Chasing Serotype Replacement in Pneumococcal Pneumonia

Increasing rates of non-pneumococcal conjugate vaccine (PCV) 13 serotypes of invasive pneumococcal disease (IPD) present a new challenge to the global containment of the infection, according to results of a multinational observational study reported in The Lancet.¹ While the newest high-valent PCV10 and PCV13 vaccines are effective in preventing IPD caused by the serotypes within the vaccines, breakthrough patterns of conversion to non-PCV13 serotypes are emerging.

Using pooled data from 7 of the European countries (Czech Republic, France, Ireland, Norway, Sweden, Spain, and the United Kingdom) monitored by the Streptococcus pneumoniae Invasive Disease network (SpIDnet), the investigators found an incidence rate ratio (IRR) of 0.53 (95% CI, 0.43-0.65) in children younger than 5 due to any serotype occurring 4 years after the introduction of the 13-valent vaccine. This occurred in sites where either the PCV13 alone was used, or in areas where both the PCV10 and PCV13 were available.

In locations where PCV13 was used exclusively, the IRR due to any PCV7 serotypes was .16 (95% CI, .07-.40), .17 (95% CI, .07-.42) for disease caused by serotypes 1, 5, and 7F, and 0.41 (95% CI, .25-.69) for serotypes 3, 6A and 19A. The pooled analysis for all non-PCV13 serotypes reached an IRR of 1.62 (95% CI, 1.09-2.42).

While the overall incidence of IPD declined by 47% as a result of the introduction of high-valent vaccines compared with prior years when the PCV7 vaccine was used (and by 55% compared with pre-PCV7 years), serotype replacement appeared to occur frequently, evidenced by the emergence of new IPD cases due to multiple non-PCV13 serotypes.

Study investigators determined that the PCV13 and PCV10 vaccines showed high efficacy against the serotypes in the disease, indicating “a positive overall effect of the vaccination programmes,” and noted that the 2 high-valent vaccines contributed to further declines in PCV7 serotypes observed in other studies.^2-4 They recommended continued monitoring of the incidence of IPD due to non-PCV13 serotypes, as well as carriage prevalence to understand the nature and implications of the serotype replacement observed in the study.

The high degree of heterogeneity in pneumococcal disease observed across all study sites presented a challenge to data collection and reporting, which the investigators tried to limit. Data for more than 20% of sampled cases was missing, and due to the fact that the PCV13 vaccine was introduced in 2011, Year 4 data was not available at all sites.

References

1. Savulescu C, Krizova P, Lepoutre A.  Effect of high-valency pneumococcal conjugate vaccines on invasive pneumococcal disease in children in SpIDnet countries: an observational multicentre study. Lancet Respir Med. 2017;5(8):648-656. doi:10.1016/S2213-2600(17)30110-8
2. Miller E, Andrews NJ, Waight PA, Slack MP, George RC. Herd immunity and serotype replacement 4 years after seven-valent pneumococcal conjugate vaccination in England and Wales: an observational cohort study. Lancet Infect Dis 2011;11(10):760-768. doi:10.1016/S1473-3099(11)70090-1
3. De Wals P, Deceuninck G, De Serres G. Effectiveness of three pneumococcal conjugate vaccines to prevent invasive pneumococcal disease in Quebec, Canada. Vaccine 2016;34(18):2053-2054. doi:10.1016/j.vaccine.2015.06.104
4. Moore MR, Link-Gelles R, Schaffner W, et al. Effectiveness of 13-valent pneumococcal conjugate vaccine for prevention of invasive pneumococcal disease in children in the USA: a matched case-control study. Lancet Respir Med 2016;4(5):399-406. doi:10.1016/S2213-2600(16)00052-7