Comprehensive review of safety in Experimental Human Pneumococcal Challenge.
<h4>Introduction</h4>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 compreh...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0284399 |
| _version_ | 1797827772695969792 |
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| author | Ryan E Robinson Christopher Myerscough Nengjie He Helen Hill Wendi A Shepherd Patricia Gonzalez-Dias Konstantinos Liatsikos Samuel Latham Fred Fyles Klara Doherty Phoebe Hazenberg Fathimath Shiham Daniella Mclenghan Hugh Adler Vicki Randles Seher Zaidi Angela Hyder-Wright Elena Mitsi Hassan Burhan Ben Morton Jamie Rylance Maia Lesosky Stephen B Gordon Andrea M Collins Daniela M Ferreira |
| author_facet | Ryan E Robinson Christopher Myerscough Nengjie He Helen Hill Wendi A Shepherd Patricia Gonzalez-Dias Konstantinos Liatsikos Samuel Latham Fred Fyles Klara Doherty Phoebe Hazenberg Fathimath Shiham Daniella Mclenghan Hugh Adler Vicki Randles Seher Zaidi Angela Hyder-Wright Elena Mitsi Hassan Burhan Ben Morton Jamie Rylance Maia Lesosky Stephen B Gordon Andrea M Collins Daniela M Ferreira |
| author_sort | Ryan E Robinson |
| collection | DOAJ |
| description | <h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Discussion</h4>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.<h4>Conclusion</h4>Outpatient human pneumococcal challenge can be conducted safely with appropriate levels of safety monitoring procedures in place. |
| first_indexed | 2024-04-09T12:53:43Z |
| format | Article |
| id | doaj.art-5ba86a5041f341e7abc5a37ebce3456c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-09T12:53:43Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5ba86a5041f341e7abc5a37ebce3456c2023-05-14T05:31:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01185e028439910.1371/journal.pone.0284399Comprehensive review of safety in Experimental Human Pneumococcal Challenge.Ryan E RobinsonChristopher MyerscoughNengjie HeHelen HillWendi A ShepherdPatricia Gonzalez-DiasKonstantinos LiatsikosSamuel LathamFred FylesKlara DohertyPhoebe HazenbergFathimath ShihamDaniella MclenghanHugh AdlerVicki RandlesSeher ZaidiAngela Hyder-WrightElena MitsiHassan BurhanBen MortonJamie RylanceMaia LesoskyStephen B GordonAndrea M CollinsDaniela M Ferreira<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Discussion</h4>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.<h4>Conclusion</h4>Outpatient human pneumococcal challenge can be conducted safely with appropriate levels of safety monitoring procedures in place.https://doi.org/10.1371/journal.pone.0284399 |
| spellingShingle | Ryan E Robinson Christopher Myerscough Nengjie He Helen Hill Wendi A Shepherd Patricia Gonzalez-Dias Konstantinos Liatsikos Samuel Latham Fred Fyles Klara Doherty Phoebe Hazenberg Fathimath Shiham Daniella Mclenghan Hugh Adler Vicki Randles Seher Zaidi Angela Hyder-Wright Elena Mitsi Hassan Burhan Ben Morton Jamie Rylance Maia Lesosky Stephen B Gordon Andrea M Collins Daniela M Ferreira Comprehensive review of safety in Experimental Human Pneumococcal Challenge. PLoS ONE |
| title | Comprehensive review of safety in Experimental Human Pneumococcal Challenge. |
| title_full | Comprehensive review of safety in Experimental Human Pneumococcal Challenge. |
| title_fullStr | Comprehensive review of safety in Experimental Human Pneumococcal Challenge. |
| title_full_unstemmed | Comprehensive review of safety in Experimental Human Pneumococcal Challenge. |
| title_short | Comprehensive review of safety in Experimental Human Pneumococcal Challenge. |
| title_sort | comprehensive review of safety in experimental human pneumococcal challenge |
| url | https://doi.org/10.1371/journal.pone.0284399 |
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