See CDC classification of Bioterrorism Agents

companies:  Innovatek

See Bioterrorism Preparedness Response Act of 2002 for more information on regulations regarding possession and transport of certain agents. Centers for Disease Control

Common Agents of Bioterrorism:

Anthrax:

Anthras is a rare but serious infectious zoonotic dsiease caused by the spore forming bacterium Bacillus antracis. In North American, animal outbreaks typically occur during summer in hot drug wather. Rare cases among humans usually follow direct contact with or processing of anthrax-infected animals or contaiminated animal products such as hides, hair or wool. (Thompson, “Anthrax on a sheep farm in winter -Texas, December 2023 -January 2024” Mobidity and Motrtality Weekly Report.)

On January 4, 2024, a male ranger aged 50-59 was evaluated at a hosptial A fro fever, leukocytosis, a black eschar on his right wrist, and extensive edema and blistered lesions on his right arm. He was febrile and had an elevated white blood cell count. Antrax was suspected to be the etiology becasue 11 days earlier he had butchered a lamb that had died suddently on his range in Texas. (Thompson, “Anthrax on a sheep farm in winter -Texas, December 2023 -January 2024” Mobidity and Motrtality Weekly Report.)

Methods of Detecting Biological Agents of Warfare

Pitfalls of PCR Approaches:

–contamination

–viability: the bacterial or viral DNA could be amplified even after a loss of viability to induce infectiona nd disease.

–toxin induced disease: Clinical samples in such cases may not necessarily harbor geneotypic information related to the causative pathogen. Example: botulinum toxin and superantigen toxin

–genetically engineered biological threats: could easily confuse health survelillance based on genotypes. Examples: modified mousepox virus with an IL-4 gene was shown to induce unexpeteced lethality in mice usually protected from mosuepox via vaccination.

–genome diversification: bacterial populations are subject to genome diversification that involves the transmission and acquisition of exogenous genetic material, producing varying abilities to cause infectiona nd disease.

–kinetics for disease: Kitetics for pathogen clearance and disease symptoms may not manifest concurrently. Example: invasion in the CNS by Venezuelan equine encephalitis virus follows clearance form the periophery in a short time. Thus, the time window where clinical genomic markers and signs are present is very short.

–DNA Microarrays for Gene Expression Profiles: A single microarray contains vast amount of DNA information. Gene arrays can be used to monitor changes in gene expression subsequent to infection. As an example, macrophages and monocyte-derived dendritic cells exposed to Mcyobacterium tuberculosis and to phylogenetically distinct protozoan (leishmania major, L. donovani, T. gondii) and helminth (Brugia malay)exhibited discrete gene expression signatures asociated with each infectious agent. For diagnostic purposes using microarrays, peripheral blood mononuclear cells (PBMCs) have been suggested as a cellular vehicle for assessing host response. Biological agent-induced chagnes in cellular gene expression can be identified, perhaps yeilding a profile of biomarkers that may distinguish one agent from another or degress of pathogenicity of classes of agents.

–specificity: Although gene expression profiles will no doubt be increasingly used to classify pathogens, specific assays such as those that provide pathogen genomic sequence information will likely continue to provide a definite basis for differentaition.  But this could change as more comprehensive databases are developed for gene pexression profiles for the purpose of detection and diagnosis.

–Sample collection and time required to pocess a micrroarray assay:The systematic acquisition of meaningful gene expression values can be achieved with as little as 2.5-10 mL of whole blood and clinical blood collection tubes allow for the preservation of RNA samples derived form blood. Still, most gene microarray hybridization steps require hours rather than minutes. Once libraries of gene expression profiles have been generated with use of whole-genome microarrays, subsets of meaningful genes would would also be sued as alternative means of detection. Alternatives include bead array technologies and microelectornic array devices which yeild information in seconds or minutes rather than hours or days. For example, by applying a positve cahrge at electrode contacts, microelectornic arrays make use of the fat that DNA molecules have a net negative cahrge to concentrate the moleucle to the desired locationa nd accelarate hybridization, which is considered to be the rate limiting step. 

Treatment 

Anti-toxin mAbs: 

For certain bacterial infection, soluble toxins are major contributors to pathogenesis. In this respect, antibody treatment may offer a better alternative to anti-biotic treatment due to toxin neutralization. For example, antibodys against Bacillus anthracis toxin are currently in clincial development. (Anthrax, Human Genome Sciences), AVP-2109 (Avanir Pharmaceuticals), Anthim (Eltusys Therapeutics, ETI-204), Valortin (PharmAthene/Mederax, MDX1303), IQNPA (IQ Corpation) and WI (National Institute of allergy and Infectious Diseases). These mAbs come from various techhnologys such as humanized murine mAbs, mAbs from naive human pahge libraries, mAbs from immune chimpanzee pahge libraries and mAbs cloned form B cells from immunized volunateers. All six mAbs inhibit the binding of PA to its receptor(s), with four of the mAbs targeting PA domain of IV. Efficacy seems to correlate with affinity for anti-PA mAbs. (Oleksewicz, Archives of Biochemistry and Biophysics 226 (2012) 124-131).