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Relationship Between Nasopharyngeal Carriage and Acute Otitis Media Due to Streptococcus Pneumoniae Among Finnish Children Aged Less Than Two Years

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Relationship Between Nasopharyngeal Carriage and Acute Otitis Media Due to Streptococcus Pneumoniae Among Finnish Children Aged Less Than Two Years CORE Metadata, citation and similar papers at core.ac.uk Provided by Julkari RITVA SYRJÄNEN Relationship Between Nasopharyngeal Carriage and Acute Otitis Media Due to Streptococcus Pneumoniae Among Finnish Children Aged Less than Two Years ACADEMIC DISSERTATION To be presented, with the permission of the Board of the School of Medicine of the University of Tampere, for public discussion in the Small Auditorium of Building M, Pirkanmaa Hospital District, Teiskontie 35, Tampere, on March 13th, 2015, at 12 o’clock. UNIVERSITY OF TAMPERE RITVA SYRJÄNEN Relationship Between Nasopharyngeal Carriage and Acute Otitis Media Due to Streptococcus Pneumoniae Among Finnish Children Aged Less than Two Years Acta Universitatis Tamperensis 2031 Tampere University Press Tampere 2015 ACADEMIC DISSERTATION University of Tampere, School of Medicine National Institute for Health and Welfare Finland Supervised by Reviewed by Docent Kari Auranen Docent Aino Ruohola University of Helsinki University of Turku Finland Finland Professor emeritus Heikki Puhakka Docent Marjo Renko University of Tampere University of Oulu Finland Finland The originality of this thesis has been checked using the Turnitin OriginalityCheck service in accordance with the quality management system of the University of Tampere. Copyright ©2015 Tampere University Press and the author Cover design by Mikko Reinikka Distributor: [email protected] http://granum.uta.fi Acta Universitatis Tamperensis 2031 Acta Electronica Universitatis Tamperensis 1520 ISBN 978-951-44-9735-3(print) ISBN 978-951-44-9736-0 (pdf) ISSN-L 1455-1616 ISSN 1456-954X ISSN 1455-1616 http://tampub.uta.fi Suomen Yliopistopaino Oy – Juvenes Print Tampere 2015 441 729 Painotuote To the versatility of life ABSTRACT Streptococcus pneumoniae causes a wide variety of diseases, ranging from relatively mild but very common mucosal diseases like otitis media and pneumonia to rarer but severe invasive diseases like bacteraemia and meningitis. These diseases cause a considerable burden worldwide. Nasopharyngeal carriage is a prerequisite for pneumococcal otitis media and viral respiratory infection contributes to its pathogenesis. Nasopharyngeal carriage also comprises the reservoir of pneumococcal strains for their spread in the population. Pneumococcal carriage is most prevalent in children. In planning effective long-term prevention strategies against pneumococcal diseases it is essential to have knowledge on the natural cause of pneumococcal carriage and on how the carriage progresses to disease. This study describes the natural course of pneumococcal nasopharyngeal carriage in a prospective follow-up of Finnish children from 2 to 24 months of age before the start of pneumococcal vaccinations. Special attention was focused on the dynamics of pneumococcal carriage during health and respiratory infection and development of pneumococcal acute otitis media (AOM). Almost all children carried pneumococci at least once during the first two year of life and in average the prevalence of carriage was 27%. The frequency of pneumococcal carriage clearly increased with age and with respiratory infection. There was no significant association between pneumococcal carriage and sex or season, but antimicrobial treatment temporarily decreased carriage frequency. During pneumococcal AOM, S. pneumoniae and especially the serotype found in the middle ear fluid was practically always found in the nasopharynx, but only half of the serotypes carried during clinical AOM were found to cause the disease. The hazard of carriage acquisition was about three times higher in association with the onset of a new respiratory infection as compared to health. The hazard of pneumococcal AOM media was significantly higher during carriage acquired around the onset of respiratory infection as compared to carriage acquired more than one month before or more than one week after the onset of respiratory infection. Of all pneumococcal AOM events, almost 80% were caused by a serotype acquired within one month before the sickness onset. Preceding episodes of homologous carriage episodes decreased the hazard of pneumococcal AOM. The pneumococcal AOM hazard during concurrent pneumococcal carriage and respiratory infection did not depend on age. The natural course of pneumococcal carriage in Finnish children is similar as observed in other industrialised countries. Viral respiratory infection is an important factor for acquisition of carriage and its progression to AOM. Age, respiratory infection and antimicrobial treatment should be considered when the results of carriage studies are interpreted. Nasopharyngeal carriage during AOM can be used as information in monitoring the serotypes causing AOM, and the use of a negative nasopharyngeal finding could be considered in excluding pneumococcal AOM in clinical praxis. Carriage studies are important tools in planning and evaluating methods for preventing pneumococcal AOM. TIIVISTELMÄ Pneumokokkibakteeri aiheuttaa laajan kirjon erilaisia sairauksia, alkaen suhteellisen lievistä mutta erittäin yleisistä limakalvojen sairauksista kuten välikorvatulehdus ja pinnallinen keuhkokuume harvinaisempiin mutta vakaviin sairauksiin kuten verenmyrkytys ja aivokalvontulehdus. Näiden sairauksien aiheuttama tautitaakka on maailmanlaajuisesti merkittävä. Nenänielukantajuus on edellytys pneumokokin aiheuttaman välikorvatulehduksen synnylle ja viruksen aiheuttama hengitystietulehdus myötävaikuttaa taudin kehittymiseen. Nenänielukantajuus toimii myös pneumokokkikantojen varastona, jota kautta pneumokokit leviävät väestössä. Pnemokokkikantajuus on yleisintä lapsilla. Tieto pneumokokkikantajuuden luontaisesta kulusta ja siitä kuinka kantajuus etenee taudiksi on välttämätöntä kun pneumokokkitaudeille suunnitellaan pitkällä tähtäimellä tehokkaita ennaltaehkäisymenetelmiä. Tämä tutkimus kuvaa pneumokokkikantajuuden luontaista kulkua suomalaisilla, lapsilla, joita seurattiin 2 kuukauden iästä 2 vuoden ikään asti ennen pneumokokkirokotusten aloittamista. Erityistä huomiota kiinnitettiin kantajuuden eroihin terveenä ollessa ja hengitystietulehduksen aikana sekä siihen, miten äkillinen pneumokokin aiheuttama välikorvatulehdus kehittyy. Melkein kaikki lapset kantoivat pneumokokkia vähintään kerran ensimmäisten kahden ikävuoden aikana ja keskimääräinen kantajuusprevalenssi oli 27 %. Pneumokokkikantajuus lisääntyi selvästi iän myötä ja hengitystietulehduksen aikana. Pneumokokkikantajuus ei liittynyt merkittävästi sukupuoleen eikä vuodenaikaan, mutta antibioottihoito vähensi kantajuutta lyhytaikaisesti. Pneumokokin aiheuttaman äkillisen välikorvatulehduksen aikana pneumokokki, ja erityisesti juuri välikorvaeritteestä löytynyt serotyyppi löytyi käytännöllisesti katsoen aina nenänielusta, mutta vain puolet välikorvatulehduksen aikana kannetuista serotyypeistä todettiin kyseisen korvatulehduksen aiheuttajiksi. Tuoreen hengitystietulehduksen alkuvaiheessa lapsilla oli noin kolme kertaa suurempi todennäköisyys saada kantajuus kuin terveenä. Äkillisen välikorvatulehduksen kehittymisen todennäköisyys oli merkittävästi suurempi silloin, kun kantajuus oli alkanut hengitystietulehduksen alkuvaiheen yhteydessä kuin silloin, jos kantajuus oli alkanut yli kuukausi ennen hengitystietulehduksen alkua tai yli viikko hengitystietulehduksen alun jälkeen. Kaikista äkillisistä välikorvatulehduksista lähes 80 % oli sellaisen serotyypin aiheuttamia, joka oli saatu kuukauden sisään ennen taudin alkua. Aikaisemmat saman serotyypin kantajuusjaksot vähensivät saman pneumokokkiserotyypin aiheuttaman äkillisen välikorvatulehduksen todennäköisyyttä. Välikorvatulehduksen todennäköisyys ei riippunut lapsen iästä, jos pneumokokkikantajuus ja hengitystietulehdus osuivat päällekkäin. Pneumokokkikantajuuden luonnollinen kulku oli suomalaisilla lapsilla samanlaista kuin muissakin teollisuusmaissa. Viruksen aiheuttama hengitystietulehdus on merkittävä tekijä kantajuuden alkamisessa ja sen etenemisessä äkilliseksi välikorvatulehdukseksi. Ikä, hengitystietulehdus ja antibioottihoito pitää ottaa huomioon kantajuustutkimusten tulosten tulkinnassa. Äkillisen välikorvatulehduksen aikaista nenänielukantajuutta voitaisiin käyttää hyväksi välikorvatulehdusta aiheuttavien pneumokokkiserotyyppien seurannassa ja negatiivisen nielunlöydöksen käyttöä pneumokokin aiheuttaman korvatulehduksen poissulkumenetelmänä voitaisiin harkita. Kantajuustutkimukset ovat tärkeitä välineitä kun suunnitellaan ja arvioidaan pneumokokin aiheuttaman äkillisen välikorvatulehduksen ennaltaehkäisyä. CONTENTS ABSTRACT ................................................................................................................................ 5 TIIVISTELMÄ ........................................................................................................................... 7 LIST OF ORIGINAL COMMUNICATIONS ................................................................. 15 ABBREVIATIONS ................................................................................................................. 16 1 INTRODUCTION ........................................................................................................ 17 2 REVIEW OF THE LITTERATURE ........................................................................ 19 2.1 Streptococcus pneumoniae as a bacterium .................................................................. 19 2.1.1 Structure of Streptococcus pneumoniae ................................................................. 19 2.1.2 Identification of Streptococcus pneumoniae .........................................................
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