Clinical recognition and management of patients exposed to biological warfare agents.

Concern regarding the use of biological agents (bacteria, viruses, or toxins) as tools of warfare or terrorism has led to measures to deter their use or, failing that, to deal with the consequences. Unlike chemical agents, which typically lead to severe disease syndromes within minutes at the site of exposure, diseases resulting from biological agents have incubation periods of days. Rather than a paramedic, it will likely be a physician who is first faced with evidence of the results of a biological attack. Provided here is an updated primer on 11 classic BW and potential terrorist agents to increase the likelihood of their being considered in a differential diagnosis. Although the resultant diseases are rarely seen in many countries today, accepted diagnostic and epidemiologic principles apply; if the cause is identified quickly, appropriate therapy can be initiated and the impact of a terrorist attack greatly reduced.

Biological weapons--a primer for microbiologists.

Biological weapons are not new. Biological agents have been used as instruments of warfare and terror for thousands of years to produce fear and harm in humans, animals, and plants. Because they are invisible, silent, odorless, and tasteless, biological agents may be used as an ultimate weapon-easy to disperse and inexpensive to produce. Individuals in a laboratory or research environment can be protected against potentially hazardous biological agents by using engineering controls, good laboratory and microbiological techniques, personal protective equipment, decontamination procedures, and common sense. In the field or during a response to an incident, only personal protective measures, equipment, and decontamination procedures may be available. In either scenario, an immediate evaluation of the situation is foremost, applying risk management procedures to control the risks affecting health, safety, and the environment. The microbiologist and biological safety professional can provide a practical assessment of the biological weapons incident to responsible officials in order to help address microbiological and safety issues, minimize fear and concerns of those responding to the incident, and help manage individuals potentially exposed to a threat agent.

Tularemia as a biological weapon: medical and public health management.

OBJECTIVE: The Working Group on Civilian Biodefense has developed consensus-based recommendations for measures to be taken by medical and public health professionals if tularemia is used as a biological weapon against a civilian population. PARTICIPANTS: The working group included 25 representatives from academic medical centers, civilian and military governmental agencies, and other public health and emergency management institutions and agencies. EVIDENCE: MEDLINE databases were searched from January 1966 to October 2000, using the Medical Subject Headings Francisella tularensis, Pasteurella tularensis, biological weapon, biological terrorism, bioterrorism, biological warfare, and biowarfare. Review of these references led to identification of relevant materials published prior to 1966. In addition, participants identified other references and sources. CONSENSUS PROCESS: Three formal drafts of the statement that synthesized information obtained in the formal evidence-gathering process were reviewed by members of the working group. Consensus was achieved on the final draft. CONCLUSIONS: A weapon using airborne tularemia would likely result 3 to 5 days later in an outbreak of acute, undifferentiated febrile illness with incipient pneumonia, pleuritis, and hilar lymphadenopathy. Specific epidemiological, clinical, and microbiological findings should lead to early suspicion of intentional tularemia in an alert health system; laboratory confirmation of agent could be delayed. Without treatment, the clinical course could progress to respiratory failure, shock, and death. Prompt treatment with streptomycin, gentamicin, doxycycline, or ciprofloxacin is recommended. Prophylactic use of doxycycline or ciprofloxacin may be useful in the early postexposure period.

Bioterrorism.

Although biological agents have been used in warfare for centuries, several events in the past decade have raised concerns that they could be used for terrorism. Revelations about the sophisticated biological-weapons programs of the former Soviet Union and Iraq have heightened concern that countries with offensive-research programs, including those that sponsor international terrorism, might assist in the proliferation of agents, culturing capability, and dissemination techniques, and might benefit in these undertakings from the availability of skilled laboratory technicians. Release of sarin nerve agent in the Tokyo subway system in 1995 by the Aum Shinrikyo cult demonstrated that in the future terrorists might select unconventional weapons. Certain properties of biological pathogens may make them the ideal terrorist weapon, including 1) ease of procurement, 2) simplicity of production in large quantities at minimal expense, 3) ease of dissemination with low technology, and 4) potential to overwhelm the medical system with large numbers of casualties. Dissemination of a biological agent would be silent, and the incubation period allows a perpetrator to escape to great distances from the area of release before the first ill persons seek medical care. Countermeasures include intelligence gathering, physical protection, and detection systems. Medical countermeasures include laboratory diagnostics, vaccines, and medications for prophylaxis and treatment. Public health, medical, and environmental health personnel need to have a heightened awareness, through education, about the threat from biological agents.

Botulinum toxin as a biological weapon: medical and public health management.

OBJECTIVE: The Working Group on Civilian Biodefense has developed consensus-based recommendations for measures to be taken by medical and public health professionals if botulinum toxin is used as a biological weapon against a civilian population. PARTICIPANTS: The working group included 23 representatives from academic, government, and private institutions with expertise in public health, emergency management, and clinical medicine. EVIDENCE: The primary authors (S.S.A. and R.S.) searched OLDMEDLINE and MEDLINE (1960-March 1999) and their professional collections for literature concerning use of botulinum toxin as a bioweapon. The literature was reviewed, and opinions were sought from the working group and other experts on diagnosis and management of botulism. Additional MEDLINE searches were conducted through April 2000 during the review and revisions of the consensus statement. CONSENSUS PROCESS: The first draft of the working group's consensus statement was a synthesis of information obtained in the formal evidence-gathering process. The working group convened to review the first draft in May 1999. Working group members reviewed subsequent drafts and suggested additional revisions. The final statement incorporates all relevant evidence obtained in the literature search in conjunction with final consensus recommendations supported by all working group members. CONCLUSIONS: An aerosolized or foodborne botulinum toxin weapon would cause acute symmetric, descending flaccid paralysis with prominent bulbar palsies such as diplopia, dysarthria, dysphonia, and dysphagia that would typically present 12 to 72 hours after exposure. Effective response to a deliberate release of botulinum toxin will depend on timely clinical diagnosis, case reporting, and epidemiological investigation. Persons potentially exposed to botulinum toxin should be closely observed, and those with signs of botulism require prompt treatment with antitoxin and supportive care that may include assisted ventilation for weeks or months. Treatment with antitoxin should not be delayed for microbiological testing.

Bioterrorism: agents of concern.

The intentional dispersal of biological agents by terrorists is a potential problem that increasingly concerns the intelligence, law enforcement, medical, and public health communities. Terrorists might choose biological agents over conventional and chemical weapons for multiple reasons, although it is difficult to predict, with certainty, which biological agents might prove attractive to terrorists. One can more confidently, however, derive a list of those few agents which, if used, would be of greatest public health consequence. It is these agents which will require the most robust countermeasures. We discuss the derivation of this short list of agents and the specific diseases involved.

A field-expedient algorithmic approach to the clinical management of chemical and biological casualties.

Warriors on the modern battlefield face considerable danger from possible attack with chemical and biological weapons. Aggravating this danger is the fact that medical resources at the lowest echelons of care, already likely to be strained to capacity during modern conventional combat, are at present inadequate to handle large numbers of chemical or biological casualties. Complicating this problem further is the austere nature of diagnostic modalities available at lower echelons. With this in mind, and given the urgency required to adequately manage chemical and biological casualties, it is likely that such casualties will initially require significant empiric care in the absence of a definitive diagnosis. Such care under field conditions, often rendered by relatively inexperienced medical personnel, might best be provided using an algorithmic approach. We have developed such an algorithm.

Immunization against potential biological warfare agents.

The intentional release of biological agents by belligerents or terrorists is a possibility that has recently attracted increased attention. Law enforcement agencies, military planners, public health officials, and clinicians are gaining an increasing awareness of this potential threat. From a military perspective, an important component of the protective pre-exposure armamentarium against this threat is immunization. In addition, certain vaccines are an accepted component of postexposure prophylaxis against potential bioterrorist threat agents. These vaccines might, therefore, be used to respond to a terrorist attack against civilians. We review the development of vaccines against 10 of the most credible biological threats.

Plague as a biological weapon: medical and public health management. Working Group on Civilian Biodefense.

OBJECTIVE: The Working Group on Civilian Biodefense has developed consensus-based recommendations for measures to be taken by medical and public health professionals following the use of plague as a biological weapon against a civilian population. PARTICIPANTS: The working group included 25 representatives from major academic medical centers and research, government, military, public health, and emergency management institutions and agencies. EVIDENCE: MEDLINE databases were searched from January 1966 to June 1998 for the Medical Subject Headings plague, Yersinia pestis, biological weapon, biological terrorism, biological warfare, and biowarfare. Review of the bibliographies of the references identified by this search led to subsequent identification of relevant references published prior to 1966. In addition, participants identified other unpublished references and sources. Additional MEDLINE searches were conducted through January 2000. CONSENSUS PROCESS: The first draft of the consensus statement was a synthesis of information obtained in the formal evidence-gathering process. The working group was convened to review drafts of the document in October 1998 and May 1999. The final statement incorporates all relevant evidence obtained by the literature search in conjunction with final consensus recommendations supported by all working group members. CONCLUSIONS: An aerosolized plague weapon could cause fever, cough, chest pain, and hemoptysis with signs consistent with severe pneumonia 1 to 6 days after exposure. Rapid evolution of disease would occur in the 2 to 4 days after symptom onset and would lead to septic shock with high mortality without early treatment. Early treatment and prophylaxis with streptomycin or gentamicin or the tetracycline or fluoroquinolone classes of antimicrobials would be advised.

Weapons of mass destruction events with contaminated casualties: effective planning for health care facilities.

Biological and chemical terrorism is a growing concern for the emergency preparedness community. While health care facilities (HCFs) are an essential component of the emergency response system, at present they are poorly prepared for such incidents. The greatest challenge for HCFs may be the sudden presentation of large numbers of contaminated individuals. Guidelines for managing contaminated patients have been based on traditional hazardous material response or military experience, neither of which is directly applicable to the civilian HCF. We discuss HCF planning for terrorist events that expose large numbers of people to contamination. Key elements of an effective HCF response plan include prompt recognition of the incident, staff and facility protection, patient decontamination and triage, medical therapy, and coordination with external emergency response and public health agencies. Controversial aspects include the optimal choice of personal protective equipment, establishment of patient decontamination procedures, the role of chemical and biological agent detectors, and potential environmental impacts on water treatment systems. These and other areas require further investigation to improve response strategies.

Smallpox as a biological weapon: medical and public health management. Working Group on Civilian Biodefense.

OBJECTIVE: To develop consensus-based recommendations for measures to be taken by medical and public health professionals following the use of smallpox as a biological weapon against a civilian population. PARTICIPANTS: The working group included 21 representatives from staff of major medical centers and research, government, military, public health, and emergency management institutions and agencies. Evidence The first author (D.A.H.) conducted a literature search in conjunction with the preparation of another publication on smallpox as well as this article. The literature identified was reviewed and opinions were sought from experts in the diagnosis and management of smallpox, including members of the working group. CONSENSUS PROCESS: The first draft of the consensus statement was a synthesis of information obtained in the evidence-gathering process. Members of the working group provided formal written comments that were incorporated into the second draft of the statement. The working group reviewed the second draft on October 30, 1998. No significant disagreements existed and comments were incorporated into a third draft. The fourth and final statement incorporates all relevant evidence obtained by the literature search in conjunction with final consensus recommendations supported by all working group members. CONCLUSIONS: Specific recommendations are made regarding smallpox vaccination, therapy, postexposure isolation and infection control, hospital epidemiology and infection control, home care, decontamination of the environment, and additional research needs. In the event of an actual release of smallpox and subsequent epidemic, early detection, isolation of infected individuals, surveillance of contacts, and a focused selective vaccination program will be the essential items of an effective control program.

Anthrax as a biological weapon: medical and public health management. Working Group on Civilian Biodefense.

OBJECTIVE: To develop consensus-based recommendations for measures to be taken by medical and public health professionals following the use of anthrax as a biological weapon against a civilian population. PARTICIPANTS: The working group included 21 representatives from staff of major academic medical centers and research, government, military, public health, and emergency management institutions and agencies. EVIDENCE: MEDLINE databases were searched from January 1966 to April 1998, using the Medical Subject Headings anthrax, Bacillus anthracis, biological weapon, biological terrorism, biological warfare, and biowarfare. Review of references identified by this search led to identification of relevant references published prior to 1966. In addition, participants identified other unpublished references and sources. CONSENSUS PROCESS: The first draft of the consensus statement was a synthesis of information obtained in the formal evidence-gathering process. Members of the working group provided formal written comments which were incorporated into the second draft of the statement. The working group reviewed the second draft on June 12, 1998. No significant disagreements existed and comments were incorporated into a third draft. The fourth and final statement incorporates all relevant evidence obtained by the literature search in conjunction with final consensus recommendations supported by all working group members. CONCLUSIONS: Specific consensus recommendations are made regarding the diagnosis of anthrax, indications for vaccination, therapy for those exposed, postexposure prophylaxis, decontamination of the environment, and additional research needs.

Air evacuation under high-level biosafety containment: the aeromedical isolation team.

Military contingency operations in tropical environments and potential use of biological weapons by adversaries may place troops at risk for potentially lethal contagious infections (e.g., viral hemorrhagic fevers, plague, and zoonotic poxvirus infections). Diagnosis and treatment of such infections would be expedited by evacuating a limited number of patients to a facility with containment laboratories. To safely evacuate such patients by military aircraft and minimize the risk for transmission to air crews, caregivers, and civilians, the U.S. Army Medical Research Institute of Infectious Diseases maintains an aeromedical isolation team. This rapid response team, which has worldwide airlift capability designed to evacuate and manage patients under high-level containment, also offers a portable containment laboratory, limited environmental decontamination, and specialized consultative expertise. This article also examines technical aspects of the team's equipment, training, capabilities, and deployments.

Cutaneous manifestations of biological warfare and related threat agents.

The specter of biological warfare (BW) looms large in the minds of many Americans. The US government has required that emergency response teams in more than 100 American cities be trained by the year 2001 to recognize and contain a BW attack. The US military is requiring active duty soldiers to receive immunization against anthrax. Dermatologists need not feel helpless in the face of a potential BW attack. Many potential agents have cutaneous manifestations that the trained eye of a dermatologist can recognize. Through early recognition of a BW attack, dermatologists can aid public health authorities in diagnosing the cause so that preventive and containment measures can be instituted to mitigate morbidity and mortality. This article reviews bacterial, viral, and toxin threat agents and emphasizes those that would have cutaneous manifestations following an aerosol attack. We conclude with clues that can help one recognize a biological attack.

Medical preparedness for a terrorist incident involving chemical or biological agents during the 1996 Atlanta Olympic Games.

During the 1996 Centennial Olympic Games in Atlanta, Georgia, unprecedented preparations were undertaken to cope with the health consequences of a terrorist incident involving chemical or biological agents. Local, state, federal, and military resources joined to establish a specialized incident assessment team and science and technology center. Critical antimicrobials and antidotes were strategically stockpiled. First-responders received specialized training, and local acute care capabilities were supplemented. Surveillance systems were augmented and strengthened. However, this extensive undertaking revealed a number of critical issues that must be resolved if our nation is to successfully cope with an attack of this nature. Emergency preparedness in this complex arena must be based on carefully conceived priorities. Improved capabilities must be developed to rapidly recognize an incident and characterize the agents involved, as well as to provide emergency decontamination and medical care. Finally, capabilities must be developed to rapidly implement emergency public health interventions and adequately protect emergency responders.

Anthrax as a potential biological warfare agent.

Anthrax is a zoonotic illness recognized since antiquity. Today, human anthrax has been all but eradicated from the industrialized world, with the vast majority of practitioners in the United States unlikely to have seen a case. Unfortunately, the disease remains endemic in many areas of the world, and anthrax poses a threat as a mass casualty-producing weapon if used in a biological warfare capacity.