After implementation of the 13-valent pneumococcal conjugate vaccine (PCV13), most non-PCV13 serotypes had low invasive pneumococcal disease (IPD) potential, according to a brief report published in Clinical Infectious Diseases. Also, the next generation of the vaccine included all but 2 of the serotypes with the highest IPD potential.

The implementation of PCVs has led to dramatic decreases in the incidence of IPD. Furthermore, vaccine serotypes have decreased in prevalence and been replaced by nonvaccine serotypes, with only minimal changes in overall pneumococcal carriage. This lack of change in carriage has been attributed to the lesser disease potential of nonvaccine serotypes.

Investigators aimed to assess invasive disease potential of non-PCV13 serotypes in France 8 years after the implementation of the vaccine in 2010 and before the launch of the next generation of PCVs. The researchers enrolled children aged 6 months to 10 years from both carriage and IPD surveillance systems in the country from January 2012 to December 2018.

Throughout the study period, they isolated 1034 pneumococcal strains among 3684 healthy children and recorded 1385 cases of IPD. The investigators identified these cases as meningitis (28%), bacteremic pneumonia (24%), and other IPDs (47.9%). Persons with IPD were significantly older (37.7 ± 29 [median age, 29.6] months) compared with healthy children (28.9 ± 23.3 [median age, 19.7] months; P < .001). From 2012 to 2018, the frequency of PCV13 serotype frequency decreased from 32.7% to 12.5% for overall IPD, 46.2% to 33.3% for meningitis, and 47.5% to 14.4% for pneumonia.


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The 3 leading serotypes among the 53 serotypes involved in IPD — 24F, 15B/C, and 12F — accounted for 15.5%, 8.4%, and 7.7% of cases, respectively, and 31.5% overall. Serotype 24F ranked first for all types of IPD. The most common of the 45 serotypes found in healthy children were 15B/C (12.6%), 23B (10.4%), 11A (8.5%), 23A (7.3%), and 15A (7.2%). For overall IPD, 9 serotypes were found to have highly significant IPD potential: 12F, 24F, 7F, 38, 14, 19A, 3, 8, and 33F. A further 2 serotypes, 22F and 10A, were close to significance. Serotypes with the highest odds ratio (OR) for overall IPD had similar ORs for both meningitis and pneumonia, except for 33F (OR 3.1; 95% CI, 1.6-6) and 10A (OR 1.6; 95% CI, 1.0-2.7), which had significant ORs for only meningitis, and serotypes 3 (OR 6.5; 95% CI, 3.6-11.6) and 8 (OR 4.5; 95% CI, 1.7-12.1), which had significant ORs for pneumonia only.

Several study limitations need to be considered when interpreting these results. First, IPD potential is affected by duration of carriage, and for patients with short durations, IPD potential may be overestimated. There was also a lack of adjustment for underlying conditions in children with IPD caused by serotypes with low invasive capacity, which are usually more frequent in children with comorbidities without underlying conditions. The investigators also did not adjust the results for age. Finally, they acknowledged that invasiveness cannot be explained by serotype alone.

Reassuringly, after PCV13 implementation, most non-PCV13 serotypes recovered from carriage have a low IPD potential, according to researchers. Also, the next generation vaccine, 20-valent PCV (PCV20), includes all but 2 (24F and 38) of the non-PCV13 serotypes with the highest IPD potential. This is of concern, though, as “serotype 24F has emerged as the leading cause of pneumococcal meningitis and other IPDs in France and Europe in children aged 0 to 23 months.”

Researchers concluded that “as long as pneumococcal vaccines are polysaccharide conjugate vaccines, the choice of serotypes to be included in new PCVs should take into account the disease potential.”

Reference

Cohen R, Levy C, Ouldali N, et al. Invasive disease potential of pneumococcal serotypes in children after PCV13 implementation [published online July 4, 2020]. Clin Infect Dis. doi:10.1093/cid/ciaa917