Title: Anthrax
1Anthrax
2Anthrax 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
3Anthrax 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
4Anthrax 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)
5Anthrax 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
6Anthrax 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
7Anthrax 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
8Anthrax 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
9Anthrax 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
10Anthrax 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
11Anthrax Epidemiology
- Mortality
- Inhalational 86-100 (despite treatment)
- Era of crude intensive supportive care
- Cutaneous lt5 (treated) 20 (untreated)
- GI approaches 100
12Anthrax 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
13Anthrax Epidemiology
- Human cases historical risk factors
- Agricultural
- Exposure to livestock
- Occupational
- Exposure to wool and hides
- Woolsorters disease inhalational anthrax
- Rarely laboratory-acquired
14Anthrax Epidemiology
- Transmission
- No human-to-human
- Naturally occurring cases
- Skin exposure
- Ingestion
- Airborne
- Bioterrorism
- Aerosol (likely)
- Small volume powder (possible)
- Foodborne (unlikely)
15Anthrax 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
16Anthrax 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
17Anthrax 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
18Anthrax 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
19Anthrax 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
20Anthrax 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
21Anthrax 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
22Microbiology
- Virulence Factors
- All necessary for full virulence
- Two plasmids
- Capsule (plasmid pXO2)
- Antiphagocytic
- 3 Exotoxin components (plasmid pXO1)
- Protective Antigen
- Edema Factor
- Lethal Factor
23Anthrax 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
24Anthrax 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
25Anthrax Pathogenesis
- Forms of natural disease
- Inhalational
- Cutaneous
- Gastrointestinal
- Determined by route of entry
- Disease occurs wherever spores germinate
26Anthrax 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
27Anthrax 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
28Anthrax 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
29Anthrax 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
30Anthrax 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
31Anthrax 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
32Anthrax 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
33Anthrax 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
34Anthrax Clinical Features
- Symptoms depend on form of disease
- Inhalational
- Cutaneous
- Gastrointestinal
35Anthrax 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
36Anthrax 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
37Anthrax 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
38Anthrax Clinical Features
- Cutaneous
- Most common areas of exposure
- Hands/arms
- Neck/head
- Incubation period
- 3-5 days typical
- 12 days maximum
39Anthrax Clinical Features
- Cutaneous progression of painless lesions
- Papule pruritic
- Vesicle/bulla
- Ulcer contains organisms, sig. edema
- Eschar black, rarely scars
24-36 hrs
days
40Anthrax Clinical Features
- Cutaneous
- Systemic disease may develop
- Lymphangitis and lymphadenopathy
- If untreated, can progress to sepsis, death
41Anthrax Clinical Features
- Gastrointestinal
- Oropharyngeal
- Oral or esophageal ulcer
- Regional lymphadenopathy
- Edema, ascites
- Sepsis
- Abdominal
- Early symptoms - nausea, vomiting, malaise
- Late - hematochezia, acute abdomen, ascites
42Anthrax Diagnosis
- Early diagnosis is difficult
- Non specific symptoms
- Initially mild
- No readily available rapid specific tests
43Anthrax 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
44Anthrax 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
45Anthrax 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
46Anthrax 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
47Anthrax 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
48Anthrax 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
49Anthrax 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
50Anthrax 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
51Anthrax 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
52Anthrax Differential Diagnosis
- Expect if anthrax
- Critically ill
- Acute abdomen
- Bloody diarrhea
- Fever
- Gastrointestinal
- Gastroenteritis
- Typhoid
- Peritonitis
- Perforated ulcer
- Bowel obstruction
53Anthrax 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
54Anthrax 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
55Anthrax Treatment
- Hospitalization
- IV antibiotics
- Empiric until sensitivities are known
- Intensive supportive care
- Electrolyte and acid-base imbalances
- Mechanical ventilation
- Hemodynamic support
56Anthrax 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
57Anthrax 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
58Anthrax 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
59Anthrax 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)
60Anthrax Treatment
- Empiric therapy
- Pregnant women
- Same as other adults
- Weigh small risks (fetal arthropathy) vs benefit
- Immunosuppressed
- Same as other adults
61Anthrax Treatment
- Alternative antibiotics
- If susceptible, or cipro/doxy not possible
- Penicillin, amoxicillin
- Gentamicin, streptomycin
- Erythromycin, chloramphenicol
- Ineffective antibiotics
- Trimethoprim/Sulfamethoxazole
- Third generation cephalosporins
62Anthrax 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
63Anthrax 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
64Anthrax 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
65Anthrax Postexposure Prophylaxis
- Who should receive PEP?
- Anyone exposed to anthrax
- Not for contacts of cases, unless also exposed
- Empiric antibiotic therapy
- Vaccination
66Anthrax 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
67Anthrax Postexposure Prophylaxis
- Antibiotic therapy
- Treat ASAP
- Prompt therapy can improve survival
- Continue for 60 days
- 30-45 days if vaccine administered
68Anthrax 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
69Anthrax 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
70Anthrax Prevention
- Vaccine
- Anthrax Vaccine Absorbed (AVA)
- Supply
- Limited, controlled by CDC
- Production problems
- Single producer Bioport, Michigan
- Failed FDA standards
- None produced since 1998
71Anthrax Prevention
- Vaccine
- Inactivated, cell-free filtrate
- Purified with Al(OH)3
- Protective Antigen
- Immunogenic component
- Necessary but not sufficient
72Anthrax Prevention
- Vaccine
- Administration
- Dose schedule
- 0, 2 4 wks 6, 12 18 months initial series
- Annual booster
- 0.5 ml SQ
73Anthrax 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
74Anthrax 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
75Anthrax Infection Control
- No person to person transmission
- Standard Precautions
- Laboratory safety
- Biosafety Level (BSL) 2 Precautions
76Anthrax 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
77Anthrax 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)
78Anthrax 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
79Anthrax 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
80Anthrax 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
81Anthrax 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
82Anthrax 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
83Anthrax 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
84Anthrax 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
85Outbreak 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
86Anthrax 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
87Anthrax Outbreak Investigations 2001
- New York City
- Exposures by nasal/facial swab cxs
- Police officer transporting the NBC sample
- 2 lab techs processing NBC sample
88Anthrax 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
89Anthrax 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
90Anthrax 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
91Anthrax 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
92Anthrax Essential Pearls
- Single inhalational case is an emergency
- Contact Local Health Departments ASAP
93Viral Hemorrhagic Fever
94Hemorrhagic Fever Viruses
- Families Responsible for VHF
- Arenaviridae
- Bunyaviridae
- Filoviridae
- Flaviviridae
95Hemorrhagic Fever Viruses
- Arenaviruses
- Argentine Hemorrhagic Fever
- Bolivian Hemorrhagic Fever
- Sabia Associated Hemorrhagic Fever
- Lassa Fever
96Hemorrhagic Fever Viruses
- Bunyaviruses
- Crimean-Congo Hemorrhagic Fever
- Rift Valley Fever
- Hantavirus Pulmonary Syndrome Hemorrhagic Fever
97Hemorrhagic Fever Viruses
- Filoviruses
- Ebola Hemorrhagic Fever
- Marburg Hemorrhagic Fever
98Hemorrhagic Fever Viruses
- Flaviviruses
- Tick-borne Encephalitis
- Kyasanur Forest Disease
- Omsk Hemorrhagic Fever
99Viral 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
100VHF Specimens
- Diagnosis is clinical, not laboratory
- No specimen accepted without prior consultation
101Handling 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
102Pneumonic Plague
103Pneumonic Plague
- Yersinia pestis
- Gram-negative coccobacillus
- Flea bite in natural conditions
- Easily transmitted direct contact person-person
- High mortality
- Pneumonic form most deadly
104Plague 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
105Plague 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
106Plague Epidemiology
- Bubonic
- Painful adenopathy (bubo) groin or axillae
- Septicemic
- Septicemia w/o adenopathy
- Pneumonic
- Severe Respiratory Symptoms (Yersinia aerosol
transmission-bioterroism threat)
107Plague Epidemiology
- Pneumonic Plague
- CAP-like Respiratory symptoms
- Sudden Onset
- Severe headache
- Abdominal pain
- Adenopathy
108Plague Differential Diagnosis
- Pneumonic Plague
- Cavitation
- Multilobar consolidation
- Highly variable CXR
- May have alveolar infiltrates
- May have massive consolidation
109(No Transcript)
110(No Transcript)
111(Yersinia) Schoenlein-Henoch Disease-bacterial
vasculitis
112Safety pin Appearance Y. pestis
113Yersinia 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
114Plague Treatment
- Streptomycin, Gentamycin
- Effectiveness
- Time of initiation
- Access to advanced supportive care
- Dose of inhaled bacilli
115Plague Alternative Treatments- Prophylaxis of
Close Contacts
- Adults, Children, Pregnant Women
- Doxycycline, Ciprofloxacin
- Mass Casualty Setting Alternative
- Above or Tetracycline
116Plague 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.
117Tularemia
118Tularemia
- Francisella tularensis
- Flu-Like Illnesses, atypical pneumonias
- Inhalation route
- 10-50 microbes -gt Infection Disease
- No Human-to-Human transmission
- Isolation not necessary
119Tularemia
- 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)
120Tularemia
- 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
121Tularemia Clinical Features
- Targets kidney, liver, lungs,lymph, spleen
- Spread bloodstream/lymph
- Organs-PMNs and focal suppurative necrosis
122Alternate Sites-Tularemia
- Aerosol bioterrorism attack lower respiratory
infection, eyes, pharynx, skin - Broken skin--gtulcerative form
- GI involvement if ingested
123(No Transcript)
124Tularemia Influenza
- Chills, coryza, cough, fever, headache, malaise,
myalgia, sore throat - Relative bradycardia ie, pulse-temperature
dissociation - Variable severity
- Same
- No dissociation
- Most symptoms similar
125Lab 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
126CXR Tularemia
- 25-50 abnormal CXR inhalation tularemia
- Peri-vascular infiltrates early
- May resemble symptoms and CXR of Anthrax, plague
or Q-fever
127Tularemia 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
128Tularemia Gram Negative Coccobacilli
- Most likely
- Acinetobacter
- Actinobacillus
- H. aphrophilus
- Bordetella spp.
- Pasturella spp.
- Least likely
- DF-3
- Brucella spp.
- Francisella spp.
129Francisella 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
130Tularemia Treatment
- Streptomycin Gentamycin
- Alternatives
- Doxycycline, Ciprofloxacin
131Tularemia 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
132Botulism
133Botulism
- Clostridium botulinum
- Most Potent Neurotoxin
- 169 USA cases in 2001
- Foodborne or in wounds, usually IVDU
134FOODBORNE 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
135FOODBORNE 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
136Botulism Transmission
- Home Canned foods, baked potatoes in aluminum
foil, cheese, fish - Wound botulism-spores germinate in open wounds
137Botulism Features
- Symmetric descending paralysis
- Motor and autonomic nerves
- Cranial nerves first affected
- Death rate 5, respiratory failure
- Recovery takes months
138Botulism 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
139Botulism Symptoms
- Alert mental status
- Fatigue, dizziness, dysarthria, facial palsy
- Vision blurred, double, ptosis
- Dysphagia, dry mouth
- Dyspnea
- Constipation
- Weakness, progressive
140Botulism Differential Diagnosis
- Notable symmetrical weakness
- Absence of sensory nerve damage
- Descending flaccid paralysis
- Prominent cranial nerve palsies
141Botulism Confused with
- Myasthenia Gravis
- Tick Paralysis
- Organophosphate intoxication
- CNS infections
- More likely than, but confused with
polyradiculoneuropathy - Guillain-Barre or Miller-Fisher syndrome
142BOTULISM
- Diagnosis of botulism is made clinically
- Health care providers suspecting botulism should
contact their State Health Department
143Botulism Treatment
- Antibiotics not useful
- Equine Antitoxin risky
- Neurologic support
- No neuromuscular blockade drugs
- Ventilatory support
144Botulism 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!
145Questions?