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.

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Jersey EDs, with participants consecutive patients seen by ED physicians January 1998 through July 2002. Based on ICD-9 codes, syndromic groups were developed for the following categories: any gastrointestinal, diarrhea, respiratory, asthma, chest pain, fever, skin, headache, and weakness. We then generated daily counts of patients by category and generated time series graphs to display the incidence of disease for these syndromic groups over the 4.5-year period. We also generated similar counts and graphs for the same syndromic groups based on the physician's choice of charting template rather than ICD-9 code and compared the results. There were 3.2 million patient visits in the database. Visual inspection of the time series graphs showed definite seasonal peaks in the diarrhea, respiratory, asthma, fever, and skin syndromic groups. There was good agreement between ICD-9 codes and templates. The existing ED database identified seasonal peaks in the incidence of several disease syndromes. Tracking physician charting template usage could potentially identify these patterns in real time. This ED database may be able to provide early warning of disease outbreaks and some types of bioterrorist attacks. 11, 2001, and the corresponding anthrax attacks, there has been considerable interest in developing pre-event surveillance methods that would be used for early detection of a bioterrorist event and prevention of widespread morbidity and mortality. Traditionally, active surveillance mechanisms to detect disease outbreaks consist of confirmatory laboratory testing after preliminary diagnosis from a physician. In many cases, the confirmation of infectious disease takes days of testing, many hours of epidemiological analysis, and significant public health resources at the local level before an outbreak is finally diagnosed. Our communities are at significant risk unless public health authorities can develop a preevent early warning system with a high degree of specificity and sensitivity for outbreak detection when patients present themselves to the emergency department or their primary health care provider. A pre-event early warning system depends on quality, "near" real-time data from the medical community. Potential sources of this information are (1) hospital emergency department encounters, (2) outpatient clinic visits, (3) pharmacy data (over the counter and prescription). All data sources have varying degrees of quality, but the hospital emergency department registration information (chief complaint at initial visit) is determined to provide the nearest real-time means for use in a pre-event surveillance system. But, is chief complaint information as reliable as International Classification of Diseases, 9th Revision (ICD-9)-coded discharge diagnosis in predicting an early event? ICD-9 diagnosis is considered to be the best indicator of patient diagnosis, but is not readily available for epidemiological analysis until 3 to 5 days after initial visit. The New York State Department of Health and Emergency Medical Ass...

A relatively new approach in the treatment of specific wounds in animal models and in patients with type A botulinum toxin is the focus of this paper. The indications or conditions include traumatic wounds (experimental and clinical), surgical (incision) wounds, and wounds such as fissures and ulcers that are signs/symptoms of disease or other processes. An objective was to conduct systematic literature searches and take note of the reactions involved in the healing process and identify corresponding pharmacokinetic data. From several case reports, we developed a qualitative model of how botulinum toxin disrupts the vicious cycle of muscle spasm, pain, inflammation, decreased blood flow, and ischemia. We transformed this model into a minimal kinetic scheme for healing chronic wounds. The model helped us to estimate the rate of decline of this toxin's therapeutic effect by calculating the rate of recurrence of clinical symptoms after a wound-healing treatment with this neurotoxin.

On September 11, 2001, the Connecticut Department of Public Health (CDPH) initiated daily, statewide syndromic surveillance based on unscheduled hospital admissions (HASS). The systems objectives were to monitor for outbreaks caused by Category A biologic agents and evaluate limits in space and time of identified outbreaks. Thirty-two acute-care hospitals were required to report their previous day's unscheduled admissions for 11 syndromes (pneumonia, hemoptysis, respiratory distress, acute neurologic illness, nontraumatic paralysis, sepsis and nontraumatic shock, fever with rash, fever of unknown cause, acute gastrointestinal illness, and possible cutaneous anthrax, and suspected illness clusters). Admissions for pneumonia, gastrointestinal illness, and sepsis were reported most frequently; admissions for fever with rash, possible cutaneous anthrax, and hemoptysis were rare. A method for determining the difference between random and systemic variation was used to identify differences of ≥3 standard deviations for each syndrome from a 6-month moving average. HASS was adapted to meet changing surveillance needs (e.g., surveillance for anthrax, smallpox, and severe acute respiratory syndrome). HASS was sensitive enough to reflect annual increases in hospitaladmission rates for pneumonia during the influenza season and to confirm an outbreak of gastrointestinal illness. Follow-up of HASS neurologic-admissions reports has led to diagnosis of West Nile virus encephalitis cases. Report validation, syndrome-criteria standardization among hospitals, and expanded use of outbreak-detection algorithms will enhance the system's usefulness.