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Efficacy of equine botulism antitoxin in botulism poisoning in a guinea pig model.
Emanuel, Andrew; Qiu, Hongyu; Barker, Douglas; Takla, Teresa; Gillum, Karen; Neimuth, Nancy; Kodihalli, Shantha.
Afiliación
  • Emanuel A; Research and Development, Emergent BioSolutions Canada Inc., Winnipeg, Manitoba, Canada.
  • Qiu H; Research and Development, Emergent BioSolutions Canada Inc., Winnipeg, Manitoba, Canada.
  • Barker D; Research and Development, Emergent BioSolutions Canada Inc., Winnipeg, Manitoba, Canada.
  • Takla T; Research and Development, Emergent BioSolutions Canada Inc., Winnipeg, Manitoba, Canada.
  • Gillum K; Battelle Biomedical Research Center, West Jefferson, Columbus, Ohio, United States of America.
  • Neimuth N; Battelle Biomedical Research Center, West Jefferson, Columbus, Ohio, United States of America.
  • Kodihalli S; Research and Development, Emergent BioSolutions Canada Inc., Winnipeg, Manitoba, Canada.
PLoS One ; 14(1): e0209019, 2019.
Article en En | MEDLINE | ID: mdl-30633746
BACKGROUND: Botulism is a disease caused by neurogenic toxins that block acetylcholine release, resulting in potentially life threatening neuroparalysis. Seven distinct serotypes of botulinum neurotoxins (BoNTs) have been described and are found in nature world-wide. This, combined with ease of production, make BoNTs a significant bioweapon threat. An essential countermeasure to this threat is an antitoxin to remove circulating toxin. An antitoxin, tradename BAT (Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)-(Equine)), has been developed and its efficacy evaluated against all seven serotypes in guinea pigs. METHODS AND FINDINGS: Studies were conducted to establish the lethal dose and clinical course of intoxication for all seven toxins, and post-exposure prophylactic efficacy of BAT product. Animals were monitored for signs of intoxication and mortality for 14 days. Guinea pig intramuscular LD50s (GPIMLD50) for all BoNTs ranged from 2.0 (serotype C) to 73.2 (serotype E) of mouse intraperitoneal LD50 units. A dose of 4x GPIMLD50 was identified as the appropriate toxin dose for use in subsequent efficacy and post-exposure prophylaxis studies. The main clinical signs observed included hind limb paralysis, weak limb, change in breathing rate/pattern, and forced abdominal respiration. Mean time to onset of clinical signs ranged from 12 hours (serotype E) to 39 hours (serotype G). Twelve hours post-intoxication was selected as the appropriate time point for intervention for all serotypes apart from E where 6 hours was selected because of the rapid onset and progression of clinical signs. Post-exposure treatment with BAT product resulted in a significantly (p<0.0001) higher survival at >0.008 scaled human dose for serotypes A, B, C, F and G, at >0.2x for serotype D and >0.04x for serotype E. CONCLUSIONS: These studies confirm the efficacy of BAT as a post-exposure prophylactic therapy against all seven known BoNT serotypes.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Botulismo / Antitoxina Botulínica Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2019 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Botulismo / Antitoxina Botulínica Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2019 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos