Anna Healey, MD

Class of 2015

October 24, 2012

BIOTERRORISM AGENTS AND PULMONARY INFECTIONS

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

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.

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

DEFINITION OF CATEGORIESCategory 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

• 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

• 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

• 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

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

• 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

• 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

• 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

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

• 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

• 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

• 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

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

• 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

• 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

• 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

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

• 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

• 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

• 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

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

• 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

• 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

• 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

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

• 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

• 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

• Hemorrhagic Fever w/ Renal Syndrome (HFRS)

• Febrile, flu-like prodrome

• Hypotension, thrombocytopenia

• Oliguria, renal failure

• Diuresis

• Improvement

• Cardiopulmonary Syndrome (HPS)

• Tachycardia, tachypnea, respiratory difficulty

• 60% mortality

HANTAVIRUS—Clinical Presentations

CATEGORY C

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

• 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

• 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

• 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

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

• 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

• 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

• 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

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

SUMMARY

• Treat what’s most likely

• Remember the buzzwords

• Don’t forget about the zebras

REFERENCES• www.mayoclinic.com

• www.cdc.gov

• www.who.int

• http://www.ncbi.nlm.nih.gov/pubmedhealth