Effects of Infant Pneumococcal Conjugate Vaccination on Serotype Distribution in Invasive Pneumococcal Disease among Children and Adults in Germany

Abstract

This study describes the effects of the introduction of universal infant pneumococcal conjugate vaccination in 2006 on invasive pneumococcal disease (IPD) among children and adults in Germany with a focus on the dynamics of serotype distribution in vaccinated and non-vaccinated age groups. Over a period of 22 years (1992–2014), microbiological diagnostic laboratories from all over Germany have been sending isolates of IPD cases to the German National Reference Center for Streptococci on a voluntary basis. Streptococcus pneumoniae isolates were serotyped using Neufeld’s Quellung method. Among children <16 years, the proportion of PCV7 serotypes among isolates from IPD cases decreased from 61.8% before vaccination (1997–2006) to 23.5% in the early vaccination period (2007–2010; p = 1.30E-72) and sank further to 5.2% in the late vaccination period (2010–2014; p = 4.59E-25). Similar reductions were seen for the separate age groups <2 years, 2-4 years and 5-15 years. Among adults, the proportion of PCV7 serotypes decreased from 43.4% in the pre-vaccination period (1992–2006) to 24.7% (p = 3.78E-88) in the early vaccination period and 8.2% (p = 5.97E-161) in the late vaccination period. Both among children and among adults, the non-PCV7 serotypes 1, 3, 7F and 19A significantly increased in the early vaccination period. After the switch from PCV7 to PVC10/PCV13 for infant vaccination in 2010, serotypes 1, 6A and 7F significantly decreased. A decrease in serotype 19A was only observed in 2013–2014, as compared to 2010–2011 (children p = 4.16E-04, adults p = 6.98E-06). Among adults, serotype 3, which strongly increased in the early vaccination period (p = 4.44E-15), remained at a constant proportion in the late vaccination period. The proportion of non-PCV13 vaccine serotypes increased over the whole vaccination period, with serotypes 10A, 12F, 23B, 24F and 38 most significantly increasing among children and serotypes 6C, 12F, 15A, 22F and 23B increasing among adults. Eight years of childhood pneumococcal conjugate vaccination have had a strong effect on the pneumococcal population in Germany, both among the target group for vaccination as well as among older children and adults.

Impact of pneumococcal conjugate vaccines on pneumococcal meningitis cases in France between 2001 and 2014: a time series analysis

“…The interaction between PCV7 introduction and antibiotic reduction led to important increases of non-vaccine and penicillin-susceptible strains, resulting in an overall rise of the number of pneumococcal meningitis (PM) cases [5]. In other neighbouring countries that introduced PCV7 without lowering antibiotic use, PCV7 introduction had different effects according to the country and the age group: in Germany, Switzerland, England and Wales a substantial reduction in IPDs was achieved [6–8], while in Spain, the impact of PCV7 was attenuated by the increase of non-PCV7 serotypes [9]. Despite these differences, some homogeneity concerning emerging serotypes (19A, 7F, 3) was observed [6, 8, 10, 11].…”

“…In other neighbouring countries that introduced PCV7 without lowering antibiotic use, PCV7 introduction had different effects according to the country and the age group: in Germany, Switzerland, England and Wales a substantial reduction in IPDs was achieved [6–8], while in Spain, the impact of PCV7 was attenuated by the increase of non-PCV7 serotypes [9]. Despite these differences, some homogeneity concerning emerging serotypes (19A, 7F, 3) was observed [6, 8, 10, 11]. In the US, overall IPD incidence rates in adults and children declined significantly during the first 3 years of PCV7 use and stabilised thereafter [12, 13].…”

Host-derived extracellular RNA promotes adhesion of Streptococcus pneumoniae to endothelial and epithelial cells

“…An increasing number of penicillin and macrolide resistant isolates and also a continuous increase in multidrug resistance (MDR, resistant to ≥ 3 classes of antimicrobials) have been reported4. The invention of a 13 th valent conjugate vaccine (Prevnar13 ® ) has generated limited protection in children5. Due to the restricted serotype coverage combined with the low vaccination status of the elderly and immunocompromised patients5, novel strategies against this pathogen are sorely needed.…”

“…The invention of a 13 th valent conjugate vaccine (Prevnar13 ® ) has generated limited protection in children5. Due to the restricted serotype coverage combined with the low vaccination status of the elderly and immunocompromised patients5, novel strategies against this pathogen are sorely needed.…”

Pneumococcal conjugate vaccine for adults: “It's tough to make predictions, …”

“…So it could be assumed that the cost-effectiveness will be greater in the Netherlands compared with countries that have implemented PCV13, covering those three serotypes. However, we do not know yet the dimension of the replacement phenomenon after introduction of PCV13 in infants: early data suggest that there is no relevant herd protection for serotype 3 [20]. Serotype 3 has a broader capsule and seems to be more frequently invasive and less frequently colonising.…”