Field Evaluation of a Human Anthrax Vaccine

Brachman, Philip S.; Gold, Herman K.; Plotkin, Stanley А.; Fekety, F. Robert; Werrin, Milton; Ingraham, Norman R.

doi:10.2105/ajph.52.4.632

Cited by 249 publications

(40 citation statements)

References 7 publications

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“…Our results indicate that at doses as high as the TD(50), Ͼ4 months of antibiotic prophylaxis may be necessary to reduce risk adequately to Ͻ1͞10,000, and it is likely considerable morbidity would occur before antibiotic prophylaxis could even be initiated. The use of anthrax vaccine as a postexposure prophylaxis that can confer long-term immunity could shorten the duration of antibiotic prophylaxis, but limited data on its postexposure efficacy exist (3,24). At doses lower than the TD(1), antibiotic prophylaxis of 60-day duration should be adequate.…”

Section: Discussionmentioning

confidence: 99%

Modeling the optimum duration of antibiotic prophylaxis in an anthrax outbreak

Brookmeyer

Johnson

Bollinger

2003

Proc. Natl. Acad. Sci. U.S.A.

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A critical consideration in effective and measured public health responses to an outbreak of inhalational anthrax is the optimum duration of antibiotic prophylaxis. We develop a competing-risks model to address the duration of antibiotic prophylaxis and the incubation period that accounts for the risks of spore germination and spore clearance. The model predicts the incubation period distribution, which is confirmed by empirical data. The optimum duration of antibiotic prophylaxis depends critically on the dose of inhaled spores. At high doses, we show that exposed persons would need to remain on antibiotic prophylaxis for at least 4 months, and considerable morbidity would likely occur before antibiotic prophylaxis could even be initiated. At very low doses, 60 days of antibiotic prophylaxis is adequate. Exposure doses can be estimated from the cumulative attack rate up to the point antibiotic prophylaxis begins. The model explains that whereas <60 days of antibiotics were enough to protect persons in the 2001 U.S. outbreak, because doses were very low, at moderate or high doses considerably longer durations would be necessary to adequately protect exposed populations.

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Section: Discussionmentioning

confidence: 99%

Modeling the optimum duration of antibiotic prophylaxis in an anthrax outbreak

Brookmeyer

Johnson

Bollinger

2003

Proc. Natl. Acad. Sci. U.S.A.

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“…The current anthrax vaccines are believed to provide protection by eliciting anthrax toxin-neutralizing PA antibodies (52). While PA-specific antibodies appear to be the primary source of protection, many animal studies have shown that inclusion of additional antigens, including EF, into PA-based vaccines results in increased levels of protection (33,53).…”

Section: Discussionmentioning

confidence: 99%

Anthrax Vaccine Precipitated Induces Edema Toxin-Neutralizing, Edema Factor-Specific Antibodies in Human Recipients

Dumas

Gross

Larabee

et al. 2017

Clin Vaccine Immunol

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Edema toxin (ET), composed of edema factor (EF) and protective antigen (PA), is a virulence factor of Bacillus anthracis that alters host immune cell function and contributes to anthrax disease. Anthrax vaccine precipitated (AVP) contains low but detectable levels of EF and can elicit EF-specific antibodies in human recipients of AVP. Active and passive vaccination of mice with EF can contribute to protection from challenge with Bacillus anthracis spores or ET. This study compared humoral responses to ET in recipients of AVP (n ϭ 33) versus anthrax vaccine adsorbed (AVA; n ϭ 66), matched for number of vaccinations and time postvaccination, and further determined whether EF antibodies elicited by AVP contribute to ET neutralization. AVP induced higher incidence (77.8%) and titer (229.8 Ϯ 58.6) of EF antibodies than AVA (4.2% and 7.8 Ϯ 8.3, respectively), reflecting the reported low but detectable presence of EF in AVP. In contrast, PA IgG levels and ET neutralization measured using a luciferase-based cyclic AMP reporter assay were robust and did not differ between the two vaccine groups. Multiple regression analysis failed to detect an independent contribution of EF antibodies to ET neutralization in AVP recipients; however, EF antibodies purified from AVP sera neutralized ET. Serum samples from at least half of EF IgG-positive AVP recipients bound to nine decapeptides located in EF domains II and III. Although PA antibodies are primarily responsible for ET neutralization in recipients of AVP, increased amounts of an EF component should be investigated for the capacity to enhance next-generation, PA-based vaccines.

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“…The experimental group was vaccinated against anthrax, whereas the control group received a placebo. Several months after the study began an outbreak of inhalational anthrax occurred, and because the vaccination proved to be effective, all workers were vaccinated and the experiment was terminated (2,7).…”

Section: Historical and Current Biological Outbreaksmentioning

confidence: 99%

Early statistical detection of anthrax outbreaks by tracking over-the-counter medication sales

Goldenberg

Shmueli

Caruana

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

140

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The recent series of anthrax attacks has reinforced the importance of biosurveillance systems for the timely detection of epidemics. This paper describes a statistical framework for monitoring grocery data to detect a large-scale but localized bioterrorism attack. Our system illustrates the potential of data sources that may be more timely than traditional medical and public health data. The system includes several layers, each customized to grocery data and tuned to finding footprints of an epidemic. We also propose an evaluation methodology that is suitable in the absence of data on large-scale bioterrorist attacks and disease outbreaks.biosurveillance ͉ time series analysis ͉ grocery data W e describe a statistical system designed for biosurveillance that is part of a larger project investigating ways to use information technology to improve clinical preparedness for bioterrorism (1). Our goal is evaluating the possible use of non-public health data, and in particular grocery sales, for the early detection of a bioterrorism attack. The potential of these data for timely detection lies in the earlier manifestation of an attack in grocery and over-the-counter (OTC) medication sales, and in their high level of detail.We begin in the next section by providing background and a characterization of an outbreak of a bioagent, focusing on anthrax. Then we describe traditional data collected from medical and public health sources and their ability to detect attacks in a timely fashion, before turning to grocery data and the detection system that we developed. We also introduce a method for evaluating the detection system in the absence of a bioagent footprint in the data, and for tuning the system to the input data. We end with some observations on the usefulness of our approach. Historical and Current Biological OutbreaksVarious bioagents have been identified as possible weapons in biological warfare. Here, we focus on anthrax to illustrate how a detection system that tracks OTC medication sales can provide more timely signals than traditional systems that track medical and public health data. The statistical framework is general, however, and can be applied for the detection of other agents.

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Field Evaluation of a Human Anthrax Vaccine

Cited by 249 publications

References 7 publications

Modeling the optimum duration of antibiotic prophylaxis in an anthrax outbreak

Modeling the optimum duration of antibiotic prophylaxis in an anthrax outbreak

Anthrax Vaccine Precipitated Induces Edema Toxin-Neutralizing, Edema Factor-Specific Antibodies in Human Recipients

Early statistical detection of anthrax outbreaks by tracking over-the-counter medication sales

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