Connectedness of two outbreaks ofLegionellosis; Bremen, 2015 and 2016

Buchholz U1, Dullin J2, Lück C3, Lachmann R1,4, Jahn HJ1, Brodhun B1, Gründel A3, Lelgemann M2

1 Robert Koch Institute, Berlin, Germany 2 County/State Health Department, Bremen, Germany3 German Reference Laboratory for Legionella, Dresden,

Germany 4 Postgraduate Training for Applied Epidemiology, Robert

Koch Institute, Berlin, Germany

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Background (1)

Bremen is a county/city and one of 16 states

Population of roughly 0.5 million persons

Five areas (North, South, East, West, Middle) and 23 districts

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Background (2)

In November 2015 an outbreak occurred in the city of Bremen („2015-outbreak“)

A total of 19 cases were reported, 3 cases had ST2151

The health department conducted an outbreak investigation, however, the source of infection could not be identified. The outbreak ended in December 2015.

A second rise of cases occurred in February 2016 („2016-outbreak“), among cases again ST2151 was identified

For outbreak management and communication purposes it was important to know if the two outbreaks were two different events or belonged

together, i.e. were likely caused by the same source which was the area where the environmental investigation had

to focus on which cases belonged to the outbreak and which did not

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Does not microbiology alone give the answer? (1)

„If patients in both outbreaks have the same sequence type theircases must be caused by the same common source.“ However: in Legionella epidemiology clones exist, such as Paris strain

(ST1), Lorraine strain (ST47) or Berlin clone (ST182) which may cause a large proportion of cases in a given area („clonal area“), e.g. city

Identification of a clonal ST in patients of two outbreaks in a clonal areawould not help in answering the above question

For Bremen the local distribution of ST is unknown

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Does not microbiology alone give the answer? (2)

„Patients with the same sequence type belong to the outbreak, patients without do not. Whereabouts of patients with the outbreak ST define the outbreak area.“ Yes, but there are potential caveats:

again there is the possibility of clones; belonging to the same clone maybe non-discriminatory

not all (or: often only few) patients have a respiratory sample yielding a ST, many do not; what to do with them? Are or are they not outbreak cases? Do theycontribute information?

also microbiology may err. Including wrongly a single patient in a relativelydistant region as an outbreak case may mislead source finding effortstremendously („important outlier“);

„whereabout“ may mean: residence, work place, restaurant visit, recreational trip, … Which of these should be included?

Microbiology and epidemiology must closely work together toadress the stated objectives

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Methods

Suspect case definition: Lab confirmed and reported case of Legionellosis withrespiratory symptoms with residence, workplace or stay in the city of Bremen with onset after 1 November, 2015

Case finding: communication with physicians through website of the Association of Statutory Health Insurance Physicians (Bremen) and press announcements

Exploratory interviews

Comparison of

age distribution

sex distribution

distribution of place of residence between cases in 2015-outbreak and 2016-outbreak

Typing of patient and environmental samples

Mab-typing

Sequence-based typing

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Results

2015-outbreak: 19 suspect (reported) cases2016-outbreak: 26 suspect (reported) cases

Sex distribution in 2015 and 2016 outbreaks did not differ significantly (p=0.32)

% male

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Results

Age distribution

Median: 61 (2015) and 57 years (2016)

P-test for „equality of populations“ in 2015/2016: 0.76

Age distribution among males/females in both outbreaks broadly similar

age age

male suspect cases female suspect cases

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Geographic distribution: city areas and city districts

Geographic distribution by area of residence

Differences not significant

by city area; p=0.87 by city district; p=0.39

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Geographic distribution (2): individual mapping

Mapping of place of residence, work and other locationsduring the incubation period

Place of residence, 2015 and Place of residence and work as well as route to work, 2015 and 2016

2016

6 km 3 km

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City districts of importance

Combination of several geographical analyses identified 5 city districts whereplace of residence, work or other stay was „associated“ with becoming a case

One „odd case“ remained whose sputum contained ST2151. However: noexposure could be identified to the outbreak area (orange). Follow-up lab tests showed that ST was not 2151.

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Epidemic curve of suspect cases

Most likely period of transmission Maximum period of transmission

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Laboratory results

2015-outbreak: L. pn. Sg1, Mab-type Benidorm, ST2151 in 3/19 cases2016-outbreak: L. pn. Sg1, Mab-type Benidorm, ST2151 in 9/26 cases

One culture confirmed suspect case: Mab-type Knoxville, ST182

Environmental samples:

From 55 buildings / institutions

118 cooling towers

22 other sources

>490 samples with >1500 isolates of which 523 yielded L.pn.SG1

but in none of them was ST2151 identified

One wellness center: Mab-type Knoxville, ST182

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Probable, confirmed, excluded case definition

Suspect:Lab confirmed and reported case of Legionellosis with respiratory symptoms withresidence, workplace or stay in the city of Bremen with onset after 1 November, 2015

Probable:Lab confirmed and reported case of Legionellosis with respiratory symptoms withresidence, workplace or stay in one of the city districts Findorff, Walle, Gröpelingen, Wolmertshausen or Häfen with onset between 1 November 2015 and 31 March 2016.

Confirmed: as probable, with Mab-type Benidorm, or ST2151

Excluded:- not compatible with suspect case definition, OR - Mab-type other than Benidorm, OR- ST other than 2151

exclusion of 3 suspect cases

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Conclusions

Did the outbreaks belong together?

2015 and 2016 outbreak with similar epidemiological and laboratorycharacteristics likely caused by the same source, both times of temporaryactivity

Which was the area where the environmental investigation had to focus on?

Most probable region of infection are the 5 city districts in Bremen West

Which cases belonged to the outbreak and which did not?

Development of case definition that allowed exclusion of suspect casesunlikely to belong to the outbreak

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Acknowledgements

Colleagues at the health department in Bremen

Denis Pineda

Ute Hauswaldt

Markus Kaschubski

Colleagues at the reference laboratory in Dresden

Professor Dr. Exner, Institute for Hygiene, University of Bonn

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Thank you for your attention

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LD outbreak, Rapid City, SD, USA 2005

„Citywide“ outbreak

Rapid city, South Dakota, 2005

Cases were significantly more likely to havepassed through several city areas (seven mapgrids) that contained or were adjacent to areaswith cooling towers positive for Legionella.

Between July and Nov 2005:

291 environmental samples(201 water, 90 biofilm) from123 sources at 73 sites

Several CT positive, none with Benidorm

OB strain identified at decorative fountainof a restaurant

O’Laughlin, BMC-ID 2007, “Restaurant outbreak of Legionnaires disease associated with a decorative fountain - an environmental and case-control study”

Outbreak period: May – October

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Incidence of probable or confirmed cases

Based on population of Bremen

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Association of decreasing disease severity and lateincubation time

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- Residence, workplace or other stay- Aerosol emitters (evaporative cooling towers, …)

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Two cases with very distinct exposure,and the wind direction at that time

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Wind directions during likely and possible periods ofexposure

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Particulate matter, temperature, wind velocity, wind speed and aerial pressure were all not pinpointing/helpful

particulatematter

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Inversion data only available by month

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Background – City of Bremen

Capital of the Federal State „Bremen“ (Bremen & Bremerhaven)

Located in the North-West of Germany

Area: 327 km²

Population: 557.000 inhabitans

Divided into 5 urban districts

(North, Middle, West, South; East)

Source: https://upload.wikimedia.org/wikipedia/commons/0/00/Bremen_Subdivisions.svg

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Outbreak confirmation

Annual number of cases of LD reported by the LHD of Bremen:

reporting year number of cases incidence 2006 3 0,52007 5 0,9

2008 4 0,72009 7 1,3

2010 3 0,52011 1 0,22012 5 0,9

2014 2 0,4

2015 23 4,2

thereof in Nov/Dec 2015 17 3,1

2016* 24 4,4

thereof in Feb/March 2016 22 4,3

on average fourcases per year

* Until 9.9.2016

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Geographic distribution (incidence by „most likely placeof infection“)

Excluded: port districts, becausedenominator very small veryhigh incidence

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Collaborating Partners/Thanks to…

Colleagues in Bremen

State health department: Ralf Stelling

LHD: Monika Lelgemann, Joachim Dullin, Denis Pineda, Ute Hauswald, Markus Kaschubski

Laboratory Bremen: Michaela Berges

And further colleagues from the Bremen Ministry of health and commercialregulatory authorities

Colleagues from the Reference Laboratory for Legionella in Dresden:

Anne Gründel, Markus Petzold

Colleagues from the Robert Koch Institute in Berlin: Udo Buchholz, Heiko Jahn, Raskit Lachmann, Christina Frank

Prof. Martin Exner, Institute for Hygiene, University of Bonn

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Background – City of Bremen: local areas

The 5 urban districts were sub divided in further 22 local centers

1. Nord => Blumental, Vegesack, Burgiesum,

2. Mitte => Mitte, Häfen

3. West => Gröpelingen, Walle, Findorf, Blockland,

4. Süd => Seehausen, Strom, Wolmertshausen, Huchting, Neustadt, Obervieland,

5. Ost => Schwachhausen, Östliche Vorstadt, Vahr, Hemelingen, Osterholz, Oberneuland, Horn-Lehe, Borgdorf

Quelle: https://upload.wikimedia.org/wikipedia/commons/0/00/Bremen_Subdivisions.svg