Efficacy of equine botulism antitoxin in botulism poisoning in a guinea pig model

Autor: Karen Gillum, Hongyu Qiu, Teresa Takla, Douglas Barker, Nancy Neimuth, Shantha Kodihalli, Andrew Emanuel
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Serotype
Bacterial Diseases
medicine.disease_cause
Toxicology
Pathology and Laboratory Medicine
Botulinum Antitoxin
0302 clinical medicine
Paralysis
Medicine and Health Sciences
Toxins
Botulism
Public and Occupational Health
Mammals
Multidisciplinary
Eukaryota
Animal Models
Infectious Diseases
Experimental Organism Systems
Toxicity
Vertebrates
Medicine
medicine.symptom
Antitoxin
Intramuscular injection
Post-Exposure Prophylaxis
Research Article
Neurotoxicology
Substance-Related Disorders
Science
Toxic Agents
Bacterial Toxins
Guinea Pigs
Neurotoxins
Intoxication
Botulinum Toxin
Research and Analysis Methods
Serogroup
Rodents
03 medical and health sciences
Mental Health and Psychiatry
medicine
Animals
Horses
business.industry
Toxin
Prophylaxis
Lethal dose
Organisms
Biology and Life Sciences
medicine.disease
030104 developmental biology
Immunology
Amniotes
Animal Studies
Antitoxins
Preventive Medicine
business
030217 neurology & neurosurgery
Zdroj: PLoS ONE
PLoS ONE, Vol 14, Iss 1, p e0209019 (2019)
ISSN: 1932-6203
Popis: BackgroundBotulism 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 findingsStudies 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 (p0.008 scaled human dose for serotypes A, B, C, F and G, at >0.2x for serotype D and >0.04x for serotype E.ConclusionsThese studies confirm the efficacy of BAT as a post-exposure prophylactic therapy against all seven known BoNT serotypes.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje