Risk-Based Critical Concentrations of Legionella pneumophila for

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Ecotoxicology and Human Environmental Health

Risk-based critical levels of Legionella pneumophila for indoor water uses Kerry A. Hamilton, Mark T. Hamilton, William Johnson, Patrick Jjemba, Zia Bukhari, Mark LeChevallier, Charles N. Haas, and Patrick L. Gurian Environ. Sci. Technol., Just Accepted Manuscript • DOI: 10.1021/acs.est.8b03000 • Publication Date (Web): 10 Jan 2019 Downloaded from http://pubs.acs.org on January 11, 2019

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Environmental Science & Technology

Risk-based critical concentrations of Legionella pneumophila for indoor residential water uses

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Kerry A. Hamiltona,b*, Mark T. Hamiltonc, William Johnsond, Patrick Jjembad,

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Zia Bukharid, Mark LeChevallierd, Charles N. Haase, P.L. Guriane

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a

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b The

School for Sustainable Engineering and the Built Environment, Arizona State University, Biodesign Institute Center for Environmental Health Engineering, Arizona State

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University

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c Microsoft

Machine Learning Research Group, 1 Memorial Drive, Cambridge, MA 02142

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d American

Water Research Laboratory, 213 Carriage Lane, Delran, New Jersey 08075

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e

Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104

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* Corresponding author. Kerry A. Hamilton. Mailing address: School for Sustainable Engineering ad the Built Environment, Arizona State University, 781 S Terrace Road, Tempe, Arizona 85281. E-mail address: [email protected]

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ABSTRACT

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Legionella spp. is a key contributor to the United States waterborne disease burden. Despite

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potentially widespread exposure, human disease is relatively uncommon, except under

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circumstances where pathogen concentrations are high, host immunity is low, or exposures

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to small-diameter aerosols occurs. Water quality guidance values for Legionella are

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available for building managers but are generally not based on technical criteria. To address

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this gap, a quantitative microbial risk assessment (QMRA) was conducted using target risk

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values in order to calculate corresponding critical concentrations on a per-fixture and

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aggregate (multiple fixture exposure) basis. Showers were the driving indoor exposure risk

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compared to sinks and toilets. Based on aggregate fixture exposures, critical concentrations

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depended on the dose response model (infection vs. clinical severity infection, CSI), risk

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target used (infection risk vs. disability adjusted life years on a per-exposure or annual

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basis), and fixture type (conventional vs. water efficient or “green”). Median critical

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concentrations based on exposure to a combination of toilet, faucet, and shower aerosols

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ranged from ~10-2 to ~100 CFU per L and ~101 to ~103 CFU per L for infection and CSI dose

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response models, respectively. As infection model results for critical L. pneumophila

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concentrations were often below a feasible detection limit for culture-based assays, the use

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of CSI model results for non-healthcare water systems with a 10-6 DALY pppy target (the

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more conservative target) would result in an estimate of ~20 CFU per L (arithmetic mean of

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samples across multiple fixtures and/or over time). Single sample critical concentrations with

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a per-exposure-corrected DALY target at each fixture would be 1050 CFU per L (faucets),

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4.3 × 105 CFU per L (toilets), and 25.2 CFU per L (showers). The absence of detectable L.

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pneumophila may be appropriate for healthcare or susceptible population settings.

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Keywords: Opportunistic pathogens; reverse quantitative microbial risk assessment

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(QMRA); Legionella pneumophila; monitoring; building water quality; green building; efficient

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Environmental Science & Technology

1. Introduction

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The importance of opportunistic pathogens such as Legionella has been increasing in

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recent years, with Legionella spp. identified in recent US Centers for Disease Control and

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Prevention (CDC) reports as the most common cause of waterborne disease outbreaks in

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the US 1, 2. Legionella causes illness primarily in individuals with underlying health

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conditions, and/or the elderly. Infection occurs when aerosols containing the bacteria are

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inhaled or aspirated by a susceptible host. Recent reviews of environmental sources of

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Legionella infections for sporadic and outbreak-associated cases 3-5 have emphasized the

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importance of building water and cooling tower design and maintenance.

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Monitoring routinely for Legionella is not typically practiced in premise plumbing systems

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except when legionellosis cases are associated with a facility. While Legionella occurrence

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in premise plumbing systems is not uncommon 6-13, monitoring for Legionella spp. on a

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routine basis may not be a cost-effective measure 14. However, in order to validate aspects

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of a water safety plan or management strategy, knowledge regarding interpretation of

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Legionella spp. sampling results can provide information regarding potential risks.

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Concentrations of L. pneumophila in cold tap water have been reported up to ~105 gene

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copies per L 12, 15, 16 and ~104 colony forming units (CFU) per L 8, 10, 11, 17, and up to ~107 CFU

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per L in hot water 8, 18 .

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Existing water quality guidance values for Legionella spp. are available for building water

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quality managers to inform the interpretation of measurements made in their water systems,

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with potable water values ranging from 102 to 105 colony forming units (CFU) per L

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associated with various desired water management actions (Table 1). In one case, a French

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guideline specifies faucets > toilets.

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It is noted here that previous assessments have demonstrated that the appropriate

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measure of risk is the average of multiple exposures 56. Therefore when few data are

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available in the literature to assess the time variability of L. pneumophila concentrations and

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doses as in the current case, the annual exposure dose in this study can be regarded as a

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time-averaged arithmetic dose even if time variability is significant 23, 45. Consequently, while

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critical concentration values calculated in association with per-exposure scenarios might be

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interpreted as a single sample concentration, critical concentration values associated with

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annual risk scenarios might be interpreted as average concentrations over multiple sampling

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events. A major limitation of the guidance documents summarized in Table 1 is that specific

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sampling locations, frequency and timing of samples taken at a given location, and

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statistically rigorous interpretation of sampling results is not specified. Simulating a full three-

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dimensional space for concentration, exposure frequency, and risk is recommended as a

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follow-on to this analysis and could help to customize risk findings to sampling results

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observed at a particular building or other setting.

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As demonstrated here (Figure 4), the ultimate decision regarding concentration limit

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values is a function of which risk target is used (e.g., 10-4 annual probability of infection or

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10-6 DALY pppy). Therefore, an analysis of how timing and extent of sampling might affect

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critical concentration conclusions is beyond the scope of the current set of models but is

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recommended for further analysis. As actions within the context of a water management plan

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are typically developed on a case-by-case basis, the current modeling approach can allow

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for lower-risk facilities to adopt different cut-offs for action.

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For the combined exposures to multiple fixtures, the concentration values (median

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10-2 to 103 L. pneumophila per L) overlap with some of the current guidance values (102 to

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105 per L, with species not specified), although the guidance values would be on the higher

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end of the simulated ranges. Specifically, median critical concentrations calculated in the

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current models ranged from ~10-2 to ~100 CFU per L and ~101 to ~103 CFU per L for 15 ACS Paragon Plus Environment

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infection and CSI dose response models, respectively. All guidance values reviewed were

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above infection dose response model estimates, and the corresponding risk values for

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various concentrations specified in the guidance can be interpreted directly from Figure 3.

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Most guidance values were consistent with, or had some management actions associated

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with, a CSI aggregate exposure model critical median concentration of