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Novel Type H Botulinum Toxin Neutralized by Standard Antitoxin

Amesh A. Adalja, MD, FACP, FACEP, June 26, 2015

Botulism is caused by the extremely potent toxin elaborated by the category A agent Clostridium botulinum. This toxin, when ingested, inhaled, or inoculated, can cause a fatal flaccid paralysis. Until recently, there were 7 known toxinotypes of botulinum toxin (labeled A through G), each able to be neutralized by the FDA-approved heptavalent antitoxin.

However, this paradigm changed with the discovery of a strain of C. botulinum isolated from an infant with botulism, which elaborated 2 toxinotypes: B and a novel toxin designated “H.”1 Type H toxin was not believed to be susceptible to neutralization with the heptavalent antitoxins based on prior experiments, thus creating a potential gap in medical countermeasures for this disease.

However, new research from the CDC, published in the Journal of Infectious Diseases, provides reassuring evidence regarding the efficacy of the heptavalent antitoxin against type H toxin.

 

Mouse and Neuronal Assays Performed

Maslanka et al employed both mouse and in vitro neuronal cell assays to assess the ability of existing antitoxins to neutralize the novel toxin. In both bioassays, it was established that the heptavalent antitoxin neutralized toxin type H. Specifically, by using multiple combinations of antitoxins, it was discovered that the type A antitoxin was the antitoxin responsible for neutralization of type H toxin.1

Additional genetic studies on the novel toxin revealed it to be a hybrid toxin composed of elements of toxinotypes A and F, which accounted for its susceptibility to antitoxin A.1

 

Efficacy of Heptavalent Antitoxin Remains Intact

Maslanka et al’s work is important because it establishes that confidence in the efficacy of our current chief countermeasure against both natural and intentional botulism is intact, despite the discovery of the new A/F hybrid toxin type H, which can cause symptomatic disease. Follow-up studies such as this one are important to perform, as confirmation of the novel toxin’s attributes was needed before embarking on a process to develop a new antitoxin. 

It is unclear why prior studies were unable to arrive at the same result that the CDC investigators did (the CDC used the FDA-approved antitoxin, while other investigators did not2), but it underscores the crucial need for reproducibility of results in science before the recognition of a new scientific fact. 

 

References

  1. 1. Maslanka SE, Luquez C, Dykes JK, et al. A novel botulinum toxin, previously reported as serotype H, has a hybrid structure of known serotypes A and F that is neutralized with serotype A antitoxin. J Infect Dis 2015; published online June 10, 2015. http://jid.oxfordjournals.org/content/early/2015/06/08/infdis.jiv327.full.pdf+html. Accessed June 23, 2015.
  2. 2. Roos R. Study: novel botulinum toxin less dangerous than thought. CIDRAP News June 17, 2015. http://www.cidrap.umn.edu/news-perspective/2015/06/study-novel-botulinum-toxin-less-dangerous-thought. Accessed June 23, 2015.