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Human Infection Challenge with Serotype 3 Pneumococcus

Robinson, Ryan, Mitsi, Elena, Nikolaou, Elissavet, Pojar, Sherin ORCID: https://orcid.org/0000-0002-7746-3279, Chen, Tao ORCID: https://orcid.org/0000-0002-5489-6450, Reiné, Jesús, Nyazika, Tinashe, Court, James, Davies, Kelly, Farrar, Madi, Gonzalez-Diaz, Patricia, Hamilton, Josh, Hill, Helen, Hitchins, Lisa, Howard, Ashleigh, Hyder-Wright, Angela, Lesosky, Maia ORCID: https://orcid.org/0000-0002-2026-958X, Liatsikos, Kostas, Matope, Agnes, McLenaghan, Daniella, Myerscough, Christopher, Murphy, Annabel, SolorzanoGonzalez, Carla, Wang, Duolao ORCID: https://orcid.org/0000-0003-2788-2464, Burhan, Hassan, Gautam, Manish, Begier, Elizabeth, Theilacker, Christian, Beavon, Rohini, Anderson, Annaliesa S., Gessner, Bradford D., 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 (2022) 'Human Infection Challenge with Serotype 3 Pneumococcus'. American Journal of Respiratory and Critical Care Medicine. (In Press)

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Abstract

Rationale: Streptococcus pneumoniae serotype 3 (SPN3) is a cause of invasive pneumococcal disease and associated with low carriage rates. Following the introduction of pediatric 13-valent pneumococcal conjugate vaccine (PCV13) programmes, SPN3 declines are less than other vaccine serotypes and incidence has increased in some populations coincident with a shift in predominant circulating SPN3 clade, from I to II. A human challenge model provides an effective means for assessing the impact of PCV13 on SPN3 in the upper airway. Objectives: To establish SPN3’s ability to colonise the nasopharynx using different inoculum clades and doses and the safety of an SPN3 challenge model. Methods: In a human challenge study involving three well characterised and antibiotic sensitive SPN3 isolates (PFESP306 [clade Ia], PFESP231 [no clade] and PFESP505 [clade II]), inoculum doses (10,000, 20,000, 80,000, 160,000 CFU/100μL) were escalated until maximal colonisation rates were achieved, with concurrent acceptable safety. Outcome measures: Presence and density of experimental SPN3 nasopharyngeal colonisation in nasal wash samples, assessed using microbiological culture and molecular methods, on days 2, 7 and 14 post-inoculation. Results: 96 healthy participants (median age 21, interquartile range 19-25) were inoculated (n=6-10 per dose group, 10 groups). Colonisation rates ranged from 30.0-70.0% varying with dose and isolate. 30.0% (29/96) reported mild symptoms (82.8% sore throat, [24/29]), one developed otitis media requiring antibiotics. No serious adverse events occurred. Conclusions: An SPN3 human challenge model is feasible and safe with comparable carriage rates to an established SPN6B human challenge model. SPN3 carriage may cause mild upper respiratory symptoms.

Item Type: Article
Subjects: WC Communicable Diseases > WC 20 Research (General)
WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 200 Bacterial infections (General or not elsewhere classified)
WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 204 Pneumococcal pneumonia. Staphylococcal pneumonia
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1164/rccm.202112-2700oc
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 23 Aug 2022 12:50
Last Modified: 23 Aug 2022 12:50
URI: https://archive.lstmed.ac.uk/id/eprint/20856

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