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吸入性炭疽兔模型中多次低剂量孢子的生理反应

Physiological Responses to Multiple Low-Doses of Spores in the Rabbit Model of Inhalation Anthrax.

作者信息

Taft Sarah C, Nichols Tonya L, Hines Stephanie A, Barnewall Roy E, Stark Gregory V, Comer Jason E

机构信息

U.S. Environmental Protection Agency, National Homeland Security Research Center, Cincinnati, OH 45224, USA.

Formerly of Battelle Memorial Institute, Columbus, OH 43201, USA.

出版信息

Pathogens. 2020 Oct 24;9(11):877. doi: 10.3390/pathogens9110877.

DOI:10.3390/pathogens9110877
PMID:33114429
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7693690/
Abstract

spores that are re-aerosolized from surface deposits after initial contamination present significant health risks for personnel involved in decontamination. To model repeated exposure to low dose spores, three groups of seven rabbits were challenged with multiple low-doses of spores 5 days a week for 3 weeks. Mortality, body temperature, heart and respiration rates, hematology, C-reactive protein, bacteremia, and serum protective antigen were monitored for 21 days post-exposure after the last of multiple doses. All rabbits exposed to a mean daily dose of 2.91 × 10 colony forming units (CFU) survived and showed minimal physiological changes attributable to exposure. One of seven rabbits receiving a mean daily dose of 1.22 × 10 CFU died and four of seven receiving a mean daily dose of 1.17 × 10 CFU died. The LD was calculated to be 8.1 × 10 CFU of accumulated dose. Rabbits that succumbed to the higher dose exhibited bacteremia and increases above baseline in heart rate, respiration rate, and body temperature. Two rabbits in the mean daily dose group of 1.17 × 10 CFU exhibited clinical signs of inhalation anthrax yet survived. This study provides a description of lethality, pathophysiology, and pathology in a controlled multiple low-dose inhalation exposure study of in the rabbit model. The data suggest that the accumulated dose is important in survival outcome and that a subset of rabbits may show clinical signs of disease but fully recover without therapeutic intervention.

摘要

初次污染后从表面沉积物中再次气溶胶化的孢子,对参与去污工作的人员构成重大健康风险。为模拟反复低剂量接触孢子的情况,将三组每组七只兔子,每周5天、持续3周接受多次低剂量孢子攻击。在最后一次多剂量给药后的暴露后21天内,监测死亡率、体温、心率和呼吸频率、血液学、C反应蛋白、菌血症和血清保护性抗原。所有平均每日剂量为2.91×10菌落形成单位(CFU)的兔子均存活,且暴露引起的生理变化极小。平均每日剂量为1.22×10 CFU的七只兔子中有一只死亡,平均每日剂量为1.17×10 CFU的七只兔子中有四只死亡。累积剂量的半数致死量经计算为8.1×10 CFU。死于较高剂量的兔子出现菌血症,心率、呼吸频率和体温高于基线水平。平均每日剂量为1.17×10 CFU组中的两只兔子表现出吸入性炭疽的临床症状,但存活下来。本研究描述了兔模型中多次低剂量吸入暴露的致死率、病理生理学和病理学。数据表明,累积剂量对生存结果很重要,并且一部分兔子可能会出现疾病的临床症状,但无需治疗干预即可完全康复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79aa/7693690/41882ac8f7fb/pathogens-09-00877-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79aa/7693690/a833b0b1df0e/pathogens-09-00877-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79aa/7693690/44ad63e2a19e/pathogens-09-00877-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79aa/7693690/41882ac8f7fb/pathogens-09-00877-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79aa/7693690/a833b0b1df0e/pathogens-09-00877-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79aa/7693690/44ad63e2a19e/pathogens-09-00877-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79aa/7693690/41882ac8f7fb/pathogens-09-00877-g003.jpg

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2
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3
Accurate and selective quantification of anthrax protective antigen in plasma by immunocapture and isotope dilution mass spectrometry.
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Analyst. 2019 Mar 25;144(7):2264-2274. doi: 10.1039/c8an02479k.
4
Development of Protective Immunity in New Zealand White Rabbits Challenged with Bacillus anthracis Spores and Treated with Antibiotics and Obiltoxaximab, a Monoclonal Antibody against Protective Antigen.新西兰白兔在接受炭疽芽孢杆菌孢子挑战并使用抗生素和抗保护性抗原单克隆抗体奥立妥昔单抗治疗后保护性免疫的发展。
Antimicrob Agents Chemother. 2018 Jan 25;62(2). doi: 10.1128/AAC.01590-17. Print 2018 Feb.
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