Botulism is a neuroparalytic disease caused by neurotoxins produced by the bacteria Clostridium botulinum. Botulinum neurotoxins (BoNTs) are among the most potent naturally occurring toxins and are a category A biological threat agent. The 7 toxin serotypes of BoNTs (serotypes A-G) have different toxicities, act through 3 different intracellular protein targets, and exhibit different durations of effect. Botulism may follow ingestion of food contaminated with BoNT, from toxin production of C botulinum present in the intestine or wounds, or from inhalation of aerosolized toxin. Intoxication classically presents as an acute, symmetrical, descending flaccid paralysis. Early diagnosis is important because antitoxin therapy is most effective when administered early. Confirmatory testing of botulism with BoNT assays or C botulinum cultures is time-consuming, and may be insensitive in the diagnosis of inhalational botulism and in as many as 32% of food-borne botulism cases. Therefore, the decision to initiate botulinum antitoxin therapy is primarily based on symptoms and physical examination findings that are consistent with botulism, with support of epidemiological history and electrophysiological testing. Modern clinical practice and antitoxin treatment has reduced botulism mortality rates from approximately 60% to < or =10%. The pentavalent botulinum toxoid is an investigational product and has been used for more than 45 years in at-risk laboratory workers to protect against toxin serotypes A to E. Due to declining immunogenicity and potency of the pentavalent botulinum toxoid, novel vaccine candidates are being developed.

Public health authorities should be vigilant to the potential for outbreaks deliberately caused by biological agents (bioterrorism). Such events require a rapid response and incorporation of non-traditional partners for disease investigation and outbreak control. The astute application of infectious disease epidemiological principles can promote an enhanced index of suspicion for such events. We discuss epidemiological indicators that should be considered during outbreak investigations, and also examine their application during bioterrorism incidents, an accidental release of an agent, outbreaks of infections that were alleged to have been deliberately initiated, and a model scenario. The Grunow & Finke epidemiological assessment tool is used to examine these historical events and the model scenario. The results received from this analysis, coupled with an understanding of epidemiological clues to unnatural events, and knowledge of how to manage such events, can aid in the improved response and resolution of epidemics.

During October 1996, an outbreak of Escherichia coli O157:H7 infections among Connecticut residents occurred. An epidemiologic investigation included enhanced surveillance and a case-control study. Clinical isolates of Escherichia coli O157:H7 were typed by pulsed-field gel electrophoresis (PFGE). Implicated cider samples were analysed by culture and polymerase chain reaction (PCR). Consumption of implicated cider was associated with illness; (matched odds ratio = undefined, 95 % confidence interval = 3.5-infinity). Ultimately, a total of 14 outbreak-associated patients were identified. All isolates analysed by PFGE yielded the outbreak-associated subtype. Escherichia coli O157:H7 was not cultured from three cider samples; PCR analysis detected DNA fragments consistent with Escherichia coli O157:H7 in one. This outbreak was associated with drinking one brand of unpasteurized apple cider. PFGE subtyping supported the epidemiologic association. PCR analysis detected microbial contaminants in the absence of live organisms. Washing and brushing apples did not prevent cider contamination.

Extended-spectrum β-lactamases (ESBLs) are enzymes produced in some gram-negative bacilli that mediate resistance to extended-spectrum cephalosporins and aztreonam. They are most common inKlebsiella spp. and Escherichia coli but are present in a variety of Enterobacteriaceae. Resistance mediated by these enzymes can be difficult to detect depending on the antimicrobial agents tested. AmpC β-lactamases are related to the chromosomal enzymes of Enterobacter andCitrobacter spp. and also mediate resistance to extended-spectrum cephalosporins and aztreonam in addition to cephamycins, such as cefoxitin. Unlike ESBLs, however, AmpC β-lactamases are not inhibited by clavulanic acid or other similar compounds. To assess the abilities of various antimicrobial susceptibility testing methods to detect ESBLs, we sent three ESBL-producing organisms, one AmpC-producing organism, and a control strain that was susceptible to extended-spectrum cephalosporins to 38 laboratories in Connecticut for testing. Eight (21.0%) of 38 labs failed to detect extended-spectrum cephalosporin or aztreonam resistance in any of the ESBL- or AmpC-producing isolates. Errors were encountered with both automated and disk diffusion methods. Conversely, seven (18.4%) labs categorized at least some of the four resistant isolates as potential ESBL producers and reported the results with the extended-spectrum cephalosporins and aztreonam as resistant as suggested by current National Committee for Clinical Laboratory Standards (NCCLS) guidelines. The percentage of laboratories that failed to detect resistance in the ESBL or AmpC isolates ranged from 23.7 to 31.6% depending on the type of enzyme present in the test organism. This survey suggests that many laboratories have difficulty detecting resistance in ESBL and AmpC-producing organisms and may be unaware of the NCCLS guidelines on modifying susceptibility testing reports for ESBL-producing strains.

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