Molecular epidemiology of pneumococcal carriage and invasive disease

Streptococcus pneumoniae, also known as pneumococcus, is a major contributor to morbidity and mortality worldwide. It is the main cause of respiratory tract infections such as otitis media and sinusitis, but also causes millions of deaths each year due to pneumonia, meningitis and septicemia, especially among children and the elderly. Pneumococci are frequently carried in the nasopharynx of healthy children attending day care centers, where up to 70% may be colonised. The purpose of the studies within this thesis was to investigate the molecular epidemiology of invasive pneumococcal disease and carriage, as well as the spread and mechanisms for spread of pneumococcal isolates with a reduced susceptibility to penicillin.

Invasive and carriage isolates from the same period of time and the same geographic area were compared. Depending on serotypes the isolates could be grouped into at least two classes. One class caused mainly invasive disease (serotype 1, 4, 7F and 9V) and the other class included serotypes found both among carriers and patients with invasive disease (6A, 6B, 14 and 19F). Moreover, serotypes and clones of invasive isolates were correlated to clinical parameters such as the APACHE 11 score (a measurement of severity of disease at admittance to the hospital), age, mortality, underlying disease and pneumococcal disease type. Serotype 1 and 7F isolates were found genetically highly related within each serotype. These types caused invasive disease mainly in young adults and previously healthy individuals, suggesting that type 1 and 7F might act as primary pathogens. In contrast, serotype 19F and 11 A caused disease mainly in elderly patients with underlying diseases, suggesting these types to act as opportunistic pathogens. An emerging frequency of antibiotic resistant pneumococci has been observed globally. During 1997-2003, in Sweden, the prevalence of PNSP (isolates with a reduced susceptibility to penicillin) remained stable around 2%, even though the prescription of antibiotics decreased. However, the prevalence of multi resistant isolates increased. Among PNSP, serotype 14 increased due to one clonal cluster, the internationally spread clone Spain9v-3 with STI 56. One reason for the successful spread was suggested to be the presence of adhesive pilus-like structures encoded by the rIrA islet. In conclusion, pneumococcal serotype in combination with clonal type is important for disease outcome. Furthermore, the recently identified pneumococcal pili may be important for successful spread of antibiotic resistant Streptococcus pneumoniae.

List of scientific papers

I. Sandgren A, Sjostrom K, Olsson-Liljequist B, Christensson B, Samuelsson A, Kronvall G, Henriques Normark B (2004). "Effect of clonal and serotype-specific properties on the invasive capacity of Streptococcus pneumoniae." J Infect Dis 189(5): 785-96. Epub 2004 Feb 16
https://pubmed.ncbi.nlm.nih.gov/14976594

II. Sjostrom K, Spindler C, Ortqvist A, Kalin M, Sandgren A, Kuhlmann-Berenzon S, Henriques-Normark B (2006). "Clonal and capsular types decide whether pneumococci will act as a primary or opportunistic pathogen." Clin Infect Dis 42(4): 451-9. Epub 2006 Jan 17
https://pubmed.ncbi.nlm.nih.gov/16421787

III. Hogberg L, Ekdahl K, Sjostrom K, Olsson-Liljequist B, Walder M, Melander E, Ringberg H, Normark BH (2006). "Penicillin-resistant pneumococci in Sweden 1997-2003: increased multiresistance despite stable prevalence and decreased antibiotic use." Microb Drug Resist 12(1): 16-22
https://pubmed.ncbi.nlm.nih.gov/16584303

IV. Sjostrom K, Blomberg C, Fernebro J, Dagerhamn J, Morfeldt E, Barocchi M, Browall S, Moschioni M, Andersson M, Albiger B, Henriques F, Rappuoli R, Normark S, Henriques-Normark B (2006). "Clonal success of piliated penicillin non-susceptible Pneumococci" (Submitted)