Robert Wood Johnson Foundation found that the H1N1 flu outbreak exposed “serious underlying gaps in the nation’s ability to respond to public health emergencies and that the current economic crisis is straining an already fragile public health system.” Although strides have been made over the past several years these preparedness gains have not made up for the decades of chronic underfunding for bio-preparedness. ³

Lessons Learned from Recent Events

This country’s state of readiness has been tested by several biological outbreaks in the past decade: an intentional one spread via the U.S. Postal Service (Anthrax), an international one transmitted primarily between healthcare workers (SARS), a multistate outbreak associated with the consumption of peanut butter and peanut butter containing products (Salmonella), and finally an outbreak of a virus that quickly spread internationally which contained genetic material from the 1918 Pandemic that in its time killed between 20 to 40 million people worldwide (2009 H1N1).

In each of these cases, a number of important lessons were recognized that can be directly applied to other epidemics regardless of their etiology. Some of these lessons included the need to rapidly identify the source of exposure and prevent illness among those exposed. It included the importance of quickly implementing and mandating compliance with standard precautions amongst all healthcare workers before the source and transmissibility of the infectious agent have been clearly identified. Another important lesson centered on the value of the “golden triangle” of response which requires critical linkages between clinicians and clinical microbiologists, the healthcare delivery system, and public health officials.

Finally, these outbreaks reinforced the fact that infectious agents can predictably spread nationally and internationally at lightning speed. With SARS for example, a single ill physician from Guangdong Province in China arrived in Hong Kong on February 21, 2003. By the next day, 12 guests had become infected and within a week an epidemic was off and running in Hong Kong, Vietnam, Singapore and Canada. ⁴ The globalization of the 2009 H1N1 influenza was ignited when many of the 2.3 million people, who flew from Mexico to more than one thousand cities worldwide in March and April of 2009, were infected with a virus that would soon spread internationally. Passengers traveled to 164 countries which matched the pattern of the epidemic. ⁵ In the end, maybe the most important lesson learned was that one cannot afford to be complacent when it comes to biologicals.

The Impact of Bio-Events

When thinking about infectious agents it is often helpful to divide them into two groups—biological weapons and those that cause emerging infectious diseases. Biological weapons involve the intentional use of use of pathogens to kill, incapacitate, or seriously impair a person, group of people, or even an entire population. Biological warfare is a military technique that can be used by nation-states or non-national groups. In the latter case, or if a nation-state uses it clandestinely, it may also be considered bioterrorism. Biological warfare has been practiced repeatedly throughout history, but according to some analysts, it offers little military benefit. ⁶

Bioterrorism is terrorism by intentional release or dissemination of biological agents that may be in a naturally-occurring or in a human-modified form. These agents are used to harm and frighten the people of a state or society, and to create an intentional public health and national security crises.

An emerging infectious disease is one that has newly appeared in a population or that has been known for some time but is rapidly increasing in incidence or geographic range. This would include the 2009 H1N1 Influenza Pandemic, SARS, and community-acquired MRSA. From a healthcare perspective the origin of the outbreak (man-made vs. natural outbreak) is less important than the etiology and infectious nature of the agent. For purposes of this article the term “bio-event” will be used generically to address outbreaks either from bio-weapons or new, emerging infectious diseases that have national or international implications.

Bio-events are typically prolonged events, varying in intensity and duration depending upon the incubation period and infectivity of the agent. They can cause severe disruptions to societal functions, especially in their efforts to curtail an outbreak. A number of community-wide infection control measures are often contemplated including cancellation of public gatherings, and the discouragement of people from going to work ill. The economic impact of such measures can be profound. For example, a nationwide school closure for a period of four weeks to contain the spread of disease, could cost conservatively between $10 and $47 billion dollars (0.1-0.3 percent of GDP) and lead to a reduction of 6 percent to 19 percent in key healthcare personnel. ⁷

For the healthcare system, a bio-event has the potential to produce large numbers of worried and ill patients who often have an ongoing need for care. Early recognition of the initial stages of an outbreak and prompt implementation of appropriate containment and control measures are extremely important. During the SARS outbreak in Canada, 77 percent of the patients were exposed in the healthcare setting. Nurses, physicians, respiratory therapists, housekeeping staff and other healthcare workers made up over half of these patients. Forty-four people died in Toronto’s outbreak, including two nurses and a doctor. ⁸

The city of Toronto experienced 247 cases of SARS as compared to Vancouver’s four cases. Reportedly this occurred because of Toronto’s delay in providing accurate and timely information to hospitals, healthcare workers and the public regarding the appropriate procedures and precautions to take to ensure optimal safety for all persons and control the spread of disease.⁹ Vancouver, on the other hand, was well prepared before the first case of SARS appeared in its community. When a cluster of unexplained cases of atypical pneumonia was reported in China, simultaneously with reemergence of influenza A H5N1 (“bird flu”) in Hong Kong, Vancouver used its well established public health communication network to issue an early health alert. This alert requested healthcare providers to be watchful for and to make appropriate notifications concerning severe influenza-like illness in returning travelers from mainland China or Hong Kong or among their close contacts. As a result, before any (SARS) patients arrived in the area, hospitals began emphasizing that barrier precautions should be applied with all acute-onset respiratory infections. ¹⁰   

What is often unclear during the early stages of an outbreak is the offending agent’s route of transmission (contact, droplet and/or aerosol).  This knowledge is needed to make appropriate personal protective equipment (PPE) recommendations, including the choice between surgical and N95 particulate masks. After SARS, the report from the Commission to Investigate the Introduction and Spread of SARS in Ontario had one overriding take-home message—abide by the precautionary principle “… that reasonable efforts to reduce risk need not await scientific proof.” For Canada, that translated into the recommended use of an N95 respirator as a minimum standard of respiratory protection for healthcare and other emergency workers during a pandemic. ¹¹ In the United States, the debate over appropriate first line respiratory protection for biological continues to wage.

Bio-events can also cause widespread shortages of supplies, resources, and personnel. It can shutdown international trade and travel (Toronto lost $1.1 billion in lost tourism). ¹² It can also cause civil disorder due to shortages of treatment and result in the potential extensive loss of life.

Preparing for the Threat

There are a number of reasons to be concerned about the growing threat of bio-events. Emerging infectious diseases are becoming more prevalent, and access to the knowledge, technology, growth mediums, and source samples required to produce these agents outside of a research setting is becoming more prevalent. Between 1977 and 1994, 29 previously unknown pathogens emerged to produce disease. Only about 1 percent of bacteria and 4 percent of viruses have been identified. Fifty percent of the nearly 1,400 microorganisms that can infect humans first caused disease in animals. ¹³ There is also direct evidence, according to the congressional report cited earlier, that terrorists are trying to acquire weapons of mass destruction (WMD), and they have the organizational sophistication to obtain and use them.

 Equally alarming is the United States’ current inability to rapidly produce vaccines and therapeutics, essential steps for adequately responding to a biological threat, whether natural or man-made. Senator Graham noted the following in his report:

“H1N1 came with months of warning. But even with time to prepare, the epidemic peaked before most Americans had access to vaccine. A bioattack will come with no such warning. Response is a complex series of links in a chain of resilience necessary to protect the United States from biological attacks. Rapid detection and diagnosis capabilities are the first links, followed by providing actionable information to federal, state, and local leaders and the general public; having adequate supplies of appropriate medical countermeasures; quickly distributing those countermeasures; treating and isolating the sick in medical facilities; protecting the well through vaccines and prophylactic medications; and in certain cases, such as anthrax, environmental cleanup.”¹⁴

From a health delivery perspective, treating and isolating the sick from bio-events in existing medical facilities may prove to be one of the biggest obstacles of preparedness. Not surprisingly, biological events have an inherent ability to highlight everything that can go wrong with the healthcare system. Minimal medical surge capability, chronic staff shortages, reduced in-patient treatment capacity, and limited alternative care options are just a few of the many obstacles healthcare providers face. During the H1N1 Pandemic, emergency departments (ED) in Pennsylvania, for example, experienced a 23 percent increase in patient volume. Nearly 38 percent of the Pennsylvania hospitals surveyed activated their emergency department surge plan, and 36 percent of them filed for an alternate care site protocol request with the PA Department of Health.¹⁵ Many hospitals across the country experienced prolonged ED wait times, ambulance diversions, and shortages of vaccines and supplies.

The U.S. public health system and healthcare providers must be prepared to address various biological agents, including pathogens that are rarely seen in the United States. The list of pathogens of concern is long, broad-based, and frightening. It includes agents that can be easily disseminated or transmitted from person-to-person, result in high mortality rates, and cause public panic and social disruption. Many of these agents will require special action for public health preparedness. High priority agents/diseases include anthrax (Bacillus anthracis), Botulism (Clostridium botulinum toxin), Plague (Yersinia pestis), Smallpox (Variola major), Tularemia (Francisella tularensis), and Viral hemorrhagic fevers (filoviruses [e.g., Ebola, Marburg] and arenaviruses [e.g., Lassa, Machupo]).

Bacteria, viruses, and toxins are the focus of concern at the most basic level. Bacteria are single celled organisms that do not require a host to reproduce and survive; they are everywhere. There are over 100,000 bacteria per square centimeter of skin. There are trillions more in your gut, nasal passages, and oral cavity. Given adequate nutrients, a single bacterial cell that divides every 20 minutes can generate 280,000 billion in a single day. A genetic mutation occurs once in every million divisions, which increases the likelihood of developing antibiotic or environmental resistances.¹⁶ These chance mutations are freely shared between bacteria. This becomes a potential problem when only certain antibiotics are stockpiled and widely dispensed during an outbreak (i.e., Cipro for Anthrax), resulting in an increased likelihood that the organism will develop resistance to the primary drugs available.

Viruses, on the other hand, are ultramicroscopic, infectious agents that replicate themselves only within cells of living organisms. They produce a vast array of diseases including cancer. In fact, 1.3 million cases of cancer per year may be treated or prevented by targeting and destroying the viruses that cause them.¹⁷ Viruses spread quickly and have a high propensity for mutations that makes them more infectious.

Biotoxins are poisonous substances produced by living cells or organisms. Botulinum toxin (“Botox”) is an example of a toxin that has a long history as a bio-weapon, is found naturally in the soil (Clostridium botulinum), and has broad medical uses beyond cosmetically hiding wrinkles (e.g., treating migraine headaches, cervical dystonias, and the muscle contractures of cerebral palsy).

Unless there is a credible forewarning of a release of a biological agent a number of epidemiological clues must be constantly monitored in order to recognize the early stages of an epidemic. These clues include an outbreak of a rare disease (anthrax), a disease not endemic to the area (i.e., Plague or Ebola), or one out of natural season (an influenza outbreak during the summer months). Other clues include the identification of organisms with unusual resistance or transmission patterns.

The early stages of a bio-event may not be immediately obvious. Signs and symptoms may be delayed or non-specific. Recognition requires astute vigilance, looking for patterns of unusual illnesses or complaints and reporting those findings to the public health authority. Once person-to-person transmission is documented anywhere in the world, diagnosis should be considered with every patient encounter. Once there is reasonable evidence of an impending threat to public health, don’t wait for proof of causation before taking steps to avert the threat, limit spread, and protect personnel.

References

1. Graham, B & Talent, J: Prevention of WMD Proliferation and Terrorism Report Card. Commission on the Prevention of Weapons of Mass Destruction Proliferation and Terrorism, January 2010.
2. Graham, B & Talent, J:  World at Risk, the Report of the Commission on the of Weapons of Mass Destruction Proliferation and Terrorism, 2008.
3. Ready or Not? Protecting the Public’s Health from Diseases, Disasters, and Bioterrorism, December, 2009.
4. CDC, MMWR, April 4, 2003, Vol. 52, No. 3.
5. NEJM 2009.
6. “The Challenge of Biological Weapons: Proposals for Greater EU Effectiveness,” Disarmament Diplomacy, Issue No. 78, July/Aug 2004.
7. Economic Cost and Health Care Workforce Effects of School Closures in the U.S., The Brookings Institute, Sept 30, 2009.
8. “Safety Is Not Negotiable: The Importance of Occupational Health and Safety to Pandemic Planning,” Law & Governance, Vol. 11 No. 9 2008, Linda Silas, Nancy Johnson, Kate Rexe.
9. ibid

10.  Skowronski DM, Petric M, Daly P, Parker RA, Bryce E, Doyle PW, et al. Coordinated response to SARS, Vancouver, Canada. Emerg Infect Dis [serial on the Internet]. 2006 Jan [date cited]. Available from http://www.cdc.gov/ncidod/EID/vol12no01/05-0327.htm.

11.  Silas, L, Johnson, N & Rexe, K: Safety Is Not Negotiable: The Importance of Occupational Health and Safety to Pandemic Planning,” Law & Governance, Vol. 11 No. 9 2008.

12.  Darby P: The Economic Impact of SARS, May 2003 – www.conferenceboard.ca/documents.aspx?did=539.

13.  Glasser, R: We are not immune: Influenza, SARS, and the collapse of public health, Harpers Magazine, July 2004.

14.  Commission on the Prevention of Weapons of Mass Destruction Proliferation and Terrorism, January 2010.

15.  Hospital Association of Pennsylvania, Nov 2009, Emergency Department Activity and H1N1 Influenza.

16.  Bryson B: A short history of nearly everything, Broadway Books, New York, 2003.

17.  Cancer Viruses, http://www.anythingbutwork.com/health/cancer-virus.htm; accessed 2/15/2010.

Dr. Howard Levitin, MD, FACEP is president and CEO of DQE Inc. and an emergency physician and clinical assistant professor of medicine at the Indiana University School of Medicine. He has served as a subject matter expert in the areas of hazardous materials, chemical and biological weapons, surge capacity care and disaster planning. Dr. Levitin was an instructor for the Department of the Army’s Toxic Chemical Training Course for Medical Support Personnel and co-author and instructor for the Department of Defense’s Domestic Preparedness Program. Dr. Levitin lectures nationally and internally on the topics of hospital disaster preparedness and the medical consequences of terrorism, has authored chapters on hazardous materials and victim decontamination for several disaster medicine textbooks, and has published extensively on a wide variety of topics related to emergency preparedness.