title: Dose response models and a quantitative microbial risk assessment framework for the Mycobacterium avium complex that account for recent developments in molecular biology, taxonomy, and epidemiology.
abstract: Mycobacterium avium complex (MAC) is a group of environmentally-transmitted pathogens of great public health importance. This group is known to be harbored, amplified, and selected for more human-virulent characteristics by amoeba species in aquatic biofilms. However, a quantitative microbial risk assessment (QMRA) has not been performed due to the lack of dose response models resulting from significant heterogeneity within even a single species or subspecies of MAC, as well as the range of human susceptibilities to mycobacterial disease. The primary human-relevant species and subspecies responsible for the majority of the human disease burden and present in drinking water, biofilms, and soil are M. avium subsp. hominissuis, M. intracellulare, and M. chimaera. A critical review of the published literature identified important health endpoints, exposure routes, and susceptible populations for MAC risk assessment. In addition, data sets for quantitative dose-response functions were extracted from published in vivo animal dosing experiments. As a result, seven new exponential dose response models for human-relevant species of MAC with endpoints of lung lesions, death, disseminated infection, liver infection, and lymph node lesions are proposed. Although current physical and biochemical tests used in clinical settings do not differentiate between M. avium and M. intracellulare, differentiating between environmental species and subspecies of the MAC can aid in the assessment of health risks and control of MAC sources. A framework is proposed for incorporating the proposed dose response models into susceptible population- and exposure route-specific QMRA models.
authors.affiliation: Department of Civil, Architectural, and Environmental Engineering, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104, USA. Electronic address: kh495@drexel.edu.
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Hamilton
authors.affiliation: Division of Environmental Health Sciences and Department of Civil Environmental and Geodetic Engineering, The Ohio State University, USA.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Weir
authors.affiliation: Department of Civil, Architectural, and Environmental Engineering, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104, USA.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Haas
mesh_terms: D000818:Animals; D018441:Biofilms; D060766:Drinking Water; D006801:Humans; D009162:Mycobacterium avium; D015269:Mycobacterium avium Complex; D015270:Mycobacterium avium-intracellulare Infection; D018570:Risk Assessment
chemical_list: D060766:Drinking Water
keywords: Aerosol; Biofilm; Dose response; Engineered water system; MAC; Mycobacterium avium complex; Mycobacterium chimaera; Mycobacterium intracellulare; Opportunistic pathogen; QMRA; Quantitative microbial risk assessment