Orange County Public Health and Bioterrorism

Hildy Meyers, M.D., M.P.H.Hildy Meyers, M.D., M.P.H.Medical DirectorMedical Director

Epidemiology & AssessmentEpidemiology & AssessmentPublic Health ServicesPublic Health Services

Orange County Health Care AgencyOrange County Health Care AgencyDecember 10, 2001December 10, 2001

Bioterrorism (BT) - Definition

Biological terrorism is the Biological terrorism is the use of microorganisms use of microorganisms (bacteria, viruses, and (bacteria, viruses, and fungi) or toxins from fungi) or toxins from living organisms to living organisms to produce death or disease in produce death or disease in humans, animals, and humans, animals, and plants.plants.

Ideal BT Agent

Can be delivered as an aerosolCan be delivered as an aerosol High disease/infection ratioHigh disease/infection ratio Maintains viability/infectivity in Maintains viability/infectivity in

environmentenvironment Vaccine or prophylaxis to protect in Vaccine or prophylaxis to protect in

manufacture and deliverymanufacture and delivery

Environmental Constraints

Sunlight - UV light kills many bacteriaSunlight - UV light kills many bacteria Wind - spreads biological agentsWind - spreads biological agents Temperature - heat inactivates many Temperature - heat inactivates many

biological agents; most are resistant to biological agents; most are resistant to freezingfreezing

Desiccation - may inactivate or inhibit Desiccation - may inactivate or inhibit growthgrowth

Agents of BT—Top Suspects

Anthrax (Anthrax (Bacillus anthracisBacillus anthracis)) Smallpox (Variola major)Smallpox (Variola major) Plague (Plague (Yersinia pestisYersinia pestis)) TularemiaTularemia ((Francisella tularensisFrancisella tularensis)) Botulism (Botulinum toxin)Botulism (Botulinum toxin) Viral hemorrhagic fevers (Filoviruses and Viral hemorrhagic fevers (Filoviruses and

Arenaviruses )Arenaviruses )

Health Care Agency Planning

Improve communicationsImprove communications Requesting fax number and/or e-mail Requesting fax number and/or e-mail

address from all O.C. physiciansaddress from all O.C. physicians Web postingsWeb postings Grand roundsGrand rounds Public Health BulletinPublic Health Bulletin

Improve surveillanceImprove surveillance Improve staff trainingImprove staff training

Bioterrorism ResponseMost important for physicians:Most important for physicians:

PreparationPreparation Familiarity with agents of BT Familiarity with agents of BT Personal/office disaster preparednessPersonal/office disaster preparedness Hospital preparednessHospital preparedness

Recognition—“the astute physician”Recognition—“the astute physician” Reporting to Orange County Public HealthReporting to Orange County Public Health——

this will activate the response systemthis will activate the response system Also notify hospital infection control, laboratory, Also notify hospital infection control, laboratory,

and administrationand administration

How to report During regular business hoursDuring regular business hours

Call EpidemiologyCall Epidemiology(714) 834-8180(714) 834-8180

After hours, weekends and holidaysAfter hours, weekends and holidaysFor physicians and health care facilitiesFor physicians and health care facilities

ONLYONLY County CommunicationsCounty Communications

(714) 628-7008(714) 628-7008Ask for Public Health Official on callAsk for Public Health Official on call

Orange County Health Care Agency Response

Case investigation and case findingCase investigation and case finding Establish diagnosisEstablish diagnosis Activate Orange County emergency plansActivate Orange County emergency plans Notify:Notify:

California Dept of Health ServicesCalifornia Dept of Health Services Centers for Disease Control & PreventionCenters for Disease Control & Prevention FBI and local law enforcementFBI and local law enforcement

Orange County Health Care Agency Response, cont.

Recommend treatment and infection control Recommend treatment and infection control

measures measures

Establish exposure date(s) and location(s)Establish exposure date(s) and location(s)

Identify exposed personsIdentify exposed persons

Follow-up cases and contactsFollow-up cases and contacts

Provide mass prophylaxis (if indicated)Provide mass prophylaxis (if indicated)

Identifying Suspicious Letters or Packages

Excessive postageExcessive postage Handwritten or poorly typed addressesHandwritten or poorly typed addresses Incorrect titles; title, but no nameIncorrect titles; title, but no name Misspellings of common wordsMisspellings of common words Oily stains, discolorations or odorOily stains, discolorations or odor No return address or postmark does not match return No return address or postmark does not match return

addressaddress Excessive weightExcessive weight Lopsided or uneven envelopeLopsided or uneven envelope

Response to Suspicious Powder or Package

Call law enforcementCall law enforcement Law enforcement performs threat assessment and Law enforcement performs threat assessment and

contacts FBI as neededcontacts FBI as needed If If nono credible threat exists, incident is closed credible threat exists, incident is closed

without further testing without further testing If credible threat existsIf credible threat exists

FBI arranges for laboratory testing of specimen FBI arranges for laboratory testing of specimen (and environment, if indicated)(and environment, if indicated)

Public Health is notifiedPublic Health is notified

Legally mandated reportingLegally mandated reporting See list of reportable diseases, also See list of reportable diseases, also

available on our web siteavailable on our web site Emergency regulations (11/5/01) have Emergency regulations (11/5/01) have

added BT agents not previously on list and added BT agents not previously on list and made them immediately reportablemade them immediately reportable

Includes:Includes:Unusual diseases Unusual diseases OutbreaksOutbreaks

What to report?

Illness associated with a ventilation Illness associated with a ventilation system system

A disease that is:A disease that is:unusual for a given geographic areaunusual for a given geographic areaoccurs outside the normal occurs outside the normal

transmission seasontransmission seasonoccurs in the absence of the normal occurs in the absence of the normal

vector for transmissionvector for transmission

Epidemiological clues to a BT outbreak: examples

Atypical host characteristics:Atypical host characteristics:Young (< 50 years)Young (< 50 years)Immunologically intactImmunologically intactNo underlying illnessNo underlying illnessNo recent international travel No recent international travel or other exposure to potential or other exposure to potential source of infectionsource of infection

Epidemiological clues to a BT outbreak, cont.

Worrisome Clinical Syndromes

Acute severe pneumonia or respiratory Acute severe pneumonia or respiratory diseasedisease

Encephalitis syndromeEncephalitis syndrome Unexplained rash with feverUnexplained rash with fever Fever with mucous membrane bleedingFever with mucous membrane bleeding Unexplained death or paralysisUnexplained death or paralysis Septicemia/toxic shockSepticemia/toxic shock

Anthrax

Anthrax - Microbiology

Bacillus anthracisBacillus anthracis - gram +, spore-forming, bacillus - gram +, spore-forming, bacillus Spores may remain infectious in environment for as long Spores may remain infectious in environment for as long

as 50 yearsas 50 years Endemic infection in animals Endemic infection in animals Spores enter host, germinate in a macrophage and Spores enter host, germinate in a macrophage and

are transported to regional lymph nodes where local are transported to regional lymph nodes where local toxins cause edema and death of tissuetoxins cause edema and death of tissue

Humans develop infection naturally from handling Humans develop infection naturally from handling contaminated fluids or hides (“Woolsorters contaminated fluids or hides (“Woolsorters Disease”) or eating contaminated raw or Disease”) or eating contaminated raw or undercooked meatundercooked meat

Respiratory Distress Stridor, Cyanosis

Chest/Neck Edema

DAYSDAYSFever

Fatigue Myalgia Malaise

Meningitis (50%) Respiratory Failure

Shock, Death

Anthrax: Clinical ProgressionAnthrax: Clinical Progression of Inhalational Disease

Exposure

Anthrax::Inhalational, N=10

Incubation (known for 6 cases)Incubation (known for 6 cases) Range: 4-6 daysRange: 4-6 days Median: 4 daysMedian: 4 days

AgeAge Range: 43-73Range: 43-73 Median: 56 yearsMedian: 56 years

7 of 10: male7 of 10: male

Anthrax:Inhalational, N=10

SymptomSymptom NumberNumberFever, chillsFever, chills 1010 (Sweats, often drenching(Sweats, often drenching 7) 7)Fatigue, malaise, lethargyFatigue, malaise, lethargy 1010Cough Cough (minimal or nonproductive)(minimal or nonproductive) 99Nausea or vomitingNausea or vomiting 99Dyspnea Dyspnea 88Chest discomfort or Chest discomfort or pleuritic pain pleuritic pain 77

Anthrax:Inhalational, N=10

SymptomSymptom NumberNumber

MyalgiasMyalgias 66

Headache Headache 55

Confusion Confusion 44

Abdominal pain Abdominal pain 33

Sore throat Sore throat 22

RhinorrheaRhinorrhea 11

WBC: Median 9.8 (7.5 – 13.3)WBC: Median 9.8 (7.5 – 13.3)Differential - neutrophilia (>70%) in 7 of 10Differential - neutrophilia (>70%) in 7 of 10

Elevated transaminases (9 of 10)Elevated transaminases (9 of 10) Hypoxemia 6 of 10Hypoxemia 6 of 10 CXR: abnormal in allCXR: abnormal in all

2—initial reading WNL2—initial reading WNL 8—pleural effusions8—pleural effusions

Often large, hemorrhagic, reaccumulatedOften large, hemorrhagic, reaccumulated 7—mediastinal widening7—mediastinal widening 7—infiltrates (some multilobar)7—infiltrates (some multilobar)

CT (N=8): Mediastinal changes present in allCT (N=8): Mediastinal changes present in all

Anthrax::Inhalational, N=10

Confirmation of Confirmation of Bacillus anthracisBacillus anthracis 7—positive blood cultures7—positive blood cultures

Blood cultures positive in all who had not Blood cultures positive in all who had not received antimicrobialsreceived antimicrobials

Negative culturesNegative culturesBronchial or pleural biopsy—specific Bronchial or pleural biopsy—specific

immunohistochemical stainingimmunohistochemical stainingPCRPCR4x rise in IgG to protective antigen (with 4x rise in IgG to protective antigen (with

confirmatory inhibition test)confirmatory inhibition test)

Anthrax::Inhalational, N=10

Initial chest X-ray showing prominent superior mediastinum and possible small left pleural effusion (Case 1, EID 11/8/01)

Chest X-ray showing diffuse consolidation consistent with pneumonia throughout the left lung. There is no evidence of mediastinal widening (Case 2, EID 11/8/01)

Chest X-ray showing mediastinal widening and a small left pleural effusion (Case 7, EID 11/8/01).

Anthrax: Patient requests for testing

There are no screening tests for anthraxThere are no screening tests for anthrax Nasal swabs are Nasal swabs are

A research toolA research tool ONLY used as part of an epidemiological ONLY used as part of an epidemiological

investigation of KNOWN anthrax exposureinvestigation of KNOWN anthrax exposure Are NOT used to determine who should be Are NOT used to determine who should be

treated or prophylaxedtreated or prophylaxed Should only be done at the request of Public Should only be done at the request of Public

HealthHealth

Asymptomatic patient WITHOUT known Asymptomatic patient WITHOUT known exposure:exposure: ReassuranceReassurance No lab testsNo lab tests

Asymptomatic patient WITH suspected (as Asymptomatic patient WITH suspected (as determined by law enforcement/FBI) or determined by law enforcement/FBI) or known exposure:known exposure: Consult with Public Health for Consult with Public Health for

recommendationsrecommendations

Anthrax: Patient requests for testing, cont.

Patient with non-specific symptomsPatient with non-specific symptoms Reports having had an exposure to unknown Reports having had an exposure to unknown

substance—not evaluated by law enforcementsubstance—not evaluated by law enforcement Does not fit any known risk profile Does not fit any known risk profile

(occupation, previously identified exposures)(occupation, previously identified exposures) Reassurance about rarity of infection and Reassurance about rarity of infection and

frequency of viral URIsfrequency of viral URIs Evaluate for symptomsEvaluate for symptoms If afebrile, instruct patient to monitor for fever If afebrile, instruct patient to monitor for fever

and other symptomsand other symptoms

Anthrax: Patient requests for testing, cont.

Anthrax: Cutaneous Incubation 1-12 daysIncubation 1-12 days Skin lesion: Macule or papule Skin lesion: Macule or papule vesicles vesicles

ulcer ulcer depressed black eschar depressed black eschar Initially often have pruritisInitially often have pruritis Usually painlessUsually painless Vesicles may surround ulcerVesicles may surround ulcer Edema usually develops, may be severeEdema usually develops, may be severe

May have fever, malaise, headache, May have fever, malaise, headache, regional lymphangitis, painful regional lymphangitis, painful lymphadenopathylymphadenopathy

Anthrax: Cutaneous, cont.

Dx: Dx: Vesicular fluid/exudate/inflammed area of Vesicular fluid/exudate/inflammed area of

escharescharGram stain (may be falsely negative)Gram stain (may be falsely negative)CultureCulture

Biopsy—Biopsy—Immunohistochemical staining, PCR, silver Immunohistochemical staining, PCR, silver

stainstain Consider blood cultureConsider blood culture

Cutaneous lesion: day 11

Cutaneous lesion on face Cutaneous lesion on neck

See also New England Journal of Medicine, November 29, 2001

Cutaneous Anthrax: D/dx EcthymaEcthyma FolliculitisFolliculitis Brown recluse spider bite Brown recluse spider bite Ecthyma gangrenosumEcthyma gangrenosum OrfOrf Pyoderma gangrenosumPyoderma gangrenosum Sweet’s syndromeSweet’s syndrome((http://www.acponline.orghttp://www.acponline.orgAmerican College of Physicians)American College of Physicians)

Cutaneous Anthrax: Clues to the diagnosis

Usually solitary lesionUsually solitary lesion Initial pruritisInitial pruritis PainlessPainless Most often on upper extremitiesMost often on upper extremities Evolution to eschar formationEvolution to eschar formation Non-pitting edemaNon-pitting edema Regional adenopathyRegional adenopathy May be associated with constitutional sxMay be associated with constitutional sx

Anthrax Treatment

InhalationalInhalational Doxycyline or ciprofloxacin, IVDoxycyline or ciprofloxacin, IV Plus: 1 or 2 other drugsPlus: 1 or 2 other drugs

Rifampin, clindamycin, Rifampin, clindamycin, chloramphenicol, vancomycin, chloramphenicol, vancomycin, clindamycinclindamycin

Not cephalosporins or trimethopirm-Not cephalosporins or trimethopirm-sulfamethoxazolesulfamethoxazole

Anthrax Epi InvestigationCDC, as of December 5

22 cases22 cases 11 inhalational—5 deaths11 inhalational—5 deaths 11 cutaneous (7 confirmed, 4 suspected)11 cutaneous (7 confirmed, 4 suspected)

All but 2 cases: postal employees or media-relatedAll but 2 cases: postal employees or media-related NJ and Washington DC mail sorting facilitiesNJ and Washington DC mail sorting facilities

Widespread environmental contaminationWidespread environmental contamination ~85 million pieces of mail processed after implicated ~85 million pieces of mail processed after implicated

letters passed through until shutdownletters passed through until shutdown Mail from these facilities distributed to metropolitan Mail from these facilities distributed to metropolitan

areas with 10.5 million peopleareas with 10.5 million people

Anthrax Epi InvestigationCDC, as of December 5, cont.

Risk for additional inhalational cases due to Risk for additional inhalational cases due to exposure to cross-contamination is very lowexposure to cross-contamination is very low

Persons remaining concerned about their risk may Persons remaining concerned about their risk may want towant to Not open suspicious mailNot open suspicious mail Keep mail away from face when openingKeep mail away from face when opening Don’t sniff mail or contentsDon’t sniff mail or contents Wash hands after handling mailWash hands after handling mail However, efficacy of these measures unknownHowever, efficacy of these measures unknown

Smallpox

Smallpox Last naturally acquired case 1977, Last naturally acquired case 1977,

SomaliaSomalia Laboratory-acquired case in 1978Laboratory-acquired case in 1978

Declared eradicated 1980Declared eradicated 1980 Vaccination program dismantledVaccination program dismantled

U.S. recommendations for routine vaccination rescinded U.S. recommendations for routine vaccination rescinded forfor

children in 1971children in 1971 health care workers rescinded in 1976health care workers rescinded in 1976 military in 1990military in 1990

Vaccination no longer required for international Vaccination no longer required for international travelers as of Jan. 1982travelers as of Jan. 1982

Last smallpox case(variola minor)

Smallpox - Epidemiology

Transmission: person-to-person primarily via Transmission: person-to-person primarily via direct respiratory droplet (face-to-face)direct respiratory droplet (face-to-face)

Most communicable from onset of rash (Most communicable from onset of rash (afterafter onset of prodrome) through first 7 days of rashonset of prodrome) through first 7 days of rash Oral mucosa lesions ulcerate and release large Oral mucosa lesions ulcerate and release large

amounts of virus into salivaamounts of virus into saliva Incubation averages 12 days (range 7-17)Incubation averages 12 days (range 7-17) Attack rate ~60% (range 38-88%)Attack rate ~60% (range 38-88%)

Smallpox: Clinical Types

Variola major: classic smallpox (30% Variola major: classic smallpox (30% mortality)mortality)

Variola minor: milder disease (1% mortality)Variola minor: milder disease (1% mortality) Flat-type (2%-5%): severe toxicity, flat, soft Flat-type (2%-5%): severe toxicity, flat, soft

lesions (95% mortality)lesions (95% mortality) Hemorrahagic (<3%): extensive petechiaeHemorrahagic (<3%): extensive petechiae

Clinical--Classic Smallpox

Prodrome (2-3 days): Acute onset with high Prodrome (2-3 days): Acute onset with high fever, malaise, and prostration with severe fever, malaise, and prostration with severe headache and backache; +/- erythematous rashheadache and backache; +/- erythematous rash

Lesions appear over 1-2 day periodLesions appear over 1-2 day period Spread of rash to lower extremities, then Spread of rash to lower extremities, then

centrally; centrally; lesions more abundant on face and lesions more abundant on face and extremitiesextremities; may be present on palms and soles; may be present on palms and soles

Smallpox vs. Chickenpox

SmallpoxSmallpox ChickenpoxChickenpox

Incubation (days)Incubation (days) 7-177-17 14-2114-21

Prodrome (days) Prodrome (days) 2-42-4 minimal/noneminimal/none

DistributionDistribution more prominentmore prominent more more prominentprominent

on face and on face and on trunkon trunk extremitiesextremities

Progression Progression synchronoussynchronous asynchronousasynchronous

Scab formation*Scab formation* 10-14 10-14 4-7 4-7

Scab separation*Scab separation* 14-28 14-28 <14<14

* Number of days after rash onset* Number of days after rash onset

http://www.who.int/emc/diseases/smallpox/slideset/index.htm

Day 5 of rashDay 2 of rash

Day 4 of rash Day 5 of rash Day 6 of rash

Day 7Day 7 Days 8-9Days 8-9

Days 10-14Days 10-14 Day 20Day 20

Day 4 of rash:Day 4 of rash:chickenpoxchickenpox

Smallpox - Vaccine Current supplies limited, up to 70 million dosesCurrent supplies limited, up to 70 million doses Used only for laboratory personnel working with Used only for laboratory personnel working with

certain smallpox-like virusescertain smallpox-like viruses Side effects and complications (per million Side effects and complications (per million

primary doses)primary doses) Inadvertent inoculation—509Inadvertent inoculation—509 Postvaccinial encephalitis—12.3Postvaccinial encephalitis—12.3 Progressive vaccinia—1.5Progressive vaccinia—1.5

Can prevent or decrease severity if given within 3-Can prevent or decrease severity if given within 3-4 days of exposure4 days of exposure

Multipuncture vaccination by bifurcated needle

Smallpox: Initial Response Plan Rapid response teams: identify cases and contactsRapid response teams: identify cases and contacts Ring vaccinationRing vaccination

Identification of priority groupsIdentification of priority groupsFace-to-face contactsFace-to-face contactsExposed to initial releaseExposed to initial releaseHousehold membersHousehold membersHealth care workers and first respondersHealth care workers and first respondersInvestigation personnelInvestigation personnel

Web Resources

CDC Bioterrorism site: CDC Bioterrorism site: http://www.bt.cdc.http://www.bt.cdc.govgov List of reportable diseases:List of reportable diseases:

http://www.oc.ca.gov/hca/docs/forms/diseases.pdfhttp://www.oc.ca.gov/hca/docs/forms/diseases.pdf Confidential morbidity reporting formConfidential morbidity reporting form

http://www.http://www.ococ.ca..ca.govgov//hcahca/docs/forms//docs/forms/morbidrepmorbidrep..pdfpdf World Health OrganizationWorld Health Organization

http://www.who.int/emc/deliberate_epi.htmlhttp://www.who.int/emc/deliberate_epi.html JAMA articles on bioterrorism (scroll down):JAMA articles on bioterrorism (scroll down):

http://jama.ama-assn.org/http://jama.ama-assn.org/