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Biologic Weapons, Emergency Medicine

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Biologic Weapons, Emergency Medicine

Basics

Description

Universal precautions with N-95 mask пїЅ

Mild, noncontagious illness пїЅ

  • Defined as naturally occurring organisms or toxins that are purified and prepared for mass dissemination with intent of causing mass morbidity, mortality, and social disruption.
  • Organisms include bacteria, viruses, and fungi.
  • Over 400 potential or actualized etiologic agents capable of being used as biologic weapon:Characterized by their relatively low cost compared with other weapons of mass destruction (WMD), high potency, and their ability to be delivered in a stealthy mannerStealth quality of biologic weapons comes from organisms natural incubation period.
  • Easy to conceal and difficult to detect:Agents often invisible to naked eye, odorless, and tasteless
  • Patients typically present to various health care facilities with host of common complaints, adding to delay in recognition of covert release of biologic weapon.
  • Victims of biologic warfare agents are exposed either via direct cutaneous contact with agent, respiratory inhalation of aerosolized agent, or via GI tract after poisoning of food or water source.
  • Characterized by their relatively low cost compared with other weapons of mass destruction (WMD), high potency, and their ability to be delivered in a stealthy manner
  • Stealth quality of biologic weapons comes from organisms natural incubation period.
  • Agents often invisible to naked eye, odorless, and tasteless

Etiology

  • Bacteria:Anthrax: Bacillus anthracisPlague: Yersinia pestisCholera: Infection from Vibrio cholerae:Presents with severe GI symptoms and rapidly leads to profound dehydrationTularemia: Francisella tularensisBrucellosis: Organism in the Brucella genusQ fever: Coxiella burnetii
  • Viruses:Smallpox: Variola virusViral encephalitides: Members of Alphavirus genus (Venezuelan equine encephalitis, Eastern equine encephalitis, and Western equine encephalitis)Viral hemorrhagic fevers: From 4 families of viruses, includes illnesses such as Ebola, Marburg, Lassa, and dengue fever
  • Toxins:RicinStaphylococcal enterotoxin BBotulinum toxinMycotoxins
  • Anthrax: Bacillus anthracis
  • Plague: Yersinia pestis
  • Cholera: Infection from Vibrio cholerae:Presents with severe GI symptoms and rapidly leads to profound dehydration
  • Tularemia: Francisella tularensis
  • Brucellosis: Organism in the Brucella genus
  • Q fever: Coxiella burnetii
  • Presents with severe GI symptoms and rapidly leads to profound dehydration
  • Smallpox: Variola virus
  • Viral encephalitides: Members of Alphavirus genus (Venezuelan equine encephalitis, Eastern equine encephalitis, and Western equine encephalitis)
  • Viral hemorrhagic fevers: From 4 families of viruses, includes illnesses such as Ebola, Marburg, Lassa, and dengue fever
  • Ricin
  • Staphylococcal enterotoxin B
  • Botulinum toxin
  • Mycotoxins

Diagnosis

Signs and Symptoms

  • Health care providers need to be alert to detect illness patterns and diagnostic clues that indicate biologic weapon release.
  • Indications of intentional release of agent include:Geographic clustering of illnesses with individuals who live, work, or attended event in close proximity (if multiple people who work in same office develop pneumonia, it could potentially represent respiratory pathogen release)Unusual age distribution for common illness (chickenpox-like illness among adult patients could represent smallpox release)≥2 patients presenting with similar unexplained illnesses (2 patients presenting with flaccid paralysis could represent botulinum toxin release)Single case of illness caused by uncommon agent (smallpox, inhalational anthrax)High volume of patients with similar presentation of symptoms associated with escalating morbidity and mortality
  • Geographic clustering of illnesses with individuals who live, work, or attended event in close proximity (if multiple people who work in same office develop pneumonia, it could potentially represent respiratory pathogen release)
  • Unusual age distribution for common illness (chickenpox-like illness among adult patients could represent smallpox release)
  • ≥2 patients presenting with similar unexplained illnesses (2 patients presenting with flaccid paralysis could represent botulinum toxin release)
  • Single case of illness caused by uncommon agent (smallpox, inhalational anthrax)
  • High volume of patients with similar presentation of symptoms associated with escalating morbidity and mortality
  • Inhalational anthrax:FeverChillsFatigue, malaise, lethargyCough, usually dry or minimally productiveNausea or vomitingDyspneaDiaphoresisChest painMyalgiasTachycardiaFeverMeningeal signs
  • Cutaneous anthrax:Skin lesion:Painless pruritic papuleTurning into vesicle that ruptures forming necrotic ulcerBlack escharSurrounding gelatinous nonpitting edema
  • Fever
  • Chills
  • Fatigue, malaise, lethargy
  • Cough, usually dry or minimally productive
  • Nausea or vomiting
  • Dyspnea
  • Diaphoresis
  • Chest pain
  • Myalgias
  • Tachycardia
  • Fever
  • Meningeal signs
  • Skin lesion:Painless pruritic papuleTurning into vesicle that ruptures forming necrotic ulcer
  • Black eschar
  • Surrounding gelatinous nonpitting edema
  • Painless pruritic papule
  • Turning into vesicle that ruptures forming necrotic ulcer
  • Abrupt onset
  • Fever, chills
  • Cough, hemoptysis, dyspnea
  • Headache
  • Vomiting
  • Swollen tender lymph nodes (buboes)
  • Skin lesions at site of inoculation (i.e., flea bite)
  • Confusion
  • Abdominal pain
  • Oliguria
  • Obtundation
  • Extensive ecchymosis
  • Acral gangrene (digits, nose, penis)
  • See "Tularemia"пїЅ chapter.
  • Typhoidal:Most likely form of disease when weaponized and delivered by aerosolFever, headache, malaiseNonproductive cough35% mortality if untreated
  • Most likely form of disease when weaponized and delivered by aerosol
  • Fever, headache, malaise
  • Nonproductive cough
  • 35% mortality if untreated
  • Incubation period 10-40 days
  • Flu-like symptoms and pleuritic chest pain for 2-10 days
  • CXR shows patchy infiltrates
  • Definitively diagnosed serologically
  • Mortality:<1% even if untreated
  • <1% even if untreated
  • Incubation period 3-60 days
  • Flu-like symptoms and neuropsychiatric symptoms (headache, depression, fatigue, and irritability)
  • Focal infection of joints and GU tract may cause localized pain, particularly back pain.
  • Diagnosis by combination of serologic testing and cultures of blood or bodily fluids.
  • Mortality: <2%
  • Incubation period 7-17 days (average is 12 days)
  • Flu-like symptoms (fever, fatigue, myalgias, headache) for ~2-3 days followed by characteristic rash:Progresses from macules to papules to pustular lesions and crusted lesionsStarts on face and extremities (including palms/soles) and spreads to trunk in 1 wkScabs over in 1-2 wk
  • Mortality:30% if untreated
  • Progresses from macules to papules to pustular lesions and crusted lesions
  • Starts on face and extremities (including palms/soles) and spreads to trunk in 1 wk
  • Scabs over in 1-2 wk
  • 30% if untreated
  • See "Hemorrhagic Fever"пїЅ chapter
  • Incubation period 1-3 wk
  • Starts as flu-like syndrome with fever, malaise, myalgias, headache, and sore throat
  • Afterward, infectious gastroenteritis syndrome, rash, and renal/hepatic dysfunction
  • Finally, hemorrhagic symptoms develop around the 5th day followed by shock and death:Mortality in 50-90% for Ebola if untreated
  • Mortality in 50-90% for Ebola if untreated

Essential Workup

  • Multiple cases of relatively young, healthy patients who present with flu-like syndrome and within days deteriorate rapidly
  • Typical cutaneous lesions appear

Diagnosis Tests & Interpretation

  • CBC
  • Electrolytes, BUN, creatinine
  • ABG
  • Cerebrospinal fluid (CSF):Anthrax: 50% with inhalation anthrax develop hemorrhagic meningitis.
  • Coagulation studies:Plague: Disseminated intravascular coagulation (DIC)
  • Blood cultures
  • Wound cultures
  • Alert lab personnel to potential concerns of clinicians.
  • Anthrax: 50% with inhalation anthrax develop hemorrhagic meningitis.
  • Plague: Disseminated intravascular coagulation (DIC)
  • Anthrax: Mediastinal widening, pulmonary infiltrate/consolidation, pleural effusion
  • Plague: Bronchopneumonia

Differential Diagnosis

  • Anthrax:InfluenzaBacterial pneumonia, bacterial meningitisBrown recluse spider biteTularemiaStreptococcal/staphylococcal skin infection
  • Plague:Tularemia, catscratch diseaseLymphogranuloma venereum, chancroidTuberculosisStreptococcal adenitisMeningitis, encephalitis, sepsis
  • Smallpox:VaricellaRash starts centrally on trunk and spreads outward:Lesions in different stages of developmentRarely involves palms or solesDisseminated molluscum contagiosumMonkeypox, drug eruptions
  • Toxins:Staphylococcal enterotoxin B:Most common cause of food poisoningCan be aerosolized in addition to being placed in food or water reservoirWhen inhaled, produces febrile type of illness that can progress to septic shock pictureRicin:Plant protein derived from castor beansCauses rapid progression from upper respiratory congestion to cardiopulmonary collapseIngestion is less toxic because GI tract does not absorb it well, but it can lead to local cytotoxic death, shock, and death.Botulinum toxin:Initially symptoms include cranial nerve dysfunction with descending paralysis that leads to respiratory failure.Mycotoxins:Highly toxic compounds produced by certain species of fungusDermal, respiratory, or GI contact can rapidly lead to multiorgan system failure and death.
  • Influenza
  • Bacterial pneumonia, bacterial meningitis
  • Brown recluse spider bite
  • Tularemia
  • Streptococcal/staphylococcal skin infection
  • Tularemia, catscratch disease
  • Lymphogranuloma venereum, chancroid
  • Tuberculosis
  • Streptococcal adenitis
  • Meningitis, encephalitis, sepsis
  • Varicella
  • Rash starts centrally on trunk and spreads outward:Lesions in different stages of developmentRarely involves palms or solesDisseminated molluscum contagiosum
  • Monkeypox, drug eruptions
  • Lesions in different stages of development
  • Rarely involves palms or soles
  • Disseminated molluscum contagiosum
  • Staphylococcal enterotoxin B:Most common cause of food poisoningCan be aerosolized in addition to being placed in food or water reservoirWhen inhaled, produces febrile type of illness that can progress to septic shock picture
  • Ricin:Plant protein derived from castor beansCauses rapid progression from upper respiratory congestion to cardiopulmonary collapseIngestion is less toxic because GI tract does not absorb it well, but it can lead to local cytotoxic death, shock, and death.
  • Botulinum toxin:Initially symptoms include cranial nerve dysfunction with descending paralysis that leads to respiratory failure.
  • Mycotoxins:Highly toxic compounds produced by certain species of fungusDermal, respiratory, or GI contact can rapidly lead to multiorgan system failure and death.
  • Most common cause of food poisoning
  • Can be aerosolized in addition to being placed in food or water reservoir
  • When inhaled, produces febrile type of illness that can progress to septic shock picture
  • Plant protein derived from castor beans
  • Causes rapid progression from upper respiratory congestion to cardiopulmonary collapse
  • Ingestion is less toxic because GI tract does not absorb it well, but it can lead to local cytotoxic death, shock, and death.
  • Initially symptoms include cranial nerve dysfunction with descending paralysis that leads to respiratory failure.
  • Highly toxic compounds produced by certain species of fungus
  • Dermal, respiratory, or GI contact can rapidly lead to multiorgan system failure and death.

Treatment

Pre-Hospital

Initial Stabilization/Therapy

  • ABCs
  • 0.9% NS fluid bolus for hypotension
  • Supplemental oxygen for hypoxemia
  • Vasopressors for persistent hypotension
  • Respiratory and contact isolation for suspected cases

Ed Treatment/Procedures

  • All treatments include:Control fever with acetaminophen.Initiate therapy for specific disease.
  • Anthrax:Initiate antibiotics:IV for inhalational or severe cutaneousAntibiotic choice depends on susceptibility.Antibiotic options:Ciprofloxacin: 1st lineDoxycyclineRifampinClindamycinVancomycin
  • Plague:Antibiotics initiated within 24 hr minimizes mortality.1st-line agents: Streptomycin or gentamicinAdd chloramphenicol if signs of meningitis or unstable patientProphylaxis: Doxycycline or ciprofloxacin
  • Brucellosis:Supportive therapyStart doxycycline 100 mg PO BID for 6 wk with the addition of streptomycin 1 g per day IM for the 1st 2-3 wk or rifampin 900 mg per day for 6 wk.
  • Q fever:Recovery occurs within 2 wk without treatment.Doxycycline shortens duration of illness.
  • Smallpox:Supportive therapyVaccine given within 4 days of initial exposure decreases chances of contracting smallpox or developing severe symptoms.Vaccinate medical staff caring for patient.Treat secondary bacterial infection.
  • Tularemia:See "Tularemia."пїЅ
  • Hemorrhagic fevers:See "Hemorrhagic Fever."пїЅ
  • Control fever with acetaminophen.
  • Initiate therapy for specific disease.
  • Initiate antibiotics:IV for inhalational or severe cutaneousAntibiotic choice depends on susceptibility.
  • Antibiotic options:Ciprofloxacin: 1st lineDoxycyclineRifampinClindamycinVancomycin
  • IV for inhalational or severe cutaneous
  • Antibiotic choice depends on susceptibility.
  • Ciprofloxacin: 1st line
  • Doxycycline
  • Rifampin
  • Clindamycin
  • Vancomycin
  • Antibiotics initiated within 24 hr minimizes mortality.
  • 1st-line agents: Streptomycin or gentamicin
  • Add chloramphenicol if signs of meningitis or unstable patient
  • Prophylaxis: Doxycycline or ciprofloxacin
  • Supportive therapy
  • Start doxycycline 100 mg PO BID for 6 wk with the addition of streptomycin 1 g per day IM for the 1st 2-3 wk or rifampin 900 mg per day for 6 wk.
  • Recovery occurs within 2 wk without treatment.
  • Doxycycline shortens duration of illness.
  • Supportive therapy
  • Vaccine given within 4 days of initial exposure decreases chances of contracting smallpox or developing severe symptoms.
  • Vaccinate medical staff caring for patient.
  • Treat secondary bacterial infection.
  • See "Tularemia."пїЅ
  • See "Hemorrhagic Fever."пїЅ

Medication

  • Chloramphenicol: 25 mg/kg IV q6h
  • Ciprofloxacin: 400 mg IV q12h or 500 mg PO BID (peds: 15 mg/kg BID PO)
  • Clindamycin: 900 mg IV q12h
  • Doxycycline: 100 mg (peds: ≥45 kg, 100 mg; if weight ≤45 kg, 2.2 mg/kg IV) PO/IV q12h
  • Gentamicin: 5 mg/kg IM or IV q24h (peds: 2.5 mg/kg IV/IM q8h)
  • Rifampin: 10 mg/kg IV not to exceed 600 mg/d
  • Streptomycin: 1 g (peds: 20-40 mg/kg) IM q12h
  • Vancomycin: 1 g IV q12h

Follow-Up

Disposition

  • Decision to treat patient as inpatient vs. outpatient will have to be made in context of overall disaster.
  • Toxic or hypoxic patients require admission.
  • Respiratory isolation
  • Contact local and state health departments for suspected or confirmed illness related to biologic weapons.
  • Infectious disease and toxicology consult for suspected illness

Follow-Up Recommendations

  • Postexposure prophylaxis and vaccinations should be continued based on the causative agent.
  • Exposed staff should have follow-up with employee health and infection control prior to returning to work.

Pearls and Pitfalls

  • Early diagnosis is difficult, and a high index of suspicion is required.
  • Failing to use personal protective equipment to protect self and staff is a pitfall.
  • Suspect biologic weapons etiology when there is geographic clustering of patients who live, work, or attended an event in close proximity.
  • Initiate therapy or prophylaxis early in suspected illness.

Additional Reading

  • Centers for Disease Control and Prevention (CDC). Recognition of illness associated with the intentional release of a biologic agent. MMWR Morb Mortal Wkly Rep. 2001;50:893-897.
  • Franz пїЅDR, Jahrling пїЅPB, Friedlander пїЅAM, et al. Clinical recognition and management of patients exposed to biological warfare agents. JAMA. 1997;278(5):399-411.
  • US Army Medical Research Institute of Infectious Diseases. Medical Management of Biological Casualties Handbook. 6th ed. Fort Detrick, Frederick, MD, April 2005.

Useful Websites

  • emergency.cdc.gov/bioterrorism/
  • sis.nlm.nih.gov/enviro/biologicalwarfare.html

See Also (Topic, Algorithm, Electronic Media Element)

  • Botulism
  • Hemorrhagic Fever
  • Tularemia

Codes

ICD9

  • V01.0 Contact with or exposure to cholera
  • V71.82 Observation and evaluation for suspected exposure to anthrax
  • V71.83 Observation and evaluation for suspected exposure to other biological agent
  • V01.3 Contact with or exposure to smallpox

ICD10

  • Z03.818 Encounter for observation for suspected exposure to other biological agents ruled out
  • Z20.09 Contact with and (suspected) exposure to other intestinal infectious diseases
  • Z20.810 Contact with and (suspected) exposure to anthrax
  • Z77.098 Contact w and expsr to oth hazard, chiefly nonmed, chemicals
  • Z20.89 Contact with and (suspected) exposure to other communicable diseases

SNOMED

  • 418307001 Exposure to biological agent (event)
  • 170475009 exposure to Bacillus anthracis (event)
  • 409510007 Inhalational exposure to biological agent (event)
  • 409511006 Exposure to biological agent by ingestion (event)
  • 444351007 Exposure to Variola virus (event)
  • 444381004 Exposure to Vibrio cholerae (event)