Large Outbreak of Botulism Associated with a Church Potluck Meal — Ohio, 2015

McCarty, Carolyn Lullo; Angelo, Kristina M.; Beer, Karlyn D.; Cibulskas-White, Katie; Quinn, Kim; Fijter, Sietske de; Bokanyi, Rick; Germain, Eric St; Baransi, Karen; Barlow, Kevin; Shafer, Gwen; Hanna, Larry; Spindler, Kelly; Walz, Elizabeth T.; DiOrio, Mary; Jackson, Brendan R; Lúquez, Carolina; Mahon, Barbara E.; Basler, Colin; Curran, Kathryn; Matanock, Almea; Walsh, Kelly A.; Slifka, Kara Jacobs; Rao, Agam K.

doi:10.15585/mmwr.mm6429a6

Cited by 37 publications

(25 citation statements)

References 2 publications

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“…Therefore, it has been suggested that the treatment with an antitoxin has limited value in symptomatic patients as most toxin will have already been internalized and be protected in the intracellular environment. The clinical experience with both foodborne botulism and wound botulism have clearly suggested the association between early administration of antitoxin and improved survival, length of hospital stay and use of ventilation [ 54 , 55 , 56 , 57 , 58 , 59 ]. Our results support this correlation as there was a significant difference in the survival rates observed between post exposure prophylactic and therapeutic efficacy studies.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic efficacy of equine botulism antitoxin in Rhesus macaques

et al. 2017

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BackgroundThere are currently no licensed vaccines available for prevention of botulism in humans. The vaccination is not desirable due to expanding therapeutic indications of botulinum toxins. The only available specific treatment for botulism is antitoxin to remove circulating toxin, thus, preventing further neuronal damage. BAT® (Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)—(Equine)) has been developed and its therapeutic efficacy evaluated against botulinum neurotoxin serotype A (BoNT/A) in Rhesus macaques.Methods and findingsIn a post-exposure prophylaxis (PEP) study, animals were exposed to 4x LD50/kg of BoNT/A and administered intravenously with either BAT (1x or 0.1x scaled human dose), or placebo at 4 hours post-exposure. The animals were monitored for 14 days. For the therapeutic intervention studies, animals were exposed to a 1.7x LD50/kg of BoNT/A and treated intravenously with either placebo or BAT at a 1x scaled human dose at the onset of clinical signs. Animals were monitored on an hourly basis for 14 or 21 days. In the PEP study, all animals tolerated equine based antitoxin without any adverse clinical signs. A 100% survival was observed in groups treated with the BAT compared to 0% survival in those treated with the placebo (p<0.001, Fisher’s exact test). BAT antitoxin prevented the development of signs of neurotoxicity of botulinum toxin. In a therapeutic study, treatment with the BAT at scaled 1x human dose after the onset of clinical signs significantly enhanced survival compared to the placebo (46.6% vs. 0%, p<0.0001, Fisher’s exact test). Additionally, treatment with the BAT delayed the progression of signs (muscular weakness, respiratory distress, oral/nasal discharge) of toxin intoxication and reduced the severity of the disease.ConclusionsA single dose of BAT, when administered to symptomatic monkeys, resulted in a statistically significant survival benefit compared to the placebo. Additionally, BAT completely protected monkeys from the clinical signs of intoxication and subsequent death when administered as PEP treatment. These data in part supported the licensure of BAT under the Animal Rule in the United States by the Food and Drug Administration.

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Section: Discussionmentioning

confidence: 99%

Therapeutic efficacy of equine botulism antitoxin in Rhesus macaques

et al. 2017

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“…11 The botulism outbreak was the largest in 40 years in the United States, and was caused by improper home canning techniques that failed to kill toxin-producing C. botulinum spores. 11 …”

Section: Introductionmentioning

confidence: 99%

Newly Designed Quinolinol Inhibitors Mitigate the Effects of Botulinum Neurotoxin A in Enzymatic, Cell-Based, and ex Vivo Assays

et al. 2017

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Botulinum neurotoxin A (BoNT/A) is one of the most deadly toxins, and is the etiological agent of the potentially fatal condition, botulism. Herein, we investigated 8-hydroxyquinoline (quinolin-8-ol) as a potential inhibitor scaffold for preventing the deadly neurochemical effects of the toxin. Quinolinols are known chelators that can disrupt the BoNT/A metalloprotease zinc-containing active site, thus impeding its proteolysis of the endogenous protein substrate, synaptosomal-associated protein 25 (SNAP-25). Using this information, the structure-activity relationship (SAR) of the quinolinol-5-sulfonamide scaffold was explored through preparation of a crude sulfonamide library, and evaluating the library in a BoNT/A LC enzymatic assay. Potency optimization of the sulfonamide hit compounds was undertaken as informed by docking studies, granting a lead compound with a submicromolar Ki. These quinolinol analogues demonstrated inhibitory activity in a cell-based model for SNAP-25 cleavage and an ex vivo assay for BoNT/A-mediated muscle paralysis.

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“…Strains of C. botulinum Group I (proteolytic C. botulinum ) are highly proteolytic, mesophilic (minimum growth temperature of 12 °C), and form very heat resistant spores that are the target of the Botulinum cook (121 °C/3 min) given to low acid canned foods [1, 2]. A failure to apply the botulinum cook to canned or bottled foods has led to foodborne botulism, such as the large outbreak in 2015 associated with potato salad prepared using improperly home-canned potatoes [13]. C. botulinum Group II (non-proteolytic C. botulinum ) is a psychrotrophic bacterium (minimum growth temperature of 3 °C), that ferments a range of carbohydrates, and forms spores of moderate heat resistance [1, 2].…”

Section: Introduction To Clostridium Botulinum and Foodborne Botulismmentioning

confidence: 99%