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Pneumococcal pneumonia

D. Goldblatt,Elizabeth Miller

Published 2019 in Thorax

ABSTRACT

Pneumococcal conjugate vaccines (PCV) were first licensed in 2000 and have been introduced into national immunisation programme in more than 145 countries. They have had a profound effect on reducing invasive pneumococcal disease (IPD) caused by serotypes in the vaccine. These reductions have been seen both in infants immunised directly with PCV and in the general population protected indirectly by reduced transmission of pneumococci from immunised infants in whom the vaccine prevented nasopharyngeal carriage. PCV7 (Prevenar7, Pfizer, New York, NY, USA) was first introduced in the UK in 2006 followed by PCV13 (Prevenar13, Pfizer, New York, NY, USA) in 2010. Both vaccines have had a striking impact on vaccine serotype IPD although a trend, seen first following PCV7, for an increase in IPD caused by serotypes not included in the vaccine(s) has been reported. Surveillance of the impact of PCVs is focused on IPD, defined as isolation of pneumococcus from an otherwise sterile site, and has been the bedrock of monitoring the serotypespecific impact of vaccination at a population level for many years. It is however, well understood that from a numerical point of view, IPD is only the tip of the iceberg, with pneumonia and otitis media caused by Streptococcus pneumoniae responsible for a much larger burden of disease. In this edition of the journal, Pick and colleagues describe the outcome of their prospective populationbased study of adult community acquired pneumonia (CAP) in two teaching hospitals in Nottingham, England. They focus on trends in pneumococcal serotype contribution to the burden of adult CAP over 5 years (2013–2018), a period associated with sustained high coverage of PCV13 in the infant schedule. Attributing an episode of pneumonia to the pneumococcus is complicated as blood cultures are only positive in approximately 10% of clinical episodes of pneumonia and the isolation of the pneumococcus from nonsterile sites such as sputum, lacks specificity for the underlying aetiology of a clinical episode of pneumonia. The ability to detect pneumococcal capsular antigen in the urine of patients with pneumococcal disease has provided a sensitive and specific way of assessing, at the level of serotype, the contribution of the pneumococcus to CAP in adults. Using a recently modified multiplex immunoassay to detect pneumococcal derived carbohydrate antigen in urine and an assay that detects a common pneumococcal cell wall carbohydrate (Cpolysaccharide) the authors were able to evaluate temporal changes in the incidence rate of hospitalised pneumococcal CAP in adults (those over 15 years of age) and the specific contributions of the 24 serotypes measured in their assay. The authors describe an increase in incidence of CAP overall and pneumococcal CAP over this period, with the latter driven by the increase in nonvaccine pneumococcal CAP and serotype 3 (ST3). Using incident rate ratios (IRRs) the authors reported a statistically significant average annual increase of 19% over this 5year period in CAP due to serotypes that are not represented in any currently licensed pneumococcal vaccine, including the 23 valent plain polysaccharide vaccine (PPV23). The only other pneumococcal CAP subgroup that showed a significant increase in IRR over the 5 years was the group of serotypes included in PCV13 and not PCV7 (PCV13non7). This category is however dominated by infection caused by serotype 3 (ST3) which in 2016/2017 and 2017/2018 ST3 represented twothirds of all PCV13non7 pneumococcal CAP cases. This dominance of ST3 among the vaccine associated serotypes complicates other associations explored by the authors. For example, the authors attempted to identify potential risk factors in those whose pneumonia is due to serotypes contained in PCV13 compared with other serotypes, which might be informative for a risk based selective PCV13 strategy in adults. A number of risk factors were identified associated with an increased susceptibility to PCV13 serotype disease including increasing age, chronic kidney disease and other risk factors while living in residential care was associated with lower risk. However, none of these associations were significant when ST3 was excluded from the analysis. The preponderance of ST3 among VT pneumococcal CAP cases in the UK study is consistent with a recent study of CAP in the US and with the serotype distribution of IPD cases in both the UK and the USA 5 and is a consequence of infant PCV13 immunisation having little impact on ST3 carriage. Since the overall CAP incidence itself irrespective of any vaccine effect may be influenced each year by external factors such as influenza or other respiratory viruses it is informative to look at the percentage of all adult CAP that is caused by vaccine serotypes. PCV7 attributable pneumonia was approximately 2% of total CAP during this period of study compared with 12.3% in 2008/9, soon after PCV7 introduction. PCV13non7 attributable CAP (after exclusion of ST3) accounted for less than 5% of the total CAP in the last 3 years compared with 10.7% in 2008/2009. This illustrates the beneficial impact of infant immunisation with PCV on adult VT CAP, at least in settings such as the UK which has achieved high PCV overage over many years. In such settings any additional benefit achieved by immunisation of adults with PCVs containing the same serotypes as those used in infants would be small, although some direct protection in adults against ST3 CAP might be achieved. Onethird of pneumococcal CAP in 2017/18 (34%) was due to serotypes in the 23 valent vaccine but not in PCV13 (PPV23non13); of these ST8 and ST12F were most prominent, serotypes also shown to be contributing to the increase in IPD in the UK. A lack of consistent evidence showing the effectiveness of PPV23 against CAP has led to PPV23non13 serotypes included in new extended multivalent pneumococcal conjugate vaccine being evaluated. Following licensure, the use of extended valency vaccines will be influenced by a number of factors including their licensed indication (IPD or both IPD and pneumonia), the age group for which they are licensed (adults only or adults and children), their serotype composition and their likely cost effectiveness, bearing in mind that they will be licensed on immunogenicity alone, and at the time of licensure there will be no direct evidence for the ability of the vaccines to prevent CAP caused by the novel serotypes contained therein. The limitation of evaluating urine with an assay that can only recognise 24 antigens is apparent from the large increase in serotypes referred to by the authors as untyped. These episodes of pneumonia were associated with a positive Cpolysaccharide urinary antigen detection test but no confirmatory 24 valent bioplex results. Great Ormond Street Institute of Child Health Biomedical Research Centre, University College London, London, UK Infectious Disease Epidemiology, LSHTM, London, UK

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