September 26, 2002
Daniel R. Lucey, MD, MPH
Welcome to BEPAST.org — website of the Center for Biologic Counterterrorism and Emerging Diseases. The Center, based in Washington DC, is hosted by the Medstar Health group, one of the nation’s largest not-for-profit hospital groups. Washington Hospital Center, the physical home of CBCED, is located just north of the Capitol building — about one minute away by helicopter. WHC is the largest hospital in the District of Columbia by a substantial margin, and includes the largest and busiest emergency room, a flight program with four helicopters, a major trauma center, and the regional burn center. Because of its unique location and special programs, the hospital received all major burn victims from the 9/11 attack on the Pentagon, and was also at the epicenter of the anthrax exposure events in the Autumn of 2001.
Website Contents
This website provides information relevant to Mitigation, Preparedness, Response, and Recovery from the medical sequelae of a terrorist attack involving biological weapons. An equally important focus will be on preparation for and response to naturally occurring outbreaks of emerging diseases, particularly outbreaks of significant national proportions. The website name “BEPAST” is our acronym for the six major “Category A” bioterrorism agents:
- Botulism
- Ebola and other viral hemorrhagic fevers
- Plague
- Anthrax
- Smallpox
- Tularemia.
Regional Preparedness Forums
We recommend that each concerned medical community should establish monthly bioterrorism preparedness forums for interested medical, public health, and first-responder personnel. Such forums have been underway in the DC Metropolitan region (DC, Maryland, and Virginia) since the beginning of 2002, and are open to all interested persons. All major Category A agents have been discussed, with an early emphasis on anthrax and smallpox. Speakers in our region have included experts from MedStar, The National Institutes of Health, Howard University, Johns Hopkins University, the National Naval Medical Center, Walter Reed Army Institute of Research, and the Army Medical Command.
Hospital Preparation
Hospital preparation for a potential bioterrorism event begins with the distribution of written information on the diagnosis, treatment, and containment of the major bioterrorism agents. The next step is to obtain a sufficient supply of additional antibiotics and respiratory (N-95) masks – both for hospital personnel and for potential patients. For the best balance of cost, efficiency, and readiness, we recommend that rapid-response antibiotics be bottled in three day supplies. It’s important to rehearse protocols with the microbiology laboratory to ensure that any clinical suspicion is communicated to the laboratory and to establish protocols for early alerting when suspicious bacterial isolates are identified. In view of the potentially devastating effects of a smallpox outbreak, it is now time for most centers to establish a training module in the use of the special bifurcated needle, providing hands-on training with an artificial deltoid muscle to allow practice in carrying out the required 15 intradermal insertions of the needle. CBCED has developed and deployed such a training module, and can offer advice based on our limited experience.
Smallpox Vaccination
Planning for smallpox vaccination — whether as a preparedness measure or as a response to a confirmed case of the disease — depends on assessments of risk, benefit, and rationale. At this writing, the CDC has just released an updated CDC Smallpox Response Plan and Guidelines document that will be discussed in an upcoming issue of Updates in Bioterrorism. Optimizing the safety of the vaccination process will be essential to maintain public health and also to maintain the public’s trust in this effort; pragmatic issues that need to be addressed and standardized include:
- How best to screen vaccine volunteers for contraindications to vaccine (such as immunodeficiency and a history of eczema)
- Whether persons vaccinated should stay home from work to minimize transmission of vaccinia virus to contacts
- How best to care for the vaccination site to minimize risk of spreading the vaccinia virus
- How to manage liability issues
- How to address financial issues related to time lost from work.
We hope the Center for Biologic Counterterrorism and Emerging Diseases will be a useful resource for the nation’s health community. Welcome to our website.
October 7, 2002
Daniel R. Lucey, MD, MPH
Updates on smallpox vaccine
The week of September 29th to October 5th brought news of progress regarding expanded stockpiles of smallpox vaccine, and new public discussions on pre-event smallpox vaccination.
On Sunday, September 29th, Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Disease (NIAID), spoke on smallpox vaccination at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy Infectious Disease (ICAAC) in San Diego. He reported the initial data that dilution of the decades-old 80 million doses of frozen smallpox vaccine (Aventis Pasteur) elicited an immune response comparable to that of the 1:5 dilution of the decades-old 15 million doses of lyophilized smallpox vaccine (Wyeth-Ayerst Laboratories). In addition, the frozen vaccine was no more reactogenic, in terms of side effects, than the lyophilized vaccine.
This important news means that there are now enough doses of smallpox vaccine for the entire US population of approximately 285 million because 1:5 dilution of both the lyophilized and frozen vaccines would make more than 400 million total vaccine doses available immediately.
Several ways to provide smallpox vaccination prior to any actual event are under discussion, and on Friday, October 4th, the various options were presented by three leaders within the Department of Health and Human Services DHHS): Dr. Fauci, Mr. Jerry Hauer, assistant secretary for emergency health preparedness, and Dr. Julie Gerberding, Director, Centers for Disease Control and Prevention (CDC). A final decision will be made by the White House and announced later. A related audio webcast will be available on the CDC website.
One possible option is to arrange for voluntary vaccination of 500,000 health care workers and public health smallpox response teams, followed by up to 10 million health-care workers, police, fire fighters, security people and others who could be involved in the response to a smallpox event. Subsequently, the vaccine could be made available on a voluntary, non-mandated basis for the general US population, even in the absence of a smallpox outbreak.
Smallpox vaccine is our least safe vaccine, and it is inevitable that a small number of significant and occasionally fatal adverse events will occur due to the live-vaccinia virus smallpox vaccine. On October 4th, the CDC placed on their website (www.bt.cdc.gov/agent/smallpox/vaccine-safety/adverse-events-chart.asp) an additional summary of the major vaccine adverse event rates in the form of a chart. The six adverse events included in the chart are encephalitis, vaccinia necrosum (increased risk in immunocompromised persons), eczema vaccinatum (which can occur in either vaccinees or their contacts who have a history of eczema), generalized vaccinia, accidental autoinoculation (e.g., of the eye), and death. Based on data from the1960s, before vaccination in the United States ended in 1972, about 15 people per 1 million vaccinated for the first time will have life-threatening adverse events and of these, one or two will die.
The higher numbers today of people with compromised immunity (due to transplantation, cancer, HIV, and other causes), and people with a history of eczema could result in even higher adverse event rates now. In addition, there are more people today in the United States who have never been vaccinated against smallpox since routine civilian vaccination ended in 1972. Adverse reactions to the vaccine in persons who receive it or who are infected through direct skin contact with vaccines are significantly higher after their primary vaccination.
November 14, 2002
Unsubstantiated terror alert for US hospitals: anthrax or explosives
Daniel R. Lucey, MD, MPH
In the early morning of November 14th, the news media reported an FBI alert for hospitals as potential targets of terrorist attacks with anthrax or explosives. The four US cities mentioned were San Francisco, Houston, Chicago, and Washington DC. It should be emphasized that these threats were reported as unsubstantiated.
In the Washington DC region, the DC Hospital Association (DCHA) organized a regional conference call at 10:30 AM. Approximately 50 persons from DC, Maryland, and Virginia participated, including clinicians, public health officials, hospital executives, infection control practitioners, laboratory personnel, Federal officials, and others. This conference call by the DCHA followed the precedent of the daily conference calls in the DC, Virginia, Maryland region during the actual anthrax attacks of October 2001. A balanced response of enhanced communication and vigilance regarding these unsubstantiated threats was discussed on the DCHA call.
Two recent documents providing relevant anthrax-related information can be found on this website under the “Top Selections” heading in the right-hand column. “Anthrax 2001: Ten Pearls” is a list of specific clinical information compiled from “lessons learned” during the Autumn 2001 anthrax attacks, both from the recent medical literature and from our own experience evaluating patients at the Washington Hospital Center. The second document is our “BE PAST” color poster, which provides a guide to the diagnosis and management of the 6 Category A agents (Botulism, Ebola-VHF, Plague, Anthrax, Smallpox, Tularemia).
MedStar – Washington Hospital Center’s 11th regional (DC, Maryland, Virginia) bioterrorism preparedness forum will take place on November 21, Thursday, from 8:30-10:30. Discussions will center around updates on preparations for anthrax and on the recognition and management of bubonic vs pneumonic plague.
Finally, the November 15th issue of the CDC’s Morbidity and Mortality Weekly Report (MMWR) (p. 1024-1026) contains updated information on the licensed FDA anthrax vaccine. Updates affect the following three existing statements from the CDC’s Advisory Committee on Immunization Practices (ACIP):
- Pre-exposure use of the vaccine
- Post-exposure vaccination and antibiotics under an Investigational New Drug (IND) application with the FDA
- Research “…toward developing an improved vaccine for preventing anthrax and new therapeutic strategies, including use of antitoxin (e.g., hyperimmune globulin) for treating anthrax.”
Anthrax-Specific Intravenous Hyperimmune Globulin
Daniel R. Lucey, MD, MPH
November 28, 2002
For over a year, efforts have been directed toward developing a new therapy against life-threatening anthrax infection for patients who are failing to respond to combination antibiotic therapy and intensive care. This investigational treatment, termed hyperimmune globulin, consists of purified and concentrated antibody against anthrax.
The February 1 2002 issue of Science (vol.295, p.777) contains a description of the new approach. The antibody against anthrax is derived from the plasma of people who have been vaccinated with the FDA-licensed anthrax vaccine. Because the anthrax vaccine consists primarily of the “Protective Antigen (PA)” of anthrax, most antibody derived from vaccinated individuals is directed against PA. Since PA is one required subunit of the two toxins produced by the anthrax bacteria, this anthrax hyperimmune globulin is primarily an antitoxin antibody. Anthrax toxin(s) are thought to play a critical role in the way that the anthrax bacteria cause fulminant illness and death.
On February 9th of this year, the Washington Hospital Center’s monthly Regional Bioterrorism Preparedness Forum heard a 2-hour presentation on anthrax vaccine and anthrax-specific hyperimmune globulin by colleagues in the Army and Navy.
In September of 2002, the Centers for Disease Control and Prevention (CDC) awarded a company called Cangene a contract to develop anthrax hyperimmune globulin as an adjunct to antibiotic therapy in very ill patients.
According to the November 15 2002 issue of Morbidity and Mortality Weekly Report (MMWR 51(45): 1024-1026), the Advisory Committee on Immunization Practices (ACIP) to the CDC has recommended that additional research be focused on new therapies for anthrax, “including use of antitoxin (e.g., hyperimmune globulin) for treating anthrax.”
Front-line clinicians, public health officials, and pharmacists — who will again be faced with an emergency in the event of a new anthrax attack — would welcome an opportunity to become familiar with the Investigational New Drug (IND) protocol under which anthrax hyperimmune globulin could potentially be made available for emergency use to treat critically ill and dying patients. Preparedness, not panic.