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 CDC Advisory Committee on Immunization Practices (ACIP) recommended immunization with the recently licensed 13-valent pneumococcal conjugate vaccine (PCV13) for high-risk (immunocompromised) adults aged ≥19 years in 2012. This was in addition to the 23-valent pneumococcal polysaccharide vaccine (PPSV23). Data on vaccine-specific uptake among these individuals were previously unavailable. This retrospective observational study analyzed PCV13 uptake in immunocompromised patients aged 19-64 years. Data were acquired from insurance claims (N = 267,022) and electronic health records (EHR; N = 572,055) from October 2011-October 2016. Descriptive statistics were provided. Demographics were similar across the two database cohorts: mean age 49.7-51.0 years, 57-62% female, and >70% white. Iatrogenic immunosuppression was the most common high-risk category (33.3-44.2%). PCV13 uptake was 7.3% (95% CI: 7.25-7.45) in insurance claims and 9.9% (95% CI: 9.80-9.96) in EHR. Patients with HIV had the highest rate of PCV13 uptake; patients with multiple risk factors were above the mean in both cohorts. A Kaplan-Meier analysis was conducted to include patients lost to follow-up, with 441,657 and 722,071 patients for insurance claims and EHR, respectively. PCV13 uptake was only slightly higher: 9.3% (95% CI: 9.14-9.47) and 13.1% (95% CI: 12.93-13.19) for insurance claims and EHR, respectively. Four years after the ACIP 2012 recommendation, PCV13 uptake in high-risk adults aged19-64 years was low at <15% in all overall analyses. Clinicians caring for these patients should ensure adherence to the ACIP recommendation to minimize the risk of pneumococcal disease.
Background Clinical trials of PCV7 demonstrate significant reductions in vaccine-type (VT) invasive pneumococcal disease (IPD), clinically diagnosed pneumonia in children less than 5 years of age and VT acute otitis media in children < 2 years of age. Observational, population-based studies demonstrate a reduction in overall IPD in US children following the introduction of PCV7 and PCV13. The cumulative impact of PCV on IPD syndromes over the 20 years following introduction into the US national immunization program has not been detailed. Methods Published and unpublished data from the Active Bacterial Core (ABC) surveillance network were used to calculate annual incidence rates of IPD and the proportional distribution by syndrome in children < 5 years of age. Cases averted were calculated from published incidence for each IPD syndrome and population data, for the pre-PCV, PCV7, and PCV13 eras. Cases averted over 2000-2009 were assumed due to PCV7 only, and those averted from 2010-2019 were assumed due to PCV13 only. It was assumed that in the absence of PCVs, disease incidence would have remained constant. Results Annual cases of overall IPD, pneumococcal meningitis, and bacteremic pneumonia each declined more than 85% between the pre PCV7 incidence and the estimated incidence for 2019 (table 1). Overall, we estimated 282,600 cases of IPD, including 30,500 cases of meningitis and 78,400 cases of bacteremic pneumonia were averted. We calculated a reduction of ~ 287,600 VT cases of IPD minimally offset by an increase of ~5,000 non-VT cases. Deaths per 100,000 children < 5 years of age attributable to IPD declined by 67% in 2009 and by 64% in 2019 compared to 1997-1999. In total, 1,628 deaths in children < 5 years were averted between 2000 and 2019. Table 1. Annual Cases of IPD by syndrome in US Children Less than 5 years of age Conclusion The substantial public health impact of PCVs over the last two decades, as measured in cases and deaths averted in children less than 5 years, re-enforces the important role vaccines play in reducing the burden of serious disease in children. Disclosures Rotem Lapidot, MD, MSCI, Pfizer (Consultant) Ruth Chapman, MSc, PhD, Evidera, Inc, (Evidera, Inc. received the funding to conduct this study.) (Consultant) Kelly Sutton, PhD, Evidera (Employee) Desmond Dillon-Murphy, MSc, PhD, Evidera, Inc. (Evidera, Inc. received the funding to conduct this study.) (Consultant) Shreeya Patel, PhD, Evidera, Inc, (Evidera, Inc. received the funding to conduct this study.) (Consultant) Erica Chilson, PharmD, Pfizer (Employee, Shareholder) Vincenza Snow, MD, Pfizer (Employee) Raymond Farkouh, PhD, Pfizer (Employee) Matthew Wasserman, MSc., Pfizer Inc. (Employee) Stephen I. Pelton, MD, Merck vaccine (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support)Sanofi Pasteur (Consultant, Other Financial or Material Support, DSMB)Seqirus Vaccine Ltd. (Consultant)
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