Medical Aspects of Chemical Warfare (2008) - The Black Vault

Toxins: Established and Emergent ThreatsTable 19-2Center for Disease Control and Prevention Classification of BioterrorismAgents/DiseasesCategory A Category B Category CAnthrax Brucellosis emerging future toxin threatsBotulismepilson toxin of Clostridium perfringensPlagueFood safety threats (Escherichia coli, Salmonella species, O157:H7,SmallpoxShigella)TularemiaGlandersViral Hemmoragic Fevers MeloidosisPsittacosisQ Feverricin toxin from Ricinus communisstaphylococcal enterotoxin BtyphusViral encephalitisWater safety threats (eg, Vibrio cholerae, Cryptosporidium parvum)Data source: Bioterrorism agents/diseases: emergency preparedness & response Web site. Available at: http://www.bt.cdc.gov/agent/agentlist-category.asp. Accessed February 10, 2007.the future because of availability; ease of productionand dissemination; and potential for high morbidityand mortality rates and major health impact.” 7 Theseemerging toxin threats are the focus of this chapter,toxins that possess the properties of the more wellknowncategory A and B agents but that have not beenconsidered likely threats to date (see Table 19-2).Emergent ThreatsThe group of biotoxins not considered immediatethreats with the potential to cause human illness anddeath is potentially very large and includes the sodiumchannel toxins BTX, 9 PbTx, 10 saxitoxin (STX), 11TTX, 12 and pumiliotoxin. 13 Others include palytoxin(PTX), which alters the sodium-potassium exchanger(sodium-potassium ATPase), 14 and the nicotinic receptoragonist, anatoxin-A. 15 Because these toxins areemployed as pharmacological tools for studying ionchannel properties, active efforts to optimize theirsynthesis are being developed. 16 If these efforts aresuccessful in generating large quantities of toxin,members of this group will need to be reevaluated fortheir potential as threat agents.ToxinsPalytoxinSynthesisPTX is an extremely potent marine neurotoxin thatacts on sodium-potassium ion pumps. First isolatedfrom the zoanthid coral (genus Palythoa) by Mooreand Scheuer, 17 PTX has long been categorized as amarine animal toxin. It has been identified in severalspecies living in close contact with zoanthid anemones(eg, some dinoflagellates, Ostreopsis species); 18Polychaete worms; 19 several species of xanthid crab(Lophozozymus pictor and Demaina toxica), 20 and severalspecies of fish. 21–23 PTX is found in the red alga Chondriaaramata. 24,25 PTX has also been associated with the bluehumphead parrotfish, 26 filefish, and serranid fish. 27The primary source is most likely a bacterium associatedwith soft corals that inhabit the digestive tract offilefish (Figure 19-1). PTX is a large (molecular weight2,678.5), water-soluble, nonproteinaceous polyether,with molecular formula C 129H 223N 3O 54. PTX has anexquisitely complex structure (see Figure 19-1). It wasfirst elucidated and synthesized in 1982 28 and is currentlyavailable from several commercial sources.Mechanism of Action and ToxicityPTX affects all excitable cells by inducing the activityof a small conductance (9–25 pS), nonselective,cationic channel, which triggers secondary activationsof voltage-dependent calcium channels and of sodiumcalciumexchange. In addition to electrically excitable617