New study highlights the need for advanced pneumococcal vaccines in the wake of pre-COVID data

In a recent study published in the Lancet Regional Health, researchers describe serotype distribution in hospitalized adults diagnosed with pneumococcal community-acquired pneumonia (CAP) in the United Kingdom (UK) in the two years before the onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic using a 24-valent serotype-specific urinary antigen detection (UAD) assay and blood cultures.

This multicenter prospective cohort study that began across three UK hospitals in Nottingham, Liverpool, and Edinburgh between April 2018 and March 2020 among adults hospitalized with CAP also evaluated the risk factors associated with CAP caused by serotypes in the different pneumococcal vaccines.

Study: Pneumococcal serotypes and risk factors in adult community-acquired pneumonia 2018–20; a multicentre UK cohort study. Image Credit: joel bubble ben/Shutterstock.com

Background

Streptococcus pneumoniae (pneumococcus) is the most common causative pathogen of CAP. Scientists have identified over 100 pneumococcal serotypes; however, of these, only two, namely, a 23-valent pneumococcal polysaccharide vaccine (PPV23) and pneumococcal conjugate vaccines (PCVs), are used in pneumococcal vaccines.

After PCV implementation in the UK, vaccine-serotype invasive pneumococcal disease (IPD) declined in all age groups, but the pneumonia caused by non-PCV serotypes surged.

A recent study showed that despite the introduction of PCV10/13 vaccines into national childhood immunization programs in the UK, PCV13 serotypes caused nearly 50% of pneumococcal CAP.

Data on the risk factors associated with pneumococcal pneumonia caused by the additional serotypes potentially covered by novel higher-valency PCVs are crucial to inform the formulation of vaccine policy. However, currently, there is a lack of this data.

Evidence before the study

Researchers extensively searched PubMed, EMBASE, and MEDLINE databases for studies published in any language between 1 January 1990 and 30 March 2021 using search terms relating to “community-acquired pneumonia” OR "CAP" OR “Streptococcus pneumoniae” AND “pneumococcal serotypes”.

They identified 28 eligible studies from Europe, North America, and Asia.

The pooled estimate of the proportion of adult pneumococcal pneumonia due to PCV13 vaccine serotypes from across Europe, North America, and Asia was 49% in one to five years following the introduction of childhood PCV10/13 immunization.

The method of serotype detection influenced these estimates; nonetheless, these were higher for Europe compared to North America (26% vs. 11%).

Other studies published up to 1 September 2023 reported coverage for PCV15 and PCV20 serotypes ranging from 34% to 45% and 58% to 69%, respectively.

In a previous study, researchers noted that serotype three and non-PCV13 serotypes have caused this increase in non-invasive pneumococcal pneumonia since 2008 in Nottingham, UK.

About the study

The present study team screened all acute admissions per study eligibility criteria daily and reviewed cases within 48 hours of admission.

They treated patients aged ≥16 with one or more symptoms of a lower respiratory tract (LRT) infection and abnormalities indicating chest infection on a chest radiograph as a CAP patient.

Pneumococcal CAP patients were diagnosed based on the following three criteria: 

a) positive pneumococcal UAD;

b) blood culture positive for S. pneumoniae;

c) positive report on the Bio-Plex24 assay.

The statistical analysis included all patients with radiologically confirmed CAP, classifying serotypes based on pneumococcal vaccines and excluding patients with multiple serotypes detected in the same sample.

Serotypes based on the content of pneumococcal vaccines were PCV13, PCV15, PCV20non13, PPV23non13, and non-vaccine types (NVT) or untyped disease.

The researchers used multivariable logistic regression to analyze the association between different serotypes and comorbidity, adjusting for age, gender, residential care status, prior vaccination, and specific comorbidities.

They also analyzed the risk of pneumococcal CAP in different clinical risk groups based on age (ages 16-64 and ≥ 65) and specific risk factors (chronic diseases, immunosuppression).

Results

Of 2,249 potential participants identified across the three sites, 1,921 adults hospitalized with CAP, of which 7.8% were admitted to critical care units, made it to the final analysis sample set. The median age of these people was 70 years, and most were male patients.

The authors diagnosed 781 patients with pneumococcal CAP, with 78 (10%) showing a positive pneumococcal blood culture. Of these, 149 samples had multiple serotypes.

The large proportion of hospitalized CAP patients (40.7%) who had single serotype pneumococcal CAP were predominantly due to serotypes covered by PCV13 and PCV15.

The PCV13 serotype pneumonia was more common in older patients and associated with a higher risk of death within 30 days and male sex. The two most prevalent serotypes in the study cohort were serotypes 3 (70.4%) and 19A (16.9%).

Likewise, ~49.4% of patients had pneumonia caused by a PCV15 serotype, with serotypes 22F and 33F being the most common. A cerebrovascular disease was a risk factor for pneumonia caused by these serotypes.

These observations are notable as these serotypes caused pneumococcal CAP despite relatively high vaccine coverage in 2019–2020 in the UK, i.e., 71.5% and 90.5% for adults ≥65 years and infants, respectively.

Moreover, the shift away from PCV13 serotypes following the introduction of infant PCV13 immunization was unsubstantial, reflecting lower vaccine efficacy against PCV13 serotypes and the persistence of serotype 3. 

Further, they detected PCV20-non13 serotypes in 24.6% of patients with pneumococcal CAP, with lower odds in males and those who had received the PPV23 vaccine.

These cases occurred more in younger people without clinical risk factors, and these patients had lower odds of readmission within 30 days.

Moreover, PPV23 serotypes accounted for 74.8% of pneumococcal CAP, with PPV23-nonPCV13 serotype CAP being more common in younger individuals and less common in males and those who had received a PPV23 vaccine.

Conclusions

To conclude, people under 65 with no pneumococcal risk factors, and, thus, not currently targeted for pneumococcal vaccination, are more likely to develop pneumonia with a PCV20-non13 serotype than other serotypes. 

Thus, researchers of this study recommended the use of higher-valency vaccines to avert considerable numbers of pneumococcal CAP cases in older adults. 

This study was conducted before the SARS-CoV-2 pandemic. However, it will be important to continue monitoring changes in pneumococcal serotype distribution in the post-pandemic years, given the social restrictions imposed during the pandemic influenced the epidemiology of pneumococcal CAP.

Monitoring the shifts in pneumococcal serotypes (serotype replacement) will remain important after introducing any new higher-valency pneumococcal vaccine because PCV15 and PCV20 vaccine use has remained high in many European countries since 2022.

Several novel higher-valency pneumococcal vaccines are under evaluation, including a 21-valent PCV, a 24-valent vaccine, and a PCV with more than 30 serotypes.

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.