Viability and Infectivity of Microorganisms in Experimental Airborne Infection

Goodlow, Robert J.; Leonard, Frederic A.

doi:10.1128/mmbr.25.3.182-187.1961

Cited by 42 publications

(31 citation statements)

References 4 publications

(4 reference statements)

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“…Numerous studies ( 11,37–40 ) have reported that response to inhalation exposure of an aerosol of pathogenic organisms is a strong function of aerosol size. To explore the variation of mortality with aerosol size, dose‐response data for guinea pigs and nonhuman primates exposed to homogeneous aerosol clouds with different aerosol sizes were fit with dose‐response models.…”

Section: Resultsmentioning

confidence: 99%

Dose‐Response Models for Inhalation of Bacillus anthracis Spores: Interspecies Comparisons

2008

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Because experiments with Bacillus anthracis are costly and dangerous, the scientific, public health, and engineering communities are served by thorough collation and analysis of experiments reported in the open literature. This study identifies available dose-response data from the open literature for inhalation exposure to B. anthracis and, via dose-response modeling, characterizes the response of nonhuman animal models to challenges. Two studies involving four data sets amenable to dose-response modeling were found in the literature: two data sets of response of guinea pigs to intranasal dosing with the Vollum and ATCC-6605 strains, one set of responses of rhesus monkeys to aerosol exposure to the Vollum strain, and one data set of guinea pig response to aerosol exposure to the Vollum strain. None of the data sets exhibited overdispersion and all but one were best fit by an exponential dose-response model. The beta-Poisson dose-response model provided the best fit to the remaining data set. As indicated in prior studies, the response to aerosol challenges is a strong function of aerosol diameter. For guinea pigs, the LD(50) increases with aerosol size for aerosols at and above 4.5 mum. For both rhesus monkeys and guinea pigs there is about a 15-fold increase in LD(50) when aerosol size is increased from 1 mum to 12 mum. Future experimental research and dose-response modeling should be performed to quantify differences in responses of subpopulations to B. anthracis and to generate data allowing development of interspecies correction factors.

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Section: Resultsmentioning

confidence: 99%

Dose‐Response Models for Inhalation of Bacillus anthracis Spores: Interspecies Comparisons

2008

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“…The F. tularensis original and ICRP‐transformed data used for constructing two aerosol‐particle‐diameter‐dependent dose‐response models are listed in Table , and include data from two studies . The maximum‐likelihood‐estimated (MLE) best‐fit dose‐response models for individual data sets for each aerosol particle diameter using the original data are listed in Table .…”

Section: Resultsmentioning

confidence: 99%

“…The second tularemia data set employed was drawn from an experimental infection study of guinea pigs and rhesus monkeys. Only the lethal 50% dose (and not outcomes of animals exposed in each dose group) was provided for four particle sizes (1, 7, 12, and 22 μ m).…”

Section: Methodsmentioning

confidence: 99%

“…In this article, we model three data sets with graded doses of pathogens delivered to hosts as monodisperse aerosols of known size with standard deviations ranging approximately from 1.22% to 2.92%. The data sets include Francisella tularensis dosing studies conducted for aerosols ranging in size from approximately 1 to 24 μ m . Creating particle‐diameter‐dependent dose‐response models that can compare the probabilities of mortality can achieve at least two things: they can provide (1) predictive estimates of lethal effect based on doses of any particle with a diameter selected within the minimum and maximum range established by the data set used to establish the model, and (2) a litmus test as to whether physical lung region deposition for bioaerosols (as described by the ICRP equation) is a dominant force responsible for the patterns of pathogenicity observed in this disease's test studies.…”

Section: Introductionmentioning

confidence: 99%

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Dose‐Response Models Incorporating Aerosol Size Dependency for Francisella tularensis

et al. 2013

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The effect of bioaerosol size was incorporated into predictive dose-response models for the effects of inhaled aerosols of Francisella tularensis (the causative agent of tularemia) on rhesus monkeys and guinea pigs with bioaerosol diameters ranging between 1.0 and 24 μm. Aerosol-size-dependent models were formulated as modification of the exponential and β-Poisson dose-response models and model parameters were estimated using maximum likelihood methods and multiple data sets of quantal dose-response data for which aerosol sizes of inhaled doses were known. Analysis of F. tularensis dose-response data was best fit by an exponential dose-response model with a power function including the particle diameter size substituting for the rate parameter k scaling the applied dose. There were differences in the pathogen's aerosol-size-dependence equation and models that better represent the observed dose-response results than the estimate derived from applying the model developed by the International Commission on Radiological Protection (ICRP, 1994) that relies on differential regional lung deposition for human particle exposure.

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“…Aerosol performance can be affected by a variety of different factors, from pre-aerosolization factors, such as pathogen growth conditions, to post-processing factors, such as concentration determination (3, 15). Thus, prior to beginning aerosol studies with animal models, it is important to characterize and understand the impact of aerosol equipment selection, pathogen handling techniques, and environmental parameters on the reproducibility of a research design.…”

Section: Discussionmentioning

confidence: 99%

A vibrating mesh nebulizer as an alternative to the Collison 3-jet nebulizer for infectious disease aerobiology

Bowling

O’Malley

Klimstra

et al. 2019

Preprint

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17Experimental infection of animals via inhalation containing pathogenic agents is essential to 18 understanding the natural history and pathogenesis of infectious disease as well as evaluation of 19 potential medical countermeasures. We evaluated whether the Aeroneb, a vibrating mesh 20 nebulizer, would serve as an alternative to the Collison, the 'gold standard' for generating 21 infectious bioaerosols. While the Collison possesses desirable properties that have contributed to 22 its longevity in infectious disease aerobiology, concerns have lingered about the volume and 23 concentration of agent required to cause disease and the damage that jet nebulization causes to 24 the agent. For viruses, the ratio of aerosol concentration to nebulizer concentration (spray factor, 25 SF), the Aeroneb was superior to the Collison for four different viruses in a nonhuman primate 26 head-only exposure chamber. Aerosol concentration of influenza was higher relative to 27 fluorescein for the Aeroneb compared to the Collison, suggesting that the Aeroneb was less 28 harsh to viral pathogens than the Collison when generating aerosols. The Aeroneb did not 29 improve the aerosol SF for a vegetative bacterium, Francisella tularensis. Environmental 30 parameters collected during the aerosols indicated that the Aeroneb generated a higher relative 31 humidity in exposure chambers while not affecting other environmental parameters. Aerosol 32 mass median aerodynamic diameter was generally larger and more disperse for aerosols 33 generated by the Aeroneb than what is seen with the Collison but ≥80% were within the range 34 that would reach the lower respiratory tract and alveolar regions. These data suggest that for viral 35 pathogens, the Aeroneb is a suitable alternative to the Collison 3-jet nebulizer. 36 Importance 37 The threat of aerosolization is often not the natural method of transmission. While selection of 38 an appropriate animal model is vital for these types of experiments, other confounding factors 39 can be controlled through a thorough understanding of experimental design and the effects that 40 different parameters can have on disease outcome. Route of administration, particle size, and 41 dose are all factors which can affect disease progression and need to be controlled. Aerosol 42 research methods and equipment need to be well characterized to optimize the development of 43 animal models for bioterrorism agents.44 45 65responses that protect the host. These effects could raise the dose required to cause disease, 66 thereby requiring large quantities of pathogens grown to high titers for aerosol experiments. 67While the process of aerosolization will always place mechanical stress on infectious agents, 68 aerosol generators that are 'gentler' than the Collison would be desirable. 69The Aerogen Solo (a.k.a Aeroneb) is a single-use nebulizer employed in clinical settings 70 for the delivery of aerosolized medication. The Aeroneb utilizes a palladium mesh perforated 71 with conical shaped holes that act as a micropump...

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Viability and Infectivity of Microorganisms in Experimental Airborne Infection

Cited by 42 publications

References 4 publications

Dose‐Response Models for Inhalation of Bacillus anthracis Spores: Interspecies Comparisons

Dose‐Response Models for Inhalation of Bacillus anthracis Spores: Interspecies Comparisons

Dose‐Response Models Incorporating Aerosol Size Dependency for Francisella tularensis

A vibrating mesh nebulizer as an alternative to the Collison 3-jet nebulizer for infectious disease aerobiology

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