Generic BAT (Botulism antitoxin heptavalent [A,B,C,D,E,F,G]) (equine) solution for injection in 20ml size vials

Background: Foodborne botulism is a rare but potentially fatal neuroparalytic illness caused by ingestion of Clostridium botulinum neurotoxins. Current treatment strategies include antitoxin administration, supportive care, and adjunctive therapies such as guanidine and 3,4-diaminopyridine. However, evidence comparing the efficacy of these interventions remain limited and inconclusive. This systematic review and meta-analysis aimed to evaluate treatment outcomes and compare the effectiveness of antitoxin, supportive care, and adjunctive therapies in managing foodborne botulism. Methods: A systematic search of PubMed and Web of Science was performed, and relevant studies were screened using predefined criteria. Data extraction and quality assessment were conducted independently by two reviewers. Pooled treatment success rates were calculated using random-effects meta-analysis with heterogeneity assessed via I² statistics. Results: 38 studies met our inclusion criteria, including case reports, case series, and observational studies. Pooled treatment success rates were high for antitoxin (95.3%, 95% CI: 91.3–97.8; p<0.001, I²=16.4%), supportive care (97.6%, 95% CI: 91.9–99.3; p<0.001, I²=0%), and guanidine (88.9%, 95% CI: 46.3–97.1; p<0.001, I²=0%). Comparative analyses showed no statistically significant differences between antitoxin alone versus combination therapy (OR 0.92, 95% CI: 0.10–8.62; p=0.94, I²=0%) or versus supportive care (OR 2.19, 95% CI: 0.28–17.14; p=0.46, I²=0%). Guanidine showed potential benefit as an adjunct, but data were limited. Conclusions: Antitoxin remains standard care for foodborne botulism, though supportive care and adjunctive treatments also show favorable outcomes. Further multicenter studies with standardized protocols are needed to optimize management.

Abstract licence: CC BY 4.0

BackgroundBotulism is a life-threatening neuroparalytic disease caused by botulinum neurotoxins. While its acute phase has been extensively studied, long-term sequelae following recovery remain insufficiently explored. This systematic review aims to comprehensively assess and synthesize available evidence on post-botulism sequelae to improve understanding and guide future research.MethodsA systematic search was conducted in MEDLINE, EMBASE via Ovid, and Web of Science from inception to 24 June 2024. Eligible studies included observational studies, case series, and case reports describing post-recovery symptoms in individuals diagnosed with foodborne, wound, or infant botulism, excluding iatrogenic cases. The risk of bias was assessed using the Critical Appraisal Skills Programme (CASP) checklists.ResultsOut of 340 screened records, 9 studies met inclusion criteria, comprising 2 case-control studies (n = 230 botulism cases, n = 669 controls) and 7 cohort studies (n = 185 botulism cases). Most studies reported some short- and/or long-term consequences of botulism. Among 3 studies homogeneously reporting sequelae symptomatology, the most frequently reported long-term symptoms included fatigue (66.2%, range 47.9%-84.6%), limitations in vigorous activities (55.8%, range 47.6%-64.0%), general weakness (57.1%, range 43.1%-76.9%), and dyspnea (42.9%, range 18.0%-92.3%). In some patients, psychosocial dysfunction persisted longer than physical impairments, over the 6-year period post intoxication. Two studies provided comparative data with control groups, demonstrating significantly higher prevalence of fatigue, weakness, and impaired health perception in botulism survivors. Additionally, 14 case reports and case series (n = 43 individuals) reported similar patterns with dyspnea, fatigue, and autonomic dysfunction among the most reported sequelae.ConclusionsThis systematic review highlights significant long-term sequelae among botulism survivors, particularly fatigue, respiratory impairment, and psychosocial dysfunction. While recovery trajectories suggest improvement over time, persistent symptoms may impact quality of life. Standardized outcome measures and longitudinal studies are needed to elucidate the burden of post-botulism sequelae further and inform clinical management strategies.

Abstract licence: CC BY

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 past century concluded that a statistically significant reduction in mortality is associated with the use of type E and type A antitoxin, but not with type B antitoxin. Animal models could be highly valuable in studying postsymptom antitoxin efficacy (PSAE). However, the few attempts to evaluate PSAE in animals relied on subjective observations and showed ∼50% protection. Recently, we developed a novel spirometry model for the quantitative evaluation of PSAE in rabbits and used it to demonstrate full protection against BoNT/E. In the current study, a 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 observed in humans, postsymptom 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-intoxicated rabbits (r=0.91, P=0.0006), but not in those intoxicated with BoNT/B (r=0.06, P=0.88). The rabbit spirometry system might be useful in the evaluation toolkit of botulism therapeutics, including those under development and intended to act when antitoxin is no longer effective. Summary: Here, we used a quantitative rabbit respiratory model to study the human-related, differential antitoxin efficacy observed in type A and type B botulism.

Abstract licence: CC BY 3.0

Botulinum neurotoxins (BoNTs), produced by Clostridium botulinum, exert their potent neuroparalytic effects by specifically targeting presynaptic cholinergic nerve terminals. BoNTs consist of a heavy chain that mediates high-affinity neuronal binding and endocytosis, and a light chain that, once translocated into the cytosol, acts as a zinc-dependent metalloprotease. The light chain cleaves SNARE proteins essential for synaptic vesicle fusion, thereby inhibiting acetylcholine release and leading to flaccid paralysis. This intoxication spans foodborne, wound, and infant botulism, all characterized by commonly observed heat-resistant endospores that enable bacterial survival under adverse conditions. BoNT intoxication induces flaccid paralysis, and both natural and synthetic neurotoxins disrupt neuronal communication by targeting synaptic components. However, BoNTs differ in their origin, mechanism of action, structure, and interactions. Clinical harnessing of non-poisoning low doses of BoNT/A and BoNT/B serotypes is used for alleviating symptoms of diverse diseases. Molecular engineering and clinical formulation enabled BoNTs optimization into pharmacologically safe and targeted therapeutic agents that replicate the selective neuronal silencing observed in their natural forms.

Abstract licence: CC BY-NC