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SOURCE, OR PART OF THE FOLLOWING SOURCE: Type Dissertation Title Legionnaires’ disease in the Netherlands, 1998–2006 Author J.W. den Boer Faculty Faculty of Medicine Year 2008 Pages 164

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2007118. DenBoer. 00_Prelims. Proef 5. 22-12-2007:18.18, page 1.

Legionnaires’ disease in the Netherlands, 1998–2006


This thesis was prepared at the Municipal Health Service Kennemerland, Haarlem, the Netherlands. The research was supported by grants of the Haarlem Tuberculosis Fund and the Public Health Foundation (Fonds ogz). The printing of the thesis was financially supported by the Public Health Foundation (Fonds ogz), Oxiod BV and Clindia Benelux BV. This thesis is printed according to the “Cradle to Cradle” design principles: “How do we love all the children of all species for all time? The goal is a delightfully diverse, safe, healthy and just world, with clean air, water, soil and power – economically, equitably, ecologically and elegantly enjoyed”, by McDonough Braungart Design Chemistry (www.mbdc.com and also www.whykiki.nl). The thesis is printed on water-proof plastic with non-toxic washable inks so that it can last for centuries or more appropriately, it can be washed, melted and re-used for any new publication. isbn: 978-90-9022710-8 Photo cover: Maurice Scheltens, Liesbeth Abbenes Lay-out cover: Baster Typesetting: TAT zetwerk, Utrecht Printing: Ecodrukkers, Nieuwkoop Copyright © 2008 Jeroen Willem den Boer, Amsterdam, the Netherlands. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, without prior permission of the author.


Legionnaires’ disease in the Netherlands, 1998–2006

academisch proefschrift ter verkrijging van de graad van doctor aan de Universiteit van Amsterdam op gezag van de Rector Magnificus Prof. Dr. D.C. van den Boom ten overstaan van een door het college voor promoties ingestelde commissie, in het openbaar te verdedigen in de Aula der Universiteit op woensdag 5 maart 2008, te 14.00 uur door Jeroen Willem den Boer geboren te Eindhoven


Promotie commissie: Promotor: Prof. dr. R.A. Coutinho Overige leden: Prof. dr. P.M.M. Bossuyt Prof. dr. ir. W.G.J. van der Meer Dr. J.M. Prins Dr. J.F.P. Schellekens Prof. dr. P. Speelman Dr. J. van Steenbergen Faculteit Geneeskunde


“Epidemic fever is caused by the air. Because all men inhale the same wind, when the air is infected with such pollutions that are hostile to the human race, the men fall sick.” Hippocrates, Breaths xi



Contents Chapter 1. General introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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part 1. epidemiology Chapter 2. A large outbreak of Legionnaires’ disease at a flower show, the Netherlands, 1999 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chapter 3. Risk factors for sporadic community-acquired Legionnaires’ disease. A three-year national case-control study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chapter 4. Use of surface water in drinking water production associated with municipal Legionnaires’ disease incidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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part 2. transmission Chapter 5. Legionnaires’ disease and gardening. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chapter 6. Genotypic comparison of clinical Legionella isolates and patient-related environmental strains in the Netherlands, 2002–2006 . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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part 3. laboratory diagnosis Chapter 7. Diagnosis of Legionella infection in Legionnaires’ disease . . . . . . . . . . . . . . . . . . 79 Chapter 8. Sensitivity of three urinary antigen tests associated with clinical severity in a large outbreak of Legionnaires’ disease in the Netherlands . . . . . . . . . . . . . . . . . . . . . . . . . 91 Chapter 9. The sensitivity of three serum antibody tests in a large outbreak of Legionnaires’ disease in the Netherlands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101

part 4. control and prevention Chapter 10. Outbreak detection and secondary prevention of Legionnaires’ disease in the Netherlands. A systematic approach.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 Chapter 11. General discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Samenvatting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Curriculum vitae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Publications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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29 30 31 32 33 34 35

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Conyn-Van Spaendonck MA. Estimation of minimum infection rates with Legionella pneumophila in an exposed population. Epidemiol Infect. 2006;134:579–584. Epub 2005 Oct 20. Den Boer, JW. Hoofdstuk 11. Legionella. In: Infectieziektebestrijding. Helsloot I. en J.E. van Steenbergen. Instituut voor Veiligheids- en Crisismanagement (cot). Den Haag 2005. Yzerman EPF, den Boer JW, Lettinga KD, Schel AJ, Schellekens J, Peeters M. Sensitivity of three serum antibody tests in a large outbreak of Legionnaires’ disease in the Netherlands. J Med Microbiol. 2006;55:561– 566. Bencini MA, Yzerman EPF, Bruin JP, den Boer JW. Drie patiënten met Legionella-pneumonie, in verband gebracht met een sauna, een koeltoren en een caravan in Nederland. Ned Tijdschr Geneeskd. 2005;149:1973–1977. Den Boer JW, Yzerman EPF. Diagnosis of Legionella infection in Legionnaires’ disease. Eur J Clin Microbiol Infect Dis. 2004;23:871–878. Verhoef LPB, Yzerman EPF, Bruin JP, Den Boer JW. Domestic exposure to legionellae for Dutch Legionnaires’ disease patients. Arch Environ Health. 2004;59:597–603. Boshuizen HC, Den Boer JW, De Melker H, Schellekens JFP, Peeters MF, Van Vliet JA, Conyn-van Spaendonck MAE. Reference Values for the serion classic elisa for detecting Legionella pneumophila antibodies. Eur J Clin Microbiol Infect Dis 2003;22:706–708. Lettinga KD, Verbon A, Weverling GJ, Schellekens JFP, Den Boer JW, Yzerman EPF, Prins J, Boersma WG, Van Ketel RJ, Prins JM, Speelman P. Legionnaires’ disease at a Dutch Flower show: Prognostic Factors and Impact on Therapy. Emerging Infectious Diseases 2002;12:1448–1454. Yzerman EPF, den Boer JW, Lettinga KD, Schellekens J, Dankert J, Peeters M. Sensitivity of three urinary antigen tests associated with clinical severity in a large outbreak of Legionnaires’ disease in The Netherlands. J Clin Microbiol 2002;40;9:3232–3236. Den Boer JW, Friesema IHM, Hooi JD. Gemelde Legionella-pneumonie in Nederland, 1987–2000. Nederlands Tijdschrift voor Geneeskunde 2002;146:315–320. Den Boer JW, Yzerman EPF, Schellekens J, Lettinga KD, Boshuizen H, Van Steenbergen J, Bosman, A, Van den Hof S, Van Vliet H, Peeters MF, Van Ketel RJ, Speelman P, Kool J, Conyn-Van Spaendonck MAE. A large outbreak of Legionnaires’ disease at a Dutch flower show. Emerging Infectious Diseases 2002;8:37–43. Den Boer JW. Aangegeven Legionella-pneumonie in Nederland. Infectieziekten bulletin 2001;12:437–438. Den Boer JW. Preventie van Legionella-pneumonie, een gerichte aanpak. Infectieziekten bulletin 2001;12: 449–451. Boshuizen HC, Neppelenbroek S, Van Vliet H, Schellekens JFP, Den Boer JW, Peeters FP, Conyn-Van Spaendonck MAE. Subclinical legionella infection in workers near the source of a large outbreak of Legionnaires’ disease. Journal of Infectious Diseases 2001;184:515–518. Den Boer JW, Bosman A, Van Steenbergen J, Van den Hof S, Hahné S, Boshuizen H, Conyn-van Spaendonck MAE. Een legionella-epidemie onder bezoekers van een beurs in Bovenkarspel. Beschrijving van de epidemie. Patient-controle onderzoek naar de bron. rivm rapport 213690 004. Bilthoven, 2001. Den Boer JW. Westfriese Flora: een terugblik. Infectieziekten bulletin 2000; 11:46–47. Boshuizen HC, Neppelenbroek SE, Van Vliet JA, Schellekens JFP, Den Boer JW, Peeters MF, Verbakel H, Heijnen MLA, Conyn-van Spaendonck MAE. Serological findings and health complaints in exhibitors working on the 1999 Westfriese Flora in Bovenkarspel. rivm report 213690.006. Bilthoven, 2000. Den Boer JW, Yzerman E, Schellekens J, Bruin JP, Van Leeuwen W, Mooijman K, Veenendaal H, Bergmans amc, Van der Zee AN, Van Ketel RJ, Tijsen H, Conyn-van Spaendonck MAE. Onderzoek naar de bron van een epidemie van legionellose na de Westfriese Flora in Bovenkarspel. rivm rapport 213690 003. Bilthoven, 2000. Friesema I, Den Boer JW, Hooi J. Legionella-pneumonie in Nederland, juli 1998 – december 1999. Beschrijving van aangegeven gevallen en risicofactoren voor infectie. Rapport GGD Zuid-Kennemerland. Haarlem, 2000. Den Boer JW, Slijkerman FAN, Yzerman EPF. De epidemie van Legionella pneumonie onder bezoekers van de Westfriese Flora in Bovenkarspel. Infectieziekten Bulletin 1999;10:72–75. Den Boer JW, De Vries A. Veteranenziekte in Zuid-Kennemerland. Rapport GGD-Zuid-Kennemerland. Haarlem, 1998.

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39 Den Boer JW, Yzerman E, Van Belkum A, Vlaspolder F, Van Breukelen FJ. Legionnaire’s disease and saunas [letter]. Lancet 1998;351:114. 40 Den Boer JW. Identifying a desired organizational framework for disease outbreak management in Kenya. Thesis for Master of Science degree in Management and Organizational Development. United States International University, 1993, Nairobi, Kenya. 41 Okello GB, Agata N, Ouma J, Cherogony SC, Tukei PM, Ochieng W, den Boer JW, Sanders EJ. Outbreak of yellow fever in Kenya. Lancet. 1993;341:489. 42 Den Boer JW. who report on the Bamako initiative in Kenya. Ministry of Health Kenya and World Health Organization Kenya country oﬃce. Nairobi, Kenya, 1992. 43 Den Boer JW, Huttjes A, Lang G, Van der Beek AM. Gezondheidsenquete. De gezondheidstoestand, het voedingspatroon, en de behoefte aan gezondheidsvoorlichting van clienten van de Gemeentelijke Sociale Dienst in de wijk Nieuw Den Helder. European Community Action Programme “Nieuw Den Helder plus”. Rapport van de Gewestelijke Gezondheidsdienst Kop van Noord-Holland. Den Helder, 1991. 44 Kromhout D, Den Boer JW, Van Oostrom A, Verkley HGM. Derde signaleringsrapport hart- en vaatziekten. Stuurgroep toekomstscenario’s gezondheidszorg. rivm Bilthoven, 1989.

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Figure 3a. Smoothed mean geometric immunoglobulin (Ig) M antibody titers to Legionella pneumophila of nearest 35 exhibitors in hall 3 and 4 per 63 cm2 of exhibition area; confirmed and probable cases among exhibitors in halls 3 and 4. = confirmed case in exhibitor; ◦ = probable case in exhibitor; Bu = bubblemat; W = whirlpool spa.

•

Figure 3b. Smoothed mean geometric IgG antibody titers to L. pneumophila of 35 exhibitors nearest to whirlpool in halls 3 and 4 per 63 cm2 of exhibition area; exhibitors ill with confirmed and probable cases in halls 3 and 4. = confirmed case in exhibitor; ◦ = probable case in exhibitor; Bu = bubblemat; W = whirlpool spa.

•

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Figure 4a. Exhibition hall, West Frisian Flower Show, Bovenkarspel, the Netherlands, 1999. Circles indicate locations in watersupply system where water samples were taken. pe = polyethylene.

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Figure 4b. Exhibition hall, West Frisian Flower Show, Bovenkarspel, the Netherlands, 1999. Assessment of risk for Legionella pneumophila infection.

Figure 4c. Exhibition hall, West Frisian Flower Show, Bovenkarspel, the Netherlands, 1999. Water samples taken and culture status.

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Figure 2. Legionnaires’ disease incidence rate standardised for age and gender per 100.000 inhabitants for 466 municipalities in the Netherlands.

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