Abstract

Background: Pneumococcal conjugate vaccines (PCV) are highly effective in preventing invasive pneumococcal disease (IPD) but deaths due to IPD still occur. We aimed to describe children who died of IPD since PCV introduction in England and Wales. Methods: Public Health England conducts enhanced IPD surveillance in England and Wales. IPD cases in PCV-eligible children aged <5 years (born since 04 September 2004 and diagnosed between 04 September 2006 and 03 September 2014) were actively followed-up by postal questionnaires and, for fatal cases, detailed information was requested prospectively from multiple sources. Results: During the 8-year period, there were 3,146 IPD cases and 150 IPD-related deaths (case fatality rate, 4.8%). Overall, 132 isolates from fatal cases were serotyped (88%) and 35 distinct serotypes were identified, with no serotype predominance. Most deaths occurred in <1 year-olds (88/150, 59%) and one year-olds (36/150, 24%). One-third (53/150, 35%) had a known risk factor for IPD. Clinical presentation varied with age but not by serotypes in the different conjugate vaccines. Meningitis was diagnosed in nearly half the fatal cases (71/150, 47%). IPD-related mortality-rate declined after PCV7 introduction from 1.25/100,000 children in 2006/07 to 0.60/100,000 in 2009/10, with a further reduction following PCV13 introduction from April 2010 to 0.39/100,000 in 2013/14 (14 deaths; IRR, 0.31; 95%CI, 0.16-0.61; P=0.0003), when most deaths were due to non-vaccine serotypes or in neonates. Conclusions: Most fatal IPD cases are currently not vaccine-preventable. Additional strategies will be required to reduce childhood pneumococcal deaths in countries with established pneumococcal vaccination programmes.