Evolution of invasive pneumococcal disease by serotype 3 in adults: a Spanish three-decade retrospective study

Sara Calvo-Silveria; Aida González-Díaz; Inmaculada Grau; José María Marimón; Emilia Cercenado; M Dolores Quesada; Antonio Casabella; Nieves Larrosa; José Yuste; Dàmaris Berbel; Marta Alonso; Fe Tubau; Sophie Belman; Irene Cadenas-Jiménez; Antonio J Martín-Galiano; M Ángeles Domínguez; Sara Martí; Josefina Liñares; Román Pallarés; Jordi Càmara; Carmen Ardanuy

doi:10.1016/j.lanepe.2024.100913

Evolution of invasive pneumococcal disease by serotype 3 in adults: a Spanish three-decade retrospective study

Lancet Reg Health Eur. 2024 May 3:41:100913. doi: 10.1016/j.lanepe.2024.100913. eCollection 2024 Jun.

Authors

Sara Calvo-Silveria^{1

2}, Aida González-Díaz^{1

2}, Inmaculada Grau^{2

3}, José María Marimón⁴, Emilia Cercenado^{2

5}, M Dolores Quesada⁶, Antonio Casabella^{7

8}, Nieves Larrosa^{9

10}, José Yuste^{2

11}, Dàmaris Berbel^{1

2}, Marta Alonso⁴, Fe Tubau^{1

2}, Sophie Belman¹², Irene Cadenas-Jiménez^{1

2}, Antonio J Martín-Galiano¹³, M Ángeles Domínguez^{1

10

14}, Sara Martí^{1

2

15}, Josefina Liñares¹, Román Pallarés^{2

3

16}, Jordi Càmara^{1

2}, Carmen Ardanuy^{1

2

14}

Affiliations

¹ Microbiology Department, Hospital Universitari de Bellvitge - IDIBELL, L'Hospitalet de Llobregat, Spain.
² Research Network for Respiratory Diseases (CIBERES), ISCIII, Madrid, Spain.
³ Infectious Diseases Department, Hospital Universitari de Bellvitge - IDIBELL, L'Hospitalet de Llobregat, Spain.
⁴ Biogipuzkoa, Infectious Diseases Area, Respiratory Infection and Antimicrobial Resistance Group, Microbiology Department, Hospital Donostia, Osakidetza Basque Health Service, Donostia - San Sebastian, Spain.
⁵ Clinical Microbiology and Infectious Disease Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
⁶ Microbiology Department, Clinical Laboratory North Metropolitan Area, Hospital Universitari Germans Trias i Pujol, UAB, Badalona, Spain.
⁷ Laboratory of Microbiology, Hospital Universitari Parc Taulí, Sabadell, Spain.
⁸ Institut d'Investigació i Innovació Parc Taulí (I3PT), Universitat Autònoma de Barcelona, Sabadell, Spain.
⁹ Microbiology Department, Hospital Universitari Vall d'Hebron, UAB, Barcelona, Spain.
¹⁰ Research Network for Infectious Diseases (CIBERINFEC), ISCIII, Madrid, Spain.
¹¹ Spanish Pneumococcal Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain.
¹² Earth Sciences Department, Barcelona Supercomputing Center - Centro Nacional de Supercomputación, Barcelona, Spain.
¹³ Core Scientific and Technical Units, Instituto de Salud Carlos III, Madrid, Spain.
¹⁴ Department of Pathology and Experimental Therapeutics, University of Barcelona, Spain.
¹⁵ Department of Medicine, School of Medicine and Health Sciences, University of Barcelona, Spain.
¹⁶ Department of Clinical Sciences, University of Barcelona, Spain.

Abstract

Background: Invasive pneumococcal disease due to serotype 3 (S3-IPD) is associated with high mortality rates and long-term adverse effects. The introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into the Spanish paediatric immunisation programme has not led to a decrease in the adult S3-IPD. We aimed to analyse the incidence, clinical characteristics and genomics of S3-IPD in adults in Spain.

Methods: Adult IPD episodes hospitalized in a Southern Barcelona hospital were prospectively collected (1994-2020). For genomic comparison, S3-IPD isolates from six Spanish hospitals (2008-2020) and historical isolates (1989-1993) were analysed by WGS (Illumina and/or MinION).

Findings: From 1994 to 2020, 270 S3-IPD episodes were detected. When comparing pre-PCV (1994-2001) and late-PCV13 (2016-2020) periods, only modest changes in S3-IPD were observed (from 1.58 to 1.28 episodes per 100,000 inhabitants year). In this period, the incidence of the two main lineages shifted from 0.38 to 0.67 (CC180-GPSC12) and from 1.18 to 0.55 (CC260-GPSC83). The overall 30-day mortality remained high (24.1%), though a decrease was observed between the pre-PCV (32.4%; 95.0% CI, 22.0-45.0) and the late-PCV13 period (16.7%; 95.0% CI, 7.5-32.0) (p = 0.06). At the same time, comorbidities increased from 77.3% (95.0% CI, 65.0-86.0) to 85.7% (95.0% CI, 71.0-94.0) (p = 0.69). There were no differences in clinical characteristics or 30-day mortality between the two S3 lineages. Although both lineages were genetically homogeneous, the CC180-GPSC12 lineage presented a higher SNP density, a more open pan-genome, and a major presence of prophages and mobile genetic elements carrying resistance genes.

Interpretation: Adult S3-IPD remained stable in our area over the study period despite PCV13 introduction in children. However, a clonal shift was observed. The decrease in mortality rates and the increase in comorbidities suggest a change in clinical management and overall population characteristics. The low genetic variability and absence of clinical differences between lineages highlight the role of the S3 capsule in the disease severity.

Funding: This study has been funded by Instituto de Salud Carlos III (ISCIII) "PI18/00339", "PI21/01000", "INT22/00096", "FI22/00279", CIBER "CIBERES-CB06/06/0037", "CIBERINFEC-CB21/13/00009" and MSD grant "IISP 60168".

Keywords: Genomics; Serotype 3; Streptococcus pneumoniae.