Botulinum neurotoxins (BoNTs), the most poisonous substances known in nature, pose significant concern to health authorities. The only approved therapeutic for botulism is antitoxin. While administered to patients only after symptom onset, antitoxin efficacy is evaluated in animals mostly in relation to time post-intoxication regardless of symptoms. This is most likely due to the difficulty to measure early symptoms of botulism in animals. In the current study, a rabbit spirometry model was developed to quantify early respiratory symptoms of type E botulism that were further used as trigger for treatment. Impaired respiration, in the form of reduced minute volume, was detected as early as 18.1±2.9 hours post-intramuscular exposure to 2 rabbit lethal dose fifty (LD50) of BoNT/E, preceding any visible symptoms. All rabbits treated with antitoxin immediately following symptom onset survived. Post-symptom antitoxin efficacy was further evaluated in relation to toxin and antitoxin dosage as well as to delayed antitoxin administration. Our system enabled us to demonstrate, for the first time, full antitoxin protection of animals treated with antitoxin after the onset of objective and quantitative type E botulism symptoms. This model may be utilized to evaluate the efficacy of antitoxins in additional serotypes of BoNT as well as that of next generation anti-BoNT drugs.
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