Elsevier

Vaccine

Volume 32, Issue 21, 1 May 2014, Pages 2399-2405
Vaccine

Differences in serious clinical outcomes of infection caused by specific pneumococcal serotypes among adults

https://doi.org/10.1016/j.vaccine.2014.02.096Get rights and content

Highlights

  • Pneumococcal serotypes causing serious adult outcomes included in both PPSV23 & PCV13.

  • Serotype 6A linked with elevated risk in three studies.

  • Nine PPSV23-unique types linked with elevated risk in 14 studies.

  • Serotypes 11A and 9N repeatedly caused elevated case-fatality rate in adults.

  • Serotypes 10A and 15B repeatedly caused elevated meningitis risk in adults.

Abstract

Background

Infections due to Streptococcus pneumoniae serotypes differ in clinical manifestations among adults, varying in propensity for severity, invasiveness, and lethality. To characterize differences in serious outcomes between pneumococcal serotypes, we systematically reviewed the literature.

Methods

After distilling 676 hits to 28 relevant articles, statistically significant differences in individual serotypes associated with serious clinical outcomes were assessed. Serotypes associated with elevated risk of serious clinical outcomes were evaluated in terms of serotypes included in licensed adult pneumococcal vaccines (i.e., 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13)). Repeated findings were considered a measure of robustness.

Results

Among adult studies evaluating serious clinical outcomes, the following serotypes were associated with elevated risk: Empyema (serotypes 1, 3, 5, 7F, 8, 19A), necrotizing pneumonia (serotype 3), septic shock (serotypes 3, 19A), meningitis (repeatedly serotypes 10A, 15B, 19F, 23F), reduced quality-adjusted life years (QALYs, serotypes 15B, 3, 10A, 9N, 19F, 11A, 31), and increased case-fatality rates (repeatedly serotypes 3, 6B, 9N, 11A, 16F, 19F, 19A).

Conclusion

Both vaccine formulations include multiple pneumococcal serotypes associated with increased risk for serious clinical outcomes. Three studies found elevated risk from serotype 6A (unique to PCV13). Fourteen studies found elevated risk from nine serotypes unique to PPSV23 (repeatedly: case-fatality—11A & 9N, meningitis—10A & 15B). Seven studies found elevated risk from serotypes not represented in either vaccine formulation (notably 16F). The pneumococcal serotypes repeatedly associated with elevated risk of serious outcomes in adults are an important consideration for vaccine policy making.

Section snippets

Methods

To identify published articles describing differences in serious clinical outcomes related to individual pneumococcal serotypes among adults, we searched the entire PubMed database through February 2014, regardless of language. The search terms were [(Streptococcus pneumoniae OR pneumococcal infections) AND (epidemiology OR pathogenicity OR mortality OR immunology OR risk factors) AND (serotyping OR bacterial typing techniques) AND adult)]. We also considered relevant articles identified from

Results

The literature review yielded studies of important clinical outcomes involving empyema (or parapneumonic effusion), necrotizing pneumonia, septic shock, meningitis (each summarized in Table 1), and lethality (as measured by case-fatality rates), summarized in Table 2. One study assessed effect on quality-adjusted life years (QALYs), as a means of aggregating clinical consequences into a single quantitative parameter (Table 1) [16].

Specific clinical outcomes

Among four adult studies evaluating empyema or parapneumonic effusion [7], [26], [27], [28], the serotypes associated with elevated risk were 1, 3, 5, 7F, 8, and 19A (Table 1). Across the four studies, serotype 1 was the serotype associated with increased risk for empyema. In one adult study evaluating necrotizing pneumonia [29], serotype 3 was associated with elevated risk. Among three adult studies evaluating sepsis or septic shock [8], [30], [31], one study found no elevations, whereas the

Risk in relation to vaccine formulations

Most pneumococcal serotypes associated with a statistically significant elevation in risk for serious clinical outcomes are included in both the PPSV23 and PCV13 formulations (Table 3). Three studies (two meningitis studies and one mortality study) found elevated risk from serotype 6A (a component of PCV13). In 14 studies, elevated risk from serotypes included only in PPSV23 was found, repeatedly 10A and 15B with meningitis and 11A and 9N with mortality. In seven study analyses, elevated risk

Discussion

This review shows that multiple pneumococcal serotypes associated with increased risk for serious clinical outcomes are included in both PPSV23 and PCV13, notably serotypes 1, 3, 6B, 19F, 19A, and 23F. However, the extent of serotype coverage offered by each vaccine for adults is not the same [5]. Three studies found elevated risk from serotype 6A, unique to PCV13. Fourteen studies found elevated risk from nine of the 11 serotypes unique to PPSV23, notably 9N, 10A, 11A, and 15B. This divergence

Conflict of interest

JDG and LKM are employees of Merck & Co., Whitehouse Station, NJ, manufacturer of 23-valent pneumococcal polysaccharide vaccine and developer of 15-valent pneumococcal conjugate vaccine.

Acknowledgements

The authors acknowledge publication searches and critiques by Scott Dolder, Julie Sievert, Brandon Palermo, Leora Suprun, and Mel Kohn.

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