1. Anna Healey, MD
Class of 2015
October 24, 2012
BIOTERRORISM AGENTS AND PULMONARY
INFECTIONS
2. LECTURE OBJECTIVES
1. Brief introduction to bioterrorism and pathogens
in Categories A, B, and C
2. Review the buzzwords, basics, presentations,
and treatment of 9 different bioterrorism agents
causing pulmonary disease
3. Maintain a high level of suspicion for these
diseases…think ZEBRAS, not horses
3. DISCLAIMERS
• Common things are common!
• You will most likely never see these diseases in the ED, as
definitive diagnoses often come later (if at all).
• Treat the most likely etiologies first---CAP, HCAP, viral
syndromes.
• Diagnosis and treatment of these conditions hinges on a high
level of suspicion, and sometimes pattern recognition.
• For the purposes of this lecture and written exams, don’t forget
to consider the rare infectious causes of pulmonary disease.
4. KEY QUALITIES OF BIOTERRORISM AGENTS
• Easy and discreet dissemination (aerosol, food/water supply)
• Delayed presentations
• Rarer diseases with low herd immunity
• Spread from person-to-person
• High morbidity and mortality
• Spread of disease causes loss of life, money, time, resources,
manpower, etc.
• Spread of disease causes public panic and social unrest
• Spread of disease requires government attention
5. DEFINITION OF CATEGORIES
Category A Category B Category C
Rare, high morbidity/mortality Uncommon disease,
moderate morbidity/mortality
Relatively common, variable
morbidity/mortality
Easily disseminated, +PTP
spread
Easily disseminated, +/- PTP
spread
Already available or easily
produced
Public panic and social
disruption
Less public panic, but greater
stealth
Requires great use of
resources and manpower to
combat
6. • Envelopes containing an
unknown white powder were sent
to several news and media
offices (as well as to the AAEM
RSA Membership Chair). Many
of the recipients developed a flu-
like illness a result of these
mailings and several died of
respiratory failure.
• Agent?
• Anthrax (Bacillus anthracis)
CASE EXAMPLE…
CATEGORY A
7. • Bacillus anthracis, Gram
positive spore-forming
bacterium
• Naturally found in livestock
and animal hides
• Farm workers at greatest
natural risk
• Spores can survive in
environment for years
• PTP spread unlikely, but may
be transmitted from dead
body
ANTHRAX—The Basics
CATEGORY A
8. • Inhalational anthrax:
• Initial cold/flu-like illness (50-
90%)
• Progression to respiratory
distress or failure (10-20%)
• Cutaneous anthrax
• Boil-like lesion forms into
necrotic ulcer
• Rarely fatal
• Gastrointestinal anthrax
• Inflammation of GI tract with
vomiting, diarrhea
• Mortality approaches 60%
ANTHRAX—Clinical Presentations
CATEGORY A
9. ANTHRAX—Treatment
• Antibiotics
• Ciprofloxacin
• Doxycycline
• Penicillin
• Raxibacumab (Abthrax) for emergency treatment of inhalational
anthrax
• Live-attenuated vaccine (BioThrax) available for at-risk
populations
CATEGORY A
10. • Kersten presents to the ED with
fever, cough, weakness,
myalgias, and diarrhea for the
past several days. Upon further
questioning, she states she
recently helped her husband
clean some rabbits he shot while
hunting in Elko, NV last week.
• Agent?
• Tularemia (Francisella tularensis)
CASE EXAMPLE…
CATEGORY A
11. • Franciscella tularensis, Gram
negative coccobacillus
• AKA “rabbit fever”, “deer fly
fever”
• Natural reservoir in hares and
small rodents in North America
• May be passed through
arthropods (ticks, deer flies) but
direct contact or inhalation also
possible
• Low inoculation necessary to
cause disease, but no PTP
spread
TULAREMIA—The Basics
CATEGORY A
12. • Pneumonic form (10%):
• Sudden flu-like illness with cough,
chest pain, difficulty breathing
• May have airway hemorrhage
causing hemoptysis
• 50% mortality if untreated
• Ulceroglandular (75%):
• Enlarged lymph nodes with
suppuration
• Skin ulcers in distribution of
lymphatic drainage
• Glandular, oculoglandular,
oropharyngeal presentations
TULAREMIA—Clinical Presentations
CATEGORY A
13. TULAREMIA—Treatment
• Antibiotics
• Streptomycin—drug of choice
• Gentamicin, doxycycline, or fluoroquinolones other options
• Limited role for post-exposure prophylaxis
• Limited number of individuals, contained exposures—doxycycline,
ciprofloxacin
• Mass exposure—triage prophylaxis
• Quarantine/isolation not necessary
• Live attenuated vaccine available for high risk groups (lab workers)
CATEGORY A
14. • Beau presents to the ED with
fever, cough, chest pain,
respiratory distress, and sepsis.
He notes no sick contacts, but
does say he disposed of a dead
rat his son found while playing
outside yesterday.
• Agent?
• Pneumonic plague (Yersinia
pestis)
CASE EXAMPLE…
CATEGORY A
15. • Yersinia pestis, Gram negative
anaerobic rod
• Natural reservoir is rodents and is
passed via flea bites from animals to
humans; also air, food, water, contact
• Certain forms (pneumonic) can spread
between people
• Historically very important
• Black Plague
• Use in bioterrorism dating back to
ancient China, medieval Europe
PLAGUE—The Basics
CATEGORY A
16. • Pneumonic Plague:
• Prodrome of flu-like illness with rapid
progress to fulminant pneumonia,
hemoptysis
• Short incubation period
• Least common, but deadliest—100%
mortality if untreated
• Bubonic Plague:
• Swollen suppurative lymph node in
distribution of bite (bubo)
• 50% mortality if untreated
• Septicemic Plague:
• Bloodstream infection, often without
presence of bubo
• Rapid death—DIC, mortality 15% with
treatment
PLAGUE—Clinical Presentations
CATEGORY A
17. PLAGUE—Treatment
CATEGORY A
• Cardiovascular and/or respiratory support
• Antibiotics
• Gentamicin or doxycycline
• Streptomycin, chloramphenicol, tetracycline
• Early antibiotics management is essential for reducing mortality
• Vaccine
• Developed late 19th century
• Reserved for laboratory and field workers with high risk of exposure
• Post exposure prophylaxis still indicated
18. • Tony works in a lab studying rare
viruses. At work one day, a vial
breaks but he cleans it up right
away. That weekend he visits his
girlfriend in San Francisco, but on
the plane he notices new bumps
on his skin. Within one week, he
is in the ED with fever, cough, and
chest pain.
• Agent?
• Smallpox (Variola)
CASE EXAMPLE…
CATEGORY A
19. • Variola major and minor, DNA
virus
• Airborne transmission, spreads
easily from person to person and
from fomites (smallpox blankets)
• Complications can be deadly
• Last natural case in 1977,
declared eradicated by WHO
SMALLPOX—The Basics
CATEGORY A
20. • Ordinary Smallpox:
• Vesicular skin lesions, which drain,
scab, and scar over the course of 2
weeks
• Malignant or Hemorrhagic Smallpox:
• Severe prodrome followed by severe
rash; bleeding into skin, GI tract,
mucous membranes
• Respiratory distress
• Nearly 100% fatal
• Secondary Bacterial Pneumonia:
• Most common, deadliest complication
• 30% mortality
SMALLPOX—Clinical Presentations
CATEGORY A
21. SMALLPOX--Treatment
• Supportive care
• Infection control, wound care, ventilator management, fluid resuscitation
• Smallpox vaccine:
• Reserved for at risk groups:
• Military, health care workers, and emergency responders
• Laboratory workers
• May give within 3 days of exposure to prevent or lessen symptoms
• Those exposed to smallpox should be quarantined
• Antivirals:
• IV Cidofovir, reserved for certain cases; efficacy unclear
CATEGORY A
22. • Kellen is upset about the birds
that live in his fruit trees. He
gets frustrated and chases them
out with a broom, but not before
breathing in some of their
droppings. Two weeks later, he
presents to the ED with fever,
cough, diarrhea, headache, and
abdominal pain.
• Agent?
• Psittacosis (Chlamydophila
psittaci)
CASE EXAMPLE…
CATEGORY B
23. • Chlamydophila psittaci, obligatory
intracellular bacterium
• AKA “parrot fever”, ornithosis
• Natural reservoir in birds, especially
parrots, pigeons, finches, and hens
• Inhalation of dried droppings from
infected birds
• Pet shop workers
• “Mouth-to-beak resuscitation”
• PTP spread rare but possible
PSITTACOSIS—The Basics
CATEGORY B
24. • Atypical Pneumonia:
• Incubation period 1-2 weeks
• Prodrome includes myalgias,
fever, diarrhea, headache,
conjunctivitis, arthralgias,
splenomegaly
• Followed by acute bacterial
pneumonia
• Complications include hepatitis,
endocarditis, myocarditis,
encephalitis
• <1% mortality
PSITTACOSIS—Clinical Presentations
CATEGORY B
25. PSITTACOSIS--TREATMENT
• Antibiotics
• Doxycycline, tetracycline, chloramphenicol
• Erythromycin second-line choice
• Cause for underdiagnosis
• Disease may relapse with early cessation of treatment (at least 2 weeks)
• No vaccine available
• Protective clothing when in contact with potentially infected birds
• Education and high level of suspicion for disease
CATEGORY B
26. • Curtis visits his family farm in
Idaho/Iowa/wherever. They raise
cattle, and on a hot day he
decides to have a glass of fresh,
unpasteurized milk. Three
weeks later, he is in the ED with
a dry cough, fever, difficulty
breathing, vomiting, and
diarrhea. In retrospect, he thinks
“milk was a bad choice”.
• Agent?
• Q Fever (Coxiella burnetti)
CASE EXAMPLE…
CATEGORY B
27. • Coxiella burnetti, obligate
intracellular bacterium
• Natural reservoir in cattle, sheep,
goats
• Inhalation, contact with milk,
urine, wool, or feces of infected
animals, or tick borne
• Infection can be caused by a
single bacterium
• PTP spread extremely rare
Q FEVER—The Basics
CATEGORY B
28. • Week 1: flu-like prodromal illness,
including fever, malaise, headache,
myalgia, nausea, diarrhea
• Weeks 2-3: 50% develop into frank
pneumonia, may result in ARDS
• May also cause granulomatous
hepatitis or vasculitis
• Chronic form similar to endocarditis,
may last decades; fatal if untreated,
must treat for years
• Diagnosed with serology, difficult to
culture
Q FEVER—Clinical Presentations
CATEGORY B
29. Q FEVER--Treatment
• Antibiotics
• Doxycycline, tetracycline, ciprofloxacin
• May also use chloramphenicol, hydroxychloroquine
• Chronic form may require years of antibiotic therapy
• Vaccine (Q-Vax)
• Whole cell inactivated vaccine, developed in Australia
• Immunity lasts years and does not require boosters
• At risk populations: farmers, veterinary personnel, stockyard workers,
tannery workers, lab workers, people with kangaroo exposure
CATEGORY B
30. • Annie loves to go camping. She
makes a trip to Yosemite and
while there, notices some mice in
her tent. Two weeks later, she is
in the ED with cough, fever,
diarrhea, respiratory distress,
and shock.
• Agent?
• Hantavirus
CASE EXAMPLE…
CATEGORY C
31. • Hantavirus, RNA virus in
Bunyaviridae family
• “Four Corners disease”, “Sin
Nombre virus”
• Contact with rodent urine, saliva,
or feces; animal bites
• August/September 2012: eight
cases of Hantavirus with three
deaths in Yosemite
• PTP possible, but uncommon
HANTAVIRUS—The Basics
CATEGORY C
33. HANTAVIRUS—Treatment
• Supportive care
• Ventilatory management, circulatory support
• Dialysis and fluid management
• No antiviral treatment available
• Prevention is key
• Pest control
• Disinfection of soiled areas
• Personal protective equipment
• Vaccine
• In development in some Asian countries, not available in US
• None yet recognized by WHO
CATEGORY C
34. • Melissa travels to Asia to visit her
boyfriend in Japan and friends in
Korea and China. She starts
developing a cold, but thinks
nothing of it. On the flight home,
her cold progresses to difficulty
breathing, cough, high fever,
myalgias, and lethargy.
• Agent?
• Severe Acute Respiratory
Syndrome (SARS Coronavirus)
CASE EXAMPLE…
CATEGORY C
35. • SARS Coronavirus, RNA virus
• Genome mapping indicated a jump
from bats to humans, likely natural
reservoirs
• Spread through aerosol route or
fomites, stable in many
environments
• First identified in 2003 during
outbreak in China, Singapore, and
Hong Kong with 8000 cases and 750
deaths
• Laboratory infections since
pandemic
SARS—The Basics
CATEGORY C
36. • Presentation similar to URI or
influenza:
• Fever, myalgias, lethargy
• Cough, sore throat, dyspnea
• CXR variable, patchy infiltrates
• May predispose to development of
bacterial pneumonia
• May have leukopenia,
thrombocytopenia; increase in
cytokines
• Lab diagnosis unreliable—PCR, ELISA
serology, immunofluorescence assay
• Mortality >50% over age 65
SARS—Clinical Presentation
CATEGORY C
37. SARS—Treatment
• Supportive care
• Respiratory support, oxygen, ventilation management, antipyretics
• Previously thought to treat with steroids and ribavirin, studies
controversial
• Antibiotics for secondary bacterial pneumonia
• Patients must be on airborne precautions
• No vaccine available
CATEGORY C
38. • Jeff meets a cute girl and takes
her out for his monthly date.
They have a great evening
despite her cold. Several days
later, he develops congestion,
cough, fever, myalgias, vomiting,
and difficulty breathing.
• Agent?
• Influenza (H1N1)
CASE EXAMPLE…
CATEGORY C
39. • Influenza A subtype H1N1
• Strain found in swine populations
(“swine flu”)
• Airborne transmission with high
rate of PTP spread
• Responsible for pandemic in
2009 causing over 18,000 deaths
worldwide
H1N1—The Basics
CATEGORY C
40. • Typical respiratory viral
syndrome
• Fever, congestion, sore
throat
• Cough, difficulty breathing
• Nausea/vomiting, diarrhea
• Malaise, lethargy
• Potential for secondary bacterial
pneumonia
• Potential for severe respiratory
decline, ARDS
H1N1—Clinical Presentations
CATEGORY C
41. H1N1--Treatment
• Supportive care
• Respiratory support and management
• Antiviral therapy
• Oseltamivir (Tamiflu) or zanamivir
• Amantidine and rimantidine second line
• Antibiotics for secondary bacterial pneumonia
• Prevention:
• Proper hand washing and hygiene
• Live or killed virus vaccines available
• Vaccine triage: pregnant women, health care workers, elderly, comorbidities
CATEGORY C
42. SUMMARY
• Treat what’s most likely
• Remember the buzzwords
• Don’t forget about the zebras
Bioterrorism: use of biological agents to cause disease, widespread damage, use of national resources, and psychological and social disturbances
Spore last forever and can be disseminated easily. Generally does not spread from person to person, but quarantine recommended. May be transmitted from contact with dead body.
Easily aerosolized, only requires 10-50 bacteria to cause infection, can remain in soil for weeks, highly incapacitating but with lower lethality, mimics other more common respiratory infections. Does not spread from person to person.
The onset of tularemia is usually abrupt, with fever, headache, chills, generalized body aches, and sore throat. A dry or slightly productive cough and substernal pain or chest tightness often occur with or without objective signs of pneumonia, such as purulent sputum, dyspnea, tachypnea, pleuritic pain, or hemoptysis. Sweats, fever and chills, progressive weakness, malaise, anorexia, and weight loss characterize the continuing illness. CXR may show infiltrate, hilar adenopathy, effusion.
PEP: depending on situation. Small, contained—proceed with PEP, mass exposure—triage PEP. Does not spread PTP so no quarantine necessary
Easily transmitted/disseminated, pneumonic plague can pass from person to person, high mortality if not recognized/treated early. Historically used in biological warfare—Han Dynasty, Mongols, Turks known for using infected bodies and animal carcasses to contaminate water supplies, reports of catapulting dead bodies over city walls
PEP still indicated even if patient is vaccinated d/t severity of disease if left untreated.
Smallpox blankets—classically Siege of Fort Pitt, 1763, American Indians attempting to push out the British and capture Ft Pitt, unsuccessful as British sent blankets intentionally exposed to smallpox to American Indians as peace gesture when in fact was biological warfare
Other complications—encephalitis, conjunctivitis, blindness, scarring, deformities of limbs/joints, secondary bacterial infections
Patients with open sores may be treated as burn pts, prevent infection and monitor fluids
Up to 200 cases annually, reports suggest underdiagnosis
Lab values include thrombocytopenia, leukopenia, elevated LFTs
Presents as atypical pneumonia and tx with doxycycline, may be dx and treated without recognizing a rarer cause for atypical PNA
May survive on surfaces for up to 60 days, very stable as an aerosol
Difficult to culture because the pathogen is intracellular
Radiographs showing the evolution of hantavirus pulmonary syndrome in a 30-year-old woman. (A) Chest radiograph before onset of illness. (B) Admission radiograph. (C) Radiograph after intubation. (D) Radiograph just before death.
Increase in cytokinessevere inflammatory response in body may worsen symptoms, respiratory issues. Some association with long-term pulmonary fibrosis, femoral head necrosis.
