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Anthrax

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Title: Anthrax


1
Anthrax
2
Anthrax History
  • Caused by Bacillus anthracis
  • Human zoonotic disease
  • Spores found in soil worldwide
  • Primarily disease of herbivorous animals
  • Sheep, goats, cattle
  • Many large documented epizootics
  • Occasional human disease
  • Epidemics have occurred but uncommon
  • Rare in developed world

3
Anthrax Bioweapon Potential
  • Many countries have weaponized anthrax
  • Former bioweapon programs
  • U.S.S.R.,U.S.,U.K., and Japan
  • Recent bioweapon programs
  • Iraq
  • Attempted uses as bioterrorism agent
  • WW I Germans inoculated Allied livestock
  • WW II Alleged Japanese use on prisoners

4
Anthrax Bioweapon Potential
  • Features of anthrax suitable as BT agent
  • Fairly easy to obtain, produce and store
  • Spores easily dispersed as aerosol
  • Moderately infectious
  • High mortality for inhalational (86-100)

5
Anthrax Bioweapon Potential
  • Aerosol method of delivery
  • Most likely method expected in BT attack
  • Would cause primarily inhalational disease
  • Spores reside on particles of 1-5 µm size
  • Optimal size for deposition into alveoli
  • Form of disease with highest mortality
  • Would infect the largest number of people

6
Anthrax Bioweapon Potential
  • Dispersed as powder
  • Frequent letter hoaxes since 1997
  • Recent letter deliveries
  • Highest risk is for cutaneous
  • Inhalational theoretically possible
  • Particle size
  • Likelihood of aerosolization
  • GI theoretically possible
  • Spores gt hands gt eating without handwashing

7
Anthrax Bioweapon Potential
  • Sverdlovsk, Russia 1979
  • Accidental release from anthrax drying plant
  • 79 human cases
  • All downwind of plant
  • 68 deaths
  • Some infected with multiples strains

8
Anthrax Bioweapon Potential
  • Estimated effects of inhalational anthrax
  • 100 kg spores released over city size of
    Washington DC
  • 130,000 3 million deaths depending on weather
    conditions
  • Economic impact
  • 26.2 billion/100,000 exposed people

9
Anthrax Epidemiology
  • Three forms of natural disease
  • Inhalational
  • Rare (lt5)
  • Most likely encountered in bioterrorism event
  • Cutaneous
  • Most common (95)
  • Direct contact of spores on skin
  • Gastrointestinal
  • Rare (lt5), never reported in U.S.
  • Ingestion

10
Anthrax Epidemiology
  • All ages and genders affected
  • Occurs worldwide
  • Endemic areas - Africa, Asia
  • True incidence not known
  • World 20,000-100,000 in 1958
  • U.S. 235 total reported cases 1955-1994
  • 18 cases inhalational since 1900, last one 1976
  • Until 2001, last previous case cutaneous 1992

11
Anthrax Epidemiology
  • Mortality
  • Inhalational 86-100 (despite treatment)
  • Era of crude intensive supportive care
  • Cutaneous lt5 (treated) 20 (untreated)
  • GI approaches 100

12
Anthrax Epidemiology
  • Incubation Period
  • Time from exposure to symptoms
  • Very variable for inhalational
  • 2-43 days reported
  • Theoretically may be up to 100 days
  • Delayed germination of spores

13
Anthrax Epidemiology
  • Human cases historical risk factors
  • Agricultural
  • Exposure to livestock
  • Occupational
  • Exposure to wool and hides
  • Woolsorters disease inhalational anthrax
  • Rarely laboratory-acquired

14
Anthrax Epidemiology
  • Transmission
  • No human-to-human
  • Naturally occurring cases
  • Skin exposure
  • Ingestion
  • Airborne
  • Bioterrorism
  • Aerosol (likely)
  • Small volume powder (possible)
  • Foodborne (unlikely)

15
Anthrax Epidemiology
  • Transmission
  • Inhalational
  • Handling hides/skins of infected animals
  • Microbiology laboratory
  • Intentional aerosol release
  • Small volume powdered form
  • In letters, packages, etc
  • Questionable risk, probably small

16
Anthrax Epidemiology
  • Transmission
  • Cutaneous
  • Handling hides/skins of infected animals
  • Bites from arthropods (very rare)
  • Handling powdered form in letters, etc.
  • Intentional aerosol release
  • May see some cutaneous if large-scale

17
Anthrax Epidemiology
  • Transmission
  • Gastrointestinal
  • Ingestion of meat from infected animal
  • Ingestion of intentionally contaminated food
  • Not likely in large scale
  • Spores not as viable in large volumes of water
  • Ingestion from powder-contaminated hands
  • Inhalational of spores on particles gt5 ?m
  • Land in oropharynx

18
Anthrax Microbiology
  • Bacillus anthracis
  • Aerobic, Gram positive rod
  • Long (1-10µm), thin (0.5-2.5µm)
  • Forms inert spores when exposed to O2
  • Infectious form, hardy
  • Approx 1µm in size
  • Vegetative bacillus state in vivo
  • Result of spore germination
  • Non-infectious, fragile

19
Anthrax Microbiology
  • Colony characteristics
  • Large (4-5mm)
  • Non-hemolytic
  • Opaque white, gray
  • Retain shape when manipulated (egg white)
  • Forms capsule at 37º C, 5-20 CO2

20
Anthrax Microbiology
  • Classification
  • Same family B. cereus, B. thuringiensis
  • Differentiation from other Bacillus species
  • Non-motile
  • Non ß-hemolytic on blood agar
  • Does not ferment salicin
  • Note Gram positive rods are usually labeled as
    contaminants by micro labs

21
Anthrax Microbiology
  • Environmental Survival
  • Spores are hardy
  • Resistant to drying, boiling lt10 minutes
  • Survive for years in soil
  • Still viable for decades in perma-frost
  • Favorable soil factors for spore viability
  • High moisture
  • Organic content
  • Alkaline pH
  • High calcium concentration

22
Microbiology
  • Virulence Factors
  • All necessary for full virulence
  • Two plasmids
  • Capsule (plasmid pXO2)
  • Antiphagocytic
  • 3 Exotoxin components (plasmid pXO1)
  • Protective Antigen
  • Edema Factor
  • Lethal Factor

23
Anthrax Microbiology
  • Protective Antigen
  • Binds Edema Factor to form Edema Toxin
  • Facilitates entry of Edema Toxin into cells
  • Edema Factor
  • Massive edema by increasing intracellular cAMP
  • Also inhibits neutrophil function
  • Lethal Factor
  • Stimulates macrophage release of TNF-a, IL-1ß
  • Initiates cascade of events leading to sepsis

24
Anthrax Pathogenesis
  • Disease requires entry of spores into body
  • Exposure does not always cause disease
  • Inoculation dose
  • Route of entry
  • Host immune status
  • May depend on pathogen strain characteristics

25
Anthrax Pathogenesis
  • Forms of natural disease
  • Inhalational
  • Cutaneous
  • Gastrointestinal
  • Determined by route of entry
  • Disease occurs wherever spores germinate

26
Anthrax Pathogenesis
  • Inhalational
  • Spores on particles 1-5 ?m
  • Inhaled and deposited into alveoli
  • Estimated LD50 2500 55,000 spores
  • Dose required for lethal infection in 50 exposed
  • Contained in imperceptibly small volume

27
Anthrax Pathogenesis
  • Inhalational
  • Phagocytosed by alveolar macrophages
  • Migration to mediastinal/hilar lymph nodes
  • Germination into vegetative bacilli
  • Triggered by nutrient-rich environment
  • May be delayed up to 60 days
  • Factors not completely understood
  • Dose, host factors likely play a role
  • Antibiotic exposure may contribute
  • Delayed germination after antibiotic suppression

28
Anthrax Pathogenesis
  • Inhalational
  • Vegetative bacillus is the virulent phase
  • Active toxin production
  • Hemorrhagic necrotizing mediastinitis
  • Hallmark of inhalational anthrax
  • Manifests as widened mediastinum on CXR
  • Does NOT cause pneumonia
  • Followed by high-grade bacteremia
  • Seeding of multiple organs, including meninges

29
Anthrax Pathogenesis
  • Inhalational
  • Toxin production
  • Has usually begun by time of early symptoms
  • Stimulates cascade of inflammatory mediators
  • Sepsis
  • Multiorgan failure
  • DIC
  • Eventual cause of death
  • Symptoms mark critical mass of bacterial burden
  • Usually irreversible by this time
  • Clearance of bacteria unhelpful as toxin-mediated
  • Early research on antitoxin promising

30
Anthrax Pathogenesis
  • Cutaneous
  • Spores in contact with skin
  • Entry through visible cuts or micro-trauma
  • Germination in skin
  • Disease begins following germination
  • Toxin production
  • Local edema, erythema, necrosis, lymphocytic
    infiltrate
  • No abscess or suppurative lesions
  • Eventual eschar formation

31
Anthrax Pathogenesis
  • Cutaneous
  • Systemic disease
  • Can occur, especially if untreated
  • Spores/bacteria carried to regional lymph nodes
  • Lymphangitis/lymphadenitis
  • Same syndrome as inhalational
  • Sepsis, multi-organ failure

32
Anthrax Pathogenesis
  • Gastrointestinal
  • Spores contact mucosa
  • Oropharynx
  • Ingestion
  • Aerosolized particles gt5 ?m
  • Intestinal mucosa terminal ileum, cecum
  • Ingestion
  • Larger number of spores required for disease
  • Incubation period 2-5 days

33
Anthrax Pathogenesis
  • Gastrointestinal
  • Spores migrate to lymphatics
  • Submucosal, mucosal lymphatic tissue
  • Mesenteric nodes
  • Germination to vegetative bacilli
  • Toxin production
  • Massive mucosal edema
  • Mucosal ulcers, necrosis
  • Death from perforation or systemic disease

34
Anthrax Clinical Features
  • Symptoms depend on form of disease
  • Inhalational
  • Cutaneous
  • Gastrointestinal

35
Anthrax Clinical Features
  • Inhalational
  • Asymptomatic incubation period
  • Duration 2-43 days, 10 days in Sverdlovsk
  • Prodromal phase
  • Correlates with germination, toxin production
  • Nonspecific flu-like symptoms
  • Fever, malaise, myalgias
  • Dyspnea, nonproductive cough, mild chest
    discomfort
  • Duration several hours to 3 days
  • Can have transient resolution before next phase

36
Anthrax Clinical Features
  • Inhalational
  • Fulminant Phase
  • Correlates with high-grade bacteremia/toxemia
  • Critically Ill
  • Fever, diaphoresis
  • Respiratory distress/failure, cyanosis
  • Septic shock, multi-organ failure, DIC
  • 50 develop hemorrhagic meningitis
  • Headache, meningismus, delirium, coma
  • May be most prominent finding
  • Usually progresses to death in lt36 hrs
  • Mean time from symptom onset to death 3 days

37
Anthrax Clinical Features
  • Laboratory Findings
  • Gram positive bacilli in direct blood smear
  • Electrolyte imbalances common
  • Radiographic Findings
  • Widened mediastinum
  • Minimal or no infiltrates
  • Can appear during prodrome phase

38
Anthrax Clinical Features
  • Cutaneous
  • Most common areas of exposure
  • Hands/arms
  • Neck/head
  • Incubation period
  • 3-5 days typical
  • 12 days maximum

39
Anthrax Clinical Features
  • Cutaneous progression of painless lesions
  • Papule pruritic
  • Vesicle/bulla
  • Ulcer contains organisms, sig. edema
  • Eschar black, rarely scars

24-36 hrs
days
40
Anthrax Clinical Features
  • Cutaneous
  • Systemic disease may develop
  • Lymphangitis and lymphadenopathy
  • If untreated, can progress to sepsis, death

41
Anthrax Clinical Features
  • Gastrointestinal
  • Oropharyngeal
  • Oral or esophageal ulcer
  • Regional lymphadenopathy
  • Edema, ascites
  • Sepsis
  • Abdominal
  • Early symptoms - nausea, vomiting, malaise
  • Late - hematochezia, acute abdomen, ascites

42
Anthrax Diagnosis
  • Early diagnosis is difficult
  • Non specific symptoms
  • Initially mild
  • No readily available rapid specific tests

43
Anthrax Diagnosis
  • Presumptive diagnosis
  • History of possible exposure
  • Typical signs symptoms
  • Rapidly progressing nonspecific illness
  • Widened mediastinum on CXR
  • Large Gram bacilli from specimens
  • Can be seen on Gram stain if hi-grade bacteremia
  • Appropriate colonial morphology
  • Necrotizing mediastinitis, meningitis at autopsy

44
Anthrax Diagnosis
  • Definitive diagnosis
  • Direct culture on standard blood agar
  • Gold standard, widely available
  • Alert lab to work up Gram bacilli if found
  • 6-24 hours to grow
  • Sensitivity depends on severity, prior antibiotic
  • Blood, fluid from skin lesions, pleural fluid,
    CSF, ascites
  • Sputum unlikely to be helpful (not a pneumonia)
  • Very high specificity if non-motile,
    non-hemolytic
  • Requires biochemical tests for gt99 confirmation
  • Available at Reference laboratories

45
Anthrax Diagnosis
  • Definitive diagnosis
  • Rapid confirmatory tests
  • Role is to confirm if cultures are negative
  • Currently available only at CDC
  • Polymerase Chain Reaction (PCR)
  • Hi sensitivity and specificity
  • Detects DNA
  • Viable bacteria/spores not required
  • Immunohistochemical stains
  • Most clinical specimens can be used

46
Anthrax Diagnosis
  • Other diagnostic tests
  • Anthraxin skin test
  • Chemical extract of nonpathogenic B. anthracis
  • Subdermal injection
  • 82 sensitivity for cases within 3 days symptoms
  • 99 sensitivity 4 weeks after symptom onset
  • Not much experience with use in U.S. not used

47
Anthrax Diagnosis
  • Testing for exposure
  • Nasal swabs
  • Can detect spores prior to illness
  • Currently used only as epidemiologic tool
  • Decision for PEP based on exposure risk
  • May be useful for antibiotic sensitivity in
    exposed
  • Culture on standard media
  • Swabs of nares and facial skin
  • Serologies
  • May be useful from epidemiologic standpoint
  • Investigational only available at CDC

48
Anthrax Diagnosis
  • Environmental samples
  • Suspicious powders
  • Must be sent to reference laboratories as part of
    epidemiologic/criminal investigation
  • Assessed using cultures, stains, PCR
  • Air sampling
  • First responders
  • Handheld immunoassays
  • Not validated
  • Useful for detecting massive contamination

49
Anthrax Diagnosis
Test Availability Time Sens Spec
Culture Most labs 1-3 days Mod High
Biochemical Large labs Hours N/A High
Skin test None 1-2 days High ?
PCR Reference Hours High High
ELISA Reference Hours Mod High
50
Anthrax Differential Diagnosis
  • Inhalational
  • Influenza
  • Pneumonia
  • Community-acquired
  • Atypical
  • Pneumonic tularemia
  • Pneumonic plague
  • Mediastinitis
  • Bacterial meningitis
  • Thoracic aortic aneurysm
  • Expect if anthrax
  • Flu rapid diagnostic
  • More severe in young pts
  • No infiltrate
  • No prior surgery
  • Bloody CSF with GPBs
  • Fever

51
Anthrax Differential Diagnosis
  • Cutaneous
  • Spider bite
  • Ecthyma gangrenosum
  • Pyoderma gangrenosum
  • Ulceroglandular tularemia
  • Mycobacterial ulcer
  • Cellulitis
  • Expect if anthrax
  • fever
  • no response to 3º cephalosporins
  • painless, black eschar
  • /- lymphadenopathy
  • usually sig. local edema

52
Anthrax Differential Diagnosis
  • Expect if anthrax
  • Critically ill
  • Acute abdomen
  • Bloody diarrhea
  • Fever
  • Gastrointestinal
  • Gastroenteritis
  • Typhoid
  • Peritonitis
  • Perforated ulcer
  • Bowel obstruction

53
Anthrax Differential Diagnosis
  • Impact of suspected BT during flu season
  • Early disease mimics influenza
  • Affects same population
  • Increased role for rapid flu tests
  • Possible development of ER protocols
  • In settings of high suspicion for BT release
  • Observation until flu test results obtained
  • Caveats
  • Possible addition of influenza to aerosol release
  • False positives/negatives
  • Must still use clinical judgement

54
Anthrax Treatment
  • Immediately treat presumptive cases
  • Prior to confirmation
  • Rapid antibiotics may improve survival
  • Differentiate between cases and exposed
  • Cases
  • Potentially exposed with any signs/symptoms
  • Exposed
  • Potentially exposed but asymptomatic
  • Provide Post-Exposure Prophylaxis

55
Anthrax Treatment
  • Hospitalization
  • IV antibiotics
  • Empiric until sensitivities are known
  • Intensive supportive care
  • Electrolyte and acid-base imbalances
  • Mechanical ventilation
  • Hemodynamic support

56
Anthrax Treatment
  • Antibiotic selection
  • Naturally occurring strains
  • Rare penicillin resistance, but inducible
    ß-lactamase
  • Penicillins, aminoglycosides, tetracyclines,
    erythromycin, chloramphenicol have been effective
  • Ciprofloxacin very effective in vitro, animal
    studies
  • Other fluoroquinolones probably effective
  • Engineered strains
  • Known penicillin, tetracycline resistance
  • Highly resistant strains mortality of untreated

57
Anthrax Treatment
  • Empiric Therapy
  • Until susceptibility patterns known
  • Adults
  • Ciprofloxacin 400 mg IV q12
  • OR
  • Doxycycline 100mg IV q12
  • AND (for inhalational)
  • One or two other antibiotics

58
Anthrax Treatment
  • Other antibiotic considerations
  • Other fluoroquinolones possibly equivalent
  • High dose penicillin for 2nd empiric agent
  • 50 present with meningitis
  • Clindamycin for severe disease
  • May reduce toxin production
  • Chloramphenicol for known meningitis
  • Penetrates blood brain barrier

59
Anthrax Treatment
  • Empiric Therapy
  • Children
  • Ciprofloxacin 10-15 mg/kg/d IV q12, max 1
    g/d OR
  • Doxycycline 2.2 mg/kg IV q12
  • (adult dosage if gt8 years and gt45 kg)
  • Add one or two antibiotics for inhalational
  • Weigh risks (arthropathy, dental enamel)

60
Anthrax Treatment
  • Empiric therapy
  • Pregnant women
  • Same as other adults
  • Weigh small risks (fetal arthropathy) vs benefit
  • Immunosuppressed
  • Same as other adults

61
Anthrax Treatment
  • Alternative antibiotics
  • If susceptible, or cipro/doxy not possible
  • Penicillin, amoxicillin
  • Gentamicin, streptomycin
  • Erythromycin, chloramphenicol
  • Ineffective antibiotics
  • Trimethoprim/Sulfamethoxazole
  • Third generation cephalosporins

62
Anthrax Treatment
  • Susceptibility testing should be done
  • Narrow antibiotic if possible
  • Must be cautious
  • Multiple strains with engineered resistance to
    different antibiotics may be co-infecting
  • Watch for clinical response after switching
    antibiotic

63
Anthrax Treatment
  • Antibiotic therapy
  • Duration
  • 60 days
  • Risk of delayed spore germination
  • Vaccine availability
  • Could reduce to 30-45 days therapy
  • Stop antibiotics after 3rd vaccine dose
  • Switch to oral
  • Clinical improvement
  • Patient able to tolerate oral medications

64
Anthrax Treatment
  • Other therapies
  • Passive immunization
  • Anthrax immunoglobulin from horse serum
  • Risk of serum sickness
  • Antitoxin
  • Mutated Protective Antigen
  • Blocks cell entry of toxin
  • Still immunogenic, could be an alternative
    vaccine
  • Animal models promising

65
Anthrax Postexposure Prophylaxis
  • Who should receive PEP?
  • Anyone exposed to anthrax
  • Not for contacts of cases, unless also exposed
  • Empiric antibiotic therapy
  • Vaccination

66
Anthrax Postexposure Prophylaxis
  • Avoid unnecessary antibiotic usage
  • Potential shortages of those who need them
  • Potential adverse effects
  • Hypersensitivity
  • Neurological side effects, especially elderly
  • Bone/cartilage disease in children
  • Oral contraceptive failure
  • Future antibiotic resistance
  • Individuals own flora
  • Community resistance patterns

67
Anthrax Postexposure Prophylaxis
  • Antibiotic therapy
  • Treat ASAP
  • Prompt therapy can improve survival
  • Continue for 60 days
  • 30-45 days if vaccine administered

68
Anthrax Postexposure Prophylaxis
  • Antibiotic agents
  • Same regimen as active treatment
  • Substituting oral equivalent for IV
  • Ciprofloxacin 500 mg po bid empirically
  • Alternatives
  • Doxycycline 100 mg po bid
  • Amoxicillin 500 mg po tid

69
Anthrax Postexposure Prophylaxis
  • Antibiotic agents
  • Children
  • Same dose adjustments as treatment
  • Weigh benefits vs. risks
  • Recommended switch if PCN-susceptible
  • Amoxicillin 80 mg/kg/day, max 500 mg tid

70
Anthrax Prevention
  • Vaccine
  • Anthrax Vaccine Absorbed (AVA)
  • Supply
  • Limited, controlled by CDC
  • Production problems
  • Single producer Bioport, Michigan
  • Failed FDA standards
  • None produced since 1998

71
Anthrax Prevention
  • Vaccine
  • Inactivated, cell-free filtrate
  • Purified with Al(OH)3
  • Protective Antigen
  • Immunogenic component
  • Necessary but not sufficient

72
Anthrax Prevention
  • Vaccine
  • Administration
  • Dose schedule
  • 0, 2 4 wks 6, 12 18 months initial series
  • Annual booster
  • 0.5 ml SQ

73
Anthrax Prevention
  • Vaccine Effective and Safe
  • Efficacy
  • gt95 protection vs. aerosol in animal models
  • gt90 vs. cutaneous in humans
  • Older vaccine that was less immunogenic
  • Protection vs inhalational but too few cases to
    confirm

74
Anthrax Prevention
  • Vaccine
  • Adverse Effects
  • gt1.6 million doses given to military by 4/2000
  • No deaths
  • lt10 moderate/severe local reactions
  • Erythema, edema
  • lt1 systemic reactions
  • Fever, malaise

75
Anthrax Infection Control
  • No person to person transmission
  • Standard Precautions
  • Laboratory safety
  • Biosafety Level (BSL) 2 Precautions

76
Anthrax Decontamination
  • Highest risk of infection at initial release
  • Duration of aerosol viability
  • Several hours to one day under optimal conditions
  • Covert aerosol long dispersed by recognition 1st
    case
  • Risk of secondary aerosolization is low
  • Heavily contaminated small areas
  • May benefit from decontamination
  • Decontamination may not be feasible for large
    areas

77
Anthrax Decontamination
  • Skin, clothing
  • Thorough washing with soap and water
  • Avoid bleach on skin
  • Instruments for invasive procedures
  • Utilize sporicidal agent
  • Sporicidal agents
  • Sodium or calcium hypochlorite (bleach)

78
Anthrax Decontamination
  • Suspicious letters/packages
  • Do not open or shake
  • Place in plastic bag or leak-proof container
  • If visibly contaminated or container unavailable
  • Gently cover paper, clothing, box, trash can
  • Leave room/area, isolate room from others
  • Thoroughly wash hands with soap and water
  • Report to local security / law enforcement
  • List all persons in vicinity

79
Anthrax Decontamination
  • Opened envelope with suspicious substance
  • Gently cover, avoid all contact
  • Leave room and isolate from others
  • Thoroughly wash hands with soap and water
  • Notify local security / law enforcement
  • Carefully remove outer clothing, put in plastic
  • Shower with soap and water
  • List all persons in area

80
Anthrax Outbreak Investigations 2001
  • Case definitions
  • Confirmed case
  • Clinically compatible syndrome
  • culture or 2 non-culture diagnostics
  • Presumptive case
  • Clinically compatible syndrome
  • 1 non-culture diagnostic or confirmed exposure
  • Exposures
  • Confirmed exposure
  • May be aided by nasal swab cultures, serology
  • Asymptomatic

81
Anthrax Outbreak Investigations 2001
  • Florida (Palm Beach)
  • 1st U.S. case since 1976 reported 10/4/01
  • 1st ever cases of intentional infection
  • Inhalational Index Case
  • 63yo man presented with fever and altered MS
  • Preceding flu-like symptoms
  • Reported by astute clinician
  • Noticed GPBs in CSF on 10/2
  • Lab confirmation by State and CDC on 10/4
  • Rapid deterioration, died on 10/5

82
Anthrax Outbreak Investigations 2001
  • Florida Case 2
  • 73yo man
  • Admitted 10/1 for pneumonia
  • Nasal swab culture on 10/5
  • PCR on pleural fluid, serology
  • Responding to antibiotics, still in hospital

83
Anthrax Outbreak Investigations 2001
  • Florida
  • Exposed
  • Anyone at worksite for gt1 hour since 8/1
  • 1/1075 nasal swabs , all given PEP
  • Confirmed powder exposure from mail

84
Anthrax Outbreak Investigations 2001
  • New York City - cutaneous cases
  • Case 1 38 yo woman, NBC employee
  • Handled suspicious letter with powder marked 9/18
  • 9/25 developed raised skin lesion on chest
  • Progressive erythema, edema over 3 days
  • 9/29 malaise and HA, lesion painless
  • 10/1 5cm oval, raised border, satellite vesicles
  • Left cervical lymphadenopathy
  • Black eschar over next few days

85
Outbreak Investigations 2001
  • New York City cutaneous cases
  • Case1
  • Vesicle fluid cx and Gram stain
  • Eschar biopsy immuno-histochemical stain
  • Powder in letter confirmed anthrax spores
  • Improving on oral ciprofloxacin

86
Anthrax Outbreak Investigations 2001
  • New York City cutaneous cases
  • Case 2 7 month old son of ABC worker
  • Visited worksite on 9/28
  • 9/29 large weeping skin lesion left arm
  • Nontender, massive edema
  • Progressed to ulcerative with black eschar
  • Initial Dx- spider bite
  • Complicated by hemolytic anemia, thrombocytopenia
  • 10/12 anthrax considered
  • 10/2 blood PCR, 10/13 skin bx IHC stain
  • No source identified, improving with ciprofloxacin

87
Anthrax Outbreak Investigations 2001
  • New York City
  • Exposures by nasal/facial swab cxs
  • Police officer transporting the NBC sample
  • 2 lab techs processing NBC sample

88
Anthrax Outbreak Investigations 2001
  • Washington, D.C.
  • Letter sent to Senator Daschle
  • Originated from Trenton, NJ
  • 28 Senate staff confirmed exposure
  • Evacuation of Senate then House

89
Anthrax Outbreak Investigations 2001
  • Trenton, New Jersey
  • 2 confirmed inhalational cases
  • Postal workers in distribution center
  • Others with symptoms, results pending
  • 2 suspicious deaths
  • Probable inhalational anthrax

90
Anthrax Outbreak Investigations 2001
As of 10/22/01 FL NY NJ DC
Inhalational 2 0 4 0
Cutaneous 0 4 0 1
Total Cases 2 4 4 1
Exposure 6 3 ? 29
Deaths (all inhalational) 1 0 2 0

91
Anthrax Essential Pearls
  • Rapidly fatal flu-like illness in previous
    healthy
  • Widened mediastinum on Chest X-ray
  • Painless black skin ulcer
  • Non-motile gram positive bacilli in specimens
  • Diagnosis primarily by routine culture
  • No person-to-person transmission
  • Rx prior to prodrome essential for survival
  • Empiric therapy - ciprofloxacin

92
Anthrax Essential Pearls
  • Single inhalational case is an emergency
  • Contact Local Health Departments ASAP

93
Viral Hemorrhagic Fever
94
Hemorrhagic Fever Viruses
  • Families Responsible for VHF
  • Arenaviridae
  • Bunyaviridae
  • Filoviridae
  • Flaviviridae

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Hemorrhagic Fever Viruses
  • Arenaviruses
  • Argentine Hemorrhagic Fever
  • Bolivian Hemorrhagic Fever
  • Sabia Associated Hemorrhagic Fever
  • Lassa Fever

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Hemorrhagic Fever Viruses
  • Bunyaviruses
  • Crimean-Congo Hemorrhagic Fever
  • Rift Valley Fever
  • Hantavirus Pulmonary Syndrome Hemorrhagic Fever

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Hemorrhagic Fever Viruses
  • Filoviruses
  • Ebola Hemorrhagic Fever
  • Marburg Hemorrhagic Fever

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Hemorrhagic Fever Viruses
  • Flaviviruses
  • Tick-borne Encephalitis
  • Kyasanur Forest Disease
  • Omsk Hemorrhagic Fever

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Viral Hemorrhagic Fevers
  • Contagious --- Moderate
  • Infective dose --- 1-10 particles
  • Incubation period --- 4-21 days
  • Duration of illness --- 7-16 days
  • Mortality ---variable
  • Persistence of organism --- unstable
  • Non-endemic in U.S.
  • No vaccine

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VHF Specimens
  • Diagnosis is clinical, not laboratory
  • No specimen accepted without prior consultation

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Handling VHF Specimens
  • Sample for serology - 10-12 ml
  • ship on dry ice
  • Tissue for immunohistochemistry
  • formalin-fixed or paraffin block
  • ship at room temperature
  • Tissue for PCR/virus isolation
  • ante-mortem, post-mortem ship on dry ice
  • Ship serum cold or on dry ice in a plastic tube

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Pneumonic Plague
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Pneumonic Plague
  • Yersinia pestis
  • Gram-negative coccobacillus
  • Flea bite in natural conditions
  • Easily transmitted direct contact person-person
  • High mortality
  • Pneumonic form most deadly

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Plague Epidemiology
  • U.S. averages 13 cases/yr (10 in 1998)
  • 30 of cases are in Native Americans in the
    Southwest. 15 case fatality rate
  • Most cases occur in summer

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Plague Epidemiology
  • U.S. averages 13 cases/yr (10 in 1998)
  • 30 of cases are in Native Americans in the
    Southwest. 15 case fatality rate
  • Most cases occur in summer

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Plague Epidemiology
  • Bubonic
  • Painful adenopathy (bubo) groin or axillae
  • Septicemic
  • Septicemia w/o adenopathy
  • Pneumonic
  • Severe Respiratory Symptoms (Yersinia aerosol
    transmission-bioterroism threat)

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Plague Epidemiology
  • Pneumonic Plague
  • CAP-like Respiratory symptoms
  • Sudden Onset
  • Severe headache
  • Abdominal pain
  • Adenopathy

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Plague Differential Diagnosis
  • Pneumonic Plague
  • Cavitation
  • Multilobar consolidation
  • Highly variable CXR
  • May have alveolar infiltrates
  • May have massive consolidation

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(Yersinia) Schoenlein-Henoch Disease-bacterial
vasculitis

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Safety pin Appearance Y. pestis
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Yersinia pestisTechnical Hints
  • Small gram-negative, poorly staining rods from
    blood, lymph node aspirate, or respiratory
    specimens
  • Safety pin appearance in Gram, Wright, Giemsa, or
    Wayson stain

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Plague Treatment
  • Streptomycin, Gentamycin
  • Effectiveness
  • Time of initiation
  • Access to advanced supportive care
  • Dose of inhaled bacilli

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Plague Alternative Treatments- Prophylaxis of
Close Contacts
  • Adults, Children, Pregnant Women
  • Doxycycline, Ciprofloxacin
  • Mass Casualty Setting Alternative
  • Above or Tetracycline

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Plague Infection Control
  • Facemasks for close patient contact
  • Avoid unnecessary close contact until on
    antibiotics 48 hours
  • Biosafety level-2 labs for simple cultures
  • No need for environmental decontamination of
    areas exposed to plague aerosol.

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Tularemia
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Tularemia
  • Francisella tularensis
  • Flu-Like Illnesses, atypical pneumonias
  • Inhalation route
  • 10-50 microbes -gt Infection Disease
  • No Human-to-Human transmission
  • Isolation not necessary

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Tularemia
  • Plague-like disease in rodents (California)
  • Deer-fly fever (Utah)
  • Glandular tick fever (Idaho and Montana)
  • Market mens disease (Washington, DC)
  • Rabbit fever (Central States)
  • OHaras disease (Japan)

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Tularemia
  • Contagious --- no
  • Infective dose --- 10-50 organisms
  • Incubation period --- 1-21 days (average3-5
    days)
  • Duration of illness --- 2 weeks
  • Mortality --- treated low
    untreated moderate
  • Persistence of organism ---months in moist soil
  • Vaccine efficacy --- good, 80

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Tularemia Clinical Features
  • Targets kidney, liver, lungs,lymph, spleen
  • Spread bloodstream/lymph
  • Organs-PMNs and focal suppurative necrosis

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Alternate Sites-Tularemia
  • Aerosol bioterrorism attack lower respiratory
    infection, eyes, pharynx, skin
  • Broken skin--gtulcerative form
  • GI involvement if ingested

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Tularemia Influenza
  • Chills, coryza, cough, fever, headache, malaise,
    myalgia, sore throat
  • Relative bradycardia ie, pulse-temperature
    dissociation
  • Variable severity
  • Same
  • No dissociation
  • Most symptoms similar

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Lab Tularemia Influenza
  • WBC normal or high
  • UA sterile pyuria
  • 5-15 have elevated LFTs
  • Culture pharynx, sputum or gastric aspirates high
    yield for Francisella tularensis
  • WBC may be normal,
  • No pyuria
  • No LFT elevation

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CXR Tularemia
  • 25-50 abnormal CXR inhalation tularemia
  • Peri-vascular infiltrates early
  • May resemble symptoms and CXR of Anthrax, plague
    or Q-fever

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Tularemia Differs from Similar Bio Weapons
Plague Anthrax Q Fever
Rapid progression Symmetrical mediastinal widening Clinically same as tularemia
Copious sputum Hemoptysis Absence of broncho-pneumonia Lab testing differentiates
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Tularemia Gram Negative Coccobacilli
  • Most likely
  • Acinetobacter
  • Actinobacillus
  • H. aphrophilus
  • Bordetella spp.
  • Pasturella spp.
  • Least likely
  • DF-3
  • Brucella spp.
  • Francisella spp.

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Francisella tularensisTechnical Hints
  • If you see
  • Tiny, gram-negative coccobacilli from blood,
    lymph node aspirate, or respiratory specimens
  • Blood isolates that grow slowly on chocolate agar
    but poorly on blood agar
  • Robust growth in BCYE requires cysteine

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Tularemia Treatment
  • Streptomycin Gentamycin
  • Alternatives
  • Doxycycline, Ciprofloxacin

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Tularemia Mass Casualty RX
  • Exposed Persons Only
  • Their contacts not at high risk
  • Streptomycin or Gentamycin, or Ciprofloxacin,
    Doxycycline
  • CDC has stockpiles, ventilators and emergency
    equipment

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Botulism
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Botulism
  • Clostridium botulinum
  • Most Potent Neurotoxin
  • 169 USA cases in 2001
  • Foodborne or in wounds, usually IVDU

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FOODBORNE BOTULISM
  • Infective dose 0.001 ?g/kg
  • Incubation period 18 - 36 hours
  • Dry mouth, double vision, droopy eyelids, dilated
    pupils
  • Progressive descending bilateral muscle weakness
    paralysis
  • Respiratory failure and death
  • Mortality 5-10, up to 25

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FOODBORNE BOTULISM
  • Among 309 persons with clinically diagnosed
    botulism reported to CDC from 1975 to 1988
  • Stool cultures for C. botulinum 51
  • Serum botulinum toxin testing 37
  • Stool botulinum toxin testing 23
  • Overall, at least one of the above tests was
    positive for 65 of all patients

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Botulism Transmission
  • Home Canned foods, baked potatoes in aluminum
    foil, cheese, fish
  • Wound botulism-spores germinate in open wounds

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Botulism Features
  • Symmetric descending paralysis
  • Motor and autonomic nerves
  • Cranial nerves first affected
  • Death rate 5, respiratory failure
  • Recovery takes months

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Botulism Incubation
  • 2 hours to 8 days (dose related)
  • Heat inactivates (gt85C for 5 minutes)
  • Lab testing Call Public Health Lab
  • Should be suspected if multiple persons
    simultaneously present with similar symptoms
    need to get good history of each persons past
    activities

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Botulism Symptoms
  • Alert mental status
  • Fatigue, dizziness, dysarthria, facial palsy
  • Vision blurred, double, ptosis
  • Dysphagia, dry mouth
  • Dyspnea
  • Constipation
  • Weakness, progressive

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Botulism Differential Diagnosis
  • Notable symmetrical weakness
  • Absence of sensory nerve damage
  • Descending flaccid paralysis
  • Prominent cranial nerve palsies

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Botulism Confused with
  • Myasthenia Gravis
  • Tick Paralysis
  • Organophosphate intoxication
  • CNS infections
  • More likely than, but confused with
    polyradiculoneuropathy
  • Guillain-Barre or Miller-Fisher syndrome

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BOTULISM
  • Diagnosis of botulism is made clinically
  • Health care providers suspecting botulism should
    contact their State Health Department

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Botulism Treatment
  • Antibiotics not useful
  • Equine Antitoxin risky
  • Neurologic support
  • No neuromuscular blockade drugs
  • Ventilatory support

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Botulism Biosafety Alert
  • Botulism toxins are extremely poisonous
  • Minute quantities acquired by ingestion,
    inhalation, or by absorption can cause death
  • All materials suspected of containing toxin must
    be handled with CAUTION!

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