Uncovering wastewater treatment plants as possible sources of legionellosis clusters through spatial statistics approach and environmental analysis.

Wastewater treatment plants (WWTPs) are suspected reservoirs of Legionella pneumophila (Lp). The required aeration and mixing steps lead to the emission and dispersion of bioaerosols potentially harboring Lp. The aim of the project is to evaluate municipal WWTPs as a possible source of legionellosis through the statistical analysis of case clusters. A space-time scanning statistical method was implemented in SaTScan software to identify and analyze WWTPs located within and close to spatiotemporal clusters of legionellosis detected in Quebec between 2016 and 2020. In parallel, WWTPs were ranked according to their pollutant load, flow rate and treatment type. These parameters were used to evaluate the WWTP susceptibility to generate and disperse bioaerosols. Results show that 37 of the 874 WWTPs are located inside a legionellosis cluster study zone, including six of the 40 WWTPs ranked most susceptible. In addition, two susceptible WWTPs located within an extended area of 2.5 km from the study zone (2.5-km buffer) were included, for a total of 39 WWTPs. The selected 39 WWTPs were further studied to document proximity of population, dominant wind direction, and surrounding water quality. Samples collected from the influent and the effluent of six selected WWTPs revealed the presence of Legionella spp. in 92.3% of the samples. Lp and Lp serogroupg 1 (Lp sg1) were detected below the limit of quantification in 69% and 46% of the samples, respectively. The presence of Legionella in wastewater and the novel statistical approach presented here provides information to the public health authorities regarding the investigation of WWTPs as a possible source of Legionella exposure, sporadic cases, and clusters of legionellosis.

Evaluating Fourier-transform infrared spectroscopy with IR Biotyper as a faster and simpler method for investigating the sources of an outbreak of legionellosis.

Fourier-transform infrared (FTIR) spectroscopy using the IR Biotyper and core genome single nucleotide polymorphism (cgSNP) analysis were performed on 12 Legionella isolates associated with an outbreak at a spa house in Kanagawa Prefecture, Japan, and 3 non-outbreak isolates. The discriminative power of FTIR spectroscopy for 48-h incubation conditions of L. pneumophila in this outbreak was lower than cgSNP-based typing but higher than serogroup typing. FTIR spectroscopy could screen outbreak isolates from a group of genetically related isolates and may be useful as an initial typing method in Legionella outbreak investigations.

Estimating the burden of illness caused by domestic waterborne Legionnaires' disease in Canada: 2015-2019.

Legionellosis is a disease caused by the bacterium Legionella that most commonly presents as Legionnaires' disease (LD), a severe form of pneumonia. From 2015 to 2019, an average of 438 LD cases per year were reported in Canada. However, it is believed that the actual number of cases is much higher, since LD may be underdiagnosed and underreported. The purpose of this study was to develop an estimate of the true incidence of illnesses, hospitalizations, and deaths associated with LD in Canada. Values were derived using a stochastic model, based on Canadian surveillance data from 2015 to 2019, which were scaled up to account for underdiagnosis and underreporting. Overall, there were an estimated 1,113 (90% CrI: 737-1,730) illnesses, 1,008 (90% CrI: 271-2,244) hospitalizations, and 34 (90% CrI: 4-86) deaths due to domestically acquired waterborne LD annually in Canada from 2015 to 2019. It was further estimated that only 36% of illnesses and 39% of hospitalizations and deaths were captured in surveillance, and that 22% of illnesses were caused by Legionella serogroups and species other than Legionella pneumophila serogroup 1 (non-Lp1). This study highlights the true burden and areas for improvement in Canada's surveillance and detection of LD.

Legionnaires' Disease Outbreak Associated With a Hot Tub Display at the North Carolina Mountain State Fair, September 2019.

OBJECTIVES: On September 23, 2019, the North Carolina Division of Public Health identified a legionellosis increase in western North Carolina; most patients had recently attended the North Carolina Mountain State Fair. We conducted a source investigation. METHODS: Cases were fair attendees with laboratory-confirmed legionellosis and symptom onset within 2 to 14 days (Legionnaires' disease) or ≤3 days (Pontiac fever). We conducted a case-control study matching cases to non-ill fair attendees as control participants and an environmental investigation, and we performed laboratory testing (Legionella bacteria culture and polymerase chain reaction) of 27 environmental samples from fairgrounds and hot tubs and 14 specimens from case patients. We used multivariable unconditional logistic regression models to calculate adjusted odds ratios for potential Legionella exposure sources and risk factors. RESULTS: Of 136 people identified with fair-associated legionellosis, 98 (72%) were hospitalized and 4 (3%) died. Case patients were more likely than control participants to report walking by hot tub displays (adjusted odds ratio = 10.0; 95% CI, 4.2-24.1). Complete hot tub water treatment records were not kept, precluding evaluation of water maintenance conducted on display hot tubs. Legionella pneumophila sequence types (STs) were consistent among 10 typed clinical specimens (ST224) but distinct from the only positive environmental sample from the fair (ST7 and ST8). CONCLUSIONS: Hot tub displays were identified as the most likely outbreak source, making this the largest hot tub-associated Legionnaires' disease outbreak worldwide. Following the investigation, the North Carolina Division of Public Health and the Centers for Disease Control and Prevention released guidance on mitigating risk of Legionella exposure from hot tub displays. Results highlight the importance of properly maintaining equipment that aerosolizes water, including hot tubs intended for display purposes only.

Prevalence and genetic distribution of Legionella spp. in public bath facilities in Kobe City, Japan.

Legionella is an important waterborne pathogen that causes legionellosis. Public baths are considered the primary cause of legionellosis infection in Japan. We investigated the prevalence and genetic distribution of 338 Legionella spp. isolates from 81 public bath facilities, including 35 hot springs and 46 other facilities, through annual periodic surveillance in Kobe, Japan, from 2016 to 2021. In addition, the genotypes of nine clinical strains of unknown infectious source from the same period were compared to those of bathwater isolates. We elucidated the differences in the distribution of Legionella species, serogroups, and genotypes between hot springs and other public baths. Legionella israelensis, L. londiniensis, and L. micdadei colonized hot springs along with L. pneumophila. The minimum spanning tree analysis based on multiple-locus variable number tandem repeat analysis (MLVA) also identified four major clonal complexes (CCs) in L. pneumophila SG1 and found that CC1 of the four CCs is a specific novel genotype with the lag-1 gene in hot springs. The same MLVA genotypes and sequence types as those of the clinical strains were not present among the strains isolated from bath water. Thus, our surveillance is useful for estimating the sources of legionellosis infection in Japan and developing prevention strategies.

Legionellosis in Poland in 2018-2021.

Objectives: The aim of this study is to compare the epidemiological situation of legionellosis in Poland in 2018-2021 to prior years, taking into account the impact of the COVID-19 pandemic in 2020-2021. Material and methods: The assessment is based on national surveillance data published in the annual bulletin "Infectious Diseases and Poisons in Poland" from 2013 to 2021, as well as data from Legionnaires' disease case reports collected and sent to the Department of Epidemiology of Infectious Diseases and Surveillance NIPH NIH - NRI by sanitary and epidemiological stations or submitted to EpiBase. Results: In Poland, both Legionnaires' disease (an acute infection that progresses to pneumonia) and Pontiac fever (a mild, flu-like sickness) are reported. In 2018-2021, a total of 255 cases of legionellosis were registered, including 236 cases of Legionnaires' disease and 19 cases of Pontiac fever. Each year, there was an increase in the number of notifications compared to the annual median number of cases from 2013-2017. The annual incidence rate in 2019 (0.23 per 100,000 population) was the highest since the start of legionellosis case registration in Poland. It declined again during the years of the COVID-19 pandemic. The notifications occurred throughout the country, but the highest notification rate was observed in the western belt of voivodeships. Pomorskie reported the highest incidence, accounting for more than 20% of all registered cases. The median incidence of Legionnaires' disease in men (0.23 per 100,000) was more than twice that of women (0.10), with the highest incidence (0.58) recorded in men 65 years of age or older. All indigenous cases of Legionnaires' disease were sporadic; all but three patients were hospitalized. State Sanitary Inspection reported 26 fatal cases of Legionnaires' disease (mortality = 11%). Twenty-four cases were linked to contaminated water systems in health-care settings, and 21 cases were likely associated with travel abroad. Summary and conclusions: Although the number of notifications has increased in recent years, Legionnaires' disease is still an infrequently diagnosed respiratory infection in Poland, and the reported incidence remains one of the lowest in the entire EU. The most affected demographic group is men aged 65 and older. Improving the early diagnosis of Legionnaires' disease in healthcare settings remains a priority.

Legionellosis on the rise: A scoping review of sporadic, community-acquired incidence in the United States.

Over the past two decades, the incidence of legionellosis has been steadily increasing in the United States though there is noclear explanation for the main factors driving the increase. While legionellosis is the leading cause of waterborne outbreaks in the US, most cases are sporadic and acquired in community settings where the environmental source is never identified. This scoping review aimed to summarise the drivers of infections in the USA and determine the magnitude of impact each potential driver may have. A total of 1,738 titles were screened, and 18 articles were identified that met the inclusion criteria. Strong evidence was found for precipitation as a major driver, and both temperature and relative humidity were found to be moderate drivers of incidence. Increased testing and improved diagnostic methods were classified as moderate drivers, and the ageing U.S. population was a minor driver of increasing incidence. Racial and socioeconomic inequities and water and housing infrastructure were found to be potential factors explaining the increasing incidence though they were largely understudied in the context of non-outbreak cases. Understanding the complex relationships between environmental, infrastructure, and population factors driving legionellosis incidence is important to optimise mitigation strategies and public policy.

Water quality influences Legionella pneumophila determination.

Legionellosis is a respiratory disease of public health concern. The bacterium Legionella pneumophila is the etiologic agent responsible for >90% of legionellosis cases in the United States. Legionellosis transmission primarily occurs through the inhalation or aspiration of contaminated water aerosols or droplets. Therefore, a thorough understanding of L. pneumophila detection methods and their performance in various water quality conditions is needed to develop preventive measures. Two hundred and nine potable water samples were collected from taps in buildings across the United States. L. pneumophila was determined using three culture methods: Buffered Charcoal Yeast Extract (BCYE) culture with Matrix-assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) identification, Legiolert® 10- and 100-mL tests, and one molecular method: quantitative Polymerase Chain Reaction (qPCR) assay. Culture and molecular positive results were confirmed by secondary testing including MALDI-MS. Eight water quality variables were studied, including source water type, secondary disinfectant, total chlorine residual, heterotrophic bacteria, total organic carbon (TOC), pH, water hardness, cold- and hot-water lines. The eight water quality variables were segmented into 28 categories, based on scale and ranges, and method performance was evaluated in each of these categories. Additionally, a Legionella genus qPCR assay was used to determine the water quality variables that promote or hinder Legionella spp. occurrence. L. pneumophila detection frequency ranged from 2 to 22% across the methods tested. Method performance parameters of sensitivity, specificity, positive and negative predictive values, and accuracy were >94% for the qPCR method but ranged from 9 to 100% for the culture methods. Water quality influenced L. pneumophila determination by culture and qPCR methods. L. pneumophila qPCR detection frequencies positively correlated with TOC and heterotrophic bacterial counts. The source water-disinfectant combination influenced the proportion of Legionella spp. that is L. pneumophila. Water quality influences L. pneumophila determination. To accurately detect L. pneumophila, method selection should consider the water quality in addition to the purpose of testing (general environmental monitoring versus disease-associated investigations).

Increased Incidence of Legionellosis after Improved Diagnostic Methods, New Zealand, 2000-2020.

Legionellosis, notably Legionnaires' disease, is recognized globally and in New Zealand (Aotearoa) as a major cause of community-acquired pneumonia. We analyzed the temporal, geographic, and demographic epidemiology and microbiology of Legionnaires' disease in New Zealand by using notification and laboratory-based surveillance data for 2000‒2020. We used Poisson regression models to estimate incidence rate ratios and 95% CIs to compare demographic and organism trends over 2 time periods (2000-2009 and 2010-2020). The mean annual incidence rate increased from 1.6 cases/100,000 population for 2000-2009 to 3.9 cases/100,000 population for 2010-2020. This increase corresponded with a change in diagnostic testing from predominantly serology with some culture to almost entirely molecular methods using PCR. There was also a marked shift in the identified dominant causative organism, from Legionella pneumophila to L. longbeachae. Surveillance for legionellosis could be further enhanced by greater use of molecular typing of isolates.

Environmental Investigation and Surveillance for Legionella in Aotearoa New Zealand, 2000-2020.

The reported rate of legionellosis is increasing in Aotearoa New Zealand (NZ) with most cases community-acquired, sporadic (non-outbreak) and without an identifiable source. This analysis used two datasets to describe the environmental sources that contribute to Legionella in NZ, based on linkages with outbreaks and sporadic clinical cases, and analysis of environmental testing data. These findings highlight the need for enhanced environmental investigation of clinical cases and outbreaks. There is also a need for systematic surveillance testing of high-risk source environments to support more rigorous controls to prevent legionellosis.

Investigation of a legionellosis outbreak in Sydney CBD - a brief report.

OBJECTIVE: To identify and control a source of Legionella in Sydney CBD. METHODS: Clinical, epidemiological, environmental and genomic techniques were employed to identify cases and the source of Legionella. RESULTS: Eleven legionellosis cases were linked to Sydney CBD with a median age of 69 years. All were hospitalised and had risk factors for Legionella infection. Eight of 11 cases identified as male. Genomic analysis linked three cases to a contaminated cooling water source in Sydney CBD, with a further case infected with a similar strain to that found in Sydney CBD. Another case, although epidemiologically linked to Sydney CBD, was infected with a genomically different strain to that found in Sydney CBD. Six other cases had no viable sample for genomic analysis. CONCLUSION/IMPLICATIONS FOR PUBLIC HEALTH: An outbreak of legionellosis is a serious public health threat that requires rapid investigation and environmental control. We were able to identify a source in Sydney CBD through the application of clinical, epidemiological, environmental and genomic techniques. Genomic analysis is a powerful tool that can be used to confirm the source location but requires close collaboration between clinicians, public health units and microbiologists to recover viable sputum cultures from cases diagnosed with legionellosis.

Can legionellosis be considered an occupational risk in the healthcare sector? A systematic review and meta-analysis.

OBJECTIVES: According to current knowledge about legionella transmission, healthcare workers (HCWs) are at an increased risk of exposure. The aim of this research was to systematically review the literature about HCWs' exposure to legionella and establish whether there is an occupational risk. STUDY DESIGN: This was a systematic review and meta-analysis. METHODS: PubMed, Scopus and Web of Science were searched to identify studies regarding the occupational risk of legionellosis for HCWs. Keywords used in the search were 'Legionella pneumophila', 'occupational medicine', 'occupational' and 'risk'. Selected studies were reviewed to assess the quality and meta-analysed. Finally, the nine epidemiological principles of Bradford-Hill criteria were used to assess whether legionellosis could be considered an occupational risk for HCWs. RESULTS: The search strategy retrieved 124 studies, and 10 studies were included in the present review. The overall study quality was low. The pooled odds ratio estimate was 2.45 (95% confidence interval: 1.52-3.96). The assessment using Bradford-Hill criteria showed that only two criteria (plausibility and coherence) were met, which is insufficient to establish an occupational risk. CONCLUSIONS: This systematic review suggests that there is a higher risk of legionella exposure for HCWs, but there is currently no clinical evidence. Further studies with appropriate study design are needed to determine whether legionella infection is an occupational risk for HCWs.

Epidemiology and direct health care costs of hospitalised legionellosis in New Zealand, 2000-2020.

BACKGROUND: Legionellosis is a collective term used for disease caused by Legionella species which result in community and hospital acquired pneumonia worldwide. The aim of this analysis was to describe the epidemiology of legionellosis hospitalisations in Aotearoa New Zealand (NZ) over a 21-year period and quantify the health care costs. METHOD: This study combined national legionellosis notification and hospital discharge data that were linked via the National Health Index (NHI) to provide a more complete dataset of hospitalised cases. The direct cost of hospital care was estimated by multiplying the diagnosis-related group cost-weight by the national price and inflating to 2020/2021 values. RESULTS: There were 1479 records matched across notifications and discharge databases, including 990 with principal and 489 with additional diagnosis of legionellosis. Incidence rose to an average of 143 cases per annum for 2016-2020, a rate of 3·2/100,000. The median LOS was 6 days (IQR 4-13·5) with direct costs of $2·1 million per annum over that period. Rates were highest in those aged 65 years and above, male, and of European/Other ethnicity. Hospitalisations showed a peak in spring and summer. CONCLUSION: The rate of hospitalised legionellosis in New Zealand rose from 2000 to 2015, largely reflecting improved diagnosis. This preventable disease results in substantial health care costs. Greater efforts are needed to identify and control sources of exposure. Surveillance could be improved by routine integration of notification and hospital discharge data.

Effect of the COVID-19 pandemic and state of emergency declarations on the relative incidence of legionellosis and invasive pneumococcal disease in Japan.

INTRODUCTION: During the COVID-19 pandemic, the incidence of many droplet-transmitted infections decreased due to increased mask-wearing and social distancing. Contrastingly, there has been concern that COVID-19 countermeasures, such as lockdowns, may increase legionellosis incidence via water stagnation. During the pandemic in Japan, four state of emergency declarations were imposed between 2020 and 2021, which makes it particularly suitable to test this hypothesis. METHODS: We use country-level surveillance data from the National Institute of Infectious Diseases to track the relative incidence of legionellosis compared to invasive pneumococcal disease (IPD) during the COVID-19 pandemic in Japan, with a focus on the periods just after state of emergency declarations were lifted. RESULTS: The absolute number of legionellosis and IPD cases decreased in 2020 and 2021 compared to previous years. The average relative incidence of legionellosis as well as the variance of the relative incidence significantly increased during the pandemic compared to previous years. There were no increases in the relative incidence of legionellosis during the periods immediately following emergency declaration liftings, but the relative incidence did increase considerably during the first two states of emergency. CONCLUSIONS: COVID-19 countermeasures appear more effective at decreasing the incidence of human-to-human transmitted infections, such as IPD, compared to environmentally-transmitted infections, such as legionellosis. Though no evidence was found to suggest that legionellosis cases increased after state of emergency declarations, public health efforts should continue to emphasize the importance of routine sanitation and water system maintenance to prevent water stagnation and Legionella spp. contamination.

Environmental Investigation during Legionellosis Outbreak, Montérégie, Quebec, Canada, 2021.

In August 2021, a legionellosis outbreak involving 7 persons occurred within a 500-meter radius in the Montérégie region of Québec, Canada. Near real-time modeling of wind direction along with epidemiologic and environmental investigations identified the possible source. Modeling wind direction could help identify likely Legionella pneumophila sources during legionellosis outbreaks.

Epidemiological and clinical characteristics of legionellosis in Northern Australia, 2010-2021.

Objective: This study describes characteristics of the legionellosis cases occurring between 2010 and 2021 in the Northern Territory (NT), Australia. Methods: We retrospectively reviewed 53 cases of legionellosis during the defined period and documented patient and clinical characteristics, diagnostics, and seasonality of infection. Results: All cases were sporadic. The incidence rate in the NT was higher than the Australian median rate (2.1 and 1.5 per 100,000 population per year respectively). Aboriginal and Torres Strait Islander patients presented at a younger age than did non-Indigenous patients (median 41 and 60 years of age respectively), and overall there was a male preponderance. There was a higher proportion of legionellosis in the months with increased humidity, with a greater number of L. longbeachae infections detected overall (59%) than of L. pneumophila (41%). The majority of cases were diagnosed serologically (57% of L. pneumophilia and 93% of L. longbeachae ). Conclusions: Legionellosis in the NT is more common, seasonal, and may be underreported due to current reliance on serological testing for diagnosis. The higher incidence of legionellosis, and the younger age of Aboriginal and Torres Strait Islander patients of the NT, have public health implications, given that the clinical presentation of legionellosis is indistinguishable from other forms of pneumonia.

Characterization of reported legionellosis outbreaks associated with buildings served by public drinking water systems: United States, 2001-2017.

This study examined 184 legionellosis outbreaks in the United States reported to the Centers for Disease Control and Prevention's Waterborne Disease and Outbreak Surveillance System, from 2001 to 2017. Drinking water characteristics examined include source water type, disinfectant type, exposure setting, geographical distribution by U.S. Census Divisions, and the public water system size (population served). This study found that most of the reported drinking water-associated legionellosis outbreaks occurred in eastern United States, including 35% in the South Atlantic, 32% in the Middle Atlantic, and 16% in the East North Central Census Divisions were linked with building water systems in healthcare and hotel settings; and were associated with buildings receiving drinking water from public water systems serving >10,000 people. Targeted evaluations and interventions may be useful to further determine the combination of factors, such as disinfectant residual type and drinking water system size that may lead to legionellosis outbreaks.

Development and Evaluation of Statewide Prospective Spatiotemporal Legionellosis Cluster Surveillance, New Jersey, USA.

Incidence of Legionnaires' disease is increasing, particularly in the Mid-Atlantic states in the United States; since 2015, New Jersey has documented ≈250-350 legionellosis cases per year. We used SaTScan software to develop a semiautomated surveillance tool for prospectively detecting legionellosis clusters in New Jersey. We varied temporal window size and baseline period to evaluate optimal parameter selections. The surveillance system detected 3 community clusters of Legionnaires' disease that were subsequently investigated. Other, smaller clusters were detected, but standard epidemiologic data did not identify common sources or new cases. The semiautomated processing is straightforward and replicable in other jurisdictions, likely by persons with even basic programming skills.

Global Perspective of Legionella Infection in Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis of Observational Studies.

Legionnaires' disease (LD) (Legionella) is a common cause of community-acquired pneumonia (CAP) in those requiring hospitalization. Geographical variation in the importance of Legionella species as an aetiologic agent of CAP is poorly understood. We performed a systematic review and meta-analysis of population-based observational studies that reported the proportion of Legionella infection in patients with CAP (1 January 1990 to 31 May 2020). Using five electronic databases, articles were identified, appraised and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Univariate and multivariate meta-regression analyses were conducted using study design, WHO region, study quality and healthcare setting as the explanatory variables. We reviewed 2778 studies, of which 219 were included in the meta-analysis. The mean incidence of CAP was 46.7/100,000 population (95% CI: 46.6-46.8). The mean proportion of Legionella as the causative agent for CAP was 4.6% (95% CI: 4.4 to 4.7). Consequently, the mean Legionella incidence rate was 2.8/100,000 population (95% CI: 2.7-2.9). There was significant heterogeneity across all studies I2 = 99.27% (p < 0.0001). After outliers were removed, there was a decrease in the heterogeneity (I2 = 43.53%). Legionella contribution to CAP has a global distribution. Although the rates appear highest in high income countries in temperate regions, there are insufficient studies from low- and middle-income countries to draw conclusions about the rates in these regions. Nevertheless, this study provides an estimate of the mean incidence of Legionella infection in CAP, which could be used to estimate the regional and global burden of LD to support efforts to reduce the impact of this infection as well as to fill important knowledge gaps.

Diagnostic accuracy of urinary antigen tests for legionellosis: A systematic review and meta-analysis.

BACKGROUND: Urinary antigen tests (UATs) have been used for the early detection of legionellosis and have demonstrated moderate sensitivity and high specificity. However, the most recent systematic review and meta-analysis published in 2009 evaluated the accuracy of UATs; since then, UAT accuracy may have changed owing to advances and developments in UAT technology and epidemiological changes in the frequency of Legionella species that cause legionellosis. Therefore, this systematic review and meta-analysis aimed to update the accuracy of UATs for legionellosis among patients with suspected pneumonia. METHODS: Overall, 1326 studies were screened, 21 of which fulfilled the eligibility criteria for quality assessment and meta-analysis. Data from 5772 patients, including 1368 (23.7%) with the target condition (i.e., suspected legionellosis), were included in the analysis. The overall quality of the included studies, which was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, was unclear. RESULTS: The calculated pooled sensitivity and specificity were 0.79 (95% confidence interval [CI], 0.71-0.85) and 1.00 (95% CI, 0.99-1.00), respectively. Subpopulation analysis revealed that the accuracy of UATs for sensitivity and specificity for Legionella pneumophilia serogroup 1 was 0.86 (95% CI, 0.78-0.91) and 1.00 (95% CI, 0.99-1.00), respectively. CONCLUSIONS: This study demonstrated that the sensitivity and specificity of UATs were moderate and high, respectively, which is comparable to the results reported in 2009. Therefore, UATs may be a useful method for the early detection of legionellosis caused by Legionella pneumophila serogroup 1. CLINICAL TRIAL REGISTRATION: The review protocol was prospectively registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000041080).