Tasneem Khan

Tsitsi Sithole

What is Bioterrorism?

The intended use of biological weapons to

cause disease in humans, animals, and plants,

as an act of war. Biological weapons

deliberately disseminate disease-producing

organisms or toxins and achieves this effect

through multiplication within a target host.

“Classic” Terrorism

Against persons and institutions.

Agri-Bioterrorism

Against crops/foods/plants

Product tampering

Directed against consumer/commercial products

• Agents of bioterrorism which include microorganisms (bacteria,

viruses, and fungi) that are capable of entering the human body by

inhalation or digestion, and thereafter multiplying – causing illness

and death

• Capable of causing epidemics.

• Include toxins produced by microorganisms, plants and animals

• Or synthetic analogues of naturally occurring toxins

• Chemicals that regulate biological functions

Intrinsic Features* Infectivity* Virulence* Lethality* Pathogenicity* Incubation period* Contagiousness* Stability

Centres for Disease Control have categorised the level of threat of biological agents based on their above mentioned features into 3 categories.

Source: http://img.medscape.com/pi/features/slideshow-slide/bioterrorism/fig2.jpg

Category A

Anthrax (Bacillus anthracis)

Smallpox (Variola major)

Plague (Yersinia pestis)

Botulism toxin (Clostridium botulinum)

Tularemia (Francisella tularensis)

Violent Hemorrhagic Fevers (VHF)

Other potential agents include:

Brucellosis (Brucella species) Glanders (Burkholderia mallei) Q fever (Coxiella burnetii) Cholera (Vibrio cholera) Salmonella sp. and Shigella sp. Venezuelan Equine Encephalitis (VEE) Staphylococcal Enterotoxin B Ricin (from castor beans) T-2 Mycotoxins …and many more!

Investigation on three levels: Clinical Epidemiological Laboratory

Epidemiologic clues for Bioterrorism: Tight cluster of cases High infection rate Unusual or localized geography Unusual clinical presentation Unusual time of year Dead animals

Aerobic, gram positive rod, spore-forming, non-motile

Virulence requires an antiphagocytic capsule and 3 toxin compounds, namely protective antigen, lethal factor and edema factor

It exists in soils worldwide

Primarily it was a disease of herbivores and exists naturally as a zoonotic disease

Human infection through contact with infected animals or contaminated products

Three Anthrax disease types: cutaneous, gastrointestinal and inhalational (seen in US in 2001)

Produces hemorrhagic mediastinitis (bleeding into the mid-chest) which rapidly progresses into a systemic infection

Incubation lasts 3 - 60 days

Secondary septasemia has a mortality rate estimated to be >80%

Initial symptoms are abrupt and develop after 72 hours. Non-specific fever, dyspnea, cough, headache and vomiting

Death can occur within hours of exposure. (Average 3 days from onset of signs in Sverdlovsk)

Drug of choice for chemoprophylaxis is Oral flouroquinolones, given to known or high risk exposures

Active immunization (vaccines) – Exists for smallpox, anthrax, botulinum toxin, and others

Smallpox has been successfully eradicated. – Milestone in history!

Chemoprophylaxis (antibiotics) – Given BEFORE the disease manifests eg. Anthrax

Personal protection – HEPA type filters (HEPA masks) for most agents (respiratory)

Treatment of the infection

Active vaccination not cost-effective for routine use

Insufficient supplies or distribution for chemoprophylaxis (leads to prioritized treatment, reserved only for known (VIP) or high risk exposures)

Treatment of the infection is limited for most agents

High mortality (>80%) even for aggressive treatment

Many vaccines have been produced but do not meet required levels of efficacy and safety and another problem facing vaccines is acceptance by people. A problem evident with the current flu vaccine. DDT Vol. 9, No. 5 March 2004

Biological Weapons Convention, to monitor the use and deployment of so-called dual-use technologies, which can mean almost anything, and to ensure greater scrutiny of scientists and the communication of scientific methodologies and data.

Problems arise with psychological trauma and post-traumatic stress-patients displaying a lot of symptoms of mental disorder rather than those of the disease and this can undermine effective treatment of those directly affected by the disease. Mass hesteria etc.

Over the next five years, the US National Institutes of Health (NIH) plan to spend hundreds of millions of dollars to discover and develop or improve treatment and prevention modalities for agents of bioterrorism. The NIH has recently funded eight centers designated as ‘Research Centers of Excellence.’ These centers have been awarded $350 000 000 to develop new antibiotics and vaccines to protect the US population from agents of bioterrorism, as well as novel means to detect them.

US government signed legislation providing $2.9 billion to enhance bioterrorism preparedness, including public health and medical strategies.

Providing a need for more extensive research into antimicrobial agents against Bacillus anthracis, Yersinia pestisand Francisella tularensis, as well as the toxins produced by Clostridium botulinum, which are believed to pose the greatest threat as bacterial bioterrorism agents.

Use of prophylactic antimicrobials- naturally occurring and engineered antimicrobial resistance. Hence we need to improve detection of antimicrobial resistance in bioterrorism agents and we must also use our understanding of the molecular pathogenesis of these three organisms to identify potential targets that can be used in the development of novel antimicrobial agents.