Experimental botulism in monkeys—A clinical pathological study

Herrero, Brunildo A.; Ecklund, Allen E.; Streett, C. Spencer; Ford, D.; King, John K.

doi:10.1016/0014-4800(67)90007-x

Cited by 74 publications

(36 citation statements)

References 5 publications

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“…There is no reliable data on the exact oral toxicity of BoNT for humans. However, from animal studies using nonhuman primates and from cases of human botulism, it is estimated that the lethal oral dose of BoNT is between 10 ng and 1 g kg Ϫ1 body weight (17,27). Generally, the lethal toxicity depends on the BoNT serotype and the route of exposure (2,8), and it may vary among individuals.…”

mentioning

confidence: 99%

The Case of Botulinum Toxin in Milk: Experimental Data

Weingart

Schreiber

Mascher

et al. 2010

Appl Environ Microbiol

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Botulinum neurotoxin (BoNT) is the most toxic substance known to man and the causative agent of botulism. Due to its high toxicity and the availability of the producing organism Clostridium botulinum, BoNT is regarded as a potential biological warfare agent. Because of the mild pasteurization process, as well as rapid product distribution and consumption, the milk supply chain has long been considered a potential target of a bioterrorist attack. Since, to our knowledge, no empirical data on the inactivation of BoNT in milk during pasteurization are available at this time, we investigated the activities of BoNT type A (BoNT/A) and BoNT/B, as well as their respective complexes, during a laboratory-scale pasteurization process. When we monitored milk alkaline phosphatase activity, which is an industry-accepted parameter of successfully completed pasteurization, our method proved comparable to the industrial process. After heating raw milk spiked with a set amount of BoNT/A or BoNT/B or one of their respective complexes, the structural integrity of the toxin was determined by enzyme-linked immunosorbent assay (ELISA) and its functional activity by mouse bioassay. We demonstrated that standard pasteurization at 72°C for 15 s inactivates at least 99.99% of BoNT/A and BoNT/B and at least 99.5% of their respective complexes. Our results suggest that if BoNTs or their complexes were deliberately released into the milk supply chain, standard pasteurization conditions would reduce their activity much more dramatically than originally anticipated and thus lower the threat level of the widely discussed "BoNT in milk" scenario.

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mentioning

confidence: 99%

The Case of Botulinum Toxin in Milk: Experimental Data

Weingart

Schreiber

Mascher

et al. 2010

Appl Environ Microbiol

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“…It is unknown if these are caused by direct action of botulinum toxin, other products of C. botulinum, or some other contaminant of spoiled food. These symptoms have never been reported in wound botulism [37] nor have corresponding signs been observed in primate experiments in which pure toxin was administered intragastrically or intravenously [16,27,33,[38][39][40]. Therefore, these symptoms may be absent in illness resulting from consumption of food deliberately contaminated with pure toxin.…”

Section: Clinical Presentationmentioning

confidence: 72%

Botulism

Sobel¹

2008

Beyond Anthrax

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“…Exposing rhesus monkeys to an aerosol lethal dose of BoNT/A (2,000 MIPLD 50 ) results in clinical signs and symptoms closely mirroring human food-borne botulism [Franz et al, 1993]. The lethal dose of BoNT for humans is not known but can be extrapolated from animal studies; the lethal dose for a 70-kg human is approximately 0.09-0.15 mg intravenously, 0.70-0.90 mg inhalationally, and 70 mg orally [Hererro et al, 1967;Scott and Suzuki, 1988;Arnon et al, 2001].…”

Section: Experimental Modelsmentioning

confidence: 98%

U.S. Army Botulinum Neurotoxin (BoNT) Medical Therapeutics Research Program: past accomplishments and future directions

Larsen

2009

Drug Development Research

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The United States Army (USA) under the auspices of the Medical Research and Material Command (USAMRMC) and the Defense Threat Reduction Agency (DTRA) sponsored several major efforts to develop an effective medical countermeasure against botulinum neurotoxin (BoNT). This review focuses on the U.S. Army's research and development efforts for a BoNT therapeutic over the period from 1975–2007. Two antitoxin preparations: Human botulism immunoglobulin (BIG) and Botulism Immune Globulin F(ab')2 Heptavalent Equine (BIGHE) were administered to humans and shown to possess acceptable efficacy and safety levels. BIGHE was deployed in Operation Desert Storm/Desert Shield. BoNT/A monoclonal antibodies were developed and are currently undergoing clinical evaluation with funding from the National Institute of Allergy and Infectious Disease (NIAID). The development of small molecules for the treatment of BoNT has also been supported. Efforts have focused on molecules to inhibit nearly every aspect of BoNT pathogenesis. This would include toxin binding, translocation, catalytic activity, and recovery following intoxication. Several compounds capable of inhibiting toxin activity or mitigating the severity of paralysis have been identified. To date, none of the compounds possess the appropriate properties (safety, efficacy, solubility) to be considered for clinical studies. Drug Dev Res 70:266–278, 2009. Published 2009 Wiley‐Liss, Inc.

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Experimental botulism in monkeys—A clinical pathological study

Cited by 74 publications

References 5 publications

The Case of Botulinum Toxin in Milk: Experimental Data

The Case of Botulinum Toxin in Milk: Experimental Data

Botulism

U.S. Army Botulinum Neurotoxin (BoNT) Medical Therapeutics Research Program: past accomplishments and future directions

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