Diagnosis and treatment of botulism: a century later, clinical suspicion remains the cornerstone.

" I know pornography when I see it, " wrote Supreme Court Justice Potter Stewart [1]. The immediate clinical diagnosis of bot-ulism and the key therapeutic decision in its management—administration of bot-ulinum antitoxin—depend on a similar logic. That is, one has to know, or at least suspect, botulism at first sight to treat it properly. Laboratory confirmation by the mouse bioassay, the standard diagnostic test for decades, can take у1 day to provide a definitive answer, is costly, and requires an animal facility [2]. Detectable toxin in the serum may be present transiently or at low levels [3]. The first diagnostic assay for botulism, developed during an outbreak investigation in 1896, was to feed the suspected food to experimental animals [4]. The current mouse assay, based on intraperitoneal injection of the mouse with serum or with fluid extracts of feces, foods, or culture broths, was standardized in the 1970s [5]. In the accompanying article by Wheeler et al. [6] from the California Department of Public Health, the authors calculate the sensitivity of the mouse bioassay for clinically defined cases of wound botulism. Wheeler and colleagues surely know wound botulism when they see it, because they consult on most wound botulism cases, and to the mind of most experts familiar with the diagnostic challenges of botulism, they are fully justified in using clinical diagnosis as the gold standard against which to measure the mouse bi-oassay's limited sensitivity. The sensitivity calculated in the article is not the intrinsic sensitivity of a test under ideal laboratory conditions, but rather that of the clinical setting, calculation of which depends on a complicated set of real-world factors. This calculation must take into account the quality of the gold standard clinical diagnosis, which depends on the initial as-tuteness of the admitting physician and the diagnostic skill of the California Department of Public Health consultant, and variations in toxin levels in clinical samples , which depend on the timeliness of sample collection, the size of the Clostrid-ium botulinum colony in the infected wound, kinetics of toxin absorption from the abscess, its migrations to the extracir-culatory compartment, and possibly other factors. One must also keep in mind that the sensitivity of mouse bioassay results may be different for the other principal forms of botulism—foodborne botulism and infant botulism. Most foodborne botulism cases are diagnosed by other expert consultants from Centers for Disease Control and Prevention (CDC) and the …