Richard James Thomas

The airborne transmission of disease relies on the ability of microbes to survive aerosol transport and, subsequently, cause infection when interacting with a host. The length of time airborne microorganisms remain infectious in aerosol droplets is a function of numerous variables. We present measurements of mass and heat transfer from liquid aerosol droplets combined with airborne survival data for Escherichia coli MRE162, an ACDP category 1 microorganism used as a model system, under a wide range of environmental conditions, droplet compositions and microbiological conditions. In tandem, these companion measurements demonstrate the importance of understanding the complex relationship between aerosol microphysics and microbe survival. Specifically, our data consist of the correlation of a wide range of physicochemical properties (e.g., evaporation rates, equilibrium water content, droplet morphology, compositional changes in droplet solute and gas phase, etc.), with airborne viability decay to infer the impact of aerosol microphysics on airborne bacterial survival. Thus, a mechanistic approach to support prediction of the survival of microorganisms in the aerosol phase as a function of biological, microphysical, environmental, and experimental (aerosol-generation and sampling) processes is presented. Specific findings include the following: surfactants do not increase bacteria stability in aerosol, while both the bacteria growth phase and bacteria concentration may affect the rate at which bacteria decay in aerosol.

Surface to hand transfer of viruses represents a potential mechanism for human exposure. An experimental process for evaluating the touch transfer of aerosol-deposited material is described based on controlling surface, tribological, and soft matter components of the transfer process. A range of high-touch surfaces were evaluated. Under standardized touch parameters (15 N, 1 s), relative humidity (RH) of the atmosphere around the contact transfer event significantly influenced transfer of material to the finger-pad. At RH < 40%, transfer from all surfaces was ® plastics. Pooled human saliva was transferred at a lower rate compared to artificial saliva, indicating the role of rheological properties. The artificial saliva data were modeled by non-linear regression and the impact of environmental humidity and temperature were evaluated within a Quantitative Microbial Risk Assessment model using SARS-CoV-2 as an example. This illustrated that the trade-off between transfer efficiency and virus survival may lead to the highest risks of fomite transmissions in indoor environments with higher humidity.

Experimental aerosol generation methods aim to represent natural processes; however the complexity is not always captured and unforeseen variability may be introduced into the data. The current practices for natural and experimental aerosol generation techniques are here reviewed. Recommendations for best practice are presented, and include characterization of starting material and spray fluid, rational selection of appropriate aerosol generators, and physical and biological characterization of the output aerosol. Reporting of bioaerosol research should capture sufficient detail to aid data interpretation, reduce variation, and facilitate comparison between research laboratories. Finally, future directions and challenges in bioaerosol generation are discussed.

Understanding airborne survival and decay of microorganisms is important for a range of public health and biodefense applications, including epidemiological and risk analysis modeling. Techniques for experimental aerosol generation, retention in the aerosol phase, and sampling require careful consideration and understanding so that they are representative of the conditions the bioaerosol would experience in the environment. This review explores the current understanding of atmospheric transport in relation to advances and limitations of aerosol generation, maintenance in the aerosol phase, and sampling techniques. Potential tools for the future are examined at the interface between atmospheric chemistry, aerosol physics, and molecular microbiology where the heterogeneity and variability of aerosols can be explored at the single-droplet and single-microorganism levels within a bioaerosol. The review highlights the importance of method comparison and validation in bioaerosol research and the benefits that the application of novel techniques could bring to increasing the understanding of aerobiological phenomena in diverse research fields, particularly during the progression of atmospheric transport, where complex interdependent physicochemical and biological processes occur within bioaerosol particles.

Particle size dictates where aerosolized pathogens deposit in the respiratory tract, thereafter the pathogens potential to cause disease is influenced by tissue tropism, clearance kinetics and the ...

Deposition of Burkholderia pseudomallei within either the lungs or nasal passages of the Balb/c murine model resulted in different infection kinetics. The infection resulting from the inhalation of B. pseudomallei within a 12 um particle aerosol was prolonged compared to a 1 um particle aerosol with a mean time-to-death (MTD) of 73.8 ± 11.3 h and 174.7 ± 14.9 h respectively. Inhalation of B. pseudomallei within 1 um or 12 um particle aerosols resulted in a median lethal dose (MLD) of 4 and 12 cfu respectively. The 12 mm particle inhalational infection was characterised by involvement of the respiratory epithelium and inflammation of the neurological path leading from the olfactory epithelium to the olfactory bulb (100%), culminating in abscessation of the brain (33%). Initial involvement of the upper respiratory tract lymphoid tissues (nasal-associated lymphoid tissue and cervical lymph nodes) was observed in both the 1 and 12 um particle inhalational infections (80-85%). Necrotising alveolitis and bronchiolitis were evident in both inhalational infections however lung pathology was greater after inhalation of the 1 mm particle aerosol with pronounced involvement of the mediastinal lymph node (50%). Terminal disease was characterised by bacteraemia in both inhalational infections with dissemination to the spleen, liver, kidneys and thymus. Treatment with co-trimoxazole was more effective than treatment with doxycycline irrespective of the size of the particles inhaled. Doxycycline was more effective against the 12 um particle inhalational infection as evidenced by increased time to death. However, both treatment regimes exhibited significant relapse when therapy was discontinued with massive enlargement and abscessation of the lungs, spleen and cervical lymph nodes observed.

This study aimed to provide data on the survival and site of damage ofEscherichia colicells following aerosolization using two different techniques, nebulization and flow focusing. Four metabolic stains were assessed for their ability to detect respiratory activities and membrane homeostasis in aerosolizedE. colicells. The degree of sublethal injury increased significantly over the 10-min period of aerosolization inE. colicells aerosolized by using the Collison nebulizer, reaching up to 99.9% of the population. In contrast, a significantly lower proportion of the population was sublethally damaged during aerosolization using the flow-focusing aerosol generator (FFAG). Concomitantly, loss of membrane homeostasis increased at a higher rate in nebulized cells (68 to 71%) than in those aerosolized by using the FFAG (32 to 34%). The activities of respiratory enzymes decreased at increased rates in nebulized cells (27 to 37%) compared to the rates of decrease in cells aerosolized by using the FFAG (59 to 61%). The results indicate that the physiology of an aerosolized bacterium is linked to the method of aerosol generation and may affect the interpretation of a range of aerobiological phenomenon.

The spectre of intentional release of pathogenic microbes and their toxins is a real threat. This article reviews the literature on adhesins of biothreat agents, their interactions with oligosaccharides and the potential for anti-adhesion compounds as an alternative to conventional therapeutics. The minimal binding structure of ricin has been well characterised and offers the best candidate for successful anti- adhesion therapy based on the Galβ1-4GlcNAc structure. The botulinum toxin serotypes A-F bind to a low number of gangliosides (GT1b, GQ1b, GD1a and GD1b) hence it should be possible to determine the minimal structure for binding. The minimal disaccharide sequence of GalNAcβ1-4Gal found in the gangliosides asialo-GM1 and asialo-GM2 is required for adhesion for many respiratory pathogens. Although a number of adhesins have been identified in bacterial biothreat agents such as Yersinia pestis, Bacillus anthracis, Francisella tularensis, Brucella species and Burkholderia pseudomallei, specific information regarding their in vivo expression during pneumonic infection is lacking. Limited oligosaccharide inhibition studies indicate the potential of GalNAcβ1-4Gal, GalNAcβ-3Gal and the hydrophobic compound, para-nitrophenol as starting points for the rational design of generic anti- adhesion compounds. A cocktail of multivalent oligosaccharides based on the minimal binding structures of identified adhesins would offer the best candidates for anti-adhesion therapy.

Presently there is a significant effort to develop and evaluate vaccines and antibiotics against the potential bioterrorism agent Yersinia pestis . The animal models used to test these countermeasures involve the deposition of small particles within the lung. However, deliberate aerosol release of Y. pestis will generate both small and large inhalable particles. We report in this study that the pathogenesis patterns of plague infections caused by the deposition of 1- and 12-μm-particle aerosols of Y. pestis in the lower and upper respiratory tracts (URTs) of mice are different. The median lethal dose for 12-μm particles was 4.9-fold greater than that for 1-μm particles. The 12-μm-particle infection resulted in the degradation of the nasal mucosa and nasal-associated lymphoid tissue (NALT) plus cervical lymphadenopathy prior to bacteremic dissemination. Lung involvement was limited to secondary pneumonia. In contrast, the 1-μm-particle infection resulted in primary pneumonia; in 40% of mice, the involvement of NALT and cervical lymphadenopathy were observed, indicating entry via both URT lymphoid tissues and lungs. Despite bacterial deposition in the gastrointestinal tract, the involvement of Peyer's patches was not observed in either infection. Although there were major differences in pathogenesis, the recombinant F1 and V antigen vaccine and ciprofloxacin protected against plague infections caused by small- and large-particle aerosols.