Anthrax. Saint Louis Unversity School of Public Health Anthrax: History Caused by Bacillus anthracis...

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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

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

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%)

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

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

Sverdlovsk, Russia 1979Accidental release from anthrax drying plant79 human cases• All downwind of plant• 68 deaths• Some infected with multiples strains

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

Anthrax: EpidemiologyThree forms of natural disease

Inhalational• Rare (<5%)• Most likely encountered in bioterrorism

Cutaneous• Most common (95%)• Direct contact of spores on skin

Gastrointestinal• Rare (<5%), never reported in U.S.• Ingestion

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

Anthrax: Epidemiology

MortalityInhalational 86-100% (despite treatment)• Era of crude intensive supportive care

Cutaneous <5% (treated) – 20% (untreated)GI approaches 100%

Incubation PeriodTime from exposure to symptomsVery variable for inhalational• 2-43 days reported• Theoretically may be up to 100 days• Delayed germination of spores

Human cases – historical risk factors

Agricultural• Exposure to livestock

Occupational• Exposure to wool and hides• Woolsorter’s disease = inhalational

anthrax• Rarely laboratory-acquired

Anthrax: EpidemiologyTransmission

No human-to-humanNaturally occurring cases• Skin exposure• Ingestion• Airborne

Bioterrorism• Aerosol (likely)• Small volume powder (possible)• Foodborne (unlikely)

TransmissionInhalational• Handling hides/skins of infected animals• Microbiology laboratory • Intentional aerosol release• Small volume powdered form

– In letters, packages, etc– Questionable risk, probably small

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

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

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

Anthrax: Microbiology

Colony characteristicsLarge (4-5mm)Non-hemolyticOpaque white, grayRetain shape when manipulated (“egg white”)Forms capsule at 37º C, 5-20% CO2

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

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

Microbiology

Virulence FactorsAll necessary for full virulenceTwo plasmids • Capsule (plasmid pXO2)

– Antiphagocytic

• 3 Exotoxin components (plasmid pXO1)– Protective Antigen– Edema Factor– Lethal Factor

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

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

Forms of natural diseaseInhalationalCutaneousGastrointestinal

Determined by route of entryDisease occurs wherever spores germinate

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

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

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

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

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

CutaneousSystemic disease• Can occur, especially if untreated• Spores/bacteria carried to regional lymph

nodes– Lymphangitis/lymphadenitis– Same syndrome as inhalational– Sepsis, multi-organ failure

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

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

Anthrax: Clinical Features

Symptoms depend on form of disease

InhalationalCutaneousGastrointestinal

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

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

Laboratory FindingsGram positive bacilli in direct blood smearElectrolyte imbalances common

Radiographic FindingsWidened mediastinum• Minimal or no infiltrates

Can appear during prodrome phase

Anthrax: Clinical FeaturesCutaneous

Most common areas of exposure• Hands/arms• Neck/head

Incubation period• 3-5 days typical• 12 days maximum

Anthrax: Clinical FeaturesCutaneous – progression of painless lesions

Papule – pruritic

Vesicle/bulla

Ulcer – contains organisms, sig. edema

Eschar – black, rarely scars

24-36 hrs

CutaneousSystemic disease may develop• Lymphangitis and lymphadenopathy• If untreated, can progress to sepsis,

Anthrax: Clinical FeaturesGastrointestinal

Oropharyngeal• Oral or esophageal ulcer

– Regional lymphadenopathy– Edema, ascites– Sepsis

Abdominal• Early symptoms - nausea, vomiting, malaise• Late - hematochezia, acute abdomen,

ascites

Anthrax: Diagnosis

Early diagnosis is difficultNon specific symptoms Initially mildNo readily available rapid specific tests

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

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

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

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

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

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

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

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

Anthrax: Differential DiagnosisCutaneous

Spider biteEcthyma gangrenosumPyoderma gangrenosumUlceroglandular tularemiaMycobacterial ulcerCellulitis

Expect if anthraxfeverno response to 3º cephalosporinspainless, black eschar+/- lymphadenopathyusually sig. local edema

Anthrax: Differential Diagnosis

GastrointestinalGastroenteritisTyphoid PeritonitisPerforated ulcerBowel obstruction

Expect if anthraxCritically illAcute abdomenBloody diarrheaFever

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

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

Anthrax: Treatment

HospitalizationIV antibiotics

Empiric until sensitivities are known

Intensive supportive careElectrolyte and acid-base imbalancesMechanical ventilationHemodynamic support

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

Anthrax: TreatmentEmpiric Therapy

Until susceptibility patterns knownAdults• Ciprofloxacin 400 mg IV q12°

ORDoxycycline 100mg IV q12°

AND (for inhalational)

One or two other antibiotics

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

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)

Anthrax: Treatment

Empiric therapyPregnant women• Same as other adults• Weigh small risks (fetal arthropathy) vs

benefit

Immunosuppressed• Same as other adults

Anthrax: TreatmentAlternative antibiotics

If susceptible, or cipro/doxy not possible• Penicillin, amoxicillin • Gentamicin, streptomycin• Erythromycin, chloramphenicol

Ineffective antibioticsTrimethoprim/SulfamethoxazoleThird generation cephalosporins

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

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

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

Anthrax: Postexposure Prophylaxis

Who should receive PEP?Anyone exposed to anthrax Not for contacts of cases, unless also exposed

Empiric antibiotic therapy Vaccination

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

Antibiotic therapyTreat ASAPPrompt therapy can improve survivalContinue for 60 days• 30-45 days if vaccine administered

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

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

Anthrax: Prevention

VaccineAnthrax Vaccine Absorbed (AVA)Supply• Limited, controlled by CDC• Production problems

– Single producer – Bioport, Michigan– Failed FDA standards– None produced since 1998

Anthrax: Prevention

VaccineInactivated, cell-free filtratePurified with Al(OH)3

Protective Antigen • Immunogenic component• Necessary but not sufficient

Anthrax: Prevention

VaccineAdministration• Dose schedule

– 0, 2 & 4 wks; 6, 12 & 18 months initial series– Annual booster

• 0.5 ml SQ

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

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

Anthrax: Infection Control

No person to person transmissionStandard Precautions Laboratory safety

Biosafety Level (BSL) 2 Precautions

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

Risk of secondary aerosolization is low• Heavily contaminated small areas

– May benefit from decontamination

• Decontamination may not be feasible for large areas

Anthrax: DecontaminationSkin, clothing

Thorough washing with soap and waterAvoid bleach on skin

Instruments for invasive proceduresUtilize sporicidal agent

Sporicidal agentsSodium or calcium hypochlorite (bleach)

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

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

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

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

Florida Case #273yo manAdmitted 10/1 for pneumoniaNasal swab culture + on 10/5PCR+ on pleural fluid, serology +Responding to antibiotics, still in hospital

FloridaExposed• Anyone at worksite for >1 hour since 8/1• 1/1075 nasal swabs +, all given PEP

Confirmed powder exposure from mail

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

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

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

New York CityExposures by nasal/facial swab cx’s• Police officer transporting the NBC

sample• 2 lab techs processing NBC sample

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

Trenton, New Jersey2 confirmed inhalational cases• Postal workers in distribution center• Others with symptoms, results pending

2 suspicious deaths• Probable inhalational anthrax

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

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

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

Hemorrhagic Fever Viruses

ArenavirusesArgentine Hemorrhagic FeverBolivian Hemorrhagic FeverSabia Associated Hemorrhagic FeverLassa Fever

BunyavirusesCrimean-Congo Hemorrhagic FeverRift Valley FeverHantavirus Pulmonary Syndrome Hemorrhagic Fever

FilovirusesEbola Hemorrhagic FeverMarburg Hemorrhagic Fever

FlavivirusesTick-borne EncephalitisKyasanur Forest DiseaseOmsk Hemorrhagic Fever

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

VHF Specimens

Diagnosis is clinical, not laboratoryNo specimen accepted without prior consultation

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

Yersinia pestisGram-negative coccobacillus

Flea bite in natural conditionsEasily transmitted direct contact person-personHigh mortalityPneumonic form most deadly

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

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

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

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

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

Francisella tularensisFlu-Like Illnesses, atypical pneumoniasInhalation route 10-50 microbes -> Infection & DiseaseNo Human-to-Human transmissionIsolation not necessary

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)

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

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.

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

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

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%

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

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

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?

Anthrax. Saint Louis Unversity School of Public Health Anthrax: History Caused by Bacillus anthracis...

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