In:
Disease Models & Mechanisms, The Company of Biologists
Abstract:
Botulinum neurotoxin (BoNT) serotypes A, B and E are responsible for most cases of human botulism. The only approved therapy for botulism is antitoxin treatment administered to patients after symptom onset. However, a recent meta-analysis of antitoxin efficacy in human botulism cases over the last century concluded that a statistically significant reduction in mortality is associated with the use of type-E and type-A but not type-B antitoxin. Animal models could be highly valuable in studying post-symptom antitoxin efficacy (PSAE). However, the only few attempts to evaluate PSAE in animals relied on subjective observations and showed approximately 50% protection. Recently, we developed a novel spirometry model for quantitative evaluation of PSAE in rabbits and used it to demonstrate full protection against BoNT/E. In the current study, comparative evaluation of PSAE in botulism types A and B was conducted using this quantitative respiratory model. A lethal dose of each toxin induced a comparable course of disease both in terms of time to symptoms (TTS, 41.9±1.3 and 40.6±1.1 h, respectively) and of time to death (TTD, 71.3±3.1 and 66.3±1.7 h, respectively). However, in accordance with the differential serotypic PSAE in human, post-symptom antitoxin treatment was fully effective only in BoNT/A-intoxicated rabbits. This serotypic divergence was reflected by a positive and statistically significant correlation between TTS and TTD in BoNT/A- (r=0.91, P=0.0006) but not in BoNT/B- (r=0.06, P=0.88) intoxicated rabbits. The rabbit spirometry system may be useful in the evaluation toolkit of botulism therapeutics, including those under development and intended to act when antitoxin is no longer effective.
Type of Medium:
Online Resource
ISSN:
1754-8411
,
1754-8403
Language:
English
Publisher:
The Company of Biologists
Publication Date:
2018
detail.hit.zdb_id:
2451104-3
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