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RS–IAP-ICSU international workshop on science & technology developments relevant to the Biological & Toxin Weapons Convention4�– 6�September�2006
SURVEILLANCE & DIAGNOSIS OF
BIOTERRORISM EVENTS
SURVEILLANCE & DIAGNOSIS OF
BIOTERRORISM EVENTS
R SWANEPOEL
SPECIAL PATHOGENS UNIT
NATIONAL INSTITUTE FOR COMMUNICABLE DISEASES
SOUTH AFRICA
R SWANEPOEL
SPECIAL PATHOGENS UNIT
NATIONAL INSTITUTE FOR COMMUNICABLE DISEASES
SOUTH AFRICA
The Threat of New, Emerging & Re-emerging Diseases
The Threat of New, Emerging & Re-emerging Diseases
• Microbial determinants (mutation, natural selection, evolution)
• Human activity (personal behavior, societal, commercial)
• Natural determinants (ecologic, environmental, zoonotic influences)
• Accidental or malicious release
• Microbial determinants (mutation, natural selection, evolution)
• Human activity (personal behavior, societal, commercial)
• Natural determinants (ecologic, environmental, zoonotic influences)
• Accidental or malicious release
…over-riding factor driving the emergence of diseases of humans and animals: Human population growth and the incredible change occurring in all ecosystems brought about by human occupation of every corner of the planet
…over-riding factor driving the emergence of diseases of humans and animals: Human population growth and the incredible change occurring in all ecosystems brought about by human occupation of every corner of the planet
White = city lights; Yellow = natural gas burnoff;Red = fires; Blue = fishing lights
FA Murphy 2002
White=city lights; Yellow=natural gas burnoff; Red=fires; Blue=fishing lights
FA Murphy 2002
Migration
Travel
Ceton CDC 2002
Tire dump,California,1997:
today’smosquitobreeding ground
Tire dump,California,1997:
today’smosquitobreeding ground
FA Murphy 2002
LAST 4 DECADES
75 IMPORTANT NEW VIRUSES
MOSTLY ZOONOTIC
LAST 4 DECADES
75 IMPORTANT NEW VIRUSES
MOSTLY ZOONOTIC
Bioterrorism surveillanceand response – voluminousnational and internationalbiblography available
Bioterrorism surveillanceand response – voluminousnational and internationalbiblography available
Bioterrorism event: areas of competenceBioterrorism event: areas of competence
Terrorist intentTerrorist intent
Choice/acquisition of bio-agentChoice/acquisition of bio-agent
Production/processingProduction/processing
DisseminationDissemination
DiseaseDisease
Intelligence/Law enforcementIntelligence/Law enforcement
Law enforcement/IntelligenceLaw enforcement/Intelligence
HealthHealth
Characteristics of a Bioterrorism EventCharacteristics of a Bioterrorism Event
• Clinical signs may not appear for days/weeks
• Initial signs likely to be non-specific
• Possibly large numbers of casualties
• Unusual epidemiology:– Non-endemic disease
– Respiratory symptoms prominent
– Diverse animal deaths
– Multiple simultaneous outbreaks
– Multi-drug resistant pathogens
– Delivery incident/vehicle/intelligence
• Clinical signs may not appear for days/weeks
• Initial signs likely to be non-specific
• Possibly large numbers of casualties
• Unusual epidemiology:– Non-endemic disease
– Respiratory symptoms prominent
– Diverse animal deaths
– Multiple simultaneous outbreaks
– Multi-drug resistant pathogens
– Delivery incident/vehicle/intelligence
Characteristics of a Bioterrorism EventCharacteristics of a Bioterrorism Event
• Diagnosis depends on high degree of awareness & availability of appropriate laboratory tests
• Concerns re availability of drugs, personnel
• Need for coordination of state & civil agencies
• Legal and forensic considerations
• Potential for major health impact
• Diagnosis depends on high degree of awareness & availability of appropriate laboratory tests
• Concerns re availability of drugs, personnel
• Need for coordination of state & civil agencies
• Legal and forensic considerations
• Potential for major health impact
Category A ListCategory A List
• Easily transmitted
• High mortality
• May cause panic and social disruption
• Need special preparedness – surveillance & diagnostics
Anthrax
Smallpox
Plague
Tularemia
Botulism
Viral haemorrhagic fevers: Marburg, Ebola, etc
• Easily transmitted
• High mortality
• May cause panic and social disruption
• Need special preparedness – surveillance & diagnostics
Anthrax
Smallpox
Plague
Tularemia
Botulism
Viral haemorrhagic fevers: Marburg, Ebola, etc
Category B ListCategory B List
• Moderately easily disseminated
• Moderate morbidity and mortality (incapacitating)
• Require enhanced surveillance
• Require specific diagnostic capacity
Q fever
Brucellosis
Glanders
Tularemia
Mosquito-borne encephalitides
Toxins
Food/water-borne pathogens
• Moderately easily disseminated
• Moderate morbidity and mortality (incapacitating)
• Require enhanced surveillance
• Require specific diagnostic capacity
Q fever
Brucellosis
Glanders
Tularemia
Mosquito-borne encephalitides
Toxins
Food/water-borne pathogens
Category C ListCategory C List
• Potential for future importance:
• Availability, ease of production & dissemination
• High morbidity & mortality
• Potential for major health impact
Nipah
Hantaviruses
Tick-borne haemorrhagic fevers
Tick-borne encephalitides
Yellow fever
Drug resistant tuberculosis
• Potential for future importance:
• Availability, ease of production & dissemination
• High morbidity & mortality
• Potential for major health impact
Nipah
Hantaviruses
Tick-borne haemorrhagic fevers
Tick-borne encephalitides
Yellow fever
Drug resistant tuberculosis
Smallpox virus as bioterror agentSmallpox virus as bioterror agent
• Highly lethal: ~30% mortality
• Human-to-human transmission
• Long incubation period
• Virus is stable: storage & transport
• Aerosol dissemination
• However, hard to obtain?
• Highly lethal: ~30% mortality
• Human-to-human transmission
• Long incubation period
• Virus is stable: storage & transport
• Aerosol dissemination
• However, hard to obtain?
…Although we officially had a small amount of the virus in the IvanovskyInstitute of Virology in Moscow…we cultivated tons of smallpox virus in our secret lab in Zagorsk … then quietly [it] added to our arsenal…Ken Alibek - Biohazard
…Although we officially had a small amount of the virus in the IvanovskyInstitute of Virology in Moscow…we cultivated tons of smallpox virus in our secret lab in Zagorsk … then quietly [it] added to our arsenal…Ken Alibek - Biohazard
Which biological agents?
AnthraxAnthrax
Sverdlovsk 1979
US Postal Services 2001
Sverdlovsk 1979
US Postal Services 2001
Vaccination status: effect on outcomeof infection, Europe, 1950-71
Vaccination status: effect on outcomeof infection, Europe, 1950-71
Clinical types of smallpox
• Without rash (Variola sine eruptione)
• Modified
• Discrete
• Semi-confluent
• Confluent
• Flat
• Haemorrhagic early/late
Stages of smallpox
• Incubation 12 days (7-17)
• Febrile illness 2-4 days
• Macules – day 1-2
• Papules – day 2-3
• Vesicles – day 4-5
• Pustules – day 4-11
• Scabs – day 8-21
• Complications/sequelae
• Differential diagnoses
• Incubation 12 days (7-17)
• Febrile illness 2-4 days
• Macules – day 1-2
• Papules – day 2-3
• Vesicles – day 4-5
• Pustules – day 4-11
• Scabs – day 8-21
• Complications/sequelae
• Differential diagnoses
RIFT VALLEY FEVERRIFT VALLEY FEVER
JAN1997JAN1997
JAN
1998
JAN
1998
JAN1999JAN1999
Laboratory requirements
Biosafety level 1-4 laboratories (BSL 1-4)
Lab practices & techniques
Standard
Special
Safety equipment (1ry barrier)
Facility design/structure (2ry barrier)
Biosafety levels
• BSL1 – not known to cause human disease
• BSL2 – associated with human disease
• BSL3 – associated with human disease & has potential for aerosol transmission
• BSL4 – exotic or life threatening agent
• BSL1 – not known to cause human disease
• BSL2 – associated with human disease
• BSL3 – associated with human disease & has potential for aerosol transmission
• BSL4 – exotic or life threatening agent
Biosafety level 4 laboratory (BSL4)
CDC
Laboratory diagnosis of an infectious disease: eg an acute viral disease
Laboratory diagnosis of an infectious disease: eg an acute viral disease
Acute phase
Virus
– antigen (Elisa)
- nucleic acid (PCR)
- infectivity (culture)
Convalescent phase
Immune response
- antibody response – IgM / IgG (Elisa)
Acute phase
Virus
– antigen (Elisa)
- nucleic acid (PCR)
- infectivity (culture)
Convalescent phase
Immune response
- antibody response – IgM / IgG (Elisa)
NUCLEIC ACID DETECTION:
PCR/RT-PCRReal-time PCR
Multiplexed PCR
Mass-tagged PCR
Mass spectrometry
DNA microarrays (panmicrobial)
NUCLEIC ACID DETECTION:
PCR/RT-PCRReal-time PCR
Multiplexed PCR
Mass-tagged PCR
Mass spectrometry
DNA microarrays (panmicrobial)
RNA extraction
30 min
RT-PCR130 min
Sample
Result
5 min
Detection
45 min
Chip
3.5 hours
LOW DENSITY CHIPS:
BUNDESWEHR INST MICROBIOLOGY
BERNARD NOCHT INST TROP MED