Assessment Of Future Scientific Needs For Live Variola Virus

In 1980, the World Health Organization (WHO) officially declared that smallpox had been eradicated. In 1986, WHO's international Ad Hoc Committee on Orthopox Virus Infections unanimously recommended destruction of the two remaining official stocks of variola virus, one at the Centers for Disease Control and Prevention and the other at the VECTOR laboratory in Siberia. In June 1999, WHO decided to delay the destruction of these stocks. Informing that decision was Assessment of Future Scientific Needs for Variola Virus, which examines: -- Whether the sequenced variola genome, vaccinia, and monkey pox virus are adequate for future research or whether the live variola virus itself is needed to assist in the development of antiviral therapies. -- What further benefits, if any, would likely be gained through the use of variola in research and development efforts related to agent detection, diagnosis, prevention, and treatment. -- What unique potential benefits, if any, the study of variola would have in increasing our fundamental understanding of the biology, host-agent interactions, pathogenesis, and immune mechanisms of viral diseases.

In 1980, the World Health Organization (WHO) officially declared that smallpox had been eradicated. In 1986, WHO's international Ad Hoc Committee on Orthopox Virus Infections unanimously recommended destruction of the two remaining official stocks of variola virus, one at the Centers for Disease Control and Prevention and the other at the VECTOR laboratory in Siberia. In June 1999, WHO decided to delay the destruction of these stocks. Informing that decision was Assessment of Future Scientific Needs for Variola Virus, which examines: Whether the sequenced variola genome, vaccinia, and monkey pox virus are adequate for future research or whether the live variola virus itself is needed to assist in the development of antiviral therapies. What further benefits, if any, would likely be gained through the use of variola in research and development efforts related to agent detection, diagnosis, prevention, and treatment. What unique potential benefits, if any, the study of variola would have in increasing our fundamental understanding of the biology, host-agent interactions, pathogenesis, and immune mechanisms of viral diseases.

Smallpox was a devastating disease that decimated human populations for centuries, and its eradication in 1980 was a monumental achievement for the global health community. Since then the remaining known strains of its causative agent, variola virus, have been contained in two World Health Organization (WHO)-approved repositories. In 1999, the World Health Assembly (WHA) debated the issue of destroying these remaining strains. Arguments were presented on the need to retain the live virus for use in additional important research, and the decision to destroy the virus was deferred until this research could be completed. In that same year, the Institute of Medicine (IOM) convened a consensus committee to explore scientific needs for the live virus. In the ten years since the first IOM report, the scientific, political, and regulatory environments have changed. In this new climate, the IOM was once again tasked to consider scientific needs for live variola virus. The committee evaluated the scientific need for live variola virus in four areas: development of therapeutics, development of vaccines, genomic analysis, and discovery research.

December 13, 2002, the president of the United States announced that smallpox vaccination would be offered to some categories of civilians and administered to members of the military and government representatives in high-risk areas of the world. The events that precipitated that historic announcement included a series of terrorist attacks during the 1990s, which culminated in the catastrophic events of 2001. Although preparedness for deliberate attacks with biologic weapons was already the subject of much public health planning, meetings, and publications as the twentieth century neared its end, the events of 2001 led to a steep rise in bioterrorism-related government policies and funding, and in state and local preparedness activities, for example, in public health, health care, and the emergency response and public safety communities. The national smallpox vaccination program is but one of many efforts to improve readiness to respond to deliberate releases of biologic agents. The Institute of Medicine (IOM) Committee on Smallpox Vaccination Program Implementation was convened in October 2002 at the request of the Centers for Disease Control and Prevention (CDC), the federal agency charged with implementing the government's policy of providing smallpox vaccine first to public health and health care workers on response teams, then to all interested health care workers and other first responders, and finally to members of the general public who might insist on receiving the vaccine. The committee was charged with providing "advice to the CDC and the program investigators on selected aspects of the smallpox program implementation and evaluation." The committee met six times over 19 months and wrote a series of brief "letter" reports. The Smallpox Vaccination Program: Public Health in an Age of Terrorism constitutes the committee's seventh and final report, and the committee hopes that it will fulfill three purposes: 1) To serve as an archival document that brings together the six reports addressed to Julie Gerberding, director of CDC, and previously released on line and as short, unbound papers; 2) To serve as a historical document that summarizes milestones in the smallpox vaccination program, and ; 3) To comment on the achievement of overall goals of the smallpox vaccination program (in accordance with the last item in the charge), including lessons learned from the program.

In the past half century, deadly disease outbreaks caused by novel viruses of animal origin - Nipah virus in Malaysia, Hendra virus in Australia, Hantavirus in the United States, Ebola virus in Africa, along with HIV (human immunodeficiency virus), several influenza subtypes, and the SARS (sudden acute respiratory syndrome) and MERS (Middle East respiratory syndrome) coronaviruses - have underscored the urgency of understanding factors influencing viral disease emergence and spread. Emerging Viral Diseases is the summary of a public workshop hosted in March 2014 to examine factors driving the appearance, establishment, and spread of emerging, re-emerging and novel viral diseases; the global health and economic impacts of recently emerging and novel viral diseases in humans; and the scientific and policy approaches to improving domestic and international capacity to detect and respond to global outbreaks of infectious disease. This report is a record of the presentations and discussion of the event.

Since smallpox eradication, the science of eradication has changed and with it, our definitions of what diseases are possible to eradicate. However, eradication must not beget complacency. As has been learned from past control or eradication attempts with a variety of viral diseases, from yellow fever to influenza, accidental or intentional reintroduction is a real threat-one that could strike anywhere and for which we need to be fully prepared. The criteria for assessing eradicability of polio, measles, and other viral infections have been debated extensively. With the elimination and eradication of several viral diseases on the horizon, issues surrounding the cessation of immunization activities become exceedingly important. In an effort to better understand the dynamics of disease eradication and post-immunization policies, the Institute of Medicine Forum on Emerging Infections hosted a two-day workshop (February 1-2, 2001) on The Consequences of Viral Disease Eradication. This book explores the principles underlying the biological challenges, medical interventions, the continuing research agenda, and operational considerations for post-immunization strategies for vaccine-preventable viral diseases, and highlights important efforts that may facilitate wise decision making.

Early detection is essential to the control of emerging, reemerging, and novel infectious diseases, whether naturally occurring or intentionally introduced. Containing the spread of such diseases in a profoundly interconnected world requires active vigilance for signs of an outbreak, rapid recognition of its presence, and diagnosis of its microbial cause, in addition to strategies and resources for an appropriate and efficient response. Although these actions are often viewed in terms of human public health, they also challenge the plant and animal health communities. Surveillance, defined as "the continual scrutiny of all aspects of occurrence and spread of a disease that are pertinent to effective control", involves the "systematic collection, analysis, interpretation, and dissemination of health data." Disease detection and diagnosis is the act of discovering a novel, emerging, or reemerging disease or disease event and identifying its cause. Diagnosis is "the cornerstone of effective disease control and prevention efforts, including surveillance." Disease surveillance and detection relies heavily on the astute individual: the clinician, veterinarian, plant pathologist, farmer, livestock manager, or agricultural extension agent who notices something unusual, atypical, or suspicious and brings this discovery in a timely way to the attention of an appropriate representative of human public health, veterinary medicine, or agriculture. Most developed countries have the ability to detect and diagnose human, animal, and plant diseases. Global Infectious Disease Surveillance and Detection: Assessing the Challenges-Finding Solutions, Workshop Summary is part of a 10 book series and summarizes the recommendations and presentations of the workshop.