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Anthrax
Saint Louis Unversity School of Public Health
Anthrax: HistoryCaused by Bacillus anthracisHuman zoonotic disease
Spores found in soil worldwidePrimarily disease of herbivorous animals• Sheep, goats, cattle• Many large documented epizootics
Occasional human disease• Epidemics have occurred but
uncommon• Rare in developed world
Saint Louis Unversity School of Public Health
Anthrax: Bioweapon PotentialMany 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
Saint Louis Unversity School of Public Health
Anthrax: Bioweapon Potential
Features of anthrax suitable as BT agent
Fairly easy to obtain, produce and storeSpores easily dispersed as aerosolModerately infectiousHigh mortality for inhalational (86-100%)
Saint Louis Unversity School of Public Health
Anthrax: Bioweapon Potential
Aerosol method of deliveryMost likely method expected in BT attackWould 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
Saint Louis Unversity School of Public Health
Anthrax: Bioweapon Potential
Dispersed as powderFrequent letter hoaxes since 1997Recent letter deliveries• Highest risk is for cutaneous• Inhalational theoretically possible
– Particle size– Likelihood of aerosolization
• GI theoretically possible– Spores > hands > eating without handwashing
Saint Louis Unversity School of Public Health
Anthrax: Bioweapon Potential
Sverdlovsk, Russia 1979Accidental release from anthrax drying plant79 human cases• All downwind of plant• 68 deaths• Some infected with multiples strains
Saint Louis Unversity School of Public Health
Anthrax: Bioweapon PotentialEstimated 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
Saint Louis Unversity School of Public Health
Anthrax: EpidemiologyThree forms of natural disease
Inhalational• Rare (<5%)• Most likely encountered in bioterrorism
event
Cutaneous• Most common (95%)• Direct contact of spores on skin
Gastrointestinal• Rare (<5%), never reported in U.S.• Ingestion
Saint Louis Unversity School of Public Health
Anthrax: EpidemiologyAll ages and genders affectedOccurs worldwideEndemic areas - Africa, AsiaTrue incidence not known
World 20,000-100,000 in 1958U.S. 235 total reported cases 1955-1994
• 18 cases inhalational since 1900, last one 1976
• Until 2001, last previous case cutaneous 1992
Saint Louis Unversity School of Public Health
Anthrax: Epidemiology
MortalityInhalational 86-100% (despite treatment)• Era of crude intensive supportive care
Cutaneous <5% (treated) – 20% (untreated)GI approaches 100%
Saint Louis Unversity School of Public Health
Anthrax: Epidemiology
Incubation PeriodTime from exposure to symptomsVery variable for inhalational• 2-43 days reported• Theoretically may be up to 100 days• Delayed germination of spores
Saint Louis Unversity School of Public Health
Anthrax: Epidemiology
Human cases – historical risk factors
Agricultural• Exposure to livestock
Occupational• Exposure to wool and hides• Woolsorter’s disease = inhalational
anthrax• Rarely laboratory-acquired
Saint Louis Unversity School of Public Health
Anthrax: EpidemiologyTransmission
No human-to-humanNaturally occurring cases• Skin exposure• Ingestion• Airborne
Bioterrorism• Aerosol (likely)• Small volume powder (possible)• Foodborne (unlikely)
Saint Louis Unversity School of Public Health
Anthrax: Epidemiology
TransmissionInhalational• Handling hides/skins of infected animals• Microbiology laboratory • Intentional aerosol release• Small volume powdered form
– In letters, packages, etc– Questionable risk, probably small
Saint Louis Unversity School of Public Health
Anthrax: Epidemiology
TransmissionCutaneous• 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
Saint Louis Unversity School of Public Health
Anthrax: Epidemiology
TransmissionGastrointestinal• 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 >5 m
– Land in oropharynx
Saint Louis Unversity School of Public Health
Anthrax: MicrobiologyBacillus anthracis
Aerobic, Gram positive rodLong (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
Saint Louis Unversity School of Public Health
Anthrax: Microbiology
Colony characteristicsLarge (4-5mm)Non-hemolyticOpaque white, grayRetain shape when manipulated (“egg white”)Forms capsule at 37º C, 5-20% CO2
Saint Louis Unversity School of Public Health
Anthrax: MicrobiologyClassification
Same family: B. cereus, B. thuringiensisDifferentiation from other Bacillus species• Non-motile• Non β-hemolytic on blood agar• Does not ferment salicin
Note: Gram positive rods are usually labeled as “contaminants” by micro labs
Saint Louis Unversity School of Public Health
Anthrax: MicrobiologyEnvironmental Survival
Spores are hardy• Resistant to drying, boiling <10 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
Saint Louis Unversity School of Public Health
Microbiology
Virulence FactorsAll necessary for full virulenceTwo plasmids • Capsule (plasmid pXO2)
– Antiphagocytic
• 3 Exotoxin components (plasmid pXO1)– Protective Antigen– Edema Factor– Lethal Factor
Saint Louis Unversity School of Public Health
Anthrax: MicrobiologyProtective Antigen
Binds Edema Factor to form Edema ToxinFacilitates entry of Edema Toxin into cells
Edema FactorMassive edema by increasing intracellular cAMPAlso inhibits neutrophil function
Lethal FactorStimulates macrophage release of TNF-α, IL-1βInitiates cascade of events leading to sepsis
Saint Louis Unversity School of Public Health
Anthrax: Pathogenesis
Disease requires entry of spores into bodyExposure does not always cause disease
Inoculation doseRoute of entryHost immune statusMay depend on pathogen strain characteristics
Saint Louis Unversity School of Public Health
Anthrax: Pathogenesis
Forms of natural diseaseInhalationalCutaneousGastrointestinal
Determined by route of entryDisease occurs wherever spores germinate
Saint Louis Unversity School of Public Health
Anthrax: PathogenesisInhalational
Spores on particles 1-5 mInhaled and deposited into alveoliEstimated LD50 = 2500 – 55,000 spores• Dose required for lethal infection in
50% exposed• Contained in imperceptibly small
volume
Saint Louis Unversity School of Public Health
Anthrax: PathogenesisInhalational
Phagocytosed by alveolar macrophagesMigration 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
Saint Louis Unversity School of Public Health
Anthrax: Pathogenesis
InhalationalVegetative 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
Saint Louis Unversity School of Public Health
Anthrax: PathogenesisInhalational
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
Saint Louis Unversity School of Public Health
Anthrax: Pathogenesis
CutaneousSpores in contact with skin• Entry through visible cuts or micro-trauma
Germination in skinDisease begins following germination• Toxin production
– Local edema, erythema, necrosis, lymphocytic infiltrate
– No abscess or suppurative lesions
• Eventual eschar formation
Saint Louis Unversity School of Public Health
Anthrax: Pathogenesis
CutaneousSystemic disease• Can occur, especially if untreated• Spores/bacteria carried to regional lymph
nodes– Lymphangitis/lymphadenitis– Same syndrome as inhalational– Sepsis, multi-organ failure
Saint Louis Unversity School of Public Health
Anthrax: PathogenesisGastrointestinal
Spores contact mucosa• Oropharynx
– Ingestion– Aerosolized particles >5 m
• Intestinal mucosa – terminal ileum, cecum– Ingestion
Larger number of spores required for diseaseIncubation period 2-5 days
Saint Louis Unversity School of Public Health
Anthrax: PathogenesisGastrointestinal
Spores migrate to lymphatics• Submucosal, mucosal lymphatic tissue• Mesenteric nodes
Germination to vegetative bacilliToxin production• Massive mucosal edema• Mucosal ulcers, necrosis
Death from perforation or systemic disease
Saint Louis Unversity School of Public Health
Anthrax: Clinical Features
Symptoms depend on form of disease
InhalationalCutaneousGastrointestinal
Saint Louis Unversity School of Public Health
Anthrax: Clinical FeaturesInhalational
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
Saint Louis Unversity School of Public Health
Anthrax: Clinical FeaturesInhalational
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 <36 hrs– Mean time from symptom onset to death ~3 days
Saint Louis Unversity School of Public Health
Anthrax: Clinical Features
Laboratory FindingsGram positive bacilli in direct blood smearElectrolyte imbalances common
Radiographic FindingsWidened mediastinum• Minimal or no infiltrates
Can appear during prodrome phase
Saint Louis Unversity School of Public Health
Anthrax: Clinical FeaturesCutaneous
Most common areas of exposure• Hands/arms• Neck/head
Incubation period• 3-5 days typical• 12 days maximum
Saint Louis Unversity School of Public Health
Anthrax: Clinical FeaturesCutaneous – progression of painless lesions
Papule – pruritic
Vesicle/bulla
Ulcer – contains organisms, sig. edema
Eschar – black, rarely scars
24-36 hrs
days
Saint Louis Unversity School of Public Health
Anthrax: Clinical Features
CutaneousSystemic disease may develop• Lymphangitis and lymphadenopathy• If untreated, can progress to sepsis,
death
Saint Louis Unversity School of Public Health
Anthrax: Clinical FeaturesGastrointestinal
Oropharyngeal• Oral or esophageal ulcer
– Regional lymphadenopathy– Edema, ascites– Sepsis
Abdominal• Early symptoms - nausea, vomiting, malaise• Late - hematochezia, acute abdomen,
ascites
Saint Louis Unversity School of Public Health
Anthrax: Diagnosis
Early diagnosis is difficultNon specific symptoms Initially mildNo readily available rapid specific tests
Saint Louis Unversity School of Public Health
Anthrax: DiagnosisPresumptive diagnosis
History of possible exposureTypical signs & symptomsRapidly progressing nonspecific illnessWidened mediastinum on CXRLarge Gram+ bacilli from specimens
• Can be seen on Gram stain if hi-grade bacteremia
Appropriate colonial morphologyNecrotizing mediastinitis, meningitis at autopsy
Saint Louis Unversity School of Public Health
Anthrax: DiagnosisDefinitive 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 >99% confirmation
– Available at Reference laboratories
Saint Louis Unversity School of Public Health
Anthrax: Diagnosis
Definitive diagnosisRapid 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
Saint Louis Unversity School of Public Health
Anthrax: DiagnosisOther 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
Saint Louis Unversity School of Public Health
Anthrax: Diagnosis
Testing for exposureNasal 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
Saint Louis Unversity School of Public Health
Anthrax: Diagnosis
Environmental samplesSuspicious powders• Must be sent to reference laboratories
as part of epidemiologic/criminal investigation
• Assessed using cultures, stains, PCR
Air samplingFirst responders• Handheld immunoassays
– Not validated– Useful for detecting massive contamination
Saint Louis Unversity School of Public Health
Anthrax: DiagnosisTest Availabilit
yTime 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
Saint Louis Unversity School of Public Health
Anthrax: Differential DiagnosisInhalational
Influenza
Pneumonia• Community-acquired• Atypical• Pneumonic tularemia• Pneumonic plague
Mediastinitis Bacterial meningitisThoracic aortic aneurysm
Expect if anthraxFlu rapid diagnostic –More severe in young
ptsNo infiltrate
No prior surgeryBloody CSF with GPBsFever
Saint Louis Unversity School of Public Health
Anthrax: Differential DiagnosisCutaneous
Spider biteEcthyma gangrenosumPyoderma gangrenosumUlceroglandular tularemiaMycobacterial ulcerCellulitis
Expect if anthraxfeverno response to 3º cephalosporinspainless, black eschar+/- lymphadenopathyusually sig. local edema
Saint Louis Unversity School of Public Health
Anthrax: Differential Diagnosis
GastrointestinalGastroenteritisTyphoid PeritonitisPerforated ulcerBowel obstruction
Expect if anthraxCritically illAcute abdomenBloody diarrheaFever
Saint Louis Unversity School of Public Health
Anthrax: Differential DiagnosisImpact of suspected BT during flu season
Early disease mimics influenzaAffects same populationIncreased 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
Saint Louis Unversity School of Public Health
Anthrax: TreatmentImmediately treat presumptive cases
Prior to confirmationRapid 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
Saint Louis Unversity School of Public Health
Anthrax: Treatment
HospitalizationIV antibiotics
Empiric until sensitivities are known
Intensive supportive careElectrolyte and acid-base imbalancesMechanical ventilationHemodynamic support
Saint Louis Unversity School of Public Health
Anthrax: Treatment
Antibiotic selectionNaturally occurring strains
• Rare penicillin resistance, but inducible β-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
Saint Louis Unversity School of Public Health
Anthrax: TreatmentEmpiric Therapy
Until susceptibility patterns knownAdults• Ciprofloxacin 400 mg IV q12°
ORDoxycycline 100mg IV q12°
AND (for inhalational)
One or two other antibiotics
Saint Louis Unversity School of Public Health
Anthrax: Treatment
Other antibiotic considerationsOther fluoroquinolones possibly equivalentHigh 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
Saint Louis Unversity School of Public Health
Anthrax: Treatment
Empiric TherapyChildren• Ciprofloxacin 10-15 mg/kg/d IV q12°, max
1 g/d ORDoxycycline 2.2 mg/kg IV q12°
(adult dosage if >8 years and >45 kg)
• Add one or two antibiotics for inhalational• Weigh risks (arthropathy, dental enamel)
Saint Louis Unversity School of Public Health
Anthrax: Treatment
Empiric therapyPregnant women• Same as other adults• Weigh small risks (fetal arthropathy) vs
benefit
Immunosuppressed• Same as other adults
Saint Louis Unversity School of Public Health
Anthrax: TreatmentAlternative antibiotics
If susceptible, or cipro/doxy not possible• Penicillin, amoxicillin • Gentamicin, streptomycin• Erythromycin, chloramphenicol
Ineffective antibioticsTrimethoprim/SulfamethoxazoleThird generation cephalosporins
Saint Louis Unversity School of Public Health
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
Saint Louis Unversity School of Public Health
Anthrax: Treatment
Antibiotic therapyDuration• 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
Saint Louis Unversity School of Public Health
Anthrax: Treatment
Other therapiesPassive 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
Saint Louis Unversity School of Public Health
Anthrax: Postexposure Prophylaxis
Who should receive PEP?Anyone exposed to anthrax Not for contacts of cases, unless also exposed
Empiric antibiotic therapy Vaccination
Saint Louis Unversity School of Public Health
Anthrax: Postexposure Prophylaxis
Avoid unnecessary antibiotic usagePotential shortages of those who need themPotential adverse effects
• Hypersensitivity• Neurological side effects, especially elderly• Bone/cartilage disease in children• Oral contraceptive failure
Future antibiotic resistance• Individual’s own flora• Community resistance patterns
Saint Louis Unversity School of Public Health
Anthrax: Postexposure Prophylaxis
Antibiotic therapyTreat ASAPPrompt therapy can improve survivalContinue for 60 days• 30-45 days if vaccine administered
Saint Louis Unversity School of Public Health
Anthrax: Postexposure Prophylaxis
Antibiotic agentsSame 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
Saint Louis Unversity School of Public Health
Anthrax: Postexposure Prophylaxis
Antibiotic agentsChildren• Same dose adjustments as treatment• Weigh benefits vs. risks• Recommended switch if PCN-susceptible
– Amoxicillin 80 mg/kg/day, max 500 mg tid
Saint Louis Unversity School of Public Health
Anthrax: Prevention
VaccineAnthrax Vaccine Absorbed (AVA)Supply• Limited, controlled by CDC• Production problems
– Single producer – Bioport, Michigan– Failed FDA standards– None produced since 1998
Saint Louis Unversity School of Public Health
Anthrax: Prevention
VaccineInactivated, cell-free filtratePurified with Al(OH)3
Protective Antigen • Immunogenic component• Necessary but not sufficient
Saint Louis Unversity School of Public Health
Anthrax: Prevention
VaccineAdministration• Dose schedule
– 0, 2 & 4 wks; 6, 12 & 18 months initial series– Annual booster
• 0.5 ml SQ
Saint Louis Unversity School of Public Health
Anthrax: Prevention
Vaccine – Effective and SafeEfficacy• >95% protection vs. aerosol in animal
models• >90% vs. cutaneous in humans
– Older vaccine that was less immunogenic– Protection vs inhalational but too few cases to
confirm
Saint Louis Unversity School of Public Health
Anthrax: Prevention
VaccineAdverse Effects• >1.6 million doses given to military by
4/2000• No deaths• <10% moderate/severe local reactions
– Erythema, edema
• <1% systemic reactions– Fever, malaise
Saint Louis Unversity School of Public Health
Anthrax: Infection Control
No person to person transmissionStandard Precautions Laboratory safety
Biosafety Level (BSL) 2 Precautions
Saint Louis Unversity School of Public Health
Anthrax: Decontamination
Highest risk of infection at initial releaseDuration 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
Saint Louis Unversity School of Public Health
Anthrax: DecontaminationSkin, clothing
Thorough washing with soap and waterAvoid bleach on skin
Instruments for invasive proceduresUtilize sporicidal agent
Sporicidal agentsSodium or calcium hypochlorite (bleach)
Saint Louis Unversity School of Public Health
Anthrax: Decontamination
Suspicious letters/packagesDo not open or shakePlace in plastic bag or leak-proof containerIf visibly contaminated or container unavailable
• Gently cover – paper, clothing, box, trash can
Leave room/area, isolate room from othersThoroughly wash hands with soap and waterReport to local security / law enforcementList all persons in vicinity
Saint Louis Unversity School of Public Health
Anthrax: Decontamination
Opened envelope with suspicious substance
Gently cover, avoid all contactLeave room and isolate from othersThoroughly wash hands with soap and waterNotify local security / law enforcementCarefully remove outer clothing, put in plasticShower with soap and waterList all persons in area
Saint Louis Unversity School of Public Health
Anthrax: Outbreak Investigations 2001
Case definitionsConfirmed 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
Saint Louis Unversity School of Public Health
Anthrax: Outbreak Investigations 2001
Florida (Palm Beach)1st U.S. case since 1976 reported 10/4/011st ever cases of intentional infectionInhalational Index Case• 63yo man presented with fever and altered
MS • Preceding flu-like symptoms• Reported by astute clinician
– Noticed GPB’s in CSF on 10/2– Lab confirmation by State and CDC on 10/4
• Rapid deterioration, died on 10/5
Saint Louis Unversity School of Public Health
Anthrax: Outbreak Investigations 2001
Florida Case #273yo manAdmitted 10/1 for pneumoniaNasal swab culture + on 10/5PCR+ on pleural fluid, serology +Responding to antibiotics, still in hospital
Saint Louis Unversity School of Public Health
Anthrax: Outbreak Investigations 2001
FloridaExposed• Anyone at worksite for >1 hour since 8/1• 1/1075 nasal swabs +, all given PEP
Confirmed powder exposure from mail
Saint Louis Unversity School of Public Health
Anthrax: Outbreak Investigations 2001New 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
Saint Louis Unversity School of Public Health
Outbreak Investigations 2001
New York City – cutaneous casesCase#1• Vesicle fluid –cx and Gram stain• Eschar biopsy +immuno-histochemical
stain• Powder in letter confirmed anthrax
spores• Improving on oral ciprofloxacin
Saint Louis Unversity School of Public Health
Anthrax: Outbreak Investigations 2001
New York City – cutaneous casesCase #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
Saint Louis Unversity School of Public Health
Anthrax: Outbreak Investigations 2001
New York CityExposures by nasal/facial swab cx’s• Police officer transporting the NBC
sample• 2 lab techs processing NBC sample
Saint Louis Unversity School of Public Health
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
Saint Louis Unversity School of Public Health
Anthrax: Outbreak Investigations 2001
Trenton, New Jersey2 confirmed inhalational cases• Postal workers in distribution center• Others with symptoms, results pending
2 suspicious deaths• Probable inhalational anthrax
Saint Louis Unversity School of Public Health
Anthrax: Outbreak Investigations 2001As 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
Saint Louis Unversity School of Public Health
Anthrax Essential Pearls
Rapidly fatal flu-like illness in previous healthyWidened mediastinum on Chest X-rayPainless black skin ulcerNon-motile gram positive bacilli in specimensDiagnosis primarily by routine cultureNo person-to-person transmissionRx prior to prodrome essential for survivalEmpiric therapy - ciprofloxacin
Saint Louis Unversity School of Public Health
Anthrax Essential Pearls
Single inhalational case is an emergency
Contact Local Health Departments ASAP
Viral Hemorrhagic Fever
Centers for Disease Control and Prevention
Hemorrhagic Fever VirusesFamilies Responsible for VHF:
ArenaviridaeBunyaviridaeFiloviridaeFlaviviridae
Centers for Disease Control and Prevention
Hemorrhagic Fever Viruses
ArenavirusesArgentine Hemorrhagic FeverBolivian Hemorrhagic FeverSabia Associated Hemorrhagic FeverLassa Fever
Centers for Disease Control and Prevention
Hemorrhagic Fever Viruses
BunyavirusesCrimean-Congo Hemorrhagic FeverRift Valley FeverHantavirus Pulmonary Syndrome Hemorrhagic Fever
Centers for Disease Control and Prevention
Hemorrhagic Fever Viruses
FilovirusesEbola Hemorrhagic FeverMarburg Hemorrhagic Fever
Centers for Disease Control and Prevention
Hemorrhagic Fever Viruses
FlavivirusesTick-borne EncephalitisKyasanur Forest DiseaseOmsk Hemorrhagic Fever
Centers for Disease Control and Prevention
Viral Hemorrhagic FeversContagious --- ModerateInfective dose --- 1-10 particlesIncubation period --- 4-21 daysDuration of illness --- 7-16 daysMortality ---variablePersistence of organism --- unstableNon-endemic in U.S.No vaccine
Centers for Disease Control and Prevention
VHF Specimens
Diagnosis is clinical, not laboratoryNo specimen accepted without prior consultation
Centers for Disease Control and Prevention
Handling VHF SpecimensSample for serology - 10-12 ml
ship on dry ice
Tissue for immunohistochemistryformalin-fixed or paraffin blockship at room temperature
Tissue for PCR/virus isolationante-mortem, post-mortem; ship on dry ice
Ship serum cold or on dry ice in a plastic tube
Pneumonic Plague
Pneumonic Plague
Yersinia pestisGram-negative coccobacillus
Flea bite in natural conditionsEasily transmitted direct contact person-personHigh mortalityPneumonic form most deadly
Centers for Disease Control and Prevention
Plague Epidemiology
U.S. averages 13 cases/yr (10 in 1998)30% of cases are in Native Americans in the Southwest. 15% case fatality rateMost cases occur in summer
Centers for Disease Control and Prevention
Plague Epidemiology
U.S. averages 13 cases/yr (10 in 1998)30% of cases are in Native Americans in the Southwest. 15% case fatality rateMost cases occur in summer
Plague Epidemiology
Bubonic Painful adenopathy (bubo) groin or axillae
Septicemic Septicemia w/o adenopathy
Pneumonic Severe Respiratory Symptoms (Yersinia aerosol transmission-bioterroism threat)
Plague Epidemiology
Pneumonic PlagueCAP-like Respiratory symptomsSudden Onset Severe headache Abdominal pain Adenopathy
Plague Differential Diagnosis
Pneumonic PlagueCavitation Multilobar consolidation
Highly variable CXRMay have alveolar infiltratesMay have massive consolidation
(Yersinia) Schoenlein-Henoch Disease-bacterial vasculitis
Safety pin Appearance Y. pestis
Centers for Disease Control and Prevention
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
Centers for Disease Control and Prevention
Plague Treatment
Streptomycin, Gentamycin Effectiveness
Time of initiationAccess to advanced supportive care Dose of inhaled bacilli
Plague Alternative Treatments-& Prophylaxis of Close Contacts
Adults, Children, Pregnant Women
Doxycycline, Ciprofloxacin
Mass Casualty Setting Alternative
Above or Tetracycline
Centers for Disease Control and Prevention
Plague Infection Control
Facemasks for close patient contactAvoid unnecessary close contact until on antibiotics 48 hoursBiosafety level-2 labs for simple culturesNo need for environmental decontamination of areas exposed to plague aerosol.
Tularemia
Tularemia
Francisella tularensisFlu-Like Illnesses, atypical pneumoniasInhalation route 10-50 microbes -> Infection & DiseaseNo Human-to-Human transmissionIsolation not necessary
Centers for Disease Control and Prevention
TularemiaPlague-like disease in rodents (California)Deer-fly fever (Utah)Glandular tick fever (Idaho and Montana)Market men’s disease (Washington, DC)Rabbit fever (Central States)O’Hara’s disease (Japan)
Centers for Disease Control and Prevention
TularemiaContagious --- noInfective dose --- 10-50 organismsIncubation period --- 1-21 days (average=3-5 days)Duration of illness --- ~2 weeksMortality --- treated : low
untreated: moderatePersistence of organism ---months in moist soilVaccine efficacy --- good, ~80%
Tularemia Clinical Features
Targets kidney, liver, lungs,lymph, spleenSpread bloodstream/lymphOrgans-PMNs and focal suppurative necrosis
Alternate Sites-Tularemia
Aerosol bioterrorism attack: lower respiratory infection, eyes, pharynx, skin
Broken skin-->ulcerative formGI involvement if ingested
Tularemia Influenza
Chills, coryza, cough, fever, headache, malaise, myalgia, sore throatRelative bradycardia ie, pulse-temperature dissociationVariable severity
Same
No dissociation
Most symptoms similar
Lab Tularemia InfluenzaWBC normal or highUA= sterile pyuria5-15% have elevated LFTsCulture pharynx, sputum or gastric aspirates high yield for Francisella tularensis
WBC may be normal, No pyuriaNo LFT elevation
CXR Tularemia
25-50% abnormal CXR inhalation tularemia Peri-vascular infiltrates earlyMay resemble symptoms and CXR of Anthrax, plague or Q-fever
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
Tularemia: Gram Negative Coccobacilli
Most likelyAcinetobacterActinobacillusH. aphrophilusBordetella spp. Pasturella spp.
Least likelyDF-3Brucella spp.Francisella spp.
Centers for Disease Control and Prevention
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
Tularemia Treatment
Streptomycin & GentamycinAlternatives:
Doxycycline, Ciprofloxacin
Tularemia: Mass Casualty RXExposed Persons Only
Their contacts not at high risk
Streptomycin or Gentamycin, or Ciprofloxacin, DoxycyclineCDC has stockpiles, ventilators and emergency equipment
Botulism
Botulism
Clostridium botulinum Most Potent Neurotoxin 169 USA cases in 2001Foodborne or in wounds, usually IVDU
Centers for Disease Control and Prevention
FOODBORNE BOTULISM
Infective dose: 0.001 g/kgIncubation period: 18 - 36 hoursDry mouth, double vision, droopy eyelids, dilated pupilsProgressive descending bilateral muscle weakness & paralysisRespiratory failure and deathMortality 5-10%, up to 25%
Centers for Disease Control and Prevention
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
Botulism Transmission
Home Canned foods, baked potatoes in aluminum foil, cheese, fishWound botulism-spores germinate in open wounds
Botulism Features
Symmetric descending paralysisMotor and autonomic nervesCranial nerves first affectedDeath rate 5%, respiratory failureRecovery takes months
Botulism Incubation2 hours to 8 days (dose related)Heat inactivates (>85°C for 5 minutes)Lab testing –Call Public Health LabShould be suspected if multiple persons simultaneously present with similar symptoms – need to get good history of each persons’ past activities
Botulism Symptoms
Alert mental statusFatigue, dizziness, dysarthria, facial palsyVision blurred, double, ptosisDysphagia, dry mouthDyspneaConstipationWeakness, progressive
Botulism Differential Diagnosis
Notable symmetrical weakness Absence of sensory nerve damageDescending flaccid paralysisProminent cranial nerve palsies
Botulism Confused with:
Myasthenia GravisTick ParalysisOrganophosphate intoxicationCNS infectionsMore likely than, but confused with polyradiculoneuropathy:Guillain-Barre´ or Miller-Fisher syndrome
Centers for Disease Control and Prevention
BOTULISMDiagnosis of botulism is made clinicallyHealth care providers suspecting botulism should contact their State Health Department
Botulism Treatment
Antibiotics not usefulEquine Antitoxin riskyNeurologic support
No neuromuscular blockade drugs
Ventilatory support
Centers for Disease Control and Prevention
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!
Questions?