Health
care providers are always on the alert for unusual clinical
presentations or unusual clustering of illness. Due to the
events since September 11, 2001, health care providers are
being asked to be extra vigilant for indications of illness
related to biologic, chemical or other offensive weapons.
The following provides a brief overview of the signs and
symptoms of five agents which have the potential to be used
as biologic weapons. These five agents are: anthrax, small
pox, plague, botulinum toxin, and tularemia. Also, attached
is a list of key references should you want additional information
on bioterrorism, including the specific agents which can
be used as biological weapons and their management. Most
of the information is available on the Internet.
Health
care providers noticing any unusual clinical presentations
or clustering of illness should contact the health unit
as soon as possible (work hours - 663-5317 ext. 2330, after
hours - 675-7523.)
Anthrax:
Three
forms of this zoonotic disease exist - cutaneous, gastrointestinal
and inhalational. The inhalational form is of most concern
in bioterrorist attacks since the Bacillus anthracis
spores are most likely to be delivered by the aerosol
route. The time from exposure to the development of clinical
illness has been known to range from 2 to 43 days but may
take as long as 60 days. This is the time period required
for the spores to germinate and produce the toxin which
results in illness. Anthrax does not spread from person-to-person.
The
clinical presentation has been described as a 2-stage illness.
The first stage presents with a nonspecific illness with
fever, malaise and fatigue. A non-productive cough and vague
chest discomfort may he present as can dyspnea, headache,
vomiting. chills, weakness, abdominal pain, and chest pain.
This stage of the illness lasts from hours to a few days.
In some patients, a brief period of apparent recovery follows.
Other patients progress directly to the second. fulminant
stage of illness.
This
second stage presents with the sudden onset of respiratory
distress with dyspnea, diaphoresis, stridor. fever. cyanosis
and shock. A chest X-ray most often shows a widened mediastinum
due to massive lvmphadenopathy which causes the stridor.
This radiologic finding in a previously well patient with
evidence of overwhelming flulike illness is pathognomonic
of advanced inhalational anthrax. Up to half of patients
develop hemorrhagic meningitis with concomitant meningismus,
delirium. and obtundation. Death usually follows in 24-36
hours. Inhalation anthrax has resulted in fatality rates
of 86% or more in the past. Modern critical care medicine
may result in somewhat lower mortality rates.
Small
pox:
Variola
virus, the etiologic agent of small pox, was spread from
person-to-person through direct deposit of infective droplets
onto the nasal, oral, or pharyngeal mucosa membranes, or
the alveoli of the lungs from close, face-to-face contact
with an infectious person. Indirect spread (i.e., not requiring
face-to-face contact with an infectious person) through
fine-particle aerosols or articles containing the virus
was less common. The incubation period for smallpox is 12
to 14 days (range: 7 to 17 days).
Symptoms
began with a 2 to 3 day prodrome of high fever, malaise,
and prostration with severe headache and backache. This
pre-eruptive stage was followed by the appearance of a maculopapular
rash (i.e., eruptive stage) that progresses to papules 1
to 2 days after the rash appeared; vesicles appeared on
the fourth or fifth day; pustules appeared by the seventh
day; and scab lesions appeared on the fourteenth day. The
rash appeared first on the oral mucosa, face, and forearms,
then spread to the trunk and legs. Lesions might erupt on
the palms and soles as well. Smallpox skin lesions were
deeply embedded in the dermis and felt like firm round objects
embedded in the skin. As the skin lesions heal, the scabs
separate and pitted scarring gradually developed.
Smallpox
patients were most infectious during the first week of the
rash when the oral mucosal lesions ulcerate and released
substantial amounts of virus into the saliva. A patient
was no longer infectious after all scabs had separated (i.e.
3-4 weeks after the onset of the rash).
During
the smallpox era, overall mortality rates were approximately
30%. Other less common but more severe forms of smallpox
included a) flat-type smallpox with a mortality rate >96%
and characterized by severe toxemia and flat, velvety, confluent
lesions that did not progress to the pustular stage; and
b) hemorrhagic-type smallpox, characterized by severe prodromal
symptoms, toxemia, and a hemorrhagic rash that was almost
always fatal; with death occurring 5 to 6 days after rash
onset.
The
lesions of small pox can initially be confused with chickenpox
except that unlike chickenpox, they are usually at the same
stage of development on any given part of the body. Hemorrhagic
cases were initially misdiagnosed as meningococcemia or
severe acute leukemia. Malignant cases were often mistaken
for hemorrhagic chickenpox or prompted surgery because of
severe abdominal pain.
Plague:
Plague
normally appears in three forms in man: bubonic, septicemic,
and pneumonic. It most commonly results from infected flea
bites which lead to the swollen tender lymph node(s) of
bubonic plague. Secondary septicemia is common, as greater
than 80 percent of blood cultures are positive for the organism
in patients with bubonic plague. However, only about a quarter
of bubonic plague patients progress to clinical septicemia.
When
used as an agent for bioterrorism, aerosolized Yersinia
pestis will result in primary pneumonic plague,
a form of the infection which is transmissible from person-to-person
by the airborne droplet route. Surgical masks should be
worn when primary pneumonic plague is suspected. The incubation
period is 1 to 6 days.
The
onset of pneumonic plague is acute and often fulminant.
The first signs of illness include high fever. chills. headache,
malaise, and myalgias, followed within 24 hours by a cough
with bloody sputum. Although bloody sputum is characteristic,
it can sometimes be watery or, less commonly, purulent.
Gastrointestinal symptoms, including nausea, vomiting, diarrhea,
and abdominal pain, may be present. Rarely, a cervical bubo
might result from an inhalational exposure. The chest X-ray
findings are variable, but most commonly reveal bilateral
infiltrates, which may be patchy or consolidated. The pneumonia
progresses rapidly, resulting in dyspnea, stridor, and cyanosis.
The fatality rate when treatment is delayed more than 24
hours after symptom onset is extremely high.
Botulinum
toxin:
Botulinum
toxin is the single most poisonous toxin known. It acts
by blocking acetylcholine release into the neuromuscular
junction and hence results in anticholinergic signs
and symptoms. Two forms of botulism could be used for bioterrorist
purposes - foodborne or inhalational. In foodborne disease,
the Clostridium botulinum bacteria has produced the
toxin in inadequately heated food. Inhalational botulism
results from aerosolized botulinum toxin and is a man-made
form of the disease which is not naturally occurring. Botulism
is not communicable from person-to-person. The onset of
symptoms depends on the quantity of toxin absorbed. It ranges
from 2 hours to 8 days in foodborne botulism but is usually
12 to 72 hours. The incubation of inhalational botulism
is uncertain because so few cases have occurred but is likely
approximately 36 hours.
Botulism
is an acute, afebrile symmetric, descending flaccid paralysis
that always begins in the bulbar musculature. It is not
possible to have botulism without having multiple cranial
nerve palsies. Cranial nerve palsies are prominent early,
with eye symptoms such as blurred vision due to mydriasis,
diplopia, ptosis, and photophobia, in addition to other
cranial nerve signs such as dysarthria, dysphonia, and dysphagia.
Flaccid skeletal muscle paralysis follows, in a symmetrical,
descending, and progressive manner. Collapse of the upper
airway may occur due to weakness of the oropharyngeal-musculature.
As the descending motor weakness involves the diaphragm
and accessory muscles of respiration, respiratory failure
may occur abruptly. Progression from onset of symptoms to
respiratory failure has occurred in as little as 24 hours
in cases of severe foodborne botulism. The anticholinergic
signs and symptoms include dry mouth, ileus, constipation,
and urinary retention. Sensory symptoms usually do not occur.
Botulinum toxins do not cross the blood/brain barrier so
the patient is not confused or obtunded.
Tularemia:
Tularemia
is a zoonotic disease cause by the bacteria Francisella
tularensis. It is transmitted to humans by direct contact
with or ingestion of infected animal tissues, through the
bites of infected arthropods. by consumption of contaminated
food or water, or from inhalation of aerosolized bacteria.
It is not transmitted from person-to-person. The incubation
period is 3-5 days with a range of 1 to 14 days. There are
a variety of clinical manifestations related to the route
of introduction of the bacteria and the virulence of the
agent. An aerosol release would have the greatest adverse
impact as an offensive bioweapon. Inhalation of F. tularensis
would result in typhoidal and pneumonic tularemia. These
two forms often occur together.
Typhoidal
tularemia has been used to describe illness in tularemia
patients with systemic infections manifesting as fever and
other constitutional signs without cutaneous or mucosal
membrane lesions or regional lymphadenitis. The onset of
tularemia is usually abrupt, with fever (38°C-40°C), headache.
chills and rigors, generalized body aches (often prominent
in the low back), coryza, and sore throat. A pulse-temperature
dissociation has been noted in as many as 42% of patients.
A dry or slightly productive cough and substernal pain or
tightness frequently occur with or without objective signs
of pneumonia, such as purulent sputum, dyspnea, tachypnea,
pleuritic pain, or hemoptysis. Nausea, vomiting, and diarrhea
sometimes occur. Sweats, fever and chills, progressive weakness,
malaise, anorexia, and weight loss characterize the continuing
illness. A case-fatality rate of 1-3% is seen in appropriately
treated natural disease.
Tularemia
pneumonia results from inhaling contaminated aerosols. It
can also result from secondary spread via the blood and
can accompany other forms of tularemia. An aerosol release
of F. tularensis would be expected to result
in acute illness with signs and symptoms of one or more
of pharyngitis, bronchiolitis, pleuropneumonitis, and hilar
lymphadenitis, accompanied by various 'manifestations of
systemic illness. Inhalational exposures, however, commonly
result in an initial clinical picture of systemic illness
without prominent signs of respiratory disease. The earliest
pulmonary radiographic findings of inhalational tularemia
may be peribronchial infiltrates, typically advancing to
bronchopneumonia in I or more lobes, and often accompanied
by pleural effusions and hilar lymphadenopathy. Signs may,
however, be minimal or absent, and some patients will show
only 1 or several small, discrete pulmonary infiltrates
or scattered granuloma. Pulmonary infection can rapidly
progress to severe pneumonia, respiratory failure, and death.
Other
forms of tularemia include:
Ulceroglandular
tularemia which is most often acquired through inoculation
of the skin or mucous membranes with blood or tissue fluids
of infected animals. It is characterized by fever, chills,
headache, malaise, an ulcerated skin lesion, and painful
regional lymphadenopathy. The skin lesion is usually located
on the fingers or hand where contact occurs.
Glandular
tularemia results in fever and tender lymphadenopathy
but no skin ulcer.
Oculoglandular
tularemia occurs after inoculation of the conjunctivae
by contaminated hands, splattering of infected tissue fluids,
or by aerosols.
Oropharyngeal
tularemia refers to primary ulceroglandular disease
confined to the throat. It is acquired through ingestion
of the organism. It produces an acute exudative or membranous
pharvngotonsillitis with cervical lymphadenopathy. It can
also cause abdominal pain, diarrhea and vomiting.
Please
see the attached list of references for further information
on bioterrorism and chemical terrorism and the management
of the five diseases referred to in this document.
Please
contact the Middlesex-London Health Unit at 663-5317 ext..
2330 if you have any questions
regarding
this document.
October
9. 2001
KEY
REFERENCES ON BIOTERRORISM
General
information:
U.S.
Army Medical Research Institute on Infectious Diseases.
USAMRIID's medical management of biologic casualties handbook.
Fourth edition. February 2001. http://www.vnh.org/BIOCASU/toc.html
United
States Army Medical Research Institute of Chemical Defense
Medical Management of Chemical Casualties Handbook. Third
edition. August 1999. http://www.vnh.org/CHEMCASU/titlep2.html
Centers
for Disease Control and Prevention. Biological and chemical
terrorism: Strategic plan for preparedness and response.
MMWR. 2000;49(RR-04):1-14. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr4904al.htm
Johnston
BL, Conly JM. Bioterrorism in 2001 - How ready are we? Can
J Infect Dis. 2001;12:77-80.
Franz
DR, Jahrling PB, Friedlander AM, et al. Clinic recognition
and management of patients exposed to biological warfare
agents. JAMA. 1997;278:399-411.
Macintyre
AG, Christopher GW, Eitzen E, et al. Weapons of mass destruction
events with contaminated casualties: Effective planning
for health care facilities. JAMA. 2000;283:242-9. http://jama.ama-assn.org/issues/v283n2/rfull/jsc90l
00.html
Centers
for Disease Control and Prevention, Web page on Public Health
Emergency Preparedness and Response. http://www.bt.cdc.gov/
Anthrax:
Inglesby
TV. Henderson DA, Bartlett, JG, et al, for the Working
Group on Civilian Biodefense. Anthrax as a biological weapon:
Medical and public health management JAMA. 1999;281:1735-45.
http://jama.ama-assn.org/issues/v281nl8/ffull/jst80027
html
Advisory
Committee on Immunization Practices. Use of anthrax vaccine
in the United States. MMWR. 2000;49(RR-15):1-20. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr4915al.htm
Small
pox:
Henderson
DA, Inglesby TV, Bartlett JG, et al, for the
Working Group on Civilian Biodefense. Smallpox as
a. biological weapon: Medical and public health management.
JAMA. 1999;281:2127-37. http://jama.ama-assn.org/issues/v28ln22/ffull/jst90000.html
Advisory
Committee on Immunization Practices. Vaccina (Smallpox)
Vaccine. MMWR. 2001;50(RR-10):1-25. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr50l0al.htm
Plague:
Inglesby
TV, Dennis DT, Henderson DA, et al, for the Working
Group on Civilian Biodefense. Plague as a biological
weapon: Medical and public health management. JAMA.
2000;283:228190. http://jama.ama-assn.org/issues/v283n17/ffull/jst90013.html
Advisory
Committee on Immunization Practices. Prevention of
plague. MMWR. 1996;45(RR14):1-I5. . http://www.cdc.gov/mmwr/preview/mmwrhtml/00044836.htm
Tularemia:
I)ennis
D.T. Inglesby TV. Henderson DA, et al, for the Working
Group on Civilian Biodefense.
Tularemia
as a biological weapon Medical and public health management.
JAMA. 2001 :285:2763-73.
http://jama.ama-assn.org/issues/v285n21/ffull/jst10001.html
Botulism:
Arson
SS. Scliechter R. Inglesby TV, et al. for the Working
Group oil Civilian Biodefense.
Botulinum
toxin as a biological weapon: Medical and public health"management.
JAMA..2001:285:1059-70.
http://jama.ama-assn.org/issues/v285n8/ffull/jst00017.html
