2. 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
3. Bioterrorism-
Use of biological agents/weapons to inflict disease and/or death on
humans, animals, plants.
Biological weapons
Microorganisms
Biologically derived bioactive substances (BDBS)
4. 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
5. Epidemiological Clues to an Event ofEpidemiological 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.
6. Biosafety level-1
Agent 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
7. Biosafety level 2
BSL1 PLUS –
limited access
biohazard sign
sharp precautions
biosafety manual
BSC available
protective clothing
Autoclave
Access to incinerator
8. 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
9. Biosafety level 4Biosafety level 4
BSL 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
10. 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
11. CRITICAL BIOLOGICAL AGENTS
CATEGORY A
Variola major (smallpox)
Bacillus anthracis (anthrax)
Yersinia pestis (plague)
Clostridium botulinum toxin (botulism)
Francisella tularensis (tularemia)
Filoviruses
Ebola hemorrhagic fever
Marburg hemorrhagic fever
Arenaviruses
Lassa (Lassa fever)
Junin (Argentine hemorrhagic fever) and related viruses
12. CRITICAL BIOLOGICAL AGENTS
CATEGORY 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
13. CRITICAL BIOLOGICAL AGENTS
CATEGORY B
Coxiella burnetti (Q fever)
Brucella species (brucellosis)
Burkholderia mallei (glanders)
Alphaviruses
Venezuelan encephalomyelitis
eastern / western equine encephalomyelitis
Ricin toxin from Ricinus communis (castor bean)
Staphylococcus enterotoxin B
14. CRITICAL BIOLOGICAL AGENTS
CATEGORY 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
15. CRITICAL BIOLOGICAL AGENTS
CATEGORY 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
17. 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
19. laboratory diagnosislaboratory diagnosis
Specimens: 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
20.
21. treatment and Preventiontreatment and Prevention
Isolation- 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
22. small pox vaccinesmall pox vaccine
Vaccinia 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: 108
Pfu/ml.
Vaccination method:
Multiple Puncture Technique with Bifurcated needle.
23. Small Pox Vaccine:New Hopes
Cell Culture vaccine
DNA Vaccine
MVA
Antivirals
(1)Cidofovir:-Neucleotide analogue; Lack of oral bio-
availability.
(2)Adefovir:-Toxicity limiting factor.
24. Anthrax: The lethalAnthrax: 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
27. 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
28. Case definition of anthraxCase definition of anthrax
• Confirmed caseConfirmed case
Clinically compatible illness
isolationisolation – confirmed by DFA
and gamma phage
lysis
Supportive tests- 1. PCR
2. IHC
3.ELISA(PA)
isolation 2 supportive
laboratory
tests
• Suspected caseSuspected case
Clinically compatible illness
No alternative diagnosis
No isolation of B. anthracis
1 supportive
Laboratory
test Epidemiologic link
to B. anthracis
exposure
29.
30. Infection management
Standard 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 BDDoxy 100 mg i.v BD ++ clindamycin 900 mg iv tds /clindamycin 900 mg iv tds /
rifampicin300 mg iv BD}, Switch – oral when stable, totalrifampicin300 mg iv BD}, Switch – oral when stable, total
duration – 60 daysduration – 60 days
Post exposure prophylaxis – ciproloxacin/ doxycyclinePost exposure prophylaxis – ciproloxacin/ doxycycline
31. Preventive vaccine
Cell 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
32.
33. 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
34. • .
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
35.
36.
37.
38. 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
39. 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
40. 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)
41.
42. 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
43. prophylaxis
Vaccine – 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
44. Biological battle against botulism
Most 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.
45.
46. laboratory diagnosislaboratory diagnosis
The 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
47.
48. 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
49. 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
50. summary
BW 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
.
51. 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
