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Meta-Analysis
. 2010 Sep 15;51(6):692-9.
doi: 10.1086/655828.

Association of serotype with risk of death due to pneumococcal pneumonia: a meta-analysis

Daniel M Weinberger  1 , Zitta B Harboe, Elisabeth A M Sanders, Moses Ndiritu, Keith P Klugman, Simon Rückinger, Ron Dagan, Richard Adegbola, Felicity Cutts, Hope L Johnson, Katherine L O'Brien, J Anthony Scott, Marc Lipsitch
Affiliations
Meta-Analysis

Association of serotype with risk of death due to pneumococcal pneumonia: a meta-analysis

Daniel M Weinberger et al. Clin Infect Dis. .

Abstract

Background: The 92 capsular serotypes of Streptococcus pneumoniae differ greatly in nasopharyngeal carriage prevalence, invasiveness, and disease incidence. There has been some debate, though, regarding whether serotype independently affects the outcome of invasive pneumococcal disease (IPD). Published studies have shown variable results with regard to case-fatality ratios for specific serotypes and the role of host factors in affecting these relationships. We evaluated whether risk of death due to IPD is a stable serotype-associated property across studies and then compared the pooled effect estimates with epidemiologic and biological correlates.

Methods: We performed a systematic review and meta-analysis of serotype-specific disease outcomes for patients with pneumonia and meningitis. Study-specific estimates of risk of death (risk ratio [RR]) were pooled from 9 studies that provided serotype-specific data on pneumonia and meningitis using a random-effects method with serotype 14 as the reference. Pooled RRs were compared with RRs from adults with low comorbidity scores to evaluate potential confounding by host factors.

Results: Significant differences were found in the RR estimates among serotypes in patients with bacteremic pneumonia. Overall, serotypes 1, 7F, and 8 were associated with decreased RRs, and serotypes 3, 6A, 6B, 9N, and 19F were associated with increased RRs. Outcomes among meningitis patients did not differ significantly among serotypes. Serotypes with increased RRs had a high carriage prevalence, had low invasiveness, and were more heavily encapsulated in vitro.

Conclusions: These results suggest that IPD outcome, like other epidemiologic measures, is a stable serotype-associated property.

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Conflict of interest statement

Conflicts of interest: SR has received travel grants from Wyeth; EAMS reports receiving unrestricted grants from Wyeth and Baxter for research, consulting fees for Wyeth and GlaxoSmithKline, lecturing fees from Wyeth and grant support from Wyeth and GlaxoSmithKline for vaccine studies. ML has received honoraria or consulting income from Pfizer, Novartis, and the Avian/Pandemic Flu Registry (Outcome Sciences), sponsored in part by Roche. KPK has received consulting and research support from Pfizer Vaccines, and consulting for Merck and Novartis. The rest of the authors declare no conflicts.

Figures

Figure 1
Figure 1
Study specific and pooled risk ratios (RRs) for death from bacteremic pneumonia compared to serotype 14. Closed diamonds represent study-specific RR+/−95% CI. Open diamonds represent the pooled RR+/−95% CI. I2 denotes the amount of variation in the RR due to heterogeneity. Only studies with ≥ 10 isolates of the serotype are shown though all studies were used to calculate the RR and evaluate heterogeneity.
Figure 2
Figure 2
(a) Comparison of RRs calculated among Danish adult bacteremic pneumonia cases compared to the pooled RR from all other studies. (b) Comparison of RRs calculated among adult Danish bacteremic pneumonia cases with no known comorbidities with the overall pooled RRs representing all studies except for the Danish low-comorbidity cases.
Figure 3
Figure 3
Relationship between serotype-specific RRs and epidemiologic and microbiological measures. Serotype specific RR among pneumonia cases is related to (a) carriage prevalence in a pediatric study in England (number of nasopharyngeal isolates) [22], (b) invasiveness [22], and (c) degree of encapsulation (area in pixels) [18]. There were no carriage isolates for types 1 or 5.
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