Invasive disease by Haemophilus influenzae in Sweden in the era of the H. influenzae type b vaccine
Author
Summary, in English
In order to answer the initial question, we studied the epidemiology, the clinical burden and antimicrobial resistance of invasive H. influenzae in Sweden 1997-2010. Two aspects of the pathogenesis of invasive H. influenzae disease were addressed; bacterial binding to the extracellular matrix and the role of complement regulator binding in invasive disease. A case report of a severe invasive H. influenzae type f infection, including an examination of contributing host factors, is also presented.
Our results suggest that invasive disease by H. influenzae has not disappeared, but the epidemiology has radically changed. We found no support for serotype replacement in young children. In adults, and especially elderly adults, the incidence of invasive disease by non-typeable H. influenzae (NTHi) increased significantly during the study period. The results also suggest an increased incidence of invasive disease by H. influenzae type f (Hif), and type f is the most common serotype in Sweden today. Cases of invasive disease by non-type b isolates that occurred in healthy adults were often severe, suggesting the existence of hypervirulent non-type b strains. The β-lactam resistance of invasive H. influenzae isolates increased during the study period, due to an increase of β-lactamase negative β-lactam resistant NTHi. A clonal expansion of a β-lactamase negative ampicillin resistant (BLNAR) clone, frequently found in invasive disease, was suggested.
The ability of H. influenzae to bind laminin, and anchor the extracellular matrix through the adhesin Protein E was confirmed. Binding to complement regulators was not higher in invasive as compared to nasopharyngeal NTHi isolates, and thus did not seem central for invasive capacity. Speculation, but no comprehensive conclusion as to what host factors relate to invasive disease by H. influenzae in adults was possible.
The results suggest that the vaccination against H. influenzae type b remains very effective 20 years after it was introduced, but that continued surveillance of incidence and antimicrobial resistance of invasive Haemophilus disease is warranted. The results also suggest that ongoing research should focus on non-typeable H. influenzae, which today dominates all types of H. influenzae infections.
Department/s
- Infectious Diseases Research Unit
- Clinical Microbiology, Malmö
- EpiHealth: Epidemiology for Health
Publishing year
2012
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2012:70
Full text
Document type
Dissertation
Publisher
Department of Laboratory Medicine, Lund University
Topic
- Microbiology in the medical area
- Infectious Medicine
Keywords
- Haemophilus influenzae
- sepsis
- epidemiology
- antimicrobial resistance
- bacterial adhesion
Status
Published
Research group
- Infectious Diseases Research Unit
- Clinical Microbiology, Malmö
- Institution of Laboratory Medicine, Medical Microbiolgy, Respiratory Pathogen Group
Supervisor
- Kristian Riesbeck
- Inga Odenholt
- Arne Forsgren
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-87189-33-3
Defence date
7 September 2012
Defence time
13:00
Defence place
CRCs Aula, Skånes Universitetssjukhus, Malmö
Opponent
- Per Olcén (Professor)