Twenty-Year Public Health Impact of 7- and 13-Valent Pneumococcal Conjugate Vaccines in US Children

Abstract

B efore 2000, children <2 years of age had the highest incidence of invasive pneumococcal diseases (IPDs) such as bacteremia, meningitis, or other infection of a normally sterile site (1). Researchers estimated that, in the United States, annual IPD incidence was 165 cases/100,000 children <12 months of age and 203 cases/100,000 children 12-23 months of age (1). Until the United States began a universal 7-valent pneumococcal conjugate vaccine (PCV7) immunization program for children in 2000, Streptococcus pneumoniae was the leading cause of bacterial meningitis (1).S. pneumoniae was also the most common bacterial cause of community-acquired pneumonia and otitis media (OM) in young children. Furthermore, in the 1990s, concerns emerged regarding the growing number of pneumococcal isolates with reduced susceptibility to fi rst-and second-line antimicrobial drugs (1).PCV7 was the fi rst pneumococcal conjugate vaccine (PCV) approved for use in children <2 years of age in the United States. Pneumococcal polysaccharide vaccines, which preceded PCVs, are not immunogenic in children <2 years of age (1,2). PCV7 overcame the challenge of poor immunogenicity among infants and young children through conjugation technology; it was introduced into the US infant immunization schedule in 2000, providing direct protection against several serotypes of invasive and noninvasive pneumococcal disease (3,4). PCV7 protects against the S. pneumoniae serotypes responsible for >80% of IPD cases among children in North America (i.e., serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) (1,4). In 2010, PCV13, a vaccine providing protection against 6 additional serotypes (i.e., serotypes 1, 3, 5, 6A, 19A, and 7F), was approved in the United States, partially because of increasing incidence of serotypes not covered by PCV7 (1,4).Clinical trial data suggested that PCV7 would be effective against IPD, OM, and according to a posthoc analysis, pneumonia (5). The effi cacy of PCV7 (and later PCV13) against all forms of pneumococcal disease was greater than expected, partly because of indirect protection gained through herd immunity (6-8). The United States was the fi rst country to introduce a PCV program for infants and, during the transition to PCV13, recommended the largest catchup program for children <5 years of age who had been vaccinated with PCV7 (9). After an initially slow uptake limited by constrained supply, the United States has achieved consistently high (>80%) 3-dose

The impact of introduction of the 10-valent pneumococcal conjugate vaccine (PCV10) on pneumococcal carriage in Nigeria

“…[1] PCV use has also substantially reduced hospital visits from pneumococcal otitis media and antibiotic use and has the potential to reduce antimicrobial resistance. [2][3][4] Nonetheless, Streptococcus pneumoniae (the pneumococcus) remains a leading cause of pneumonia and invasive diseases (meningitis, bacteraemic pneumonia and bacteraemia). [1] In 2015, pneumococcal disease still caused approximately 300,000 deaths among children aged 1-59 months globally, and over 50% of these deaths occurred in the African sub-region.…”

Validation of Fourier Transform Infrared Spectroscopy for Serotyping of Streptococcus pneumoniae

“… S. pneumoniae is still among the leading causes of infection-induced mortality, especially in developing countries ( 7 ). The introduction of PCVs in the early 2000s and their implementation in childhood vaccination programs has greatly decreased the incidence of IPD caused by VT serotypes ( 19 – 22 ). This effect was also initially observed in the unvaccinated adult population in the United States and was attributed to herd immunity ( 64 , 65 ).…”

“…More importantly, this vaccine does not protect infants below the age of two, which is the age group with the highest incidence of severe disease and the highest level of carriage. The protein conjugate vaccines (PCVs) were first implemented in the U.S. childhood vaccination programs in the early 2000s because of their projected efficacy in infants, as well as their promising potential in providing long-lasting immunity ( 19 – 22 ). The current PCVs protect against 10 (PCV10) or 13 (PCV13) different serotypes, but in the meantime, higher valency PCVs (PCV15 and PCV20) have been licensed for adults and are (or soon will be) available ( 23 – 27 ).…”

Estimating population-based incidence of community-acquired pneumonia and acute otitis media in children and adults in Ontario and British Columbia using health administrative data, 2005–2018: a Canadian Immunisation Research Network (CIRN) study

“…Substantial benefits of the childhood PCV have been observed in the USA in preventing healthcare visits for otitis media and hospitalisations for pneumonia in children. 45 But more recently, partial replacement with non-vaccine serotype IPD across all age groups and an increase in non-PCV13 IPD hospitalisation in children aged <5 years have been reported in some high-income countries, including Canada. 46–48 This could also apply to non-IPDs, such as CAP; the lack of considerable benefit of pneumococcal vaccines observed in our study may have resulted from pneumococcal serotype replacement with non-vaccine serotypes.…”

“…Substantial benefits of the childhood PCV have been observed in the USA in preventing healthcare visits for otitis media and hospitalisations for pneumonia in children 45. But more recently, partial replacement with non-vaccine serotype IPD across all age groups and an increase in non-PCV13 IPD hospitalisation in children aged <5 years have been reported in some high-income countries, including Canada 46–48.…”