Botulinum Toxin as a Biological WeaponMedical and Public Health Management

Infant Botulism Treatment and Prevention Program, California Department of Health Services, 2151 Berkeley Way, Room 506, Berkeley, CA 94704, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 03/2001; 285(8):1059-1070. DOI: 10.1001/jama.285.8.1059


The Working Group on Civilian Biodefense has developed consensus-based
recommendations for measures to be taken by medical and public health professionals
if botulinum toxin is used as a biological weapon against a civilian population.Participants
The working group included 23 representatives from academic, government,
and private institutions with expertise in public health, emergency management,
and clinical medicine.Evidence
The primary authors (S.S.A. and R.S.) searched OLDMEDLINE and MEDLINE
(1960–March 1999) and their professional collections for literature
concerning use of botulinum toxin as a bioweapon. The literature was reviewed,
and opinions were sought from the working group and other experts on diagnosis
and management of botulism. Additional MEDLINE searches were conducted through
April 2000 during the review and revisions of the consensus statement.Consensus Process
The first draft of the working group's consensus statement was a synthesis
of information obtained in the formal evidence-gathering process. The working
group convened to review the first draft in May 1999. Working group members
reviewed subsequent drafts and suggested additional revisions. The final statement
incorporates all relevant evidence obtained in the literature search in conjunction
with final consensus recommendations supported by all working group members.Conclusions
An aerosolized or foodborne botulinum toxin weapon would cause acute
symmetric, descending flaccid paralysis with prominent bulbar palsies such
as diplopia, dysarthria, dysphonia, and dysphagia that would typically present
12 to 72 hours after exposure. Effective response to a deliberate release
of botulinum toxin will depend on timely clinical diagnosis, case reporting,
and epidemiological investigation. Persons potentially exposed to botulinum
toxin should be closely observed, and those with signs of botulism require
prompt treatment with antitoxin and supportive care that may include assisted
ventilation for weeks or months. Treatment with antitoxin should not be delayed
for microbiological testing.

Download full-text


Available from: Trish M Perl
  • Source
    • "After the endocytotic uptake of BoNT-A from postsynaptic terminals, the light chain of BoNT-A cleaves SNAP-25 [79, 80]. This renders ACh-containing vesicles unable to dock and fuse to the presynaptic membrane. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Botulinum toxin A (BoNT-A) is a bacterial zinc-dependent endopeptidase that acts specifically on neuromuscular junctions. BoNT-A blocks the release of acetylcholine, thereby decreasing the ability of a spastic muscle to generate forceful contraction, which results in a temporal local weakness and the atrophy of targeted muscles. BoNT-A-induced temporal muscle weakness has been used to manage skeletal muscle spasticity, such as poststroke spasticity, cerebral palsy, and cervical dystonia. However, the combined effect of treadmill exercise and BoNT-A treatment is not well understood. We previously demonstrated that for rats, following BoNT-A injection in the gastrocnemius muscle, treadmill running improved the recovery of the sciatic functional index (SFI), muscle contraction strength, and compound muscle action potential (CMAP) amplitude and area. Treadmill training had no influence on gastrocnemius mass that received BoNT-A injection, but it improved the maximal contraction force of the gastrocnemius, and upregulation of GAP-43, IGF-1, Myo-D, Myf-5, myogenin, and acetylcholine receptor (AChR) subunits α and β was found following treadmill training. Taken together, these results suggest that the upregulation of genes associated with neurite and AChR regeneration following treadmill training may contribute to enhanced gastrocnemius strength recovery following BoNT-A injection.
    Full-text · Article · Nov 2013 · Neural Plasticity
  • Source
    • "Botulinum neurotoxin (BoNT), the most poisonous substance known, exists as seven toxin types A-G that are distinguished by the inability of polyclonal antibodies specific for one toxin type to neutralize any of the other six toxin types [1]. Variants or subtypes within BoNT/A, B, E and F have been designated by adding an Arabic number to the toxin type, e.g., A1, A2, etc. [2]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Sanger and shotgun sequencing of Clostridium botulinum strain Af84 type Af and its botulinum neurotoxin gene (bont) clusters identified the presence of three bont gene clusters rather than the expected two. The three toxin gene clusters consisted of bont subtypes A2, F4 and F5. The bont/A2 and bont/F4 gene clusters were located within the chromosome (the latter in a novel location), while the bont/F5 toxin gene cluster was located within a large 246 kb plasmid. These findings are the first identification of a C. botulinum strain that contains three botulinum neurotoxin gene clusters.
    Full-text · Article · Nov 2013 · PLoS ONE
  • Source
    • "The flaccid muscle paralysis caused by BoNT/A lasts for several months (Cherington, 1998). Therefore, patients who have already developed the syndrome have to be put under respiratory intensive care for this long duration of paralysis (Greenfield et al., 2002; Arnon et al., 2001; Rosenbloom et al., 2002). The estimated cost for each botulism patient under respiratory supportive care could be as high as US $350,000 (Wein and Liu, 2005). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Botulinum neurotoxin serotype A (BoNT/A) is the most potent poison of biological origin known to mankind. The toxicity of BoNT/A is due to the inhibition of neurotransmission at cholinergic synapses; this is responsible for the symptom of flaccid paralysis at peripheral neuromuscular junctions. At a molecular level, the BoNT/A effect is due to its inhibition of stimulated acetylcholine (ACh) release from presynaptic nerve terminals. Currently, there is no antidote available to rescue BoNT/A-poisoned synapses. Here, we report an example of rescuing botulinum-poisoned cultured mouse spinal cord neurons by treatment with Mastoparan-7 (Mas-7), which is known to be a phospholipase A2 activator compound. Mas-7, a naturally occurring bee venom peptide, was delivered to botulinum-poisoned neurons via a drug delivery vehicle (DDV) construct prepared using the recombinant non-toxic heavy chain (HC) fragment of BoNT/A itself. In this method, the BoNT/A HC component in the DDV served as a neuron specific drug targeting molecule. We found that Mas-7 delivered into BoNT/A intoxicated spinal cord cells restored over 40% their property of stimulated neurotransmitter release. Rescue from cell poisoning did not occur from inhibition of the endopeptidase activity of BoNT/A light chain (LC) against its well-known substrate, SNAP-25 that is mechanistically involved in the cholinergic neuroexocytosis process. Rather, Mas-7 induced a physiological host response apparently unrelated to SNAP-25, but linked to the phospholipase-mediated signal transduction pathway.
    Full-text · Article · Sep 2013 · Toxicon
Show more