Multiple Sources of the Outbreak of Legionnaires’ Disease in Genesee County, Michigan, in 2014 and 2015

Legionnaires’ disease (LD) is a severe pneumonia caused by Legionella pneumophila, a bacterium that grows in warm water systems and is transmitted via aerosols. Over the past 15 y, the incidence in the United States increased 4.5-fold to 1.89 per 100,000 people in 2015 (Shah et al. 2018). The associated burden of disease is substantial: $>95\%$ of the cases are hospitalized, and the case fatality rate is $7\%\text{to}8\%$. Although most LD cases are sporadic (CDC 2011), our understanding of the sources of LD comes almost entirely from outbreaks. L. pneumophila is now responsible for the majority ( $57\%–63\%$) of waterborne disease outbreaks in the United States and for all of the outbreak-associated deaths (Benedict et al. 2017; McClung et al. 2017). Most outbreaks of LD have been associated with exposure to aerosols from warm water systems in large buildings that house vulnerable populations, such as hospitals and long-term care facilities (Garrison et al. 2016). Cooling towers and other aerosol sources also have frequently been associated with large LD outbreaks (van Heijnsbergen et al. 2015; Petzold et al. 2017; Caicedo et al. 2019).

In 2014 and 2015, a marked increase of reported LD cases was observed in Genesee County, Michigan, United States. Contemporaneously, a crisis with the potable water supply of the city of Flint, Michigan, occurred (Ruckart et al. 2019). In April 2014, the source of drinking water for Flint was switched from water provided by the Detroit Water and Sewerage Department to Flint River water, which was treated and distributed without corrosion inhibitor (Masten et al. 2016; Pieper et al. 2017). Shortly after the switch, residents noted changes in the color, odor, and taste of their tap water, as well as skin rashes. Following reports of high lead levels in Flint water (Edwards 2015) and in the blood of young children residing in Flint (Hanna-Attisha et al. 2016), a public health emergency was declared. Public health agencies investigated lead exposure as well as the LD cases. The Michigan Department of Health and Human Services (MDHHS) reported an outbreak of LD in Genesee County in 2014 and 2015 and associated the majority of cases with one hospital in Genesee County (MDHHS 2018). Tap water surveys conducted by academic researchers showed L. pneumophila DNA markers were detectable in Flint hospital plumbing in October 2015 but not in Flint homes and small buildings in August 2015 (Schwake et al. 2016; Rhoads et al. 2017). However, a modeling study (Zahran et al. 2018) suggested the outbreak was caused by system-wide proliferation of L. pneumophila in the potable water supply of the City of Flint, enabled by low chlorine levels in the distribution network after the switch to Flint River water as the source. Given the lack of clarity about the cause(s) of the 2014–2015 LD outbreak, this study was initiated to investigate the LD outbreak in Genesee County in 2014 and 2015. The objective of this investigation was to independently identify relevant sources of L. pneumophila that likely resulted in the outbreak. Based on the descriptive epidemiology and published literature, we focused on three potential sources: a) a hospital, b) residences receiving City of Flint water, and c) cooling towers or other outdoor aerosol sources.

We found evidence for three sources of a large, community-wide LD outbreak among Genesee County residents in 2014 and 2015. There was strong evidence (CDC class I; CDC 2019) for a hospital-associated outbreak in 2014 and 2015, as well as indications (CDC class II; CDC 2019) that in 2014 a proportion of cases was associated with residences served by City of Flint water and select cooling towers in Flint. The data did not allow us to determine the attributable risk of the three sources, but multivariate analysis showed an increased risk with residential exposure to Flint water and select cooling towers in 2014 only. Both sources remained associated with LD occurrence after mutual adjustment in the Poisson model. For hospital A exposure, we could not compute incidence rates of the exposed and nonexposed population in the absence of an appropriate population denominator, but the association was supported by: a) the large proportion of cases with prior exposure to hospital A, of which the inpatient exposure was significantly higher than expected on the basis of Medicare admissions among local hospitals; b) the presence of high levels of L. pneumophila SG1 in the hospital plumbing system; c) the alignment of the implementation of effective Legionella control measures with the subsidence of hospital A–associated cases; and d) the clustering of the two ST1 clinical isolates from cases exposed to hospital A with ST1 isolates from the hospital water system in 2016 and 2017, as well as from a LD case exposed to the same hospital in 2016. The appearance of two epidemiologically unrelated ST1 isolates from other U.S. regions in this cluster is not uncommon (Mercante et al. 2018; David et al. 2017). Although the isolates examined in this study span several years, it has been noted in previous hospital-associated outbreaks of ST1 that hospitals were colonized by a limited number of distinct ST1 populations and that highly genetically similar strains could be isolated from the same hospital water systems over multiple years (Oberdorfer et al. 2008; David et al. 2017). For the other sources, no environmental Legionella data and isolates were available, except four isolates from one of the cooling towers, which were genotypically distinct from the clinical isolates. The limitation of having only a few isolates and predominantly from one of the sources underscores the importance of timely sampling of all potential L. pneumophila sources to support identification of source(s) that gave rise to the outbreak.

The aerosol model we used was simple and did not take plume rise, terrain roughness, or buildings into account. The emission rate of each aerosol source was assumed equal and constant, which was very likely not the actual situation. Hence, the aerosol model outcome reflects potential rather than actual concentrations and impact on case residences. The significant increase in IRR when a case residence was closer to the cooling towers was reflecting the actual situation in 2014.

Our investigation sheds new light on the outbreak of LD in Genesee County. The two earlier studies of this same outbreak (MDHHS 2018; Zahran et al. 2018) did not report multiple sources. A descriptive epidemiological evaluation (MDHHS 2018) identified hospital exposure but not the associations with residential exposure to Flint water and cooling towers, underlining the need to include analytical epidemiological approaches in outbreak investigations. Zahran et al. (2018) recognized 25 (rather than 42; Table 2) cases exposed at hospital A, conducted a modeling study focusing on Flint water, and reported an association between LD risk and the low free chlorine concentrations after the switch to Flint River as source, and a temporal association between LD risk and the switch and switch-back and the boil water advisories. However, several assumptions in their models do not seem to be supported by available data and literature. They did not use the actual LD onset date from the medical records to determine the time window for Legionella exposure of the cases but an approximation that differed from the onset date we established from the medical records by four or more days for 31% of the cases. They assumed residents living in Flint Census tracts received City of Flint water, whereas our data sources indicate that this is not always the case. They used the boil-water advisories to assume change in (shower) behavior, which is not supported by data. They used commuter data to associate the LD cases who lived outside Flint with exposure to City of Flint water, whereas the LD case data show that, of the 57 cases that were living outside the City of Flint water-supply zone, the vast majority (72%, 41 cases) did not work (they were disabled or retired); 21% (12 cases) did work, of whom only 2 worked in Flint (no data about 4 cases). Zahran et al. also translated data from the free chlorine monitoring sites to the (Census tract of the) case residences, whereas literature suggests that this cannot be done reliably in a highly looped network, particularly under the dynamic water-treatment operation and distribution water quality in the period of the water switch and without accurate data about residence time and chlorine decay (Blokker et al. 2014; Masten et al. 2016). The last LD cases who received City of Flint water at their residence did so in August 2015, 2 months before the switch-back (see figure 3). These findings emphasizes the need for accurate case history evaluation to reconstruct and assign exposure status for each case as adequately as possible prior to statistical modeling of outbreak data to avoid bias in associations between case status and potential determinants.

Previous LD outbreaks have been associated with a single source by a single ST (Phin et al. 2014; George et al. 2016; David et al. 2017; Weiss et al. 2017). Spatial and geographical clusters of otherwise unrelated LD outbreaks have been reported in New York City, USA, and Sydney, Australia (MacIntyre et al. 2018). An outbreak of ST345 in Germany was associated with aerosols from wastewater treatment plants and cooling towers (Petzold et al. 2017). One previous outbreak in a hotel in Spain was associated with two different STs in two different sources: ST23 in a spa pool and air-conditioning system and ST578 in the hotel plumbing system (Sánchez-Busó et al. 2016). This study is the first report of a multiple ST LD outbreak in the United States with epidemiological evidence to link the outbreak to three sources. The retrospective nature of the investigation precluded the collection of additional evidence regarding possible relationships among sources. Hospital A, the residences on City of Flint water, and possibly the cooling towers were connected to the City of Flint water network, and the high iron and low chlorine content of the water may have created more favorable conditions in water systems that were vulnerable to proliferation of L. pneumophila. Even so, other cooling towers and another large hospital B in Flint were not associated with the LD cases. High L. pneumophila concentrations were detected also in hospital B’s plumbing system in October 2015 (Schwake et al. 2016). No L. pneumophila was detected in small buildings, including single-family residences, in Flint in August 2015. Therefore, if the Flint water switch created more favorable conditions for L. pneumophila to grow in connected water systems (Schwake et al. 2016; Rhoads et al. 2017), the local conditions of the building water system and water use probably determined whether it could lead to an outbreak. Hence, key to LD outbreak prevention is proper design, operation, and maintenance of specific water systems in buildings. Guidelines for Legionella control in building water systems have been made available (Parr et al. 2015; ASHRAE 2018), and health care facilities are now called on to implement them (Centers for Medicare and Medicaid Services 2017). Implementing hyperchlorination alone was not effective in controlling the nosocomial outbreak in hospital A. This lack of effectiveness had been reported before (Lin et al. 2011) and emphasizes the importance of applying evidence-based methods (Lin et al. 2011; EPA 2016) to ensure sustainable Legionella control. Country-wide implementation of guidelines to control Legionella in public buildings and in cooling towers has been successful in France in stopping further increase in LD incidence and (large) outbreaks and was associated with a $>50\%$ decrease in nosocomial LD (Hartemann and Hautemaniere 2011; Campèse et al. 2015; French Public Health Agency 2019). Nevertheless, as in the United States, community-acquired LD remains substantial in France (French Public Health Agency 2019), and guidance to homeowners to control Legionella in their home water systems may help reduce future occurrence (Government of Western Australia 2019). LD is largely preventable; the increasing incidence over past years and the high associated burden of disease and fatality rate warrant implementation of prevention and control measures, as scientists have suggested (U.S. National Academies of Sciences, Engineering, and Medicine Committee 2019). Cases of LD need rapid follow-up, with L. pneumophila testing of LD cases and suspected environmental sources, to identify the source(s) and implement evidence-based control measures to prevent further spread of LD.

This study was financed by the Department of Development, Technology and Budget of the State of Michigan. The authors thank the Michigan Department of Health and Human Services (MDHHS) for agreeing to use the data they had available and MDHHS and the Genesee County Health Department for sharing information about the data collection process at the time of the outbreak. In addition, the authors thank M.S. Dworkin (University of Illinois at Chicago), L. Fitzpatrick (George Washington University), P. Hartemann (University of Lorraine, France), P. Hunter (University of East Anglia, England), and T. Wade (U.S. Environmental Protection Agency) for the helpful discussions and recommendations related to study design, outcomes, and the manuscript. The authors also thank L. Portengen of IRAS for statistical support and L. Rosenthal and N. Slaats of KWR for management of the project.

The authors declare they have no actual or potential competing financial interests.