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Robinson, Ryan, Myerscough, Christopher, He, Nengjie, Hill, Helen, Shepherd, Wendi A., Gonzalez, Patricia, Liatsikos, Kostas, Latham, Samuel, Fyles, Fred, Doherty, Klara, Hazenberg, Phoebe, Shiham, Fathimath, Mclenghan, Daniella, Adler, Hugh 
ORCID: https://orcid.org/0000-0003-4437-2298, Randles, Vicki, Zaidi, Seher, Hyder-Wright, Angela, Mitsi, Elena, Burhan, Hassan, Morton, Ben ORCID: https://orcid.org/0000-0002-6164-2854, Rylance, Jamie ORCID: https://orcid.org/0000-0002-2323-3611, Lesosky, Maia ORCID: https://orcid.org/0000-0002-2026-958X, Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116, Collins, Andrea ORCID: https://orcid.org/0000-0002-4094-1572 and Ferreira, Daniela ORCID: https://orcid.org/0000-0002-0594-0902
(2023)
'Comprehensive review of safety in Experimental Human Pneumococcal Challenge'. PLoS ONE, Vol 18, Issue 5, e0284399.
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Abstract
Introduction:
Experimental Human Pneumococcal Challenge (EHPC) involves the controlled exposure of adults to a specific antibiotic-sensitive Streptococcus pneumoniae serotype, to induce nasopharyngeal colonisation for the purpose of vaccine research. The aims are to review comprehensively the safety profile of EHPC, explore the association between pneumococcal colonisation and frequency of safety review and describe the medical intervention required to undertake such studies.
Methods:
A single-centre review of all EHPC studies performed 2011–2021. All recorded serious adverse events (SAE) in eligible studies are reported. An unblinded meta-analysis of collated anonymised individual patient data from eligible EHPC studies was undertaken to assess the association between experimental pneumococcal colonisation and the frequency of safety events following inoculation.
Results:
In 1416 individuals (median age 21, IQR 20–25), 1663 experimental pneumococcal inoculations were performed. No pneumococcal-related SAE have occurred. 214 safety review events were identified with 182 (12.85%) participants presenting with symptoms potentially in keeping with pneumococcal infection, predominantly in pneumococcal colonised individuals (colonised = 96/658, non-colonised = 86/1005, OR 1.81 (95% CI 1.28–2.56, P = <0.001). The majority were mild (pneumococcal group = 72.7% [120/165 reported symptoms], non-pneumococcal = 86.7% [124/143 reported symptoms]). 1.6% (23/1416) required antibiotics for safety.
Discussion:
No SAEs were identified directly relating to pneumococcal inoculation. Safety review for symptoms was infrequent but occurred more in experimentally colonised participants. Most symptoms were mild and resolved with conservative management. A small minority required antibiotics, notably those serotype 3 inoculated.
Conclusion:
Outpatient human pneumococcal challenge can be conducted safely with appropriate levels of safety monitoring procedures in place.
| Item Type: | Article |
|---|---|
| Subjects: | WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 217 Pneumococcal infections |
| Faculty: Department: | Clinical Sciences & International Health > Clinical Sciences Department |
| Digital Object Identifer (DOI): | https://doi.org/10.1371/journal.pone.0284399 |
| SWORD Depositor: | JISC Pubrouter |
| Depositing User: | JISC Pubrouter |
| Date Deposited: | 09 May 2023 14:28 |
| Last Modified: | 09 May 2023 14:28 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/22443 |
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