The following article, written for the at-press FCMS newsletter for its 
members, is provided as a public service. It will be updated as new CDC and 
other information becomes available. (October 24, 2001)

BIOTERRORISM AND THE COMMUNITY PHYSICIAN
By Mary Schmidt, MD; Jane Pollner, MD; and Dan Hanfling, MD

As physicians, we are on the frontline of addressing bioterrorism with our
patents when they ask for help and guidance.  It is our responsibility to
the community to recognize the symptoms of an infection from a biological
attack, such as anthrax, so local and national resources can be activated.
In addition, we need to inform our patients of any preventative actions that
should be taken.  All physicians in our area need to be aware of how the
Virginia State and federal emergency systems will respond to a bioterrorism
crisis.  Although this article addresses bioterrorism, we cannot forget the
possibility of chemical terrorism (more than 50 agents have been listed as
possible chemical weapons) and nuclear warfare.

The recognized microbiologic agents that could be involved in a terrorism
attempt include several bacteria and viruses.  These agents are particularly
appealing as they can be dispersed as aerosols as a small, 1 - 10 micron
particulate, allowing for prolonged suspension into the air, which would
disperse deep into the terminal bronchial tree and alveoli.  Almost any
sprayer or bomb could be used as the dispensing device.  The most likely and
devastating infections would be those caused by Bacillus anthracis
(anthrax), Variola major (smallpox), Francisella tularensis (tularemia),
Yersinia pestis (plague), Clostridium botulism toxin (botulism), and viral
hemorrhagic fever.  Other biologic agents which can be used as biological
weapons include infections that are uncommon in the United States such as
Brucellosis, Coxiella burnetti (Q fever), Burkholderia mallei (glanders),
and a variety of viruses which can have devastating effects such as
respiratory failure (hantavirus), encephalitis (Nipah) and yellow fever.
Toxins produced from bacteria such as Staphylococcus aureus and Clostridium
perfringens and ricin toxin from castor beans can also be used as a biological
weapon. Deliberate contamination of the soil or water by some of these
agents is a possibility although it may be less effective than
aerosolization, and chlorine in the water supply is effective in killing most
of the bacterial organisms.  A review of some of the agents is described
below.

ANTHRAX:  Anthrax is a gram-positive spore-forming bacteria usually
transmitted directly from infected animals and animal products to humans.
The inoculated skin and draining lymph nodes become inflamed and necrotic.
The pathologic affect of the organism is from the production of edema toxin
and lethal toxin released from the organism.  Bacillus anthracis spores
germinate when inhaled and cause notable mediastinal widening.  Meningitis
occurs in 50% of affected individuals.  The incubation period of spore-
inhaled disease can be as early as 2 days or as late as 8 weeks.  The
initial symptoms are cough, fatigue and fever with rapid progression to
death in 1-3 days.  Without antibiotics, the mortality rate is 90%.  The
spores can also be ingested causing nausea, vomiting, and bloody diarrhea.
Ingestion can also cause an oral/pharyngeal form with focal necrosis and
edema of the throat, which may lead to death.  Anthrax is not spread from
person to person.  Blood cultures and/or ELISA testing of blood CXR, will
be helpful in making the diagnosis. Nasal swabs are used for epidemiologic
surveillance and are not helpful as a diagnostic tool. The antibiotics of
choice are ciprofloxacin or doxycycline until sensitivity testing has been
performed, as many propagated forms used for bioterrorism are resistant to
penicillin.  A 10-day course of antibiotics is acceptable for cutaneous
disease, which responds well to therapy and a 28-day course for systemic
disease.  Prophylaxis of exposed individuals consists of a 60-day course of
ciprofloxacin or 2 weeks of antibiotics after the third dose of the vaccine.
An attenuated anthrax vaccine has been developed which has conferred
immunity to anthrax in rhesus monkeys. The CDC states that its plan for 
preventing anthrax after exposure would be with antibiotics and that it has 
enough available to prophylactically treat at least two million people.

BOTULISM:  Botulism is a paralytic illness caused by the neuro-toxin of
Clostridium botulinum. This can be acquired from eating contaminated food or
contact with contaminated soil.  The toxin can be aerosolized and used as a
biological weapon.  Most cases of botulism we see are from eating
contaminated home-canned foods or when infants swallow spores which turn
into toxin-producing bacteria in the intestines.  Botulism toxin is 100,000
times more potent than the sarin nerve gas.  It binds to the presynaptic
nerve terminal at the neuromuscular junction causing bulbar palsies and
descending skeletal muscle weakness, which can progress to respiratory
failure.  Symptoms begin 18 - 36 hours after oral ingestion or inhalation.
The diagnosis is made by EMG analysis and is often a diagnosis of exclusion
of other acute neuromuscular disorders such as Guillian-Barre syndrome.
State labs and the CDC can identify the toxin from body fluid samples and
nasal mucosa if inhaled.  If ingested, the organism can be isolated on stool
culture media.  The treatment of botulism is antitoxin and supportive
therapy.  The mortality rate is 5% if recognized and treated.

PLAGUE:  “The Plague” is caused by Yersinia pestis, a gram-negative
coccobacillus.  Typically it is transmitted from infected rodents to fleas
to humans or by handling infected animals.  It can be aerosolized as a
biological weapon.  The organism can cause cutaneous disease, lymphadenitis
called buboes, meningitis, sepsis, and pneumonitis. Pneumonic plague has an
incubation period of 2-3 days, presenting with cough, often bloody, and
flu-like symptoms that quickly progress to sepsis.  Chest X-ray is typically a
bronchoalveolar pattern.  The organism has a striking safety pin-like
appearance on gram stain and grows slowly at routine incubation temperatures.
An immunoassay is available to detect F1 capsular antigen.  A four-fold rise 
in
antibody levels is also diagnostic.  Chloramphenicol and doxycycline are the
antibiotics of choice for sepsis and should be given for 10 to 14 days.
Individuals with contacts to those infected will need to be prophylaxed with
doxycycline or i.m. gentamicin or streptomycin.  The mortality rate of an
attack would initially be about 30-50% with the rest requiring 
hospitalization.  Yersinia pestis is contagious and would require strict 
isolation.

SMALLPOX:  Variola major is a highly contagious virus and thought to be the
potentially most devastating bioterroist threat.  The initial aerosolized
virus could rapidly be spread from one individual to another.  The organism
can stay active in linens and on countertops. The last vaccinations in the
United States were done in 1972.  It is thought the immunogenicity of the
vaccines is 20 to 30 years; therefore, no one in the United States is
immune.  The organism is virulent, and a small innoculum could be
devastating.  The incubation period is 7-17 days.  The illness presents with
high fever and headache.  These symptoms are followed by a large
vescicular-pustular rash, which in 30% of cases is followed by organ failure 
and
death.  The infected individual as well as all contacts need to be isolated.
ELISA testing of blood, PCR, or viral culture of the throat or vesicles can
make a diagnosis.  There is laboratory evidence that the antiviral Cidofovir
may be therapeutic.  The CDC has stockpiled several million doses of
vaccine; however, these are not available to health care providers or the
public.  The HHS has announced plans to accelerate production of a new
smallpox vaccine, but this will not be ready for 1 to 2 years.

TULAREMIA:  Franciella tularensis is an intracellular gram-negative
coccobacillus, which is usually transmitted through skin or mucous membranes
from infected animals or through the bite of infected mosquitoes, deerflies, 
or ticks.  It could also be spread in an aerosol or by contaminated food and 
water.  There are two presentations of tularemia, ulceroglandular and sepsis 
also known as the typhoidal form.  The ulceroglandular is a necrotic 
lymphadentisis occurring near the site of a cutaneous inoculation.  An 
aerosolized innoculum would cause sepsis, which presents with fever, cough, 
and subternal chest pain.  Diagnosis can be made
by culturing blood, skin, or affected ulcers and sputum or by acute and
convalescent serology. Streptomycein or gentamicin is the treatment of choice
for a total of 10 to 14 days.  Cloramphenicol and doxycycline can be used
but are bacteriostatic and should not be used with severe disease.  A
live-attenuated vaccine has been available in the investigational setting.
There is no person-to-person spread of tularemia.

VIRAL HEMMORHAGIC FEVER:  Hemmorhagic fever viruses are all RNA viruses
although from a variety of families and named after their location of origin
in Africa and South America.  The recently described Hantavirus in North
America is also a virus in this class, as are Ebola and Marburg.  The
incubation period is 4-21 days.  Microvascular damage with increased
permeability causes hypotension, shock and microhemorrhages.  Initial
symptoms are fever, myalgias, and lethargy.  Lassa fever is associated with
neurological complications, Ebola with DIC, and yellow fever with jaundice.
Patients need to be in contact isolation.  Diagnosis is by ELISA or PCR.
Virus isolation can be performed in a biocontainment laboratory.  Ribaviron
and/or immune serum may be helpful as adjunctive therapy to supportive care.
The balance of intravascular fluid management with ongoing increased
vascular permeability can be difficult to manage.

Any bioterrorism event will cause a manpower crisis in both providing heath
care to the affected and distributing preventive agents to the exposed.  We
will soon have in place information resources on index diseases, rapid
diagnostic options, and treatment protocols for infected individuals, their
families, and other potential victims as well as reporting and tracking
mechanisms.

The Centers for Disease Control and Prevention remains in charge of
protecting the nation’s public health.  They have been working over the past
several years to prepare for a bioterrorism or chemical emergency and have
tried to build a more robust public health infrastructure at the state and
local levels.  A grant from the CDC established the Bioterrorism
Preparedness and Resource Program in Virginia.  The program is based in
Richmond and is funded for four major areas:  Epidemiology and Disease
Surveillance; Laboratory Capacity for Biological Agents; Laboratory Capacity
for Chemical Agents; and Health Alert Network.  Epidemiologists are being
hired to help with increased surveillance, identifying training needs of
state and local health departments, expansion of laboratory facilities,
implementing and validating laboratory procedures for identification and
confirmation of biological and chemical agents associated with terrorism,
and increasing communication with district health department staff.  There
is also in development an expansion of the program to provide relevant
information to physicians, hospitals, and the general public.

Since September 11, the public is asking about the availability and
usefulness of specific antibiotics and vaccines in the event of an act of
bioterrorism.  The CDC, through the National Pharmaceutical Stockpile
program, keeps caches of emergency equipment at eight undisclosed locations
around the country.  In 1999, it was recommended that these stockpiles
contain treatment for organophosphates, vesicants, smallpox, anthrax,
pneumonic plague, tularemia, and botulism.  These “push packages” are to be
ready for transport to any location into he United States within 12 hours of
a terrorist attack using biological or chemical agents.  The push packages
were designed to treat 10,000 people, with the goal of increasing capacity
to treat 10 million people for an anthrax incident, and 40 million people
for a smallpox incident.

There already have been reports of healthy people requesting prescriptions
for antibiotics and of the supply of some drugs becoming short.  The
Infectious Disease Society of America (IDSA) is advising against hospitals
or individuals stockpiling antibiotics, for the following reasons.
Stockpiling can rapidly deplete the supply of drugs needed to treat patients
who need treatment for current medical problems and could create  a
potential for the misuse of these medications. The IDSA also believes this
practice is unethical since it destabilizes a system already in place to
deal with an emergency.  Cost is also of concern.  According to a local
pharmacy, the cost of a 6-week course of ciprofloxacin, the recommended
course to present anthrax, is $1,600.  A six-week course of doxycycline is
$180.

It has become apparent that we must redouble efforts to improve our
readiness and capability for handling a large-scale disaster in Fairfax
County.  The healthcare community must be able to mitigate fully threats
such as the use of chemical weapons or biological agents.  Federal efforts
have heretofore been slow to focus on the hospitals and the medical community,
and, as a result, many healthcare institutions are sorely lacking in their
ability to respond to any crisis that might arise.  For example, it will be
necessary quickly to provide comprehensive decontamination for chemically
exposed patients.  Such an endeavor requires facilities capable of
performing such a function and an inventory of personal protective equipment
(PPE).  Inova Fairfax Hospital began developing plans for a mass
decontamination facility in 1998.  This commitment has been implemented into
the Disaster Plans and is part of the design plan for the emergency room
expansion process.  They have acquired the appropriate PPE for their staff
and started a training program for their physicians and nurses. Inova has
created an Emergency Management and Disaster Preparedness Task Force to
guide planning and preparation across the entire health system so that they
can be ready for the possibility of bioterrorism or any newly emergency
virulent pathogens threatening our populace.

Preparations for conventional multiple casualty incidents have been
relatively straightforward.  The Emergency Medical Services division of the
Fairfax County Fire and Rescue Department is currently proposing the
development of an updated disaster preparedness program that includes the
placement of pre-deployed disaster medical pallets. These would contain
patient treatment items that would be needed in any large-scale disaster
situations and would place special triage and treatment bags on all
emergency medical vehicles.  The plan also calls for the purchase of a large
transport vehicle that could serve as a treatment facility at the disaster
scene or to supplement patient care at a community healthcare facility.

A comprehensive communications plan is a high priority for emergency
situations, and Inova Fairfax Hospital is prepared to assume the role of the
regional Command Hospital in the event of a disaster incident.
Implementation of the Command Hospital is meant to create a reliable
comprehensive communications link from the field level providers at the
scene to other regional healthcare facilities that would be receiving
patients from the disaster scene.  We also need to be able to monitor the
public health sector.  This should include a health surveillance system that
can help identify worrisome trends that may alert us to the possibility of
an incident or exposure and help to disseminate information to healthcare
providers on the diagnostic, therapeutic, and epidemiological consideration.

Patients arriving at your office with flu-like symptoms should be evaluated 
and treated as a viral illness.  Use of a nasal swab for rapid influenza 
evaluation during influenza season will help with a quick diagnosis.  The 
emergency room and physicians are equipped to deal with a potential bio or 
chemical hazard. Should you have a
septic patient in your office or at home, send them to the Emergency Room
for evaluation, as you would normally do.  If you have reason to suspect
your patient has an illness consistent with a biohazard exposure from a
known event, send the patient directly to the Emergency Room. Should an
individual call concerned about anthrax without exposure to a known event,
direct them to contact their local health department, or if closed, the
Virginia State Department of Health.  All of the infectious disease
consultants in Northern Virginia are aware of how to diagnose and handle a
bioterrorist threat and are available to assist you.  Once a diagnosis of an
intentional biological infection has occurred, the Health Department and FBI
will organize a response to the situation. Should you be concerned about a
chemical exposure, call the Fairfax County Fire Department or the police at
911.  The following are important phone numbers and web sites:

Fairfax County Health Department – 703-280-0584
VA State Health Department after-hours line – 1-800-468-8892
Fairfax County Fire Department/Hazmat unit – CDC – 1-770-488-1700

www.bt.CDC.gov
wwww.idsociety.org
www.hopkns-biofense.org