Thomas V. Inglesby

Smallpox Vaccination: A Review, Part II. Adverse Events

Smallpox vaccination of health care workers, military personnel, and some first responders has begun in the United States in 2002-2003 as one aspect of biopreparedness. Full understanding of the spectrum of adverse events and of their cause, frequency, identification, prevention, and treatment is imperative. This article describes known and suspected adverse events occurring after smallpox vaccination.

Augmentation of hospital critical care capacity after bioterrorist attacks or epidemics: Recommendations of the Working Group on Emergency Mass Critical Care‡

The Working Group on Emergency Mass Critical Care was convened by the Center for Biosecurity of the University of Pittsburgh Medical Center and the Society of Critical Care Medicine to provide recommendations to hospital and clinical leaders regarding the delivery of critical care services in the wake of a bioterrorist attack resulting in hundreds or thousands of critically ill patients. In these conditions, traditional hospital and clinical care standards in general, and critical care standards in particular, likely could no longer be maintained, and clinical guidelines for U.S. hospitals facing these situations have not been developed. The Working Group offers recommendations for this situation.

Management of Anthrax

From 3 October 2001 through 16 November 2001, in the United States, there were 18 confirmed cases of inhalational and cutaneous anthrax, an additional 4 suspected cases of cutaneous anthrax, and 5 deaths due to inhalational anthrax. Although the number of cases was relatively small, this experience brought bioterrorism and its potential to sharp focus as thousands of people began receiving prophylactic antibiotics after possible exposure to anthrax spores. These events have resulted in a substantial impact on the health care system, including the rewriting of pneumonia guidelines, new emphasis on identification of microbial etiology, substantial infusion of funds for bioterrorism-related research, and a sudden mandate for regional disaster and public health planning. This article provides clinicians with clinically relevant information about the diagnosis and management of anthrax.

Smallpox Vaccination: A Review, Part I. Background, Vaccination Technique, Normal Vaccination and Revaccination, and Expected Normal Reactions

Because smallpox could be a factor in bioterrorism, the United States has provided guidelines for smallpox vaccination of certain members of the population, including health care workers and first responders, as well as military personnel. A plan for more extensive vaccination, if it is needed in the event of a bioterrorist attack, is being developed under the aegis of the Centers for Disease Control and Prevention. The characteristics of smallpox vaccine, the technique of administration, and the expected reactions to primary vaccination and revaccination are outlined in this article.

Anthrax 2001: observations on the medical and public health response.

THIS ARTICLE DESCRIBES ASPECTS of the medical and public health response to the 2001 anthrax attacks based on interviews with individuals who were directly involved in the response. It has been more than 18 months since B. anthracis spores were discovered in letters sent through the U.S. postal system. The specific purpose and perpetrator(s) of these attacks remain unknown. A total of 22 people developed anthrax as a result of the mailings, 11 suffered from the inhalational form of the disease, and 5 of these people died. Thousands of workers—including health care, public health, environmental, and law enforcement professionals—participated in the response to the attacks. Thousands more were directly affected, including individuals working in facilities contaminated by the attacks and their families. The immediate and continuing medical and public health response to the anthrax attacks of 2001 represents a singular episode in the history of public health. After-action assessments of the response to the anthrax attacks could offer invaluable opportunities to better understand and remedy the systemic vulnerabilities revealed by America’s only experience with an anthrax attack. Yet there still has been no comprehensive published analysis of the response to these events. In December 2001, the Center for Strategic International Studies convened a meeting, which included high-level government officials directly involved in managing the crisis, to discuss the response and review lessons learned. The report describing this meeting has been withheld from public distribution by the Department of Defense, which supported the meeting, on the grounds that the document contains sensitive information.1 The “response” to the anthrax attacks was extremely complex, and any analysis that purports to assess the response must account for this complexity. The unprecedented nature of the attacks and the context in which the response occurred are also crucial to understanding what happened and why. The long-standing neglect of federal, state, and local public health agencies, and the highly stressed condition of U.S. medical facilities, which routinely work at the limits of their capacity, are acknowledged by virtually all informed observers. That the medical and public health institutions involved in the response functioned as well as they did is a tribute to the extraordinary efforts of the individuals involved. Despite the commitment and hard work of the individuals in these professional communities, what was revealed by the anthrax attacks was an unacceptable level of fragility in systems now properly recognized as vital to national defense. Too many citizens, elected leaders, and national security officials still have limited understanding of the degree to which 22 cases of anthrax rocked the public health agencies and hospitals involved in the response to this small bioterrorist attack. Most of the vulnerabilities in the medical and public health systems revealed by the response remain unaddressed. It is not the purpose of this article to praise or criticize individuals who responded to the 2001 anthrax attack. The emphasis here is on how to improve response systems. The article seeks to identify the strategic and organizational successes and shortcomings of the health response to the anthrax attacks so that medical and public health communities as well as elected officials can learn from this crisis. The recent international spread of Severe Acute Respiratory Syndrome (SARS) is illustrating once more the importance of effective public health response systems. Initial impressions of the Centers for Disease Control and Prevention’s response to SARS indicate that the agency has improved several aspects of epidemic response that were problematic in the aftermath of the 2001 anthrax at-

Public health and medical responses to the 1957-58 influenza pandemic.

As the U.S. prepares to respond this fall and winter to pandemic (H1N1) 2009, a review of the 1957-58 pandemic of Asian influenza (H2N2) could be useful for planning purposes because of the many similarities between the 2 pandemics. Using historical surveillance reports, published literature, and media coverage, this article provides an overview of the epidemiology of and response to the 1957-58 influenza pandemic in the U.S., during which an estimated 25% of the population became infected with the new pandemic virus strain. While it cannot be predicted with absolute certainty how the H1N1 pandemic might play out in the U.S. this fall, lessons from the 1957-58 influenza pandemic provide useful and practical insights for current planning and response efforts.

Clinical Management of Potential Bioterrorism-Related Conditions

The agents most likely to be used in bioterrorism attacks are reviewed, along with the clinical syndromes they produce and their treatment.

Preventing the Use of Biological Weapons: Improving Response Should Prevention Fail

This article presents an overview of the nature and scope of the challenges posed by biological weapons, and offers ways by which the infectious diseases professional community might address the challenges of biological weapons and bioterrorism.

Biosecurity: Responsible Stewardship of Bioscience in an Age of Catastrophic Terrorism

BIOLOGICAL RESEARCH has undergone tremendous growth and transformation since 1876, when Robert Koch identified Bacillus anthracis as the causative agent of anthrax, since the structure of DNA was solved in 1953, and even since a “rough draft” of the human genome was completed in February 2001. This expansion of knowledge and the powers it brings shows no signs of slowing, and will undoubtedly bring vast benefits in diagnosing, preventing, and curing disease, and in improving agriculture. However, a plentiful array of the same tools, techniques, and knowledge that have beneficent uses could, if misapplied, be used to destroy human life or agriculture on a mass scale. While it is not a new phenomenon that technologies can have positive and negative consequences, biological science is unique in that its powers over both life and death are profound, and the culture of bioscience is open and relatively available, particularly when compared to nuclear weapons research. In the aftermath of the anthrax attacks of 2001 and the terrorist assaults on the World Trade Towers, policymakers awakened to these inherent powers of biological research and began calling for more governmental controls. The Patriot Act (2001)1 and the Public Health Security and Bioterrorism Preparedness and Response Act of 20022 imposed new regulations on the conduct of research involving “select agents”—the several dozen pathogens that the Centers for Disease Control and Prevention judges to be the most dangerous potential biological weapons. In recent months, the White House Office of Science and Technology Policy has met with representatives of professional science societies, private industry, and others to discuss restricting access to “sensitive homeland security information” generated within government agencies, possibly including data published in scientific journals, lest advances in knowledge and technology inadvertently fuel terrorist attacks using biological weapons. As debate proceeds about whether or how to more closely govern the practice of biological research, it is critical that the profound stakes are understood for both national security and bioscience: a broad scope of research in the life sciences could conceivably be applied towards biological weapons development, but this same research will be essential to creating the medicines, vaccines, and technologies needed to counter the threat of bioterrorism and naturally occurring disease. Efforts to monitor comprehensively all bioscience research that has potentially destructive applications would subsume huge swaths of science, gravely tax civilian research resources, and could discourage scientists from pursuing advances in fields important to medicine and agriculture, fields we urgently need to advance in order to address the grave vulnerabilities currently imposed by bioweapons. The problem of biosecurity in an age of bioterrorism is how to constrain malignant applications of powerful bioscience responsibly without damaging the generation of essential knowledge. Over time, we must construct a network of “checks and balances”: regulations, incentives, cultural expectations and practices that encourage and enable progress in scientific understanding so that knowledge can be brought to bear on human needs, while simultaneously assuring responsible stewardship of powerful knowledge so that it is not used for malevolent purposes. Such stewardship will have to evolve— rapidly, in concert with the pace of advances in the life sciences—to embrace a network of international agreements, legal regulations, professional standards, ethical mores, and catalogues of “best practices” pertinent to

Moratorium on Research Intended To Create Novel Potential Pandemic Pathogens

Research on highly pathogenic organisms is crucial for medicine and public health, and we strongly support it. This work creates a foundation of new knowledge that provides critical insights around the world’s most deadly infectious diseases, and it can lay groundwork for the future development of new diagnostics, medicines, and vaccines. Almost all such research can be performed in ways that pose negligible or no risk of epidemic or global spread of a novel pathogen. However, research that aims to create new potential pandemic pathogens (PPP) (1)—novel microbes that combine likely human virulence with likely efficient transmission in humans—is an exception to that rule. While this research represents a tiny portion of the experimental work done in infectious disease research, it poses extraordinary potential risks to the public. Experiments that create the possibility of initiating a pandemic should be subject to a rigorous quantitative risk assessment and a search for safer alternatives before they are approved or performed. Yet a rigorous and transparent risk assessment process for this work has not yet been established. This is why we support the recently announced moratorium on funding new “gain-offunction” (GOF) experiments that enhance mammalian transmissibility or virulence in severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and influenza viruses. This realm of work roughly corresponds with the work we have termed PPP above. Because the term “gain of function” in other contexts can be used to describe techniques of scientific research that have nothing to do with the creation of novel potential pandemic pathogens, we think the term can be too broad and can mislead. Throughout this commentary, we focus on research designed to create PPP strains of influenza virus, the type of research that initially attracted attention, leading to the moratorium and for which the most discussion has already occurred. Other types of gain-of-function research on influenza and studies intended to enhance pathogenicity or transmissibility of MERS and SARS coronaviruses may or may not fit the definition of PPP research and further clarification is needed and ongoing. As we discuss near the end of this article, it will be essential to clarify the different risks and benefits entailed by different types of experiments covered by the funding pause (2). The purpose of this research funding pause is to complete “a robust and broad deliberative process . . . that results in the adoption of a new [U.S. Government] gain-of-function research policy” (3). The moratorium would stop new funding for the following: