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AIMSRC

Definition

Characteristics of Biological weapons.

Epidemiological Clues of Biological warfare.

Biosafety levels

Biological warfare agents with emphasis on Smallpox , Anthrax, plague and botulism as a Biological

weapon.

Countermeasures for BT event.

Steps to be followed in event of bioterrorism.

Summary.

Lay outLay out

Bioterrorism-

Use of biological agents/weapons to inflict disease and/or death on humans, animals, plants.

Biological weapons

Microorganisms

Biologically derived bioactive substances (BDBS)

The ideal biological weaponHigh morbidity and mortality.

Potential person to person spread.

Low infective dose and infective by aerosol.

Lack of rapid diagnostic capability

Lack of universally available effective vaccine

Potential to cause anxiety

Availability of pathogen and feasibility of production.

Environmental stability

Potential to be weaponised

Epidemiological Clues to an Event of Epidemiological Clues to an Event of Bioterrorism.Bioterrorism.

Large no of ill persons with similar disease or syndromes presenting around the same time.

Failure of common diseases to respond to usual therapy.

Higher mortality or morbidity than expected with a common disease or syndrome.

Unusual ,atypical or genetically engineered strain of the agent.

Disease with unusual geographic or seasonal distribution.

Similar genetic type among agents isolated temporally or spatially distinct sources.

Biosafety level-1Agent unlikely to cause disease in healthy adult.

Standard microbiological practices.

No biological safety cabinet

Laboratory facility- open bench top, sink and cleanable bench top surfaces

Biosafety level 2BSL1 PLUS –

limited access biohazard sign

sharp precautions

biosafety manual

BSC available

protective clothing

Autoclave

Access to incinerator

Biosafety level 3

BSL 2 PLUS – BSL 2 PLUS – controlled access

Decontamination of all

laboratory waste

Decontamination of outer clothing

Baseline serum taken from all employees and stored at -70

All manipulation performed in BSC

Respiratory protection

No air re-circulation

Negative air pressure

Biosafety level 4Biosafety level 4BSL 3 PLUS – BSL 3 PLUS –

clothing change to enter

shower to exit

dedicated on site decontamination

all work done in BSC

Full body positive pressure suit

Separate building or isolation zone

Dedicated air system

CRITICAL BIOLOGICAL AGENTS

CATEGORY A– High priority agents that pose a threat to national security

because they:

can be easily disseminated or transmitted person-to-person.

cause high mortality, with potential for major public health impact

might cause panic and social disruption

require special public health preparedness

CRITICAL BIOLOGICAL AGENTS

CATEGORY AVariola major (smallpox)

Bacillus anthracis (anthrax)

Yersinia pestis (plague)

Clostridium botulinum toxin (botulism)

Francisella tularensis (tularemia)

FilovirusesEbola hemorrhagic feverMarburg hemorrhagic fever

ArenavirusesLassa (Lassa fever)Junin (Argentine hemorrhagic fever) and related viruses

CRITICAL BIOLOGICAL AGENTSCATEGORY B

• Second highest priority agents that include those that:

are moderately easy to disseminate

cause moderate morbidity and low mortality

require specific enhancements of CDC’s diagnostic capacity and enhanced disease surveillance

CRITICAL BIOLOGICAL AGENTSCATEGORY B

Coxiella burnetti (Q fever)

Brucella species (brucellosis)

Burkholderia mallei (glanders)

AlphavirusesVenezuelan encephalomyelitiseastern / western equine encephalomyelitis

Ricin toxin from Ricinus communis (castor bean)

Staphylococcus enterotoxin B

CRITICAL BIOLOGICAL AGENTSCATEGORY B

• Subset of Category B agents that include pathogens that are food- or waterborne

• Salmonella species 1984- USA

• Shigella dysenteriae 1996 USA

• Escherichia coli O157:H7

• Vibrio cholerae

• Cryptosporidium parvum

CRITICAL BIOLOGICAL AGENTSCATEGORY C

Third highest priority agents include emerging pathogens that could be engineered for mass dissemination in the future because of:

Availability

ease of production and dissemination

potential for high morbidity and mortality and major health impact

Preparedness for Category C agents requires ongoing research to improve detection, diagnosis, treatment, and prevention

CRITICAL BIOLOGICAL AGENTSCATEGORY C

Nipah virus

Hantaviruse

Tickborne hemorrhagic fever viruses

Tickborne encephalitis viruses

SARS corona virus

Multidrug-resistant tuberculosis

Small pox, lingering threat of worst kind

Last natural case – 1977 Somalia.

Last case – laboratory acquired , 1978 ,UK

Eradication of the disease – 8th may1980.

Officially remaining stocks – CDC.Atlanta - Vector , Siberia

Large population of susceptible persons- US (SINCE 1972) Rest of the world(1982)Credible biological weapon – high CFR (30% in unvaccinated population) - low infectious dose -not adequate vaccine -no life saving drug -deliberate spread by aerosol possible

• Communicability– Starts with rash onset– Persists until last scab

• Secondary attack rate 30-45%

laboratory diagnosislaboratory diagnosisSpecimens: Vesicular, Pustular fluids, Scabs, scrapings, biopsies.

Storage and transport- 4 c(6hrs), -20 - -70

Presumptive Identification: Demonstrating large eosinophilic cytoplasmic inclusion bodies from vesicles. (giemsa)

Isolation: Characteristic Pocks on CAM of Chick embryo

Human & Primate cell cultures.(gold standard)

Molecular methods: PCR & RFLP for further characterization.

Biosafety level 4 containment conditions

treatment and Preventiontreatment and PreventionIsolation- negative pressure isolation facilities.

Disinfection.

Identification of contacts.

Vaccination and surveillance of contacts.

Air borne and contact precautions of health care providers regardless of immunization status.

CDC guidelines(Release of vaccine in the event of bioterrorism) pre-exposure prophylaxis (laboratory personnel) post exposure prophylaxis (ring vaccination strategy)

No treatment approved by FDA.Doubtful role of vaccinia immunoglobulin

small pox vaccinesmall pox vaccineVaccinia virus: Derived from Edward Jenner,s original cowpox strain.

Dryvax (Calf Lymph Vaccine): Lyophilized preparation of live Vaccinia virus grown on skin of Calves, pustules harvested.

Concentration of virus: 108Pfu/ml.

Vaccination method:

Multiple Puncture Technique with Bifurcated needle.

Small Pox Vaccine:New HopesCell Culture vaccine

DNA Vaccine

MVA

Antivirals

(1)Cidofovir:-Neucleotide analogue; Lack of oral bio- availability.

(2)Adefovir:-Toxicity limiting factor.

Anthrax: The lethal Anthrax: The lethal weaponweapon

History of anthrax goes back to biblical times.

Inhalational anthrax reported occasionally in recent times.

1979- epidemic of inhalational antharax - Sverdlovsk, Russia 77 cases of inhalational antharax -, 66 deaths. Accidental release of aerosol containing B.anthracis spores.

1st bioterrorism related cases of anthrax in US – OCTOBER 2001

Following terrorist attacks in WTC and pentagon

• 22 cases of anthrax. 11 confirmed as inhalational anthrax 11- cutaneous anthrax (7 confirmed and 4 suspected)

• 5 deaths, inhalational anthrax (CFR 45%)

Epidemiologic Epidemiologic findings offindings ofbioterrorism-related bioterrorism-related anthrax, US,2001anthrax, US,2001

Contdd

CONNECTICUT 1 CASEFLORIDA 2 CASESMARYLAND THREENEW JERSY 5NEW YORK CITY 8PENNSYLVANIA1VIRGINIA2

20 patients handled mail/exposed to worksites where B.anthracis contaminated mail processed

B.anthracis isolates from cases, powder containing envelopes and environmental samples- compared by molecular typing

All isolates – indistinguishable by molecular typing same antimicrobial susceptibility pattern.

Sensitive to penicillin.

Post exposure anti-microbial prophylaxis

Case definition of anthraxCase definition of anthrax• Confirmed caseConfirmed caseClinically compatible illness

isolationisolation – confirmed by DFA and gamma phage

lysis

Supportive tests- 1. PCR 2. IHC

3.ELISA(PA)

isolation 2 supportive laboratorytests

• Suspected caseSuspected caseClinically compatible illnessNo alternative diagnosisNo isolation of B. anthracis

1 supportiveLaboratory test Epidemiologic link

to B. anthracis exposure

Infection managementStandard barrier and isolation precautions.

Cremation of corpses infected with anthrax

treatment

Inhalational anthrax- multidrug regimen{Cipro400 mg i.v BD/Inhalational anthrax- multidrug regimen{Cipro400 mg i.v BD/ Doxy 100 mg i.v BD Doxy 100 mg i.v BD + + clindamycin 900 mg iv tds / clindamycin 900 mg iv tds /

rifampicin300 mg iv BD}, Switch – oral when stable, total rifampicin300 mg iv BD}, Switch – oral when stable, total duration – 60 daysduration – 60 days

Post exposure prophylaxis – ciproloxacin/ doxycyclinePost exposure prophylaxis – ciproloxacin/ doxycycline

Preventive vaccineCell free filtrate protective antigen with alum.

BIOPORT CORPORATION IN LANSING MICHIGAN.

Efficacy against both cutaneous and inhalational anthrax.

Schedule- 0,2,4weeks -6,12,18 months.

Currently used by U.S armed forces.

Vaccination of entire population – not cost effectve

No documented instance in recent times.

Suspicious incidents- pneumonic plague outbreak, Surat bubonic plague outbreak , Beed

Potential of being used as a bioweapon- “pneumonic plague”

WHO – 50 kg of aerosolized Y. pestis

Y. pestis- aerosol -1hour, 10kmaerosol -1hour, 10km

Infectious dose-100-500 organisms

Plague as a biological weaponPlague as a biological weapon

150,000 affected- 36,000 deaths

• .

6300, suspected cases.

876- presumptive cases,54 fatalities

Isolation- sputum of 11 pneumonia patients.

6 rodents- Beed, 1- surat.

Biochemical, genetic , immunological similarity of Surat and Beed isolates

Original source of infection ?

Return of plague to India?

NATION is poorly eqipped to handle an outbreak of this nature

Reasons to suspect plague related biological attack

• Plague in non endemic area.

• Plague without usual bubo formation.

• Previously healthy persons with severe community acquired pneumonia especially if haemoptysis is present.

• Previously healthy persons with septic shock like illness.

• Community acquired pneumonia due to gram negative bacilli.

• “Rodent die – off”

• Large no of CAP than expected

• large no of septic shock than expected

•

CDC Case classification of plague• suspected casesuspected case –

Clinically compatible case lacking presumptive or confirmatory laboratory results

.• Probable caseProbable case - Clinically

compatible case with available presumptive laboratory results

.• Confirmed case-Confirmed case-

Clinically compatible case with available confirmatory laboratory results.

• Presumptive diagnosis-Presumptive diagnosis- detection of F1 antigen (IF -serum Ab titre to F1 antigen

without a history of plague vaccination.

• Confirmatory diagnosisConfirmatory diagnosis• isolation/ 4 fold increase in

titre of serum Ab to F1 Ag

laboratory diagnosislaboratory diagnosis

BSL 2/3 agent.

simple clinical activities and culture- BSL2

Activities involving high potential for aerosol or droplet production and animal studies- BSL3

Specimens – blood, sputum,bronchial washings (pneumonic plague) Bubo aspirates, blood (bubonic plague)

Infection control – respiratory isolation of the pt (48 hrs).

Environmental decontamination,

Strict precautions in handling body of plague victims

treatment Streptomycin - DOC

confirmation, isolation till sputum culture negative

prophylaxisVaccine – formalin killed whole cell vaccine

(2000 million organisms/ml).

Poor efficacy against pneumonic plague in laboratory animals

Not recommended as a protection against a biological attack.

Treatment- post-exposure prophylaxis- ciprofloxacin500mg every 12hrs Doxycycline 100mg12hrs Discontinued as threat has passed

Biological battle against botulismMost poisonous substance known.

LD 50- 0.003 microgram/kg body wt

I.P- 12-72 hours ( following aerosol exposure <1 hr )

No reported deliberate botulism poisoning

Theoretical epidemicTheoretical epidemic – 1g aerosolized botulinum toxin-5 million deaths

Water borne and food borne routes also feasible, occur in conjunction with aerosolization.

laboratory diagnosislaboratory diagnosisThe standard laboratory diagnostic test- mouse bio-assay.

Isolation and identification of neurotoxin from sera and other samples (stool, gastric specimens, vomitus, suspected food)

Aerosolized toxin- not usually identifiable in serum or stool: - by ELISA on nasal mucous membrane or BAL for 24 hrs after inhalation.

Pus from wound, biopsy tissues, fecal and gastric specimens – culture

Prophylaxis

Antitoxin –trivalent equine anti-toxin.

Connaught laboratories,ltd, Willowdale, Ontario

Less likely to be useful, if administered after 72 hours

In US- laboratory workers and military personnel

In the event of a biological weapons incident

Detection : epidemiological and microbiological clues.

Case definition : epidemiological assesment

Notification

Epidemiological investigation: to differentiate between naturally occurring epidemic and a terrorist attack

Medical intervention – isolation of cases and treatment.

Prophylaxis

Awareness

summaryBW although challenging to develop, still easier and cheaper to obtain than nuclear weapons

Various microbes are available with potential to act as a BW.

Newer genetic manipulation technique may allow newer chimera to come.

Small Pox & Anthrax are the most probable BW weapons.

Health care personnel, microbiolgists, epidemiologists – case detection

.

summary– Preparation for a biological mass disaster requires

coordination of diverse groups of medical and non-medical personnel

– Preparation can not occur without support and participation by all levels of government

– Preparation must be a sustained and evolutionary process