Recognizing and Responding to an attack with A Biological Weapon. (Editorial).

September 11, 2001, was a wake-up call for most Americans. The tragic events on this date propelled us into a new era of emergency preparedness. Gaps in our standard planning were identified, especially in our ability to handle biological and chemical weapons. Although previous attempts had been made to alert health care professionals about the risk of an attack with biological weapons,' the tragedy on September 11 focused our awareness on this possibility. The recent intentional anthrax exposure involving multiple people in Florida,. New York, Washington, DC, and New Jersey galvanized our collective efforts to prepare for a biological attack--especially an attack resulting in mass casualties. (2)

Unlike a chemical attack or an attack with an explosive device, the initiation of a mass casualty biological event will probably go unnoticed. (3) Recognition of such an event will likely occur within the emergency departments (EDs) and ambulatory care clinics of multiple hospitals and possibly over wide geographic areas. Recognition of a biological attack will hinge on illness surveillance at individual facilities, shared surveillance with public health departments, and clinical acumen of the ED and primary care staff.

The purpose of a functional surveillance network (internal and external) is the rapid detection of changes in the illness burden of a facility or community. The surveillance network must be able to identify unusual changes in volume of patients, types of illness, and unexpected changes in mortality. Changes in the illness burden should signal the need for a careful examination of individual cases to identify the nature of the change. If the nature of the change causes suspicion, it should prompt communication with local and national health authorities. Clinicians will play a vital role in the initial recognition of a biological attack and in ensuring a successful response.

The media have clearly identified the vulnerability of our health care system in recognizing and responding to an attack. Physician education and rapid access to readily usable reference tools are crucial initial steps toward this type of emergency preparation. As a result of these concerns and our location in a major urban area, we designed two Tables to be posted in EDs and primary care settings for quick reference. They are based on published work from the Centers for Disease Control and Prevention and the Working Group on Civilian Biodefense.

These groups have identified and characterized the most likely biological weapons. (4-9) Six agents or classes of agents head the list of likely weapons: smallpox, anthrax, pneumonic plague, botulinum toxin, tularemia, and viral hemorrhagic fevers. These agents have been or can be used as weapons, dispersed as an aerosol, have a high case fatality rate, and are associated with significant morbidity. Several (ie, smallpox, pneumonic plague, and viral hemorrhagic fevers) may also present secondary dangers to health care providers and others by person-to-person transmission.

The initial presentation of disease in patients affected by any of these six agents or classes of agent is nonspecific and will mimic flu-like illness or a number of viral syndromes. Medical surveillance at the facility level is important to identify a relatively sudden change in the illness burden presenting in the ED or in admissions to the hospital.

Surveillance and knowledge of the clinical, laboratory, diagnostic, and epidemiologic features of these potential weapons will play a significant role in early detection. The ability of the microbiology laboratory to quickly and accurately identify pathogens will be critical to early diagnosis and treatment of victims. This need will be ongoing to separate potential victims of bioterrorism from patients having influenza and community-acquired pneumonia.

The response will require a coordinated effort, including communication with local and national health officials, handling of patients in a manner that protects staff and environment, early initiation of appropriate therapy, and the use of prophylaxis (vaccine or antibiotic) when appropriate.

If we are fortunate, these Tables will find their place on ED bulletin boards and office walls where they will only gather dust awaiting an event that never occurs. In less fortunate circumstances, we hope that these Tables may provide a quick reference for staff who have to cope with crowded 'and panicked emergency rooms and physicians' offices.

Brian P. Schmitt, MD, MPH 

Mondira Bhattacharya, MD

Dale N. Gerding, MD

VA Chicago Health Care System-Lakeside Division

333 E Huron

Chicago, IL 60611

Department of Medicine

Northwestern University Medical School

Chicago, IL

References

(1.) Osterholm M: Bioterrorism: a real modern threat. Emerging Infections 5. Scheld w, Craig w, Hughes J (eds). Washington, DC, ASM Press, 2001, pp 213-222

(2.) Rogers D, Terhune C: Daschle office is among new anthrax sites. Wall Street Journal, October 16, 2001, pp A3-A4

(3.) Vastag B: Experts urge bioterrorism readiness. JAMA 2001; 285:30-32

(4.) Henderson D, Ingelsby T, Bartlett J, et al: Smallpox as a biological weapon: medical and public health management. JAMA 1999; 281:2127-2137

(5.) Inglesby T, Dennis D, Henderson D, et al: Plague as a biological weapon: medical and public health management. JAMA 2000; 283:2281-2290

(6.) Dennis D, Inglesby T, Henderson D, et al: Tularemia as a biological weapon: medical and public health management. JAMA 2001; 285:2763-2773

(7.) Arnon S, Schechter R, Inglesby T, et al: Botulinum toxin as a biological weapon: medical and public health management. JAMA 2001; 285:1059-1070

(8.) Inglesby T, Henderson D, Bartlett J, et al: Anthrax as a biological weapon: medical and public health management. JAMA 1999; 281:1735-1745

(9.) Centers for Disease Control and Prevention: Leads from the morbidity and mortality weekly report, Atlanta, Ga: Update: Management of patients with suspected viral hemorrhagic fever--United States. JAMA 1995; 274:374-375

TABLE 1. Clues to the Specific Etiologic Agent Used in a Biological
Attack

Diagnostic
Features        Smallpox               Anthrax

Epidemiologic   Multiple cases of      Sudden appearance
 clues and      what may initially     of multiple case of
 warning signs  resemble "adult        severe flu-like
                chickenpox";           illness with
                fever; malaise;        fulminant course
                painful, centrifugal,  and high mortality
                pustular rash


Diagnostic      Guarnieri bodies       CXR: Widened
 studies        seen under oil         mediastinum pleural
                                       effusion; Peripheral
                                       blood smear: gram-
                                       positive bacilli on
                                       unspun or buffy
                                       coat smear, CSF:
                                       gram-positive bacilli

Microbiology    Electron microscopy    Blood culture with
                                       large gram-positive
                                       organism of
                                       Bacillus species


Pathology       Lesions mainly in      Hemorrhagic
                skin and mucous        mediastinitis;
                membranes;             hemorrhagic
                secondary bacterial    thoracic
                infection; death       lymphadenitis;
                occurs from toxemia    hemorrhagic
                associated with        meningitis
                circulating immune
                complexes and
                variola antigens

Incubation      12-14 days             Limited info; from
 period                                the accidental
                                       outbreak in
                                       Sverdlovsk, 2-43 days
                                       before clinical
                                       illness developed

Clinical        Unlike chickenpox,     Radiographically,
 pearls         lesions in any one     does not present as a
                part of the body are   bronchopneumonia,
                in the same stage      unlike pneumonic
                of development         plague or tularemia;
                                       however, 3 of 8 patients
                                       in the US bioterrorism
                                       outbreak had
                                       pulmonary infiltrates

Diagnostic      Pneumonic
Features        Plague                  Botulism

Epidemiologic   Sudden appearance       Outbreak of large
 clues and      of multiple patients    number of cases with
 warning signs  with fever, cough,      acute, afebrile,
                SOB, hemoptysis,        descending paralysis
                and chest pain; GI      with prominent
                symptoms common;        bulbar palsies; death
                fulminant course        by respiratory failure
                and high mortality

Diagnostic      CXR: Pulmonary          Clinical: Afebrile
 studies        infiltrates or          descending paralysis
                consolidation;          with diplopia,
                Physical exam:          dysarthria, dysphagia,
                Infrequent cervical     and/or dysphonia; clear
                bubo and purpuric       sensorium; toxin in
                skin lesions            blood, GI tract, or stool


Microbiology    Gram-negative
                bacilli with
                bipolar staining
                on Wright, Giemsa,
                or Wayson's stain

Pathology       Lobular exudation;      Irreversible binding
                bacillary aggregation;  to cholinergic synapses
                necrotic areas          with enzymatic
                in pulmonary            blocking of
                parenchyma              acetylcholine
                                        release; recovery
                                        results from
                                        sprouting of new
                                        motor axon twigs
                                        (weeks to months)

Incubation      1-6 days, usually       Foodhorne:
 period         2-4 days                2 hrs to 8 days;
                                        Airborne:
                                        12-72 Isours (?)



Clinical        Hemoptysis suggests     Differs from other
 pearls         plague rather           flaccid paralyses in its
                than anthrax            prominent CN palsies
                                        disproportionate to
                                        milder weakness and
                                        hypotonia below the neck;
                                        also, no sensory losses



Diagnostic                               Viral Hemorrhagic
Features        Tularemia                Fever

Epidemiologic   Sudden appearance of     Early: abrupt onset fever
 clues and      multiple patients in     myalgia, and prostration
 warning signs  urban setting with       with mild decrease in BP,
                URT symptoms and         flushing, and petechiae;
                bronchitis rapidly       Later: shock, hemorrhage,
                progressing to           neurologic changes,
                pleuropneumonia          vomiting, and diarrhea
                with high mortality

Diagnostic      CXR: Bilateral           Neutrophilia; DIG in
 studies        pulmonary infiltrates    Ebola and Marburg;
                or pleural effusions     jaundice in yellow fever
                and pneumonia





Microbiology    Gram-negative            Virologic studies: ELISA
                coccobacilli in          or reverse transcriptase
                sputum, blood,           PCR; viral isolation in
                or tracheobronchial      biocontainment
                secretions; DFA          laboratory

Pathology       Pleural effusion;        Neutrophilia,
                lobar pneumonia          hypofibrinogenemia,
                or patchy infiltrates;   thrombocytopenia,
                in other routes of       and microangiopathic
                infection, patients      hemolytic anemia;
                may have skin, eye,      vascular permeability,
                pharyngeal, or           abnormalities in
                GI disease               circulatory regulation



Incubation      1-14 days (inhalational  2 days to 3 weeks
 period         exposure)





Clinical                                 Wide group of viral agents
 pearls                                  with a broad range of
                                         symptoms and risk of
                                         spread to contacts.
                                         Hepatitis prominant with
                                         yellow fever




SOB = Shortness of breath, GI = gastrointestinal, URT = upper
respiratory tract, BP = blood pressure, CXR = chest x-ray, CSF =
cerebrospinal fluid, DIC = disseminated intravascular coagulation, DFA =
direct fluorescent antibody, ELISA = enzyme-linked immunosorbent assay,
PCR = polymerase chain reaction, CN = cranial nerve.
TABLE 2. Response to Specific Biological Weapons

Type of
Response      Smallpox               Anthrax

Reporting     Notify Infectious      Notify Infectious
 possible     Disease Service;       Disease Service;
 attack       Notify AOD;            Notify AOD;
              Notify local public    Notify local public
              health department;     health department;
              CDC Emergency          CDC Emergency
              Preparedness           Preparedness
              and Response:          and Response:
              (770-488-7100);        (770-488-7100);
              Notify FBI             Notify FBI
              and police             and police

Protection    Decontamination:       Decontamination;
 of staff,    clothing and           clothing and skin
 patients,    bedding is             washed with soap
 and          autoclaved or          and water; Infection
 environment  laundered in hot       control: standard
              water with             precautions and no
              bleach; disinfectants  isolation required
              for standard
              infection control;
              Infection control:
              airborne precautions,
              gloves, gowns,
              and musks;
              VIG for
              immunosuppression

Treatment     Supportive therapy     Fluoroquinolones,
 of victims   and antibiotics for    tetracyclines, or
              secondary bacterial    penicillins for
              infections             60 days





Prophylaxis   Vaccinate staff,       Fluoroquinolones;
              patients, and          vaccine if available
              general population



Type of       Pneumonic
Response      Plague                 Botulism

Reporting     Notify Infectious      Notify Infectious
 possible     Disease Service;       Disease Service;
 attack       Notify AOD;            Notify AOD;
              Notify local public    Notify local public
              healtls department;    health department;
              CDC Emergency          CDC Emergency
              Preparedness           Preparedness
              and Response:          and Response:
              (770-488-7100);        (770-488-7100);
              Notify FBI             Notify FBI
              and police             and police

Protection    No decontamination;    Decontamination;
 of staff,    Infection control:     clothing and skin
 patients,    In hospital, droplet   washed with
 and          precautions x first    soap and water;
 environment  48 hours of            contaminated
              antibiotic treatment;  surfaces cleaned
              close contacts of      with 0.1%
              victims not taking     hypochlorite bleach;
              antibiotics do not     Infection control:
              require isolation--    standard precautions;
              if symptoms occur      isolation not required
              in 7 days, treat




Treatment     Gentamicin or          Supportive care: for
 of victims   streptomycin,          weeks to months;
              fluoroquinolones,      passive immunization
              tetracyclines,         with equine antitoxin
              chloramphenicol




Prophylaxis   Vaccine: No





Type of                              Viral Hemorrhagic
Response      Tularemia                    Fever

Reporting     Notify Infectious      Notify Infectious
 possible     Disease Service;       Disease Service;
 attack       Notify AOD;            Notify AOD;
              Notify local public    Notify local public
              health department;     health department;
              CDC Emergency          CDC Emergency
              Preparedness           Preparedness
              and Response:          and Response:
              (770-488-7100);        (770-488-7100);
              Notify FBI             Notify FBI
              and police             and police

Protection    No decontamination;    Decontamination;
 of staff,    Infection control:     soiled linens autoclaved
 patients,    Isolation is not       or incinerated;
 and          recommended            environmental surfaces
 environment  (no human to human     cleaned and disinfected
              transmission);         with standard procedures;
              standard precautions   Infection control:
                                     contact precautions,
                                     airborne precautions may be
                                     necessary if coughing or
                                     vomiting or bleeding
                                     profusely




Treatment     Contained casualty     Supportive care;
 of victims   situation: parenteral  Ribavirin in
              streptomycin,          some VHF patients
              gentamicin,            (Lassa and South American
              doxycycline,           VHF)
              ciprofloxacin;
              Mass: doxycycline
              or ciprofloxacin

Prophylaxis   Doxycycline or         Vaccine for yellow fever
              ciprofloxacin;
              vaccine not
              recommended


AOD = Administrator on duty, VIG = vaccinia immune globlin, VHF = viral
hemorrhagic fever.