Abstract and Introduction

Abstract

Ongoing surveillance after pneumococcal conjugate vaccination (PCV) deployment is essential to inform policy decisions and monitor serotype replacement. We report serotype and disease severity trends in 3,719 adults hospitalized for pneumococcal disease in Bristol and Bath, United Kingdom, during 2006–2022. Of those cases, 1,686 were invasive pneumococcal disease (IPD); 1,501 (89.0%) had a known serotype. IPD decreased during the early COVID-19 pandemic but during 2022 gradually returned to prepandemic levels. Disease severity changed throughout this period: CURB65 severity scores and inpatient deaths decreased and ICU admissions increased. PCV7 and PCV13 serotype IPD decreased from 2006–2009 to 2021–2022. However, residual PCV13 serotype IPD remained, representing 21.7% of 2021–2022 cases, indicating that major adult PCV serotype disease still occurs despite 17 years of pediatric PCV use. Percentages of serotype 3 and 8 IPD increased, and 19F and 19A reemerged. In 2020–2022, a total of 68.2% IPD cases were potentially covered by PCV20.

Introduction

Streptococcus pneumoniae remains the leading bacterial cause of community-acquired pneumonia, despite widespread use of effective pneumococcal vaccines with >100 recognized pneumococcal serotypes. In the United Kingdom, unconjugated 23-valent pneumococcal polysaccharide vaccine (PPV23) is offered to all adults ≥65 years of age and persons ≥2 years of age who are at increased risk for pneumococcal disease. In September 2006, a 7-valent pneumococcal conjugate vaccine (PCV7) was implemented into the national childhood immunization program, then replaced with a 13-valent PCV (PCV13) in April 2010. The PCVs were given at a 2 + 1 schedule but replaced with a 1 + 1 schedule in April 2020^[1]. Because PCVs prevent carriage acquisition in addition to protection against disease, both PCVs had a large and major direct and indirect (herd) effect on pneumococcal disease caused by the respective serotypes^[2–4].

By 2016‒2017, PCV7 pneumococcal serotype disease had virtually disappeared in children and decreased to a large degree in adults. Invasive pneumococcal disease (IPD) caused by PCV13 serotypes has also decreased substantially but subsequently plateaued, with a residual incidence of 8 IPD cases/100,000 population in England^[5–7]. At the same time, pneumococcal cases caused by non-PCV13 serotypes increased across all age groups, especially in older adults, resulting in no net reduction in total IPD cases in older adults in 2016‒2017 compared with the pre-PCV13 period, a phenomenon known as serotype replacement^[5–7]. Monitoring those effects nationally is vital for planning of healthcare use and developing new preventive strategies, including use of higher-valent pneumococcal vaccines^[8,9].

The effect of serotype replacement has not been reported in the United States; data suggest that the incidence on nonvaccine serotype disease has remained stable, in both children and older adults^[10]. Clarification of the reasons for differences seen in studies from the United States and United Kingdom is needed because serotype replacement is a threat to the effectiveness of current vaccine programs, and PCV scheduling remains a policy decision area. It remains unclear why such differences occur; however, several factors might be involved, such as methods differences in surveillance approaches, exposure to pneumococcal transmission, risk factor profiles between patient populations, and serotype interactions^[11]. Small differences in carriage prevalence and clonal lineages might result in greatly different rates of IPD because serotype-specific invasiveness varies by orders of magnitude.

In England, the UK Health Security Agency conducts national IPD surveillance, which includes limited data on noninvasive pneumococcal disease, clinical phenotype, and disease severity^[5–7]. Evidence from a large pneumococcal pneumonia cohort in Nottingham, UK, suggests there are relatively few differences between patients with PCV13 and non-PCV13 serotype respiratory infections^[12]. Nevertheless, changing serotype distribution could result in changes in pneumococcal disease phenotypes, which might have implications for use of available polyvalent serotype-specific pneumococcal vaccines. Furthermore, the COVID-19 pandemic has disrupted the epidemiology of multiple respiratory infections^[13,14] and provided new insights into virus–bacteria–host interactions. Many countries, including the United Kingdom, implemented measures such as social distancing and school closures that were intended to decrease SARS-CoV-2 transmission and alleviate pressure on healthcare services^[15]. Those measures reduced the transmission of other respiratory pathogens^[14] but it is unclear to what extent they disrupted pneumococcal transmission^[16,17]. The measures might also have caused changes in serotype distribution of pneumococcal infection and disease.

In this retrospective cohort study conducted at 3 large National Health Service (NHS) hospitals, which represent all secondary care provision within a defined geographic area, we examined trends in pneumococcal serotype distribution in adults after PCV7 and PCV13 implementation into the childhood immunization program and the effect of the COVID-19 pandemic over the first 3 years. We report confirmed pneumococcal disease incidence during 2006–2022, both overall and by vaccine serotypes, and assess trends in severity of pneumococcal disease in hospitalized adults.