Calvo-Silveria Sara, González-Díaz Aida, Grau Inmaculada, Marimón José María, Cercenado Emilia, Quesada M Dolores, Casabella Antonio, Larrosa Nieves, Yuste José, Berbel Dàmaris, Alonso Marta, Tubau Fe, Belman Sophie, Cadenas-Jiménez Irene, Martín-Galiano Antonio J, Domínguez M Ángeles, Martí Sara, Liñares Josefina, Pallarés Román, Càmara Jordi, Ardanuy Carmen
Microbiology Department, Hospital Universitari de Bellvitge - IDIBELL, L'Hospitalet de Llobregat, Spain.
Research Network for Respiratory Diseases (CIBERES), ISCIII, Madrid, Spain.
Lancet Reg Health Eur. 2024 May 3;41:100913. doi: 10.1016/j.lanepe.2024.100913. eCollection 2024 Jun.
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.
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).
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.
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.
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".
3型血清型侵袭性肺炎球菌疾病（S3-IPD）与高死亡率和长期不良影响相关。13价肺炎球菌结合疫苗（PCV13）引入西班牙儿童免疫规划后，成人S3-IPD并未减少。我们旨在分析西班牙成人S3-IPD的发病率、临床特征和基因组学。
前瞻性收集巴塞罗那南部一家医院收治的成人IPD病例（1994 - 2020年）。为进行基因组比较，对来自六家西班牙医院的S3-IPD分离株（2008 - 2020年）和历史分离株（1989 - 1993年）进行全基因组测序（WGS，Illumina和/或MinION）分析。
1994年至2020年期间，共检测到270例S3-IPD病例。比较PCV引入前（1994 - 2001年）和PCV13引入后期（2016 - 2020年），S3-IPD仅出现适度变化（从每10万居民年1.58例降至1.28例）。在此期间，两个主要谱系的发病率从0.38变为0.67（CC180 - GPSC12），从1.18变为0.55（CC260 - GPSC83）。30天总体死亡率仍然很高（24.1%），尽管在PCV引入前（32.4%；95.0%CI，22.0 - 45.0）和PCV13引入后期（16.7%；95.0%CI，7.5 - 32.0）之间有所下降（p = 0.06）。同时，合并症从77.3%（95.0%CI，65.0 - 86.0）增至85.7%（95.0%CI，71.0 - 94.0）（p = 0.69）。两个S3谱系在临床特征或30天死亡率方面无差异。尽管两个谱系在基因上均一，但CC180 - GPSC12谱系呈现出更高的单核苷酸多态性密度、更开放的泛基因组，以及携带耐药基因的原噬菌体和可移动遗传元件的大量存在。
在研究期间，尽管儿童引入了PCV13，但我们地区的成人S3-IPD保持稳定。然而，观察到克隆转变。死亡率下降和合并症增加表明临床管理和总体人群特征发生了变化。谱系间低遗传变异性和无临床差异突出了S3荚膜在疾病严重程度中的作用。
本研究由卡洛斯三世健康研究所（ISCIII）“PI18/00339”、“PI21/01000”、“INT22/00096”、“FI22/00279”、CIBER“CIBERES - CB06/06/0037”、“CIBERINFEC - CB21/13/00009”以及默克雪兰诺公司资助“IISP 60168”。
