Bayes, Bugs, and Bioterrorists: Lessons Learned from the Anthrax Attacks

Thompson, Kimberly M.; Armstrong, Robert E.; Thompson, Donald F.

doi:10.21236/ada435051

Cited by 4 publications

(14 citation statements)

References 4 publications

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“…Natural strains of B. anthracis are sensitive to several antibacterial agents, which can be used to treat anthrax. , The most effective and commonly used drug for the treatment of anthrax is ciprofloxacin, , a broad-spectrum quinolone antibacterial. − Following the mailings of letters containing lethal B. anthracis spores in the autumn of 2001 in the United States, it is estimated that as much as 1 billion dollars worth of ciprofloxacin was prescribed to treat individuals who potentially were exposed to the spores …”

mentioning

confidence: 99%

Drug Interactions with Bacillus anthracis Topoisomerase IV: Biochemical Basis for Quinolone Action and Resistance

Aldred

McPherson²,

Wang³

et al. 2011

Biochemistry

216

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Bacillus anthracis, the causative agent of anthrax, is considered a serious threat as a bioweapon. The drugs most commonly used to treat anthrax are quinolones, which act by increasing DNA cleavage mediated by topoisomerase IV and gyrase. Quinolone resistance most often is associated with specific serine mutations in these enzymes. Therefore, to determine the basis for quinolone action and resistance, we characterized wild-type B. anthracis topoisomerase IV, the GrlAS81F and GrlAS81Y quinolone-resistant mutants, and the effects of quinolones and a related quinazolinedione on these enzymes. Ser81 is believed to anchor a water-Mg2+ bridge that coordinates quinolones to the enzyme through the C3/C4 keto acid. Consistent with this hypothesized bridge, ciprofloxacin required increased Mg2+ concentrations to support DNA cleavage by GrlAS81F topoisomerase IV. The three enzymes displayed similar catalytic activities in the absence of drugs. However, the resistance mutations decreased the affinity of topoisomerase IV for ciprofloxacin and other quinolones, diminished quinolone-induced inhibition of DNA religation, and reduced the stability of the ternary enzyme-quinolone-DNA complex. Wild-type DNA cleavage levels were generated by mutant enzymes at high quinolone concentrations, suggesting that increased drug potency could overcome resistance. 8-Methyl-quinazoline-2,4-dione, which lacks the quinolone keto acid (and presumably does not require the water-Mg2+ bridge to mediate protein interactions), was more potent than quinolones against wild-type topoisomerase IV and was equally efficacious. Moreover, it maintained high potency and efficacy against the mutant enzymes, effectively inhibited DNA religation, and formed stable ternary complexes. Our findings provide an underlying biochemical basis for the ability of quinazolinediones to overcome clinically-relevant quinolone resistance mutations in bacterial type II topoisomerases.

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mentioning

confidence: 99%

Drug Interactions with Bacillus anthracis Topoisomerase IV: Biochemical Basis for Quinolone Action and Resistance

Aldred

McPherson²,

Wang³

et al. 2011

Biochemistry

216

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“…Effective communication is critical in the management of an animal disease outbreak (11,25,50,53). However, several factors can often impede communication needs and efforts during times of emergency.…”

Section: What Are the Issues?mentioning

confidence: 99%

Section: What Are the Issues?mentioning

confidence: 99%

“…Another factor that hinders communication is the barrier between the public and animal health community (20,21,31,33,53,55). The 1999 outbreak of West Nile virus in New York City is a good example of how a lack of communication and organization between federal, state, and local agencies and the private sector impedes response efforts when dealing with the early stages of an infectious disease outbreak (20,31,53,55). Officials indicated that the lack of leadership in the initial stages of the outbreak and the lack of sufficient channels for communication were primarily responsible for the delay in the initial response to this outbreak (53,55).…”

Section: What Are the Issues?mentioning

confidence: 99%

“…The 1999 outbreak of West Nile virus in New York City is a good example of how a lack of communication and organization between federal, state, and local agencies and the private sector impedes response efforts when dealing with the early stages of an infectious disease outbreak (20,31,53,55). Officials indicated that the lack of leadership in the initial stages of the outbreak and the lack of sufficient channels for communication were primarily responsible for the delay in the initial response to this outbreak (53,55). Communication and coordinated surveillance efforts between the public and animal health communities were lacking, as key public health officials were not aware of the similarities in the clinical symptoms occurring in the birds and humans until many days or weeks after the human outbreak began (20,31,53,55).…”

Section: What Are the Issues?mentioning

confidence: 99%

See 2 more Smart Citations

Agroterrorism: Where Are We in the Ongoing War on Terrorism?

Crutchley

Rodgers

Whiteside

et al. 2007

Journal of Food Protection

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The U.S. agricultural infrastructure is one of the most productive and efficient food-producing systems in the world. Many of the characteristics that contribute to its high productivity and efficiency also make this infrastructure extremely vulnerable to a terrorist attack by a biological weapon. Several experts have repeatedly stated that taking advantage of these vulnerabilities would not require a significant undertaking and that the nation's agricultural infrastructure remains highly vulnerable. As a result of continuing criticism, many initiatives at all levels of government and within the private sector have been undertaken to improve our ability to detect and respond to an agroterrorist attack. However, outbreaks, such as the 1999 West Nile outbreak, the 2001 anthrax attacks, the 2003 monkeypox outbreak, and the 2004 Escherichia coli O157:H7 outbreak, have demonstrated the need for improvements in the areas of communication, emergency response and surveillance efforts, and education for all levels of government, the agricultural community, and the private sector. We recommend establishing an interdisciplinary advisory group that consists of experts from public health, human health, and animal health communities to prioritize improvement efforts in these areas. The primary objective of this group would include establishing communication, surveillance, and education benchmarks to determine current weaknesses in preparedness and activities designed to mitigate weaknesses. We also recommend broader utilization of current food and agricultural preparedness guidelines, such as those developed by the U.S. Department of Agriculture and the U.S. Food and Drug Administration.

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Considerations for estimating microbial environmental data concentrations collected from a field setting

Silvestri

Yund

Taft

et al. 2016

J Expo Sci Environ Epidemiol

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In the event of an indoor release of an environmentally persistent microbial pathogen such as Bacillus anthracis, the potential for human exposure will be considered when remedial decisions are made. Microbial site characterization and clearance sampling data collected in the field might be used to estimate exposure. However, there are many challenges associated with estimating environmental concentrations of B. anthracis or other spore-forming organisms after such an event before being able to estimate exposure. These challenges include: (1) collecting environmental field samples that are adequate for the intended purpose, (2) conducting laboratory analyses and selecting the reporting format needed for the laboratory data, and (3) analyzing and interpreting the data using appropriate statistical techniques. This paper summarizes some key challenges faced in collecting, analyzing, and interpreting microbial field data from a contaminated site. Although the paper was written with considerations for B. anthracis contamination, it may also be applicable to other bacterial agents. It explores the implications and limitations of using field data for determining environmental concentrations both before and after decontamination. Several findings were of interest. First, to date, the only validated surface/sampling device combinations are swabs and sponge-sticks on stainless steel surfaces, thus limiting availability of quantitative analytical results which could be used for statistical analysis. Second, agreement needs to be reached with the analytical laboratory on the definition of the countable range and on reporting of data below the limit of quantitation. Finally, the distribution of the microbial field data and statistical methods needed for a particular data set could vary depending on these data that were collected, and guidance is needed on appropriate statistical software for handling microbial data. Further, research is needed to develop better methods to estimate human exposure from pathogens using environmental data collected from a field setting.

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Bayes, Bugs, and Bioterrorists: Lessons Learned from the Anthrax Attacks

Cited by 4 publications

References 4 publications

Drug Interactions with Bacillus anthracis Topoisomerase IV: Biochemical Basis for Quinolone Action and Resistance

Drug Interactions with Bacillus anthracis Topoisomerase IV: Biochemical Basis for Quinolone Action and Resistance

Agroterrorism: Where Are We in the Ongoing War on Terrorism?

Considerations for estimating microbial environmental data concentrations collected from a field setting

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