The Increasing Importance Of Non-Culture Methods In Diagnosis And Serotyping Of Invasive Pediatric Pneumococcal Infections Revealed The Continuous Dominance Of Vaccine Serotypes In The Era Of Pcv13 Vaccination

Purpose: We evaluated the role of non-culture methods for diagnosis in evaluating the impact of continued 13-valent pneumococcal conjugate vaccine (PCV13) use in the private market in pediatric invasive pneumococcal disease (pIPD) in Portugal (2012-2015). Methods & Materials: The pIPD cases were identified and isolates were submitted to a central laboratory for further characterization. In possible pIPD cases where culture of pleural or cerebrospinal fluid was negative, real-time PCR reactions targeting conserved (lytA and cpsA) genes and capsule specific genes were used to detect and serotype pneumococci. Results: The most frequently detected serotypes were: 3 (n = 32, 13.8%), 14 (n = 23, 9.9%), 1 (n = 23, 9.9%), 7F (n = 15, 6.4%), 19A (n = 13, 5.6%), 6B and 15B/C (both n = 12, 5.2%), and 24F, 10A and 12B (all with n = 10, 4.3%). The use of PCR to detect and serotype pneumococci in both pleural and cerebrospinal fluid samples contributed to 20% (n = 47) of all pIPD. Serotype 3 was mostly detected by PCR (n = 21/32, 65.6%) and resulted from a relevant number of vaccine failures. The incidence of pIPD varied in the different age groups but without a clear trend. There were no obvious declines of the incidence of pIPD due to serotypes included in any of the PCVs, and PCV13 serotypes still accounted for the majority of pIPD (53%). Conclusion: Our study indicates that a higher vaccination uptake may be necessary to realize the full benefits of PCVs, even after 15 years of use, and highlights the importance of using molecular methods in pIPD surveillance, since these can lead to substantially increased case ascertainment and the identification of particular serotypes as causes of pIPD.