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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