Deterministic Models of Inhalational Anthrax in New Zealand White Rabbits
Deterministic Models of Inhalational Anthrax in New Zealand White Rabbits
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DOI：
10.1089/bsp.2013.0067
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发表时间：
2014-02-01
期刊：
影响因子：
--
通讯作者：
Gutting, Bradford
中科院分区：
文献类型：
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作者：
Gutting, Bradford
在新西兰白色（NZW）兔吸入艾姆斯菌株B后，建立了描述吸入性炭疽的细菌动力学的计算模型。炭疽病用于参数化模型的数据包括气道、肺组织、引流淋巴结和血液中的细菌数量。初始细菌数为孢子沉积量。第一个模型是单指数常微分方程（ODE），具有3个速率参数，描述了粘纤毛（物理）清除、免疫清除（细菌杀灭）和细菌生长。在暴露后36小时，ODE模型预测家兔中有1.7x10（7）个细菌，这与实际实验的数据（36小时时为4.0x10（7）个细菌）一致。接下来，在单ODE模型的基础上，开发了基于生理的生物动力学（PBBK）分区模型，其中1个生理分区是气道管腔，另一个是兔体（肺组织、淋巴结、血液）。2个隔室与描述细菌从气道转运到体内的参数相关联。PBBK模型预测在36小时时体内有4.9x10（7）个细菌，到45小时时，模型显示所有清除机制都饱和，表明兔子会很快死于感染。与ODE模型一样，PBBK模型的结果与实验室观测结果吻合良好。这些数据进行了讨论沿着的需要和潜在的应用模型的风险评估，药物开发，并作为一个一般援助的实验研究吸入性炭疽。
Computational models describing bacterial kinetics were developed for inhalational anthrax in New Zealand white (NZW) rabbits following inhalation of Ames strain B. anthracis. The data used to parameterize the models included bacterial numbers in the airways, lung tissue, draining lymph nodes, and blood. Initial bacterial numbers were deposited spore dose. The first model was a single exponential ordinary differential equation (ODE) with 3 rate parameters that described mucociliated (physical) clearance, immune clearance (bacterial killing), and bacterial growth. At 36 hours postexposure, the ODE model predicted 1.7x10(7) bacteria in the rabbit, which agreed well with data from actual experiments (4.0x10(7) bacteria at 36 hours). Next, building on the single ODE model, a physiological-based biokinetic (PBBK) compartmentalized model was developed in which 1 physiological compartment was the lumen of the airways and the other was the rabbit body (lung tissue, lymph nodes, blood). The 2 compartments were connected with a parameter describing transport of bacteria from the airways into the body. The PBBK model predicted 4.9x10(7) bacteria in the body at 36 hours, and by 45 hours the model showed all clearance mechanisms were saturated, suggesting the rabbit would quickly succumb to the infection. As with the ODE model, the PBBK model results agreed well with laboratory observations. These data are discussed along with the need for and potential application of the models in risk assessment, drug development, and as a general aid to the experimentalist studying inhalational anthrax.