Date of Award

8-2015

Document type

Thesis

Degree Name

PhD (Doctor of Philosophy)

First Supervisor

Professor Hilary Humphreys

Second Supervisor

Dr Mary Meehan

Third Supervisor

Dr Imelda Vickers

Funder/Sponsor

Pfizer (Ireland)

Keywords

Vaccines, Conjugate

Abstract

The 7 and 13 valent pneumococcal conjugate vaccines (PCV7/13) were introduced to the Irish childhood immunisation schedules in 2008 and 2010, respectively. The effects of these vaccines on pneumococcal serotypes and antimicrobial susceptibilities among paediatric non-invasive isolates in Irish paediatric hospitals were investigated from 2009–2014. Encouragingly, the frequency of PCV7 serotypes declined among carriage and non-invasive infections such as conjunctivitis, non-bacteraemic lower respiratory tract infection and otitis media. Furthermore, four of the additional six serotypes targeted by PCV13; 1, 5, 6A and 7F were infrequent or did not occur. The prevalence of pneumococci non-susceptible to at least one antimicrobial ranged between 21–41% from 2009–2014. However, antimicrobial non-susceptible clones such as England14 -9 Spain9V -3, Spain6B -2 expressing PCV7/13 serotypes 14, 9V and 6B declined considerably from 2009 onwards. These results highlight the positive impact of PCV7/13 on several of their target serotypes. However, fluctuations occurred in the frequency of PCV13 serotypes 19A and 3. The fluctuation observed in serotype 19A also included antimicrobial non-susceptible 19A of clonal complex 320.

Overall, the incidence of non-vaccine type (NVT) pneumococci amongst carriage and non-invasive infections increased. Common NVT pneumococci included 11A, 15B/C, 35B, and 15A. A significant increase in antimicrobial non-susceptible NVT also occurred, the most frequent being serotype 35B of ST558, serotype 15A of Sweden15A -25, and its variants. Continued surveillance will determine if NVT increase in prevalence with sustained conjugate vaccine use.

Additionally, the distribution of eight virulence genes among carriage and noninvasive pneumococci was investigated. The distribution of these varied among different serotypes and infections, with frequent serotypes likely to possess a greater repertoire of virulence factors. A variant zmpC gene was associated with non-typeable (NT) pneumococci causing conjunctivitis. Finally, a novel neuraminidase gene, nanO2 was identified among these NT conjunctivitis isolates and we confirmed expression of this gene.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

File Size

3.25 MB

Comments

A thesis submitted for the degree of Doctor of Philosophy from the Royal College of Surgeons in Ireland in 2015.