Parapneumonic effusions related to Streptococcus pneumoniae: serotype and disease severity trends from 2006 to 2018 in Bristol, UK

Rationale Streptococcus pneumoniae epidemiology is changing in response to vaccination and some data suggest empyema incidence is increasing. However, differences exist between UK and USA studies. We describe trends in the clinical phenotype of adult pneumococcal pleural infection, including simple parapneumonic effusions (SPE) in the pneumococcal conjugate vaccination (PCV) era. Objectives To determine whether there were differences in pneumococcal disease presentation and severity associated with pleural infection. Methods A retrospective cohort study, all adults ≥16 years admitted to three large UK hospitals, 2006-2018 with pneumococcal disease. 2477 invasive pneumococcal cases were identified: 459 SPE and 100 pleural infection cases. Medical records were reviewed for each clinical episode. Serotype data were obtained from the UK Health Security Agency national reference laboratory. Results Incidence increased over time, including non-PCV-serotype disease. PCV7-serotype disease declined following paediatric PCV7 introduction, but the effect of PCV13 was less apparent as disease caused by the additional six serotypes plateaued with serotypes 1 and 3 causing such parapneumonic effusions from 2011 onwards. Patients with pleural infection had a median survival 468 days (95% CI 340-590), versus 286 days (95% CI 274-335) in those with SPE. Pleural infection associated with frank pus had lower 90-day mortality than pleural infection without pus (0% versus 29%, P <0.0001). 90-day mortality could be predicted by baseline increased RAPID (Renal, Age, Purulence, Infection source, and Dietary factors) score (HR15.01, 95% CI 1.24-40.06, P =0.049). Conclusions Pneumococcal infection continues to cause severe disease despite the introduction of PCVs. The predominance of serotype 1 and 3 in this adult UK cohort is in keeping with previous studies in paediatric and non-UK studies. Rising non-PCV serotype disease and limited impact of PCV13 on cases caused by serotypes 1 and 3 offset the reductions in adult pneumococcal parapneumonic effusion disease burden observed following introduction of the childhood PCV7 programme. What is already known on this topic The epidemiology of pneumococcal infection is changing in both adults and children following pneumococcal conjugate vaccine (PCV) introduction, as a result of direct and indirect vaccine effects. Other studies have reported that serotypes 1 and 3 disproportionately cause pneumococcal pleural disease; however, the clinical phenotype of parapneumonic effusions associated with pneumococcal infection in adults following PCV introduction is not well described. What this study adds In this study which presents the largest cohort of patients with a single-organism pleural infection, we demonstrate an increasing incidence of parapneumonic effusions related to Streptococcus pneumoniae in adults, attributable to serotype 1 and 3 disease, despite the introduction of PCV13 in the UK childhood vaccination programme. Interestingly, our data suggest that pneumococcal pleural infection is associated with improved survival up to one-year compared to patients with pneumococcal simple parapneumonic effusions. How this study might affect research, practice or policy Careful assessment of the need for specialist respiratory and thoracic surgical intervention in the context of increasing incidence of adult parapneumonic effusions related to Streptococcus pneumoniae will be required, in addition to ongoing monitoring of the effect on serotype distribution and clinical phenotype of current and future vaccines against pneumococcus. ### Competing Interest Statement CH is Principal Investigator of the AvonCAP study which is an investigator-led University of Bristol study funded by Pfizer. AF is a member of the Joint Committee on Vaccination and Immunization (JCVI) and chair of the World Health Organization European Technical Advisory Group of Experts on Immunization (ETAGE) committee. In addition to receiving funding from Pfizer as Chief Investigator of this study, he leads another project investigating transmission of respiratory bacteria in families jointly funded by Pfizer and the Gates Foundation. The other authors have no relevant conflicts of interest to declare. ### Funding Statement CH was funded by the National Institute for Health Research [NIHR Academic Clinical Fellowship (ACF-2015-25-002). DTA was funded by an NIHR Doctoral Research Fellowship (DRF-2018-11-ST2-065). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Health Research Authority, UK (IRAS 265437). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data used in this study are sensitive and cannot be made publicly available without breaching patient confidentiality rules. Therefore, individual participant data and a data dictionary is not available to other researchers.