Carriage of Streptococcus Pneumoniae in Infants With Acute Otitis Media and in Infants Attending Day-care Centers
Condition: Streptococcus Pneumoniae; Nasopharyngeal Carriage
MeSH terms: Pneumonia; Pneumonia, Pneumococcal; Otitis; Otitis Media
Study type: Interventional

Summary: 
      Rationale

      In Belgium, a unique situation exists for two reasons: on the one hand, the pneumococcal
      conjugate vaccine (PCV) program, which started in 2007, has quickly reached high coverage in
      infants: 3-dose coverage rose from 89 % in 2008 to 96.5 % in 2012 in Flanders and from 80.7 %
      in 2009 to 89.2 % in 2012 in Wallonia; and on the other hand, serotype coverage has moved
      from PCV7 (since 2007) to PCV13 (since 2011) and very recently to PCV10 (since July 2015 in
      Flanders and expected in May 2016 in the French Community). Invasive pneumococcal disease
      (IPD) surveillance has demonstrated a major impact on PCV13 serotypes in infants < 2 years of
      age. The impact of the current change in PCV-program is hard to predict, but could eventually
      result in a re-emergence of serotypes not covered by PCV10 (i.e. 3, 6A and 19A).

      With this unique situation the foundation was laid for a carriage study during which the
      nasopharyngeal carriage of Streptococcus pneumonia (Sp) and other common colonizers of the
      nasopharynx will be studied in infants with acute otitis media (AOM) and in healthy infants
      attending day-care centers (DCC), two populations with high reported pneumococcal carriage.
      Young children are an important reservoir and major source of transmission of bacteria to the
      whole community and thus the preferred population to study nasopharyngeal (NP) carriage.

      Aim of the study

      The main aim of this study is to evaluate if changes in the conjugate anti-pneumococcal
      vaccination program in Belgium have an impact on the nasopharyngeal carriage of Pneumococcus
      in infants aged 6-30 months suffering from AOM or attending day-care, in order to guide
      future pneumococcal vaccine program decisions and vaccine development, and to feed AOM
      treatment guidelines in a PCV-program environment. The study will monitor overall
      pneumococcal carriage, the serotypes involved and the sensitivity of the isolated strains to
      antibiotics. In addition, the rhinopharyngeal carriage of other common nasopharyngeal
      colonizers associated with disease, in particular Haemophilus influenzae, will be studied in
      order to evaluate if changes in pneumococcal carriage impact on the carriage of those
      pathogens. In infants with AOM, the study will also monitor the clinical course of the AOM
      and a second nasopharyngeal sample will be taken in case of antibiotic treatment failure or
      AOM recurrence to identify any association with the carried pathogen.
    

Detailed description: 
      Study populations

      Two infant populations with high (50 % and more) reported carriage of Sp were identified and
      will be approached for this study:

        1. Infants aged 6-30 months presenting with acute otitis media (according to specific
           clinical and otoscopic criteria) at their first line general physician or paediatrician
           and who have not recently received antibiotics and have no severe underlying disease
           (AOM infants).

        2. Healthy infants aged 6-30 months attending a day-care center and not recently having
           received antibiotics (DCC infants).

      Investigator(s), study sites

      75-87 paediatricians and general practitioners (GPs), and approximately 75 DCC throughout the
      whole of Belgium. Paediatricians in first line hospitals are allowed to participate.

      The Primary objective

      is to detect significant prevalence change of Sp serotypes 19A or 6A carriage over the
      observation period (three years, 2016-2018) in each of both study populations (AOM or DCC
      infants).

      Number of subjects

      In the first year (2016), 700 and from the second year ( 2016-2017) onward 900, patients with
      AOM (between the ages of 6 and 30 months) will be included every year. The same number of
      healthy infants attending DCC will be included each year. Sample size was calculated to allow
      comparison between children recruited in the first winter season, who have received PCV13 for
      all or the majority of their pneumococcal vaccinations, and the children in the following
      seasons, who will have received PCV10 for the majority or all of their pneumococcal
      vaccinations. Some over-recruitment will be done during the first winter (2016) of infants
      vaccinated in the region that has not yet changed from PCV13 to PCV10, since these infants
      will have received PCV13 for their 12 months booster too. The proposed sample size allows to
      detect changes as low as 3 % for 19A and 6A combined, and 4 % for each of them separately
      with 80 % power, in each of the AOM and day-care infant groups.

      Period of observation

      Since Sp carriage as well as AOM are most prevalent in and around the winter season,
      recruitment will be scheduled focusing on this period. In 2016, recruitment of infants
      presenting with AOM is foreseen from January till end of May, but can be extended to June if
      necessary to achieve the target number. Thereafter, infants with AOM will be recruited every
      year from October till end of May (starting October 2016). For healthy infants attending DCC
      recruitment is planned to start in March 2016, and thereafter every season from October 1st
      till May 31st. The current protocol covers the first observation period, from 2016 to 2018
      covering 3 winter seasons.
    

Intervention name(s): Nasopharyngeal sampling with a swab
Intervention type(s): Other
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: nasopharyngeal carriage; Streptococcus pneumoniae; acute otitis media; day-care centers