SURVEILLANCE REPORT. Legionnaires disease in Europe.

Transcription

1 SURVEILLANCE REPORT Legioaires disease i Europe

2 ECDC SURVEILLANCE REPORT Legioaires disease i Europe 2009

3 This report of the Europea Cetre for Disease Prevetio ad Cotrol (ECDC) was writte by Phillip Zucs. Ackowledgemets The author would like to thak all ELDSNet members for their hard work ad dedicatio i reportig atioal Legioaires disease data ad reviewig this report. Suggested citatio: Europea Cetre for Disease Prevetio ad Cotrol. Legioaires disease i Europe Stockholm: ECDC; Stockholm, September 2011 ISBN doi /58495 Europea Cetre for Disease Prevetio ad Cotrol, 2011 Reproductio is authorised, provided the source is ackowledged.

4 SURVEILLANCE REPORT Legioaires disease i Europe 2009 Table of cotets 1 Backgroud Methods Time, place ad subject uder surveillace Data aalysis Results Cases Data completeess Case classificatio ad otificatio rate Time ad place Age ad geder Presumable settig of ifectio Laboratory data Evirometal ivestigatio Deaths Case-fatality ratio, case classificatio ad mortality otificatio rate Time ad place Age ad geder Settig Laboratory data Cluster status Diagostic delay Adjusted predictors of fatal outcome i cofirmed cases Clusters Frequecy, size, classificatio ad outcome Time ad place Age ad geder Settig Laboratory data Evirometal ivestigatio Adjusted predictors of clusterig i cofirmed cases Discussio Coclusios for Europea Legioaires disease surveillace Refereces Aex iii

5 Legioaires disease i Europe 2009 SURVEILLANCE REPORT Abbreviatios CFR CI ECDC EEA ELDSNet EQA EU EWGLINET OR PCR ROC TESSy Case-fatality ratio Cofidece iterval Europea Cetre for Disease Prevetio ad Cotrol Europea Ecoomic Area Europea Legioaires Disease Surveillace Network Exteral quality assurace Europea Uio Europea Surveillace Scheme for Travel Associated Legioaires Disease Odds ratio Polymerase chai reactio Receiver operatig characteristic The Europea Surveillace System iv

6 SURVEILLANCE REPORT Legioaires disease i Europe 2009 Executive summary This surveillace report is based o Legioaires disease surveillace data collected from 25 EU Member States, Icelad ad Norway for Altogether, cofirmed ad probable cases of Legioaires disease were reported, resultig i a otificatio rate of 11.2 cases per millio populatio. The slightly decreasig tred observed sice 2006 was maitaied, the otificatio rate remaiig cosiderably below the estimated Europea icidece rate of 100 per millio. Natioal otificatio rates raged from close to zero i Polad, Romaia ad Slovakia to 32 per millio i Sloveia, with Frace, Italy ad Spai accoutig for 66 of reported cases. The peak moth of oset of Legioaires disease was September, with more tha half of the cases experiecig their symptom oset betwee July ad October. Sevety-seve percet of all cases were 50 years or older. I both geders, the otificatio rate icreased with age. Overall, males were almost three times more frequetly otified with Legioaires disease tha were females. More tha two thirds of cases were reported to have bee commuity-acquired. They were followed i decreasig frequecy by cases presumably ifected while travellig domestically, travellig abroad, stayig i a hospital or ifected while exposed to a o-hospital healthcare settig. Overall, 82 of cases were cofirmed by uriary atige detectio ad 9 by culture. Coutries joiig the EU/EEA after 2000 proved more likely ot to report ay cofirmatio by culture or polymerase chai reactio, but to have verified the majority of their cases by a sigle high atibody titre. Although the curret EU case defiitio for Legioaires disease accepts cases verified by sigle high titres as probable cases, these should be treated with cautio give the relatively high backgroud prevalece of such titres i some coutries ad the kow serological cross-reactivity of Legioella with other bacteria. Of the culture-cofirmed cases, 99.1 were due to Legioella peumophila ad 87.6 to L. peumophila serogroup 1. A evirometal ivestigatio was carried out i 17 of cases with available iformatio. The likelihood of such a ivestigatio was two times higher i fatal compared with o-fatal cases ad 12 times higher i clustered compared with sporadic cases. The reported overall case fatality of 11 was well withi the expected rage. I decreasig order of magitude of associatio, L. peumophila serogroups 6 ad 10, older age ad reportig coutry with low outcome reportig were foud to be idepedet predictors of fatal outcome i cofirmed cases of Legioaires disease. Oset of disease i autum ad witer icreased the effect of the ifectio settig o disease outcome i commuity-acquired ad travel-associated cases, but ot i healthcare-associated cases. Geder was ot idepedetly associated with fatal outcome. The 27 EU/EEA Member States reported 101 clusters of Legioaires disease ivolvig 254 cases. The proportio of clustered cases represeted 6.5 of all cases ad the average cluster size was two cases to each cluster, cotiuig a tred i cluster size that had bee decreasig sice a peak i I decreasig order of magitude of associatio, reportig coutry with icomplete cluster status reportig, travel history ad patiet age betwee 60 ad 79 years were foud to be idepedet predictors of clusterig i cofirmed cases of Legioaires disease. Geder was ot idepedetly associated with clusterig. Causative Legioella species ad serogroup could ot be cotrolled for sice all clustered cofirmed cases with available iformatio had bee due to L. peumophila serogroup 1 (or ukow serogroup). This data aalysis has two importat limitatios. Firstly, it is based o data from passive surveillace systems with rather icomplete reportig o some variables. Cliical outcome ad cluster status were reported as ukow for approximately 30 of cases of Legioaires disease i Whether or ot a evirometal ivestigatio was carried out was reported as ukow for 60 of the cases. Secodly, ELDSNet curretly does ot collect data o risk factors such as uderlyig coditios or smokig status, although they are crucial i uderstadig ad explaiig the epidemiology of Legioaires disease, especially its more severe outcomes. Member States are well advised to thik about ways to either itegrate cluster ad evirometal ivestigatio status, as well as sequece-based typig results, i their case databases or use record likage methods to provide more complete iformatio. Coutries should also explore the possibility of ecouragig relevat updates from their local ad regioal levels of public health admiistratio for more complete reportig of cliical outcome. ELDSNet should cosider idetifyig EU/EEA Member States that are already collectig uderlyig coditios ad smokig status as part of their routie Legioaires disease surveillace ad discuss the best way for them to report these importat data to the Europea level. Sice Europea retrospective passive Legioaires disease surveillace i aual itervals caot be primarily geared towards fast-paced outbreak detectio ad cotrol, a importat strategic goal to cosider could be to icrease the ascertaimet of cases of Legioaires disease, agreeig withi ELDSNet o a otificatio rate (e.g. 100 cases per millio populatio) as the target for Europe ad moitorig the progress every year. 1

7 Legioaires disease i Europe 2009 SURVEILLANCE REPORT 1 Backgroud As a ifectio, Legioaires disease is exceptioal: it is ot trasmitted from huma to huma but through Legioella-cotamiated aerosols emaatig from ma-made water systems [1]. Legioaires disease has bee foud to accout for up to 4 of commuity-acquired [2] ad osocomial peumoia [3]. I commuity-acquired cases, Legioaires disease frequetly leads to hospitalisatio ad has bee associated with a case fatality of 9 13 i Cataloia [4] ad Frech [5] surveillace data spaig at least a decade. It was first described as a separate cliical etity i the aftermath of a large outbreak [6], ad there have bee several more large outbreaks sice [7-9], attractig much professioal ad public attetio. Legioaires disease is otifiable at atioal level i all Member States of the Europea Uio (EU) ad the Europea Ecoomic Area (EEA). It is also otifiable at Europea level [10]. Util 2010, Europea Legioaires disease surveillace was carried out by the Europea Surveillace Scheme for Travel Associated Legioaires Disease (EWGLINET). From 1995 owards, this etwork also collected, aalysed ad published aggregate aual data of all cases of Legioaires disease that had bee reported i the Member States, regardless of their travel history. Sice April 2010, the etwork is coordiated by the Europea Cetre for Disease Prevetio ad Cotrol (ECDC). Its ew ame, Europea Legioaires Disease Surveillace Network (ELDSNet), ad the chage from collectig aggregate to collectig disaggregate data reflects the itetio to ehace geeral Legioaires disease surveillace ad put it o a more equal footig with the surveillace of travel-associated cases. This is the first detailed aual Legioaires disease surveillace report published by ECDC. 2

8 SURVEILLANCE REPORT Legioaires disease i Europe Methods 2.1 Time, place ad subject uder surveillace The data electroically trasmitted from the omiated ELDSNet members i each coutry to the Europea Surveillace System (TESSy) database icluded all cases of Legioaires disease that had bee reported to the 27 EU Member States, Icelad ad Norway i To be take ito accout, the cases had to meet the cliical, laboratory ad epidemiologic criteria laid dow i the EU case defiitio for cofirmed ad probable cases of Legioaires disease (see page 4)[11]. Travel-associated cases were to be reported oly by their coutries of residece. Cases were to be classified as travel-associated if they had stayed at a accommodatio site away from home durig their icubatio period of two to 10 days prior to fallig ill. Cases were to be reported as havig formed part of a cluster if they had bee exposed to the same suspected source as at least oe other case with their dates of oset o more apart tha two years. The other cluster case(s) did ot have to have occurred i Data aalysis To be icluded, cases ot oly had to be reported as fulfillig the EU case defiitio; the report also had to provide the iformatio o the method used for diagostic laboratory testig that would support the case classificatio. To esure that the data aalysis at Europea level is doe based o the same date ad thus the same umber of cases as i each Member State, etwork members report their so-called date used for statistics which ca be the date of oset, diagosis or otificatio. This aalysis was restricted to cases with a date used for statistics from The distributio of all cases ad of the subsets of fatal ad cluster cases by relevat idepedet variables was described. Uivariate aalysis served to scree the data for possible associatios betwee these idepedet variables ad the outcomes death ad clusterig. Fially, logistic regressio modellig was used to adjust these associatios for cofoudig. The models were fitted to cofirmed cases by forward selectio of variables testig sigificat at p = 0.05 by Wald test for dichotomous variables or by likelihood ratio test for omial variables with more tha two categories ad for iteractio terms. Each model s goodess-of-fit was assessed by the area uder the receiver operatig characteristic (ROC) curve plottig the model s sesitivity agaist the proportio of false positives with regard to the outcome. Associatios betwee idepedet ad outcome variables were quatified by estimatig odds ratios (OR) ad calculatig their 95 cofidece itervals (CI). All aalyses were carried out based o the cases where the variable(s) ivolved had o missig values. 3

9 Legioaires disease i Europe 2009 SURVEILLANCE REPORT EU case defiitio of Legioaires disease [11] Cliical criteria: Ay perso with peumoia. Laboratory criteria for case cofirmatio: At least oe of the followig three: Isolatio of Legioella spp. from respiratory secretios or ay ormally sterile site; Detectio of Legioella peumophila atige i urie; Legioella peumophila serogroup 1 specific atibody respose. Laboratory criteria for a probable case: At least oe of the followig four: Detectio of Legioella peumophila atige i respiratory secretios or lug tissue, e.g. by DFA staiig usig moocloal-atibody derived reagets; Detectio of Legioella spp. ucleic acid i a cliical specime; Legioella peumophila o-serogroup 1 or other Legioella spp. specific atibody respose; L. peumophila serogroup 1, other serogroups or other Legioella species: sigle high titre i specific serum atibody. Epidemiological criteria: At least oe of the followig two epidemiological liks: Evirometal exposure; Exposure to the same commo source. Case classificatio Possible case NA Probable case Ay perso meetig the cliical criteria AND at least oe positive laboratory test for a probable case OR a epidemiological lik. Cofirmed case Ay perso meetig the cliical ad the laboratory criteria for case cofirmatio. 4

10 SURVEILLANCE REPORT Legioaires disease i Europe Results 3.1 Cases For 2009, the 29 ELDSNet Member States reported cases of Legioaires disease, 38 of which had to be excluded due to missig iformatio o the diagostic laboratory tests used. Amog the excluded cases were all cases reported from Cyprus (=3) ad the Czech Republic (=20) sice both coutries supplied the missig iformatio oly several moths after the reportig deadlie Data completeess Reportig was more tha 90 complete for date of oset, age, geder, importatio status, probable coutry of ifectio, causative pathoge, ad evirometal fidigs ad positive samplig site wheever a evirometal ivestigatio had bee carried out (Table 1). Reportig was 60 to 90 complete for outcome, cluster status, exposure settig ad matchig cliical ad evirometal isolates. Reportig was 40 complete for evirometal ivestigatio status, ad less tha 1 complete for sequece-based typig results. Table 1 Completeess of reportig i 26 coutries by variable Variable Miimum Maximum Overall completeess Completeess Coutries Completeess Coutries Date of oset Age Geder Outcome Cluster Cluster Id a Imported Probable coutry of ifectio b Pathoge Sequece type Settig Evirometal ivestigatio Legioella foud c Positive samplig site d Matchig isolates e a Completeess determied i cases reported to have formed part of a cluster. b Completeess determied i cases reported to have bee imported. c Completeess determied i cases reported to have prompted a evirometal ivestigatio. d Completeess determied i cases for which positive fidigs i a evirometal ivestigatio were reported. e Completeess determied i cases reported to have prompted a evirometal ivestigatio Case classificatio ad otificatio rate Of the cases icluded i the aalysis, (92.2) met the EU defiitio of cofirmed cases ad 429 (7.8) were probable cases. All probable cases were based o laboratory criteria, i.e. oe of them was defied purely o epidemiologic grouds (cotact with a cofirmed case or exposure to a eviromet with laboratorycofirmed presece of Legioella). The otificatio rate i 2009 amouted to 11.2 per populatio, cotiuig the slight decreasig tred observed sice 2006 (Figure 1) Time ad place Of cases of Legioaires disease reported with a date of oset, betwee 197 ad 773 cases occurred each moth. The distributio showed a peak i September, as typically see with this disease, ad 50.6 of all cases experieced their symptom oset betwee July ad October (Figure 2). The cases were reported by 27 EU ad EEA Member States, with Frace, Italy ad Spai accoutig for Natioal otificatio rates raged from close to zero i Polad, Romaia ad Slovakia to 32 per i Sloveia (Table 2). The mea 5

11 Legioaires disease i Europe 2009 SURVEILLANCE REPORT otificatio rate was seve times higher i coutries that joied the EU/EEA before 2000 (13.4/ , 95 CI ) tha i those joiig after (1.8/ , 95 CI ). Figure 1 Reported cases ad otificatio rate of Legioaires disease i the EU/EEA a by year of reportig, / / Participatig coutries (), by year b a EWGLINET member coutries ot belogig to the EU/EEA were excluded for b Complete data from Cyprus ad the Czech Republic were supplied oly after the reportig deadlie ad therefore could ot be take ito accout. Figure 2 Reported cases of Legioaires disease i the EU/EEA by moth of oset, 2009 (=5 327) Ja Feb Mar Apr May Ju Jul Aug Sep Oct Nov Dec 1 EU Member States that joied after 2000: Bulgaria, Cyprus, Czech Republic, Estoia, Hugary, Latvia, Lithuaia, Malta, Polad, Romaia, Slovakia, Sloveia. 6

12 SURVEILLANCE REPORT Legioaires disease i Europe 2009 Table 2 Reported cases ad otificatio rate of Legioaires disease by reportig coutry, EU/EEA, 2009 Coutry* Cases Populatio Notificatio rate () (N) (/millio) Sloveia Spai Demark Icelad Italy Frace Netherlads Swede Austria Luxembourg Malta Portugal Belgium Norway Hugary Germay Uited Kigdom Estoia Filad Irelad Greece Latvia Bulgaria Slovakia Polad Romaia Lithuaia * Complete data from Cyprus ad the Czech Republic were supplied oly after the reportig deadlie ad therefore could ot be take ito accout Age ad geder Age ad geder were reported for cases, (77.1) of which were 50 years or older. I both geders, the otificatio rate icreased with age (Table 3). Overall, males were almost three times more frequetly otified with Legioaires disease tha were females. This geder differece could be see i all age groups to varyig degrees, but was most proouced i the 30 to 39 year-olds with a male-to-female rate ratio of 4.7. Age treds i the 10 EU/EEA coutries with the highest umbers of reported cases of Legioaires disease were ot cogruet with two distict age distributio patters emergig (Figure 3). The otificatio rates of Frace, Italy ad Spai, the coutries accoutig for two thirds of all reported cases, exhibited a steady, uiterrupted icrease with age. The rates of most remaiig coutries peaked i the age group betwee 60 ad 69, levellig off thereafter. 7

13 Legioaires disease i Europe 2009 SURVEILLANCE REPORT Table 3 Reported cases ad otificatio rate of Legioaires disease by geder ad age group, EU/EEA, 2009 Age (years) Cases () Male Female Notif. rate (/millio) Cases () Notif. rate (/millio) Cases () Notif. rate (/millio) Figure 3 Notificatio rate of Legioaires disease i the 10 EU/EEA coutries with the highest umbers of reported cases, by coutry ad age group, 2009 Cases () Age group Presumable settig of ifectio Iformatio o the presumable settig of ifectio was available for cases of Legioaires disease, more tha two thirds of which were reported to have bee commuity-acquired. They were followed i decreasig frequecy by cases presumably ifected while travellig domestically, travellig abroad, stayig i a hospital or ifected while exposed to a o-hospital healthcare settig (Table 4). Comparig coutries with more tha 10 reported cases, the distributio of settigs revealed cosiderable heterogeeity (Table 5). This was most proouced i the proportio of cases associated with travellig abroad for which the highest value (Norway) differed 67-fold from the lowest (Italy). Nie coutries, icludig four coutries with more tha 10 reported cases, reported o osocomial case of Legioaires disease i AT DE DK ES FR GB IT NL PT SE 8

14 SURVEILLANCE REPORT Legioaires disease i Europe 2009 Table 4 Reported cases of Legioaires disease by settig, EU/EEA, 2009 Settig Commuity Domestic travel Travel abroad Nosocomial No-hospital healthcare Other Table 5 Reported cases of Legioaires disease by coutry ad settig, EU/EEA, 2009 Settig Coutry a Commuity ( b ) Domestic travel ( b ) Travel abroad ( b ) Nosocomial ( b ) Other healthcare ( b ) Other ( b ) Subtotal Ukow () Austria 65 (70.7) 5 (5.4) 12 (13.0) 7 (7.6) 3 (3.3) Belgium 6 (12.0) 3 (6.0) 20 (40.0) 1 (2.0) 5 (10.0) 15 (30.0) (37.5) 80 Bulgaria (100.0) 4 Demark 63 (58.3) 4 (3.7) 35 (32.4) 5 (4.6) 1 (0.9) ( Estoia 1 (25.0) (75.0) (33.3) 6 Filad (100.0) 22 Frace 812 (67.3) 163 (13.5) 68 (5.6) 98 (8.1) 65 (5.4) Germay 123 (48.8) 21 (8.3) 60 (23.8) 30 (11.9) 2 (0.8) 16 (6.3) (49.8) 502 Greece 10 (66.7) 2 (13.3) 2 (13.3) 1 (6.7) Hugary 23 (85.2) 1 (3.7) 1 (3.7) 2 (7.4) (58.5) 65 Irelad 2 (33.3) 0 4 (57.1) 1 (16.7) Icelad 5 (71.4) (28.6) Italy 878 (73.5) 174 (14.6) 18 (1.5) 104 (8.7) 16 (1.3) 4 (0.3) (0.3) Latvia (100.0) (66.7) 3 Luxembourg (100.0) 5 Malta 2 (50.0) 0 1 (25.0) (25.0) Netherlads 117 (47.4) 18 (7.3) 107 (43.3) 0 5 (2.0) (1.6) 251 Norway (100.0) (32.4) 34 Polad 0 2 (28.6) 5 (71.4) (30.0) 10 Portugal 46 (85.2) 5 (9.3) 2 (3.7) 0 1 (1.9) (43.8) 96 Romaia (100.0) (66.7) 3 Slovakia 2 (100.0) Sloveia 65 (100.0) Swede (100.0) 114 Spai 989 (82.0) 119 (9.9) 20 (1.7) 60 (5.0) 10 (0.8) 8 (0.7) (2.0) UK 173 (46.4) 37 (9.9) 144 (38.6) 19 (5.1) (0.3) (68.4) 554 (11.2) 524 (10.6) 333 (6.7) a Complete data from Cyprus ad the Czech Republic were supplied oly after the reportig deadlie ad therefore could ot be take ito accout. b Row percetages with each subtotal as the deomiator Laboratory data The cases of Legioaires disease reported for 2009 were cofirmed by laboratory tests, 81.7 of which were uriary atige detectios ad 9.3 were cultures (Table 6). The distributio of diagostic laboratory methods was stable from 2005 to 2009 (Aex, Figure A). The distributio of most methods by reportig coutry varied substatially (Table 7). While all but three coutries reported at least some case cofirmatios by uriary atige test, coutries that joied the EU/EEA after 2000 proved more likely ot to report ay cofirmatio by culture (OR=16.3; 95 CI= ) or polymerase chai reactio (PCR; OR=19.2; 95 CI= ), but to have cofirmed the majority of their cases by a sigle high atibody titre (OR=8.0; 95 CI= ). 108 (2.2) 44 (0.9) (8.1)

15 Legioaires disease i Europe 2009 SURVEILLANCE REPORT Table 6 Reported diagostic laboratory methods, EU/EEA, 2009 (more tha oe method per case possible) Laboratory method Uriary atige test Culture Sigle high titre Nucleic acid amplificatio, e.g. PCR Fourfold titre rise Direct immuofluorescece Other Table 7 Reported diagostic laboratory methods by reportig coutry, EU/EEA, 2009 (more tha oe method per case possible) Coutry a Uriary atige test () Culture () Laboratory method Sigle high titre () PCR () Fourfold titre rise () Direct immuofluorescece () Austria 63 (68.5) 18 (19.6) 6 (6.5) 2 (2.2) 3 (3.3) 0 92 Belgium 52 (65.0) 12 (15.0) 10 (12.5) 3 (3.8) 3 (3.8) 0 80 Bulgaria 3 (75.0) 0 1 (25.0) Demark 31 (25.2) 66 (53.7) 8 (6.5) 14 (11.4) 4 (3.3) Estoia 6 (100.0) Filad 5 (22.7) 3 (13.6) 14 (63.6) Frace 957 (79.4) 220 (18.2) 18 (1.5) 2 (0.2) 9 (0.7) Germay b 360 (69.4) 23 (4.4) 67 (12.9) 61 (11.8) 8 (1.5) Greece 15 (78.9) 0 3 (15.8) 1 (5.3) Hugary 14 (21.5) 0 49 (75.4) (3.1) 65 Irelad 7 (100.0) Icelad 4 (57.1) 2 (28.6) 0 1 (14.3) Italy (94.8) 22 (1.8) 31 (2.6) 1 (0.1) 7 (0.6) 1 (0.1) Luxembourg 5 (100.0) Latvia (100.0) 0 3 Malta 4 (100.0) Netherlads 207 (68.8) 43 (14.3) 17 (5.6) 20 (6.6) 14 (4.7) Norway 30 (88.2) 2 (5.9) 1 (2.9) 1 (2.9) Polad 4 (36.4) 1 (9.1) 5 (45.5) 0 1 (9.1) 0 11 Portugal 85 (88.5) 8 (8.3) 2 (2.1) 1 (1.0) Romaia (66.7) 0 1 (33.3) 0 3 Swede 64 (44.1) 12 (8.3) 37 (25.5) 24 (16.6) 8 (5.5) Slovakia 0 1 (50.0) 1 (50.0) Sloveia 59 (90.8) 0 3 (4.6) 1 (1.5) 2 (3.1) 0 65 Spai (95.8) 22 (1.8) 26 (2.1) 0 4 (0.3) UK 303 (81.0) 67 (17.9) 2 (0.5) 0 2 (0.5) (81.7) 522 (9.3) 303 (5.4) 132 (2.3) 69 (1.2) 3 (0.1) a Complete data from Cyprus ad the Czech Republic were supplied oly after the reportig deadlie ad therefore could ot be take ito accout. b Oe case with laboratory method coded as Other (ad with a epidemiologic lik) ot show. Of cofirmed ad probable cases for which the causative species was idicated, (99.8) were reportedly due to Legioella peumophila ad (89.8) to L. peumophila serogroup 1 (Table 8). For cofirmed cases, the correspodig figures were (99.9) ad (94.3), respectively. Of 445 culturecofirmed cases that were ot additioally cofirmed by uriary atige testig, 441 (99.1) were due to 10

16 SURVEILLANCE REPORT Legioaires disease i Europe 2009 L. peumophila ad 390 (87.6) to serogroup 1 (Table 8). For 33 culture-cofirmed cases, the Legioella species ad serogroup were missig or reported as ukow. The sequece type was oly reported for 44 cases, 40 of which were from oe coutry. The distributio i Europe, therefore, could ot be aalysed. Table 8 Reported cases of Legioaires disease ad Legioella isolates by species ad serogroup, EU/EEA, 2009 a Species ad All cases Cofirmed cases Culture-cofirmed cases b serogroup c c c L. peumophila Serogroups Mixed Ukow L. bozemaii L. logbeachae L. maceacherii 1 0 L. micdadei a Does ot iclude 11 Germa cases with pathoge coded as Other meaig Legioella other tha L. peumophila serogroup1. b Does ot iclude 50 cases cofirmed by culture ad uriary atige test ad reported as L. peumophila serogroup 1 to exclude cases possibly assumed by default to belog to this serogroup. c Percetage of the colum total Evirometal ivestigatio The evirometal follow-up status was kow for cases, 371 (16.8) of which had prompted a ivestigatio of the implicated site(s). Of domestic cases with kow follow-up status, 326 (17.7) had bee followed by a evirometal ivestigatio. Domestic cofirmed cases were o more likely to lead to a evirometal ivestigatio tha were probable cases (OR=1.0; 95 CI= ). However, domestic fatal cases were more likely to prompt a ivestigatio tha o-fatal cases (OR=1.6; 95 CI= ). Fourtee coutries reported a kow evirometal follow-up status for more tha half of their domestic cases (Table 9). I four of these coutries, however, a ivestigatio was carried out i less tha 10 of cases. Three coutries accoutig for 59.9 of all domestic cases reported the evirometal follow-up status as ukow for all or early all of the implicated sites. For 324 of 326 domestic evirometal ivestigatios, fidigs were reported. Legioella was foud i 125 ivestigatios (38.6) ad ot foud i 188 ivestigatios (58.0) while results were ukow i 11 istaces (3.4). I coutries with eight or more reported domestic evirometal ivestigatios, the percetage of Legioella detectios raged from 17.4 to 100 (Table 10). Of 120 ivestigatios with positive fidigs, 77 (64.2) retrieved Legioella from the water system without further specificatio, 26 (21.7) from the hot water system, 4 (3.3) from a whirlpool, 3 (2.5) from the cold water system, 1 (0.8) from a coolig tower ad 9 (7.5) from other samplig sites. Matchig cliical ad evirometal Legioella isolates were foud i 28 domestic cases from five coutries ad thus i 73.7 of 38 cases where both isolates were available. 11

17 Legioaires disease i Europe 2009 SURVEILLANCE REPORT Table 9 Evirometal follow-up status of reported domestic cases of Legioaires disease by reportig coutry, EU/EEA, 2009 Coutry* Ivestigatio No ivestigatio Status ukow Austria Belgium Demark Estoia Frace Germay Greece Hugary Icelad Irelad Italy Malta Netherlads Polad Portugal Slovakia Sloveia Spai UK * Excludes coutries with settig of ifectio reported as ukow for all cases. Complete data from Cyprus ad the Czech Republic were supplied oly after the reportig deadlie ad therefore could ot be take ito accout. Table 10 Legioella fidigs of domestic evirometal ivestigatios by reportig coutry, EU/EEA, 2009 Coutry* Detectio No detectio Result ukow Austria Belgium Demark Estoia Greece Hugary Icelad Irelad Italy Malta Netherlads Polad Portugal Slovakia Spai UK * Excludes coutries with settig of ifectio reported as ukow for all cases. Complete data from Cyprus ad the Czech Republic were supplied oly after the reportig deadlie ad therefore could ot be take ito accout. 12

18 SURVEILLANCE REPORT Legioaires disease i Europe Deaths Case-fatality ratio, case classificatio ad mortality otificatio rate A kow cliical outcome was reported for (67.6) of all reported cases of Legioaires disease. Of these cases, 404 (10.8) died: 386 (11.4) of cofirmed cases ad 18 (5.3) of 342 probable cases. Fatal cases were more tha twice as likely to meet the defiitio of a cofirmed case (OR=2.3; 95 CI= ) ad more tha five times as likely to have bee cofirmed by culture (OR=5.5; 95 CI= ). The mortality rate i 2009 was 0.8 per millio populatio ad has bee stable sice Time ad place The distributio of deaths by moth of disease oset revealed a tred towards higher case-fatality ratios i the colder moths of the year (Figure 4). Fatal cases were more likely to occur with a disease oset i Jauary, February ad October to December tha with a oset from March to September (OR=1.7; 95 CI= ). The overall case-fatality ratio i coutries with less tha 25 ukow outcomes was 9.1, ragig from zero to 60, ad from 3.1 to 17.1 whe oly takig coutries with more tha 10 reported cases ito accout (Table 11). A fatal case was 40 more likely to have bee reported by a coutry with more tha 25 ukow outcomes tha by a coutry with a more complete follow-up (OR=1.4; 95 CI= ) Age ad geder I males, 273 (10.1) of cases with a kow outcome were reported to have died, i females 130 (12.6) of cases (Table 12). Case fatality showed a icrease with age, reachig 25.8 i those 80 years ad older. The oly age groups i which males had a slightly higher case fatality tha females were those from 50 to 69 years. Overall, females were 30 more likely to have died from Legioaires disease tha males (OR=1.3; 95 CI= ), ad compared to cases below 40 years of age, the likelihood of a fatal outcome was twice as high (OR=2.1; 95 CI= ) i cases aged 40 to 59, five times as high (OR=5.0; 95 CI= ) i cases aged 60 to 79, ad 13 times as high (OR=12.8; 95 CI= ) i cases aged 80 years ad older. The tred towards a icrease of case-fatality with age was observed i all coutries, most evidetly i those with more tha 10 reported deaths (Aex, Table 1). Figure 4 Reported deaths from Legioaires disease ad case-fatality ratio (CFR) by moth of oset, EU/EEA, 2009 Cases () CFR () Ja Feb Mar Apr May Ju Jul Aug Sep Oct Nov Dec 0 Deaths Cases CFR 13

19 Legioaires disease i Europe 2009 SURVEILLANCE REPORT Table 11 Reported outcomes of Legioaires disease ad case fatality by reportig coutry, EU/EEA, 2009 Coutry a Survival () Death () Ukow () Case-fatality b Austria 84 (91.3) 8 (8.7) 0 (0) Belgium 39 (48.8) 4 (5) 37 (46.3) 80.a. c Bulgaria 0 (0) 0 (0) 4 (100) 4.a. Demark 102 (82.9) 21 (17.1) 0 (0) Estoia 6 (100) 0 (0) 0 (0) 6 0 Filad 21 (95.5) 1 (4.5) 0 (0) Frace 966 (80.1) 125 (10.4) 115 (9.5) Germay 467 (93) 35 (7) 0 (0) Greece 14 (93.3) 1 (6.7) 0 (0) Hugary 59 (90.8) 5 (7.7) 1 (1.5) Icelad 6 (85.7) 1 (14.3) 0 (0) Irelad 4 (57.1) 2 d (0) 1 (42.9) 7 0 Italy 421 (35.2) 66 (5.5) 710 (59.3) a. Latvia 3 (100) 0 (0) 0 (0) 3 0 Luxembourg 2 (40) 3 (60) 0 (0) Malta 4 (100) 0 (0) 0 (0) 4 0 Netherlads 234 (93.2) 17 (6.8) 0 (0) Norway 29 (85.3) 1 (2.9) 4 (11.8) Polad 10 (100) 0 (0) 0 (0) 10 0 Portugal 37 (38.5) 4 (4.2) 55 (57.3) 96.a. Romaia 3 (100) 0 (0) 0 (0) 3 0 Slovakia 1 (50) 1 (50) 0 (0) Sloveia 63 (96.9) 2 (3.1) 0 (0) Spai 730 (59.3) 61 (5) 440 (35.7) a. Swede 0 (0) 0 (0) 114 (100.0) 114.a. UK 20 (5.3) 48 (12.8) 306 (81.8) 374.a. e 2074 (85.9) 221 (9.2) 118 (5.0) a Complete data from Cyprus ad the Czech Republic were supplied oly after the reportig deadlie ad therefore could ot be take ito accout. b Deomiator: kow outcomes (survivals ad deaths). c Not applicable where > 25 of outcomes ukow. d Not directly due to Legioaires disease, therefore ot take ito accout. e Icludes oly coutries where < 25 of outcomes ukow. Table 12 Reported case-fatality (CFR) of Legioaires disease by geder ad age group, EU/EEA, 2009 Age (y) Deaths Male Female CFR Deaths CFR Deaths CFR 14

20 SURVEILLANCE REPORT Legioaires disease i Europe Settig Case-fatality of Legioaires disease was highest amog cases acquired i healthcare facilities (maily hospitals ad ursig homes), followed i decreasig order by commuity-acquired ad travel-associated cases (Table 13). Compared with commuity-acquired cases, travel-associated cases were 30 less likely to have died (OR=0.7; 95 CI= ), whereas fatal outcomes amog healthcare-associated cases were more tha four times as likely (OR=4.2; 95 CI= ). Table 13 Reported case-fatality of Legioaires disease, by settig, EU/EEA, 2009 Settig reported Case-fatality Healthcare Commuity Domestic travel Travel abroad Other Laboratory data Of 404 fatal cases of Legioaires disease, 95 (23.5) were cofirmed by culture as compared to 319 (9.6) of cases who survived (OR=2.9; 95 CI= ). Of species ad serogroups accoutig for more tha five cases of Legioaires disease, L. peumophila serogroups 6 ad 10 showed the highest case-fatality ratios, regardless of whether the aalysis was doe o the etire dataset or restricted to cofirmed or culture-cofirmed cases (Table 14). Amog culture-cofirmed cases, these two serogroups had a 14-fold higher likelihood of beig associated with death tha all other L. peumophila serogroups together (OR=14.3; 95 CI= ). Table 14 Reported case-fatality (CFR) of Legioaires disease by Legioella species ad serogroup, EU/EEA, 2009 a Species ad serogroup Deaths All cases Cofirmed cases Culture-cofirmed cases b CFR Deaths CFR Deaths L. peumophila Serogroups Mixed Ukow L. bozemaii L. logbeachae L. maceacherii L. micdadei Ukow species a Does ot iclude 11 Germa cases with pathoge coded as Other meaig Legioella other tha L. peumophila serogroup1. b Does ot iclude 40 cases cofirmed by culture ad uriary atige test ad reported as L. peumophila serogroup 1 to exclude cases possibly assumed by default to belog to this serogroup. CFR 15

21 Legioaires disease i Europe 2009 SURVEILLANCE REPORT Cluster status Cluster status was reported for cases with kow outcome. Death occurred i 13 (7.9) of 164 clustered cases ad 240 (10.9) of sporadic cases, the two groups ot differig sigificatly from each other (OR=0.7; 95 CI= ) Diagostic delay The media diagostic delay, i.e. the delay betwee date of oset ad date of diagosis was six days (0 255 days) with 73 of cases diagosed withi the first week of illess ad 93 of cases diagosed withi the first two weeks. Of 193 cases diagosed withi the first two days after oset of disease, 37 (19.2) died compared with 105 (9.4) of cases who were diagosed with a delay greater tha two days (OR=2.3; 95 CI= ) Adjusted predictors of fatal outcome i cofirmed cases I decreasig order of magitude of associatio, causative Legioella species ad serogroup, patiet age, settig of ifectio, seaso of disease oset ad coutry-specific completeess of outcome reportig were foud to be idepedet predictors of fatal outcome i cofirmed cases of Legioaires disease reported i 2009 (Table 15). Geder was ot idepedetly associated with fatal outcome. The seaso of oset modified the effect of the ifectio settig o disease outcome i commuity-acquired ad travel-associated cases, but ot i healthcareassociated cases. The goodess-of-fit of the uderlyig logistic regressio model was fair with a area uder the receiver-operatig curve of Table 15 Adjusted predictors of fatal outcome of Legioaires disease, EU/EEA, 2009 Risk factor Odds ratio 95 cofidece iterval Cases exposed () Legioella species ad serogroup L. peumophila serogroups 6 ad 10 versus all other species ad serogroups Age years versus 39 years years versus 39 years years versus 39 years Settig of ifectio by seaso of oset Sprig/ summer a : Travel versus commuity Healthcare versus commuity Autum/ witer b : Travel versus commuity Healthcare versus commuity Seaso of oset by settig of ifectio Autum/ witer versus sprig/ summer Commuity Travel Healthcare Coutry-specific outcome reportig Icomplete c versus complete a March to September. b Jauary, February, October to December. c 25 of outcomes coded as Ukow. 3.3 Clusters Frequecy, size, classificatio ad outcome I 2009, 101 clusters of Legioaires disease were reported, 23.5 less tha 2008 ad 10.6 less tha the average aual umber of clusters reported from 2002 to 2008 (Figure 5). Correctig for Italia clusters that were ot reported i 2009 but i previous years, the declie betwee 2008 ad 2009 amouted to The 101 clusters ivolved 254 cases, represetig 6.5 of cases with kow cluster status. O average, there were two cases to each cluster, cotiuig a tred i cluster size that had bee decreasig sice a peak i 2001, iterrupted oly by a smaller peak from 2005 to 2007 (Figure 5). 16

22 SURVEILLANCE REPORT Legioaires disease i Europe 2009 Of cofirmed ad 298 probable cases with kow cluster status, 239 (6.7) ad 15 (5.0), respectively, formed part of a cluster. Cofirmed cases were o more likely to cluster tha probable cases (OR=1.3; 95 CI= ). Thirtee (7.9) of 164 fatal cases ad 240 (10.9) of o-fatal cases with kow cluster status had formed part of a cluster (OR=0.7; 95 CI= ). Case-fatality did ot differ betwee clustered ad sporadic cases of Legioaires disease (see Sectio 3.2.6). Figure 5 Reported clusters of Legioaires disease ad average umber of cases per cluster by year of reportig, EU/EEA, Clusters () Cases per cluster () * Clusters Cases per cluster * Does ot iclude Italia clusters as they were ot reported Time ad place The proportio of clustered cases by moth of oset peaked at betwee 8 ad 10 i Jauary, May ad September (Figure 6). Ulike the patter observed for fatal cases, clustered cases were ot associated with ay particular seaso (OR March to September =1.1; 95 CI= ). The overall proportio of clustered cases i coutries with less tha 25 ukow cluster statuses was 6.0, ragig from 2.2 to 30.0, ad from 2.2 to 15.9 whe oly takig coutries with more tha 10 reported cases ito accout (Table 16). A clustered case was eight times more likely to have bee reported by a coutry with more tha 25 ukow cluster statuses tha by a coutry with more complete cluster status iformatio (OR=7.9; 95 CI= ) Age ad geder Clusterig of reported cases of Legioaires disease was kow to have occurred i 179 (6.4) of male cases ad 73 (6.9) of female cases (Table 17). There was o sigificat differece betwee the geders (OR=1.1; 95 CI= ). Clusterig appeared to icrease with age before droppig off amog cases aged 80 years ad older. Icompatible with this tred, a relatively high proportio amog those aged 20 to 29 was due to three female cases who carried udue umerical weight because of the small geder ad age group-specific deomiator. Overall, statistically, oly the age group from 60 to 79 differed sigificatly from the others i icreasig the likelihood of clusterig by 50 (OR=1.5; 95 CI= ). The tred towards icreasig clusterig with age was also observed i Member States with higher umbers of reported cases (Aex, Table 2). 17

23 Legioaires disease i Europe 2009 SURVEILLANCE REPORT Figure 6 Reported clusterig of Legioaires disease by moth of oset, EU/EEA, 2009 Cases () Clustered cases () Ja Feb Mar Apr May Ju Jul Aug Sep Oct Nov Dec Clustered cases () Cases Clustered cases () 0 Table 16 Reported clusterig of Legioaires disease by reportig coutry, EU/EEA, 2009 Coutry a Clusters Clustered () Sporadic () Ukow () Cluster ratio b Austria 1 2 (2.2) 90 (97.8) 0 (0) Belgium 1 1 (1.3) 53 (66.3) 26 (32.5) 80.a. c Bulgaria 0 0 (0) 4 (100.0) 0 (0) 4 0 Demark 9 10 (8.1) 111 (90.2) 2 (1.6) Estoia 0 0 (0) 6 (100.0) 0 (0) 6 0 Filad 0 0 (0) 0 (0) 22 (100.0) 22.a. Frace 0 0 (0) 0 (0) (100.0) a. Germay (2.6) 489 (97.4) 0 (0) Greece 0 0 (0) 15 (100.0) 0 (0) 15 0 Hugary 0 0 (0) 65 (100.0) 0 (0) 65 0 Icelad 0 0 (0) 7 (100.0) 0 (0) 7 0 Irelad 0 0 (0) 7 (100.0) 0 (0) 7 0 Italy Ukow 28 (2.3) (97.7) 0 (0) Latvia 0 0 (0) 3 (100.0) 0 (0) 3 0 Luxembourg 0 0 (0) 4 (80.0) 1 (20.0) 5 0 Malta 0 0 (0) 4 (100.0) 0 (0) 4 0 Netherlads (10.4) 0 (0) 225 (89.6) 251.a. Norway 1 4 (11.8) 30 (88.2) 0 (0) Polad 1 3 (30.0) 7 (70.0) 0 (0) Portugal 1 8 (8.3) 88 (91.7) 0 (0) Romaia 0 0 (0) 3 (100.0) 0 (0) 3 0 Slovakia 0 0 (0) 1 (50.0) 1 (50.0) 2.a. Sloveia 0 0 (0) 65 (100.0) 0 (0) 65 0 Spai (8.2) (89.2) 32 (2.6) Swede 0 0 (0) 0 (0) 114 (100) 114.a. UK (15.5) 306 (81.8) 10 (2.7) d (5.9) (92.9) 45 (1.2) a Complete data from Cyprus ad the Czech Republic were supplied oly after the reportig deadlie ad therefore could ot be take ito accout. b Deomiator: kow outcomes (clustered ad sporadic cases). c Not applicable where > 25 of cluster statuses ukow. d Icludes oly coutries where < 25 of cluster statuses ukow. 18

24 SURVEILLANCE REPORT Legioaires disease i Europe 2009 Table 17 Reported clusterig of Legioaires disease by geder ad age group, EU/EEA, 2009 Age (y) Clustered Male Female Clustered Clustered Clustered Clustered Clustered Settig The proportio of clustered cases was highest amog those who presumably cotracted Legioaires disease while travellig abroad, followed by domestic travellers, healthcare-associated ad commuity-acquired cases (Table 18). Compared with o-travel-associated cases, cases i domestic travellers were three times more likely to form part of a cluster (OR=3.1; 95 CI= ) while this likelihood was fivefold i cases who had travelled abroad (OR=5.0; 95 CI= ). The average cluster size was biggest i clusters of commuity-acquired ad domestic travel-related cases with five ad four cases per cluster, respectively. Table 18 Reported clusterig of Legioaires disease, by settig, EU/EEA, 2009 Settig cases reported Clusters Clustered cases Cases per cluster Travel abroad* Domestic travel Healthcare Commuity Other * Data quality, especially of cluster size compromised by a) clusters spaig up to two years ad therefore ot reported etirely i 2009; ad b) poor reportig of cluster status ad/or cluster idetifiers by a umber of coutries that caot easily lik their cluster data to the cases ivolved Laboratory data Of 254 clustered cases of Legioaires disease, 31 (12.2) were cofirmed by culture as compared to 208 (5.7) of sporadic cases (OR=2.3; 95 CI= ). Sice all clustered cases with a kow culture result were due to L. peumophila serogroup 1, the associatio of pathoge ad case clusterig could ot be estimated (Aex, Table 3) Evirometal ivestigatio A evirometal ivestigatio esued i 81 (64.3) of 126 clustered cases ad 248 (13.2) of sporadic cases of Legioaires disease. The likelihood of a evirometal ivestigatio was 12 times higher i clustered cases (OR=11.8; 95 CI= ). Legioella was foud i 43 (54.4) of 79 evirometal ivestigatios followig clustered cases ad i 74 (32.2) of 230 ivestigatios followig sporadic cases. Positive fidigs were more tha twice as likely if the evirometal ivestigatio was prompted by a clustered case (OR=2.5; 95 CI= ). Matchig cliical ad evirometal Legioella isolates were foud i 8 (66.7) of 12 clustered cases ad 18 (90) of 20 sporadic cases where both isolates were available. The differece was ot sigificat (OR=0.2; 95 CI= ). 19

25 Legioaires disease i Europe 2009 SURVEILLANCE REPORT Adjusted predictors of clusterig i cofirmed cases I decreasig order of magitude of associatio, coutry-specific completeess of cluster status reportig, settig of ifectio ad patiet age were foud to be idepedet predictors of clusterig i cofirmed cases of Legioaires disease reported i 2009 (Table 19). Geder was ot idepedetly associated with clusterig. Causative Legioella species ad serogroup could ot be cotrolled for sice all clustered cofirmed cases with available iformatio had bee due to L. peumophila serogroup 1 (or ukow serogroup). The goodess-of-fit of the uderlyig logistic regressio model was poor with a area uder the receiver-operatig curve of Table 19 Adjusted predictors for case clusterig of Legioaires disease, EU/EEA, 2009 Risk factor Odds ratio 95 cofidece iterval Cases exposed () Coutry-specific reportig of cluster status Icomplete a versus complete Settig of ifectio Travel versus o-travel-related Age years versus others a 25 of cluster statuses coded as Ukow. 20

26 SURVEILLANCE REPORT Legioaires disease i Europe Discussio Legioaires disease remais severely uderascertaied i Europe. I the EU, Icelad ad Norway, approximately people died from peumoia i 2008 [12]. Based o this mortality, ad assumig a case-fatality of 10 [2], a estimated persos suffer from peumoia every year. Assumig further that 4 of these cases are due to Legioella [2,3], there could possibly be up to cases of Legioaires disease aually, almost 10 times the cases otified i Europe i A mixture of uderdiagosis ad uderreportig, the uderascertaimet appears to be pa-europea with eve the highest coutry-specific otificatio rate, 32 per millio populatio i Sloveia, remaiig cosiderably below the estimated Europea icidece rate of 103 per millio. Compared with log-time Member States, otificatio rates were sigificatly lower i the less affluet, predomiatly cetral ad easter Europea coutries joiig the EU/EEA after This suggests that i additio to the omipreset limited cliical awareess, a lack of resources, especially i terms of laboratory capacity, may cotribute to the uderascertaimet of Legioaires disease i some of the ewer Member States. The observed frequecy peak of Legioaires disease i late summer is i lie with commo microbiological kowledge of Legioellae growig best at temperatures betwee 20 C ad 42 C [13]. It is also cosistet with published fidigs of a statistical associatio betwee warm ad humid weather ad Legioaires disease [14,15]. The icreasig icidece of Legioaires disease with age ad its predilectio for males see i 2009 have bee described previously [16]. Iterestigly, coutry-specific age treds differed amog the coutries accoutig for the highest umbers of reported cases. While age distributios i Demark, the Netherlads, Swede ad the Uited Kigdom peaked betwee 60 ad 69 years, they showed a more cotiuous icrease towards the oldest age group i Frace, Italy ad Spai. This differece could be due to uderdiagosis of elderly cases i coutries with lower otificatio rates. Overall, 68 of Legioaires disease cases were reported to have bee commuity-acquired ad 22 to have bee travel-associated. The coutry-specific distributio of cases related to foreig ad domestic travel appeared to mostly reflect Europea tourist flows with higher proportios of foreig travel i cetral, orth-wester ad orther Europe ad higher proportios of domestic travel i souther Europe. The reported virtual absece of osocomial cases of Legioaires disease eve i some coutries with sizeable overall umbers of reported cases is probably rather suggestive of uderascertaimet tha of superior hospital maiteace. As observed i previous years [16], over 80 of cases were cofirmed by uriary atige detectio. The coutries joiig the EU/EEA after 2000, however, were eight times more likely tha older Member States to have verified the majority of their cases by sigle high atibody titre. Although the curret EU case defiitio for Legioaires disease accepts cases cofirmed by sigle high titres as probable, they should be treated with soud cautio give the relatively high backgroud prevalece of such titres i some coutries [17] ad the kow serological crossreactivity of Legioella with other bacteria [18]. Culture accouted oly for 9 of reported laboratory tests overall with coutries joiig the EU/EEA after 2000 beig 16 times more likely tha older Member States ot to have cofirmed ay cases by culture at all. Eve amog cluster cases, oly 12 were culture-cofirmed. Epidemiologically, this gives rise to cocer as most outbreak ivestigatios fall short of idetifyig the source i the absece of a cliical Legioella isolate that ca be matched to a evirometal isolate. Amog cofirmed cases of Legioaires disease, 94 were reported to have bee caused by L. peumophila serogroup 1. This icludes all cases cofirmed by uriary atige test. Some coutries are kow to iterpret each positive uriary atige test result as idicative of L. peumophila serogroup 1 although two commo test kits have bee reported to detect o-serogroup 1 L. peumophila with a sesitivity of 29 ad 51, respectively [19]. Limitig the deomiator to culture-cofirmed cases decreased the proportio attributable to L. peumophila serogroup 1 to a probably more realistic 87. L. peumophila sequece types were oly reported for 44 cases from three coutries. This is i stark cotrast with the 521 etries from 14 EU/EEA coutries listed i the EWGLI Sequece-Based Typig (SBT) Database for Although listigs i the SBT database are by microbiological isolatio date, ad isolatio ad case reportig may have ot always occurred i the same year, most missig sequece types are probably due to difficulties i likig them to case data at atioal level. Relatively few cases, 17 of those with available iformatio, had prompted a evirometal ivestigatio, the likelihood beig 1.6 times higher i fatal compared with o-fatal cases, ad 12 times higher i clustered compared with sporadic cases. The depedece of evirometal ivestigatios o a high idex of suspicio was further evideced by the fact that matchig cliical ad evirometal isolates were reported for 77 of cases where both were available. Less restrictive iitiatio of such ivestigatios might have reduced this overall success rate. Coutry-specific evirometal Legioella detectio ratios varied substatially but are difficult to iterpret without takig ito accout laboratories performace i exteral quality assurace (EQA) schemes. 21