Epidemiology, vaccine effectiveness, and risk factors for mortality for pneumococcal disease among hospitalised adults in Singapore: a case-control study

Retrospective case-control study of patients tested for pneumococcal disease with streptococcal urinary antigen testing and at least one sterile site culture, during their admission to a tertiary hospital in Singapore from 2015 to 2017. Patients were defined as cases of IPD or non-IPD, or as controls, based on laboratory results and clinical diagnoses. Multivariable models were constructed to determine factors associated with IPD/non-IPD, and risk factors for mortality from pneumococcal disease. Vaccine effectiveness against IPD/non-IPD was estimated using a variation of the test-negative design.

We identified 496 pneumococcal disease cases, of whom 92 (18.5%) had IPD. The mean age of cases was 69.1 ± 15.4 years, and 65.5% were male. Compared with controls (N = 9181), IPD patients were younger (mean age 61.5 ± 16.3 years, vs 72.2 ± 16.1 years in controls; p < 0.001) and with less co-morbidities [median Charlson’s score 1 (IQR 0–4), vs 3 (1–5) in controls; p < 0.001]. IPD patients also had the highest proportions with intensive care unit (ICU) admission (20.7%), inpatient mortality (26.1%) and longest median length of stay [9 (IQR 8–17) days]. On multivariable analysis, IPD was negatively associated with prior pneumococcal vaccination (adjusted relative risk ratio = 0.20, 95%CI 0.06–0.69; p = 0.011). Risk factors for mortality among pneumococcal disease patients were ICU admission, diagnosis of IPD, age ≥ 85 years and Charlson’s score > 3.

Patients with pneumococcal disease (especially IPD) were younger and had less co-morbidities than controls, but had higher risk of severe clinical outcomes and mortality. Pneumococcal vaccination effectiveness against IPD was estimated to be about 80%, and should be encouraged among high-risk patients.