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: 30.39). 03/2001; 285(8):1059-1070. DOI: 10.1001/jama.285.8.1059

ABSTRACT Objective
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.

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    ABSTRACT: Botulism commonly occurs when the anaerobic, gram-positive bacterium Clostridium botulinum, under suitable conditions, produces botulinum neurotoxins. Named A-F, these toxins are the immediate causative agent of the clinical symptoms of symmetrical, descending neurological deficits, including respiratory muscle paralysis. We present five cases of foodborne botulism occurring in Greenland, two with fatal outcome, caused by ingestion of tradionally preserved eider fowl. In the cases of the survivors, antitoxin and supportive care, including mechanical ventilation, were administered. In these cases recovery was complete. Microbiological assays, including toxin neutralization bioassay, demonstrated the presence of neurotoxin E in two survivors. The third survivor was shown by PCR to have the BoNT type E gene in faeces. This is the first report of cases of fatal botulism in Greenland. It underscores the importance of prompt coordinated case management effort in a geographically isolated area such as Greenland.
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    ABSTRACT: To cause food-borne botulism, botulinum neurotoxin (BoNT) in the gastrointestinal lumen must traverse the intestinal epithelial barrier. However, the mechanism by which BoNT crosses the intestinal epithelial barrier remains unclear. BoNTs are produced along with one or more non-toxic components, with which they form progenitor toxin complexes (PTCs). Here we show that serotype A1 L-PTC, which has high oral toxicity and makes the predominant contribution to causing illness, breaches the intestinal epithelial barrier from microfold (M) cells via an interaction between haemagglutinin (HA), one of the non-toxic components, and glycoprotein 2 (GP2). HA strongly binds to GP2 expressed on M cells, which do not have thick mucus layers. Susceptibility to orally administered L-PTC is dramatically reduced in M-cell-depleted mice and GP2-deficient (Gp2(-/-)) mice. Our finding provides the basis for the development of novel antitoxin therapeutics and delivery systems for oral biologics.
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