1. Facilitator notes:
Session 2: Clinical and epidemiological aspects of Legionnaires’ disease
ECDC, 2011
Major revision: 2018

2. Objectives Specific objectives of this session:
Review knowledge of pathogenesis, pathophysiology and clinical presentation of Legionella in humans
Discuss underpinning epidemiology of Legionnaire’s disease
Understand epidemiological surveillance systems within Europe
Discuss European Guidelines in relation to Legionnaire’s disease
Understand legislative aspects
Facilitator notes:

3. Content
The pathological, physiological and clinical features of Legionnaires’ disease
Epidemiological overview of Legionnaires’ disease, in particular in the context of Europe
European guidelines for control and prevention of travel associated Legionnaires’ disease and their under-pinning rationale
Legal context

4. Legionnaires’ disease
Severe atypical pneumonia caused by Legionella bacterium
Incubation period:
usually considered 2-10 days (median 6/7 days)
in outbreak situations documented up to 19 days
Flu-like illness, fever, headache, dry cough, confusion, diarrhoea, multi organ failure
Case fatality:
~10% for community acquired / travel associated
may be up to 30% for nosocomial acquired LD
Low attack rate (less than 5%)

6. Outcome Long term outcomes Restrictive pulmonary disease
Weakness and fatigue
Neurological problems
Poor memory and concentration
Retrograde amnesia
Cerebellar dysfunction –causing problems with balance, motor control

7. Pontiac fever Mild illness without pneumonia
Incubation period hours
Flu-like illness lasting several days
0% mortality
High attack rate (> 90%)
Often only identified as part of an outbreak

8. Cause of Legionnaires' disease
>60 Legionella species
At least 19 species associated with human infection
L. pneumophila % of all infections
Serogroup 1 - most common cause of illness

9. Legionnaires’ disease: modes of infection
Inhalation of aerosol particles into the lung
Particles must be small enough to get down to the lung alveoli but large enough to contain at least one bacterial cell
Aspiration can occur - especially for nosocomial patients
Person to person transmission
Not proven
Suspicion once described in NEJM 2016 [1]
[1] Correia AM, Ferreira JS, Borges V, Nunes A, Gomes B, Capucho R, Gonçalves J, Antunes DM, Almeida S, Mendes A, Guerreiro M. Probable person-to-person transmission of Legionnaires’ disease. New England Journal of Medicine Feb 4;374(5):497-8.

10. Legionnaires’ disease: incubation periods
2-10 days for most cases - typically 6-7 days
But
Legionnaires' disease outbreak, Netherlands, 1999
incubation (2-19 days), median (7 days), 16% of cases >10 days
Legionnaires' disease outbreak, Melbourne, 2000
incubation (1-16 days), median (6 days), 7% of cases >10 days
Legionnaires' disease outbreak, Japan, 2008
incubation (2-14 days), 5% of cases > 10 days (incubation period definition inclusion criteria may have introduced bias due to most recent visit being used)
Collecting information for 14 days prior onset of symptoms is reasonable compromise

11. Who is at risk? Smokers Heavy drinkers People aged 50 years or more
Certain occupational groups
Immunosuppressed by treatment or disease
Underlying disease (e.g. diabetes, chronic heart disease)
Hospital transplant patients
Men more than women
Recent travel

12. Where are the risks?
Industrial sites with water cooling devices or large buildings with wet cooling systems used for air conditioning
Hot and cold water systems used in
Hospitals
Hotels/holiday accommodation/office buildings
Whirlpool spas
Cruise ships
Domestic premises
Fountains/car washes
Humidifiers
Respiratory therapy equipment

13. Legionnaires’ disease: laboratory diagnosis is essential
Cannot establish a diagnosis on clinical grounds
Prompt diagnosis reduces mortality
Accurate diagnosis improves understanding of epidemiology
Diagnosis should be linked to national and international case definitions

14. Why case definitions are needed
To set national and international standards for defining cases
To verify the diagnosis
To compare case details within and between countries
To facilitate national and international investigations and collaborations
To develop best practice within and between countries

15. EU Case definition: Legionnaires’ disease ICD code A48.1
Case Classification - Probable case
Any person with pneumonia
AND either laboratory evidence of at least one of the following:
Detection of Legionella pneumophila antigen in respiratory secretions or lung tissue 
Detection of Legionella spp. nucleic acid in a clinical specimen
L. pneumophila non-serogroup 1 or other Legionella spp. specific antibody response
L. pneumophila  serogroup 1, other serogroups or other Legionella species: single high titre in specific serum antibody
OR any person with pneumonia and at least one of the following epidemiological links:
Environmental exposure
Exposure to the same common source

16. EU Case definition: Legionnaires’ disease ICD code A48.1
Case Classification - Confirmed Case
Any person with a diagnosis of pneumonia AND with laboratory evidence of at least one of the following:
Isolation (culture) of Legionella species from respiratory secretions or any normally sterile site
The presence of L. pneumophila urinary antigen determined using validated reagents/kits
L. pneumophila  serogroup 1 significant antibody rise in paired serum sample
COMMISSION IMPLEMENTING DECISION of 8 August 2012 amending Decision 2002/253/EC laying down case definitions for reporting communicable diseases to the Community network under Decision No 2119/98/EC of the European Parliament and of the Council

17. Legionnaires’ disease in Europe 2016
1.37
notification rate N/100000
7069
reported cases
30 reporting countries
8.2%
case fatality %
441
reported deaths

18. Total European cases: country of report 2016

19. Total European cases: rate per 100,000 population 2016

20. Total European cases: Age-specific rate per 100,000 population 2016

21. Total European cases: Gender-specific rate per 100,000 population 2016

22. Age-specific rate per 100,000 population, EU/EEA, Germany, France, Spain, Italy 2016

23. Age-specific rate per 100,000 population, EU/EEA, UK, Portugal, Netherlands, Denmark, 2016

24. Added value of European surveillance
Monitor trends between countries
Monitor trends within countries
Identify where national surveillance needs improving
Target support to under-diagnosing countries
training schemes
laboratory expertise - EQA schemes
Develop European standards for a surveillance strategy and control and prevention legislation
Collaborate on research and surveillance projects

25. Total European cases

26. Total European cases: rate per 100,000 population 2007-2016

27. Cases by country of report

28. Cases by country of report

29. Cases by country of report

30. Case fatality (%), EU/EEA, France, Germany, Denmark, UK, Netherlands, 2007 - 2016

31. Percentage (%) of fatal cases by age group, EU/EEA, France, Germany, Denmark, UK, Netherlands,

32. In a summary…
Legionnaires' disease remains an uncommon, mainly sporadic respiratory infection with low notification rates in EU/EEA countries
The number of reported cases steadily increased over the last years
Different trend among countries – an increasing trend in most of them
Different notification rates among European countries (range from 0.00 – cases per 100,000 population in 2016)
Higher notification rate among men
Higher notification rate among older people

33. Europe’s first recognised travel associated outbreak
Benidorm, Spain
1973 and 1980
One of the first international outbreak investigations took place when this hotel in Spain had two outbreaks, the first in 1973 before legionella was discovered and the second soon after. A case control study was conducted that showed the showers to be the source of infection and the person who used them first each morning the most likely one to get infected.

34. The Guidelines
Address differences in national responses to cluster alerts
Standardise investigation procedures across Europe
Increase protection of Europeans from acquiring legionnaires’ disease as a result of travel
This shows the countries of infection that were visited by more than 5 cases in 2008.
Italy and France often come at the top of this list because they both report a large number of cases with travel in their own country of residence.

35. Case definitions for travel associated Legionella infection
Single cases Cases associated with one or more nights away from home in tourist or business accommodation in the two to ten days before onset of illness and where the accommodation site has not been associated with any other cases in the previous two years Clusters/outbreaks Two or more cases who stayed at the same accommodation site in the two to ten days before onset of illness and whose illness is in the same two year period [1]
[1] ECDC Legionella Toolbox:

36. Legal Context 1
Legionella is spread by any mechanism/operation that can generate aerosols or water droplets therefore cases are usually linked to man made water/cooling systems
Poorly maintained/designed water/cooling systems are usually the sources of infection and because of this there is usually someone to blame and potential for legal remedy.

37. Legal Context 2
Most countries have legislation governing the control of Legionella in water/cooling systems, e.g. health and safety legislation
Because of this, breaches of such legislation can lead to prosecution and if cases can be linked to such breaches, then the patient has recourse to legal means to gain compensation.

38. Facilitator notes:
Acknowledgements The creation of this training material was commissioned in 2010 by ECDC to Health Protection Agency (UK) and the University of Chester (UK) with the direct involvement of Louise Brown, Janice Gidman, Emma Gilgunn-Jones, Ian Hall (on behalf of the ECDC Legionnaires Disease Outbreak Toolbox Development Group), Tim Harrison, Rob Johnston, Carol Joseph, Sandra Lai, John Lee, Falguni Naik, Nick Phin, Michelle Rivett, and Susanne Surman-Lee. The revision and update of this training material was commissioned in 2017 by ECDC to Transmissible (NL) with the direct involvement of Arnold Bosman and Kassiani Mellou.