Environmental fungal bioaerosol risk modelling

David Kahn

doi:10.17918/00010999

Fungi are responsible for a burden of human morbidity and mortality that is becoming understood to be more expansive than previously thought. This thesis evaluates the human health risks posed by outdoor environmental exposure to airborne fungal propagules. First, a hazard analysis of fungal pathogens on the global scale is presented, with the goal of assessing the current state of research efforts towards them, how they have been historically understudied and misunderstood, and what differentiates fungal pathogens and the risks they pose from microbes of other types. Then, analyses of two fungi of particular interest -- the model opportunistic pathogen Cryptococcus neoformans and the dimorphic specifically pathogenic Coccidioides spp. -- are presented. Systematic literature reviews that sought peer-reviewed studies documenting the experimental exposure of mammalian hosts to quantitative challenges of these two types of fungi were conducted in order to parameterize dose-response models which are a required element of the Quantitative Microbial Risk Assessment framework. Modelling efforts for C. neoformans were inconclusive in that no records of experiments were discovered which met established inclusion criteria for respiratory dose-response modelling, but hazards posed by quantitative exposure are described via a dose-stratified analysis of time-stratified experimental survival data. Modelling efforts for Coccidioides spp. successfully converged on eight novel dose-response parameterizations, five of which are appropriate for use in modelling the risks posed by respiratory exposure and three of which are appropriate for exposure by other routes. Given these findings, an additional targeted literature review was conducted to parametrize an exposure assessment model to ascertain the dose delivered to a population of interest under occupational exposure scenarios. Outputs of the most situationally relevant Coccidioides spp. dose-response model were combined with outputs of the exposure model to characterize risks posed to agricultural workers in eight scenarios likely to be experienced by them as a result of occupational activities. Construction of and results from this comprehensive application of the Quantitative Microbial Risk Assessment framework applied for occupational exposure to Coccidioides spp. are presented in full, along with discussion of their limitations and the potential for use of components of the framework for future risk analyses. Finally, a synthesis of risks posed to humans by pathogenic fungi is presented, considering broad evidence from the global stage, as well as the analyses of C. neoformans and Coccidioides spp. This work presents a continuum of the hazards posed to humans by exposure to aerosolized fungi by qualitatively assessing fungal pathogens in a broad sense and by quantitatively assessing two fungi that are on opposite ends of that hazard spectrum: C. neoformans to which human exposure is thought to be nearly ubiquitous but whose pathogenesis is heavily driven by host immune status and Coccidioides spp. to which hazardous human exposure may only occur during isolated exposure events and whose pathogenesis is specifically dose dependent. In full, this work assesses broad and specific risks to human health posed by the aeromycobiome.

Environmental fungal bioaerosol risk modelling

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Environmental fungal bioaerosol risk modelling

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