Abstract

Background The 7-valent (PCV7) and 13-valent (PCV13) pneumococcal conjugate vaccines are highly effective in preventing invasive pneumococcal disease (IPD) caused by vaccine serotypes. Vaccine failure (vaccine-type IPD after age-appropriate immunisation) is rare. Little is known about the risk, clinical characteristics or outcomes of PCV13 compared to PCV7 vaccine failure. Methods Public Health England conducts IPD surveillance and provides a national reference service for serotyping pneumococcal isolates in England and Wales. We compared the epidemiology, rates, risk factors, serotype distribution, clinical characteristics, and outcomes of IPD in children with PCV13 and PCV7 vaccine failure. Results A total of 163 episodes of PCV failure were confirmed in 161 children over eight years (04 September 2006 to 03 September 2014) in ten birth cohorts. After three vaccine doses, PCV7 and PCV13 failure rates were 0.19/100,000 (95% CI, 0.10-0.33; 57 cases) and 0.66/100,000 (95% CI, 0.44-0.99; 104 cases) vaccinated person-years, respectively. Children with PCV13 failure were more likely to be healthy (87/105 [82.9%] vs. 37/56 [66.1%]; P=0.02), present with bacteremic lower respiratory tract infection (61/105 [58.1%] vs. 11/56 [19.6%]; P<0.001) and develop empyema (41/61 [67.2%] vs. 1/11 [9.1%]; P<0.001) compared to PCV7 failures. Serotypes 3 (n=38, 36.2%) and 19A (n=30, 28.6%) were responsible for most PCV13 failures. Five children died (3.1%; 95% CI, 1.0-7.1%), including four with co-morbidities. Conclusions PCV failure is rare and, compared to PCV7 serotypes, the additional PCV13 serotypes are more likely to cause bacteremic lower respiratory tract infection and empyema in healthy vaccinated children.