Nasopharyngeal Carriage of S. Pneumoniae

Official title

Observatory of Streptococcus Pneumoniae Nasopharyngeal Carriage in Infants With Acute Otitis Media (AOM) and in Healthy Children"

Overview

This nasopharyngeal (NP) carriage surveillance study was requested by the European Agency for the Evaluation of Medicinal Products as a post-licensing commitment to determine whether the use of the pneumococcal conjugate vaccines (PCVs) including 7 then 13 valents (introduced in 2001 and 2010, respectively) caused a shift in the distribution of Streptococcus pneumoniae serotypes in children with acute otitis media and modified the resistance of this bacterial species to antibiotics.

Detailed description

Since September 2001, 54 pediatricians who are part of a research and teaching network (ACTIV) throughout France participated at this prospective study. From October to June of each subsequent year, children of both sexes suffering from suppurative acute otitis media (AOM) with fever and/or otalgia (in order to increase the probability of pneumococcal AOM), aged 6 to 36 months, were enrolled. And a second group of healthy children aged 6 months to 15 years were also enrolled for the main study.

For ancillary study a subgroup of AOM children were enrolled for assessment of E. coli (ESBL) resistance.

Interventions

• Other nasopharyngeal sample (mandatory)
  A mandatory nasopharyngeal swab is planned for each included patient: patients aged 6 to 36 months with AOM and control children (healthy) aged 6 months to 15 years. The bacteriological analyses will be carried out by the French National Reference Centre for Pneumococci.
• Other Stools collection or anorectal swab samples (optional)
  For a subgroup of AOM children aged 6 to 36 months, stools samples or anorectal swab samples were collected for assessment of E. coli (ESBL) resistance
• Other nasopharyngeal sample (optional)
  Optional nasopharyngeal swabs from children with AOM aged 6 to 36 months to assess the association of various respiratory viruses (SARS-CoV-2, RSV, Influenza A, Influenza B) with different pneumococcal serotypes.

Primary outcome measures

• S. Pneumoniae colonisation [Time frame: at inclusion]
• S. Pneumoniae colonisation involving to vaccine serotypes [Time frame: at inclusion]
• S. Pneumoniae colonisation involving to non vaccine serotypes [Time frame: at inclusion]
• Reduced of sensitivity to penicillin [Time frame: at inclusion]
• Detect the emergence of new serotypes [Time frame: at inclusion]
• Association of Pneumococcal Serotypes with Respiratory Viruses [Time frame: at inclusion]

Secondary outcome measures (3)

• Detect the emergence of resistance S. pneumoniae [Time frame: at inclusion]
• Evaluation of nasopharyngeal carriage of other bacteria [Time frame: at inclusion]
• For the ancillary study, the resistance of E. coli (ESBL) will be evaluated. [Time frame: at inclusion]

Eligibility criteria

children seen on an outpatient

Inclusion criteria

• both sexes
• suffering from suppurative AOM or healthy children

• age: 6 months to 36 months for AOM
• age: 6 months to 15 years for healthy children
• informed consent from parents or guardians
• Children who haven't received antibiotic treatment within 7 days before enrollment,

Exclusion criteria

• severe underlying disease,
• inclusion in the study during the previous 12 months
• Children with bullous myringitis cannot be included.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

France · 1 center

• ACTIV — Créteil

Publications

• Levy C, Varon E, Bechet S, Bonacorsi S, Cohen R. Similarities and Differences Between Countries When Estimating the Effect of Higher-valency Pneumococcal Conjugate Vaccines on Colonization and Acute Otitis Media. Pediatr Infect Dis J. 2025 May 1;44(5):e184-e186. doi: 10.1097/INF.0000000000004686. Epub 2025 Jan 21. No abstract available. PMID 39841925
• Ouldali N, Cohen R, Levy C, Gelbert-Baudino N, Seror E, Corrard F, Vie Le Sage F, Michot AS, Romain O, Bechet S, Bonacorsi S, Angoulvant F, Varon E. Pneumococcal susceptibility to antibiotics in carriage: a 17 year time series analysis of the adaptive evolution of non-vaccine emerging serotypes to a new selective pressure environment. J Antimicrob Chemother. 2019 Oct 1;74(10):3077-3086. doi: 10.10 PMID 31280295
• Rybak A, Levy C, Bonacorsi S, Bechet S, Vie le Sage F, Elbez A, Varon E, Cohen R. Antibiotic Resistance of Potential Otopathogens Isolated From Nasopharyngeal Flora of Children With Acute Otitis Media Before, During and After Pneumococcal Conjugate Vaccines Implementation. Pediatr Infect Dis J. 2018 Mar;37(3):e72-e78. doi: 10.1097/INF.0000000000001862. PMID 29227464
• Birgy A, Bidet P, Levy C, Sobral E, Cohen R, Bonacorsi S. CTX-M-27-Producing Escherichia coli of Sequence Type 131 and Clade C1-M27, France. Emerg Infect Dis. 2017 May;23(5):885. doi: 10.3201/eid2305.161865. No abstract available. PMID 28418829
• Cohen R, Varon E, Doit C, Schlemmer C, Romain O, Thollot F, Bechet S, Bonacorsi S, Levy C. A 13-year survey of pneumococcal nasopharyngeal carriage in children with acute otitis media following PCV7 and PCV13 implementation. Vaccine. 2015 Sep 22;33(39):5118-26. doi: 10.1016/j.vaccine.2015.08.010. Epub 2015 Aug 11. PMID 26271823
• Cohen R, Levy C, Bonnet E, Thollot F, Boucherat M, Fritzell B, Derkx V, Bingen E, Varon E. Risk factors for serotype 19A carriage after introduction of 7-valent pneumococcal vaccination. BMC Infect Dis. 2011 Apr 18;11:95. doi: 10.1186/1471-2334-11-95. PMID 21501471
• Cohen R, Bingen E, Levy C, Thollot F, Boucherat M, Derkx V, Varon E. Nasopharyngeal flora in children with acute otitis media before and after implementation of 7 valent pneumococcal conjugate vaccine in France. BMC Infect Dis. 2012 Mar 7;12:52. doi: 10.1186/1471-2334-12-52. PMID 22397629
• Levy C, Vie le Sage F, Varon E, Chalumeau M, Grimprel E, Cohen R. Pediatric Ambulatory and Hospital Networks for Surveillance and Clinical Epidemiology of Community-Acquired Infections. J Pediatr. 2018 Mar;194:269-270.e2. doi: 10.1016/j.jpeds.2017.11.050. Epub 2018 Feb 22. No abstract available. PMID 29637893

Identifiers

NCT: NCT04460313 · ACT0806

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗