Botulinum Neurotoxin Detection Methods for Public Health Response and Surveillance

Abstract

Botulism outbreak due to consumption of food contaminated with botulinum neurotoxins (BoNTs) is a public health emergency. The threat of bioterrorism through deliberate distribution in food sources and/or aerosolization of BoNTs raises global public health and security concerns due to the potential for high mortality and morbidity. Rapid and reliable detection methods are necessary to support clinical diagnosis and surveillance for identifying the source of contamination, performing epidemiological analysis of the outbreak, preventing and responding to botulism outbreaks. This review considers the applicability of various BoNT detection methods and examines their fitness-for-purpose in safeguarding the public health and security goals.

Critical Analysis of Neuronal Cell and the Mouse Bioassay for Detection of Botulinum Neurotoxins

“…In efforts to avoid animal suffering, a multitude of BoNT detection methods has been developed with minimal use of animals. These include in vivo simulation assays, such as the hemidiaphragm assay and local injection assays [57,59,62,[78][79][80][81][82], numerous in vitro assays using immunological detection methods, endopeptidase assays, or a combination of the two such as the endopeptidase-mass spectrometry assay [83][84][85][86][87][88], and cell-based assays [89].…”

“…When selecting a BoNT detection assay, it is important to consider the end goal, such as laboratory diagnosis of botulism, detection in food or environmental samples, regulatory actions, pharmaceutical activity and properties, and toxicity evaluations of novel BoNTs [83,91].…”

“…Applications for BoNT detection include fundamental research, investigations of environmental samples or food products for epidemiologic investigations, food safety laboratory studies, analysis of clinical samples, quantification of pharmacologic BoNTs, and diagnosis of botulism. Each application has specific needs and requirements [83]. For food safety studies, the presence of biologically active or inactive BoNTs would indicate potential contamination of the food.…”

“…However, these assays may not detect novel BoNTs and BoNTs for which the assays have not been validated, and require careful and thorough validation, ideally between independent laboratories. Several recent reviews provide detailed and comprehensive information on in vitro detection methods for BoNTs [83,84,87,88,91].…”

Biosecurity Threat Posed by Botulinum Toxin

“…205 cases in 2016) [24]. The diagnosis of botulism involves the clinical presentation and laboratory identification of BoNTs in serum and other clinical specimens (vomitus, gastric aspirate, nasal swabs or stool) [11,[25][26][27], or in suspected food [28]. The mouse bioassay (MBA) is still considered to be the gold standard for laboratory testing due to its high sensitivity [27].…”