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Pneumococcal nasopharyngeal colonisation in adults

Adler, Hugh ORCID: (2019) Pneumococcal nasopharyngeal colonisation in adults, Thesis (Doctoral), Liverpool School of Tropical Medicine.

H Adler PhD thesis for LSTM Archive.pdf - Accepted Version

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Background: Pneumococcal colonisation, although usually asymptomatic, is key to the pathogenesis of invasive disease. Colonisation is infrequently detected in older adults, despite their high rates of pneumococcal disease; this may relate to sampling from the wrong site or reliance on culture-based rather than molecular diagnostic methods. Anti-pneumococcal immunity (including responses to vaccination) declines with age, but the immunogenicity of colonisation in older adults has not been studied. Alongside innate immunity, three specific defence mechanisms exist against pneumococcal disease: herd immunity, adaptive immunity (conferred by natural or vaccine-induced antibodies) and antibiotics. Current pneumococcal vaccines confer incomplete protection against pneumococcal disease in older adults.
Research Questions:
1. Can experimental human pneumococcal colonisation be safely established in older adults?
2. What is the rate of experimental colonisation in older adults?
3. Do anti-pneumococcal antibodies (natural or post-vaccination) prevent experimental colonisation in older adults?
4. Is experimental colonisation immunogenic in older adults?
5. What is the optimal sampling site and diagnostic methodology for detecting colonisation in older adults?
6. What do colonisation studies of the general adult population reveal about herd immunity and pneumococcal antimicrobial resistance in the community?
Findings: Experimental colonisation was established in 39% of volunteers (n = 25/64) with no adverse events. Experimental colonisation was unaffected by previous pneumococcal polysaccharide vaccination or baseline anti-capsular antibody levels. Although the rate of experimental colonisation was similar to that of younger volunteers in previous studies, the immune responses were markedly different: older adults did not demonstrate serotype-specific immune boosting following pneumococcal colonisation. Furthermore, pneumococcal challenge without colonisation led to a drop in specific antibody levels. Nasal wash culture appeared to be the optimal detection strategy compared with molecular testing of nasal wash, oropharyngeal swab or saliva.
In a review of all prospective experimental human pneumococcal colonisation volunteers between 2010 and 2017, community-acquired colonisation was identified at baseline in 6.5% (n = 52/795) using nasal wash culture. The commonest serotype was 3 (a vaccine serotype), but otherwise non-vaccine serotypes predominated. There were no changes in serotype distribution over time. 15% of isolates (n = 8/52, all identified in 2015 or later) were resistant to at least one of the antibiotics tested.
Conclusions: Experimental pneumococcal colonisation is feasible and safe in older people. However, the immunological effects are different to those identified in younger adults in previous studies. We found no evidence that the niche of colonisation changes with age. Nasal wash culture detected higher-than-expected rates of community-acquired colonisation in young adults, with the dominance of non-vaccine serotypes suggesting that the limits of herd immunity have been reached. New pneumococcal vaccines are needed for older adults, and the experimental colonisation model could be used in early phase testing of candidate vaccines. If such vaccines continue to rely on serotype-specific protection, then community colonisation studies could inform the serotype composition.

Item Type: Thesis (Doctoral)
Subjects: QW Microbiology and Immunology > QW 50 Bacteria (General). Bacteriology. Archaea
QW Microbiology and Immunology > Immunity by Type > QW 551 Acquired immunity. Artificial immunity
QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 575 Antibodies
QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 800 Biological products producing immunity
QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 806 Vaccination
WV Otolaryngology > Nose and Paranasal Sinuses > WV 300 General works
WV Otolaryngology > Pharyngeal Region > WV 400 General works
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Depositing User: Lynn Roberts-Maloney
Date Deposited: 08 Aug 2019 08:29
Last Modified: 08 Nov 2019 02:02


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