Source attribution of community-acquired cases of Legionnaires’ disease–results from the German LeTriWa study; Berlin, 2016–2019
Authors: Buchholz Udo , Jahn Heiko Juergen , Brodhun Bonita , Lehfeld Ann-Sophie , Lewandowsky Marina M. , Reber Franziska , Adler Kristin , Bochmann Jacqueline , Förster Christina , Koch Madlen , Schreiner Yvonne , Stemmler Fabian , Gagell Corinna , Harbich Edith , Bärwolff Sina , Beyer Andreas , Geuß-Fosu Ute , Hänel Martina , Larscheid Patrick , Murajda Lukas , Morawski Klaus , Peters Uwe , Pitzing Raimund , von Welczeck Andreas , Widders Gudrun , Wischnewski Nicoletta , Abdelgawad Inas , Hinzmann Anke , Hedeler Denis , Schilling Birte , Schmidt Silvia , Schumacher Jakob , Zuschneid Irina , Atmowihardjo Iskandar , Arastéh Keikawus , Behrens Steffen , Creutz Petra , Elias Johannes , Gregor Martina , Kahl Stefan , Kahnert Henning , Kimmel Viktor , Lehmke Josefa , Migaud Pascal , Mikolajewska Agata , Moos Verena , Naumann Maria-Barbara , Pankow Wulf , Scherübl Hans , Schmidt Bernd , Schneider Thomas , Stocker Hartmut , Suttorp Norbert , Thiemig Dorina , Gollnisch Carsten , Mannschatz Uwe , Haas Walter , Schaefer Benedikt , Lück Christian 
Published: November 2020

Introduction
Sources of infection of most cases of community-acquired Legionnaires’ disease (CALD) are unknown.

Objective
Identification of sources of infection of CALD.

Setting
Berlin; December 2016–May 2019.

Participants
Adult cases of CALD reported to district health authorities and consenting to the study; age and hospital matched controls.

Main outcome measure
Percentage of cases of CALD with attributed source of infection.

Methods
Analysis of secondary patient samples for monoclonal antibody (MAb) type (and sequence type); questionnaire-based interviews, analysis of standard household water samples for Legionella concentration followed by MAb (and sequence) typing of Legionella pneumophila serogroup 1 (Lp1) isolates; among cases taking of additional water samples to identify the infectious source as appropriate; recruitment of control persons for comparison of exposure history and Legionella in standard household water samples. For each case an appraisal matrix was filled in to attribute any of three source types (external (non-residence) source, residential non-drinking water (RnDW) source (not directly from drinking water outlet), residential drinking water (RDW) as source) using three evidence types (microbiological results, cluster evidence, analytical-comparative evidence (using added information from controls)).

Results
Inclusion of 111 study cases and 202 controls. Median age of cases was 67 years (range 25–93 years), 74 (67%) were male. Among 65 patients with urine typable for MAb type we found a MAb 3/1-positive strain in all of them. Compared to controls being a case was not associated with a higher Legionella concentration in standard household water samples, however, the presence of a MAb 3/1-positive strain was significantly associated (odds ratio (OR) = 4.9, 95% confidence interval (CI) 1.7 to 11). Thus, a source was attributed by microbiological evidence if it contained a MAb 3/1-positive strain. A source was attributed by cluster evidence if at least two cases were exposed to the same source. Statistically significant general source types were attributed by calculating the population attributable risk (analytical-comparative evidence). We identified an external source in 16 (14%) cases, and RDW as source in 28 (25%). Wearing inadequately disinfected dentures was the only RnDW source significantly associated with cases (OR = 3.2, 95% CI 1.3 to 7.8) and led to an additional 8% of cases with source attribution, for a total of 48% of cases attributed.

Conclusion
Using the appraisal matrix we attributed almost half of all cases of CALD to an infectious source, predominantly RDW. Risk for LD seems to be conferred primarily by the type of Legionella rather than the amount. Dentures as a new infectious source needs further, in particular, integrated microbiological, molecular and epidemiological confirmation.