Serotype-specific differences in short- and longer-term mortality following invasive pneumococcal disease

Abstract

Invasive pneumococcal disease (IPD), caused by infection with Streptococcus pneumoniae, has a substantial global burden. There are over 90 known serotypes of S. pneumoniae with a considerable body of evidence supporting serotype-specific mortality rates immediately following IPD. This is the first study to consider the association between serotype and longer-term mortality following IPD. Using enhanced surveillance data from the North East of England we assessed both the short-term (30-day) and longer-term (⩽7 years) independent adjusted associations between individual serotypes and mortality following IPD diagnosis using logistic regression and extended Cox proportional hazards models. Of the 1316 cases included in the analysis, 243 [18·5%, 95% confidence interval (CI) 16·4-20·7] died within 30 days of diagnosis. Four serotypes (3, 6A, 9N, 19 F) were significantly associated with overall increased 30-day mortality. Effects were observable only for older adults (⩾60 years). After extension of the window to 12 months and 36 months, one serotype was associated with significantly increased mortality at 12 months (19 F), but no individual serotypes were associated with increased mortality at 36 months. Two serotypes had statistically significant hazard ratios (HR) for longer-term mortality: serotype 1 for reduced mortality (HR 0·51, 95% CI 0·30-0·86) and serotype 9N for increased mortality (HR 2·30, 95% CI 1·29-4·37). The association with serotype 9N was no longer observed after limiting survival analysis to an observation period starting 30 days after diagnosis. This study supports the evidence for associations between serotype and short-term (30-day) mortality following IPD and provides the first evidence for the existence of statistically significant associations between individual serotypes and longer-term variation in mortality following IPD.

Keywords: Mortality; pneumococcal infections; serotype; survival analysis.

Fig. 1.

Crude mortality rates at 30 days, 12 months and 36 months post-diagnosis with invasive pneumococcal disease by age groups.

Fig. 2.

Predicted marginal probabilities of survival after 30 days following diagnosis with invasive pneumococcal disease by serotype. The grey line indicates the average for each age group. Probabilities are adjusted for sex, deprivation, serotype, clinical presentation and number of risk factors.

Fig. 3.

Predicted marginal probabilities of survival after 12 months following diagnosis with invasive pneumococcal disease by serotype. The grey line indicates the average for each age group. Probabilities are adjusted for sex, serotype and risk factors (number of, chronic renal disease, and immunosuppression).

Fig. 4.

Predicted marginal probabilities of survival after 36 months following diagnosis with invasive pneumococcal disease by serotype. The grey line indicates the average for each age group. Probabilities are adjusted for sex, pneumococcal vaccination status, deprivation, serotype, and risk factors (chronic liver disease, chronic lung disease, and immunosuppression).

Fig. 5.

Adjusted Kaplan–Meier survival curves for time since diagnosis of all cases of invasive pneumococcal disease. (a) All serotypes by age group, (b) significantly associated serotypes for all ages, (c) significantly associated serotypes for ages 0–39 years, (d) significantly associated serotypes for ages ⩾40 years. Survival function is adjusted within each age group for sex, deprivation quintile, clinical presentation, chronic heart disease, chronic liver disease, chronic lung disease, and immunosuppression. Only the two serotypes significantly associated with survival from the multivariable model are shown individually.