key: cord-0733766-p4ef26qx
authors: Ye, Jung-Jr; Zheng, Jun-Yuan; Chen, Ya-Hsuan; Kao, Ya-Ling; Kao, Yu-Chin; Chao, Shao-Wen
title: Investigation of a cluster of Legionnaires’ disease during the outbreak of coronavirus disease 2019 pandemic in northeastern Taiwan, June 2021
date: 2022-05-05
journal: J Microbiol Immunol Infect
DOI: 10.1016/j.jmii.2022.04.008
sha: 51be564c83999e77f744696edb633f8d56fbacff
doc_id: 733766
cord_uid: p4ef26qx

Purpose To describe the investigation and intervention of a cluster of Legionnaires’ disease detected during the outbreak of coronavirus disease 2019 (COVID-19) pandemic. Methods From June 7 to 22, 2021, 15 cases in the neighborhood near our hospital were detected. Information about residence, workplace, hospital visit, and potential exposures was collected. Sampling and decontamination were performed for potential sources. Results All 15 patients had pneumonia when visiting the emergency room with negative COVID-19 test results. Most patients were male (73.3%) with the mean age of 65.7 years. The most common comorbidities were diabetes mellitus (40.0%) and hypertension (40%). The most common symptom was fever (93.3%). Two (13.3%) patients needed mechanical ventilators. Fever subsided within 2 days of treatment for most cases (85.7%). Five cases had exposure history at our hospital, and the other 10 lived or worked in the area within 2 kilometers of our hospital, mostly in buildings A and B. Water sampling was carried out for our hospital, buildings A and B; one water sample from a cooling tower in our hospital cultured positive for Legionella bacteria. Early testing and treatment for suspected cases were carried out for the outbreak, and all cases were discharged with pneumonia resolution. Conclusion This was a community outbreak of Legionnaires’ disease near our hospital. COVID-19 tests were repeated frequently before testing for Legionnaires’ disease during the COVID-19 pandemic. Early recognition of Legionnaires’ disease and timely treatment improved outcome.

Legionnaires' disease was first identified in 1976 in a pneumonia outbreak among American Legion members attending their annual meeting in Philadelphia. 1 Infection occurs through inhalation of aerosols containing Legionella bacteria. 2 The most frequently identified species isolated from patients with Legionnaires' disease was Legionella pneumophila serogroup 1, which has been recognized as an important cause of both hospital and community-acquired pneumonia. 2 A prior epidemiological study of Legionella pneumophila infection in Taiwan reported an incidence rate of 4.7% among pneumonia patients. 3 In a retrospective study of Legionnaires' disease in a 1200-bed tertiary hospital in southern Taiwan, 61 cases were identified over a 9-year period. Among them, 30 (49.2%) and 20 (32.8%) had healthcareassociated and community-acquired pneumonia, respectively, including 11 (18.0%) caregivers. 4 Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in Wuhan, China, in December 2019. 5 The disease rapidly became an ongoing pandemic crisis worldwide. 6 The pandemic had a smaller impact in Taiwan in 2020 than in most other countries; however, an outbreak in northern Taiwan occurred in May 2021, resulting in more than 15000 confirmed cases with more than 800 deaths within the following three months.

In June 2021, we detected a cluster of Legionnaires' disease during the COVID-19 pandemic. From June 7 to 22, 2021, 15 Legionnaires' disease cases were detected in individuals living or working in the neighborhood near our hospital, including two hospital staff members. This number was three times that observed in our hospital in the previous 3 years combined, including 2 cases, 2 cases, and 1 case detected in 2018, 2019, and 2020, respectively (JJ Ye, unpublished data). This study aimed to determine whether this cluster was a nosocomial or community outbreak, investigate the potential sources, and analyze the clinical features, control measures and outcomes.

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This retrospective study was conducted at Chang Gung Memorial Hospital (CGMH)-Keelung branch, which is a 1100-bed regional teaching hospital providing both primary and tertiary health care in northeastern Taiwan. The study protocol was approved by the Institutional Review Board of CGMH-Keelung branch (Number: 202101475B0). The ethics committee granted a waiver for informed consent to be obtained from patients because the existing medical data and investigation reports were analyzed anonymously and maintained with confidentiality.

Legionnaires' disease was defined as a new or progressive pulmonary infiltrate on chest radiography, along with the presence of symptoms and signs of lower respiratory tract infection, and a positive result for the urinary Legionella antigen test. 4 A commercial urine antigen test (Abbott BinaxNOW Legionella urinary antigen test kit; Abbott Laboratories,

The epidemiological investigations were performed by the Infection Control Team of CGMH-Keelung as soon as possible after a diagnosis was confirmed. Each patient was interviewed by phone to collect information about residence, profession, workplace, and potential exposures (including travel, hospital visit, spa/ pool, fountains, grocery stores, drinking water supply issues, car washes, and aerosol-generating devices or equipment) within 14 days prior to symptom onset. The data of urinary Legionella antigen test in the previous 5 years, and the number of confirmed COVID-19 cases with positive reverse transcription-polymerase chain reaction (RT-PCR) test based on nasopharyngeal swabs in our hospital from April to July 2021 were collected and analyzed.

Routine testing for Legionella bacteria with culture and free residual chlorine in water was performed in our hospital every six months for cooling towers and the water supply system in transplant wards, and annually for other water supply systems. A 300 ml water sample was collected from selected sites for culture and testing. The most recent routine testing prior to the reported Legionnaires' disease outbreak was performed in April 2020, and all water samples were negative for Legionella bacteria. To investigate potential sources of the reported cluster of Legionnaires' disease, water sampling was carried out by the Infection from faucets in toilets, 2 from water dispensers, and 2 swab samples from air conditioner vents. Thirty-six water samples from building A included 2 from water cooling towers, 17 from cisterns; 9 from garden ponds, fountains, and sprinklers; 5 from bathrooms and 3 from water dispensers. Four water samples from building B included 1 from a garden pond and 3 from cisterns. Each sample was cultured on the media of buffered charcoal yeast extract (BCYE) agar. Colonies suspected to be Legionella were incubated on BCYE agar with Lcysteine. 7 Microscopic examination was used to verify suspect colonies. Identification of isolates was performed using Matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS, Autoflex II; Bruker Daltonics, Germany) and MALDI Biotyper 3.1 database system. Samples from our hospital and administrative office were also tested with RT-PCR targeting major intrinsic protein (MIP) gene.

All patients presented with pneumonia on chest radiograph when arriving at the emergency room (ER), and were then admitted to wards for treatment. Most patients were male (73.3%) with mean age 65.7 years. The most common concomitant diseases were diabetes mellitus (40.0%) and hypertension (40%). Fourteen patients had no smoking history and one had quit smoking years earlier. The most common symptom was fever (93.3%), followed by cough (66.7%) and gastrointestinal upset (26.7%) ( Table 3 ). The days from symptom onset to hospital visit ranged from 1 to 5 days, with mean 2.3 days (Tables 1, 3) . Five (33.3%) patients had bilateral pneumonia and 13 patients had mean C-reactive protein (CRP) of 226.0 mg/L.

Other abnormal laboratory data included hyponatremia (60%), elevated liver enzymes (40%) and leukocytosis (40%). Three patients used O2 masks and two used mechanical ventilators (Table 3 ). The days from hospitalization to diagnosis ranged from 1 to 9 days with mean 3.5 days (Tables 2, 3 ). One patient with 9 days until diagnosis had end-stage renal disease with insufficient urine for urinary antigen test. Thirteen cases were treated with levofloxacin, two received azithromycin for pneumonia treatment, and four (26.7%) received delayed treatment. Fever subsided within two days of treatment for most cases (12/14, 85.7%) and all patients were discharged with resolution of pneumonia ( Table 3 ). The hospital stays ranged J o u r n a l P r e -p r o o f from three to 58 days with mean 13.7 days (Tables 2, 3 ). All cases had at least two negative COVID-19 RT-PCR test results based on nasopharyngeal swabs. Nine cases had sputum cultures and all showed growth of normal flora (Table 2 )

Symptom onset date of cases are shown in Figure 1 . The dates of diagnosis are shown in Figure 2 ). We also advised clinical physicians, in online conferences or meetings, to administer levofloxacin or azithromycin early for suspected cases before Legionnaires' disease was confirmed. Decontamination was carried out for the water cooling towers and cisterns in our hospital on June 17, 2021, and for water systems in other buildings later. The cooling towers were shut down and sodium hypochlorite was added to keep free residual chlorine of at least 5 -15 mg/L for at least 1 hour. After the disinfection period, the cooling tower water was drained into waste disposal, and all accessible system equipment J o u r n a l P r e -p r o o f was physically cleaned. Then the system was refilled with clean water, the recirculating pump was switched on, and sodium hypochlorite was added again. The system was drained after the disinfection period and refilled. Finally, we reinstated comprehensive effective water treatment, including use of biocide, and returned the control equipment to normal operation. including outdoors, and all swimming pools, water parks, spas, or entertainment places were ordered to be closed. Several reports mentioned that Legionnaires' disease cases may increase in recently reopened buildings during the COVID-19 pandemic, probably due to growth of Legionella in low-flow water pipes with inadequate disinfection. 14-16 However, this was not the situation of our cluster. After decontamination of the water cooling towers and cisterns in the potential sources, no additional cases were reported.

disease. During the COVID-19 pandemic, all pneumonia patients must be admitted via ER to isolated wards, and tested for COVID-19 repeatedly. The American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) guidelines for community-acquired pneumonia recommend that only severe cases be tested with Legionella urinary antigen test or those with epidemiological indications, 17 and our first six cases required more days for diagnosis and initiation of treatment for Legionnaires' disease than the cases that followed.

Cases 2 and 5 needed mechanical ventilator use, and Legionnaires' disease was tested and confirmed after respiratory failure. When the outbreak was observed, we informed clinicians at ER and wards to perform Legionella urinary antigen tests for all pneumonia patients, and this helped to shorten the time for diagnosis. Early empiric use of fluoroquinolones or macrolides to cover suspected Legionnaires' cases was also carried out based on ATS/IDSA guidelines, 17 In prior studies of community-acquired Legionnaires' disease in Taiwan, the mortality rates ranged from 9.8% to 24.1%, and ventilator use rates ranged from 18.4% to 50%. 4, [18] [19] [20] [21] The characteristics, comorbidities, and initial presentations of our cases were similar to those reported in previous studies. Most patients were older adult males with underlying diseases, including diabetes mellitus, hypertension, or malignancy. Fever, cough, and gastrointestinal upset were common, with abnormal laboratory findings, including leukocytosis, hyponatremia, increasing liver enzymes, and high CRP levels. Smoking history was common in prior studies; 4, 18-21 however, only one case among those in the present study had smoking history. Among studies in Taiwan, about 70% of patients had bilateral pneumonia, 20, 21 but other studies showed that the most common pattern was patchy, unilobar infiltrate progressing to consolidation of the lung tissue. 22, 23 Compared with other studies in Taiwan, patients in the present study had lower rates of mortality and ventilator use, and most cases (10/15, 66.7%) had unilateral pneumonia. With proactive screening for Legionnaires' disease during the outbreak, more cases may be detected with minor severity or at an early stage than prior studies in Taiwan This study has several limitations. First, blood and respiratory samples were not collected from these cases for culture and isolation, and serogroup or sequence-based typing was not performed. Therefore, we do not know if these cases were caused by the same strain, or whether the strain detected in the cooling tower in our hospital was at cause. Another important challenge was the lack of comprehensive investigation of potential sources. Water samples were only collected from our hospital and buildings A and B, and other public and private construction sites or water systems in this area were not investigated. As a result, some potential sources may have been overlooked.

In conclusion, this study examined and reported a community outbreak of Legionnaires' disease in the neighborhood around our hospital. COVID-19 testing was repeated frequently before testing for Legionnaires' disease during the COVID-19 pandemic. Early recognition of Legionnaires' disease, detecting the outbreak, and providing timely treatment and intervention improved the individual and overall outcomes. J o u r n a l P r e -p r o o f 

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The authors declare that they have no competing interests. No funding sources had any role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript.J o u r n a l P r e -p r o o f