Anthrax as a Biological Weapon, 2002

109

117

Bacillus anthracis is surrounded by an antiphagocytic polypeptide capsule composed of poly ␥-D-glutamic acid (␥DPGA). ␥DPGA has been identified recently as a potential target for vaccine development. Studies of the role of ␥DPGA in disease have been hampered by the poor Ab response to this antigen and the lack of immunochemical reagents. As a consequence, neither the extent of ␥DPGA production during anthrax nor the protective activity of ␥DPGA Abs in inhalation anthrax are known. Here we report production of IgG Abs to ␥DPGA in mice following an immunization regimen using ␥DPGA in combination with agonist mAbs to CD40. mAbs were produced that are specific for ␥DPGA. Passive immunization with ␥DPGA mAbs protected >90% of mice in a pulmonary model of anthrax that was lethal in control mice (P < 0.0001). Use of ␥DPGA mAb in an antigen detection immunoassay found that the appearance of ␥DPGA in serum coincided with the emergence of bacteremia. These studies identify CD40 stimulation as a means for production of Ab and generation of mAbs against a weakly immunogenic antigen and demonstrate that the capsule is an effective target for immunoprotection and for antigen detection in the diagnosis of anthrax.

mentioning

confidence: 62%

mAbs toBacillus anthraciscapsular antigen for immunoprotection in anthrax and detection of antigenemia

Kozel

Murphy

Brandt

et al. 2004

109

117

“…Anthrax is one of the most extensively researched biological warfare agents (2)(3)(4)(5)(6). Nevertheless, important aspects of the disease remain poorly understood, in particular, the human response to low-dose exposure and the temporal progression of the disease, especially the dose dependence of the incubation period.…”

mentioning

confidence: 99%

Sverdlovsk revisited: Modeling human inhalation anthrax

Wilkening

2006

103

Several models have been proposed for the dose-response function and the incubation period distribution for human inhalation anthrax. These models give very different predictions for the severity of a hypothetical bioterror attack, when an attack might be detected from clinical cases, the efficacy of medical intervention and the requirements for decontamination. Using data from the 1979 accidental atmospheric release of anthrax in Sverdlovsk, Russia, and limited nonhuman primate data, this paper eliminates two of the contending models and derives parameters for the other two, thereby narrowing the range of models that accurately predict the effects of human inhalation anthrax. Dose-response functions that exhibit a threshold for infectivity are contraindicated by the Sverdlovsk data. Dose-dependent incubation period distributions explain the 10-day median incubation period observed at Sverdlovsk and the 1-to 5-day incubation period observed in nonhuman primate experiments.bioterrorism ͉ dose-response function ͉ incubation period

“…5, page 2247). To investigate these issues, we formulated a mathematical model to compare several response strategies to a mass-casualty airborne anthrax attack in a large city.…”

mentioning

confidence: 99%

Emergency response to an anthrax attack

Wein

Craft

Kaplan

2003

185

128

We developed a mathematical model to compare various emergency responses in the event of an airborne anthrax attack. The system consists of an atmospheric dispersion model, an agedependent dose-response model, a disease progression model, and a set of spatially distributed two-stage queueing systems consisting of antibiotic distribution and hospital care. Our results underscore the need for the extremely aggressive and timely use of oral antibiotics by all asymptomatics in the exposure region, distributed either preattack or by nonprofessionals postattack, and the creation of surge capacity for supportive hospital care via expanded training of nonemergency care workers at the local level and the use of federal and military resources and nationwide medical volunteers. The use of prioritization (based on disease stage and͞or age) at both queues, and the development and deployment of modestly rapid and sensitive biosensors, while helpful, produce only second-order improvements.