ArticlesEffect of 13-valent pneumococcal conjugate vaccine on admissions to hospital 2 years after its introduction in the USA: a time series analysis
Introduction
The addition of the seven-valent pneumococcal conjugate vaccine (PCV7) to the USA's standard infant vaccination schedule in 2000 was a major public health milestone. Longitudinal observational studies1, 2 showed that invasive pneumococcal disease in young children caused by vaccine serotypes fell substantially soon after the vaccine was introduced. An analysis3 of Nationwide Inpatient Sample data—which covers roughly 20% of inpatients in the USA, maintained by the Agency for Healthcare Research and Quality—showed similar vaccine-associated reductions for the number of infants admitted to hospital for all causes of pneumonia as early as 2004. Admissions to hospital for invasive pneumococcal disease and pneumococcal pneumonia in adults also fell substantially by the 2003–04 season,4 as did admissions for both invasive pneumococcal disease and pneumococcal or lobar pneumonia across all age groups.4 Because these diseases are more common in people older than 65 years, about 90% of the cases prevented were judged to have been in adults even though it was the children who were immunised, showing the effect of herd protection.4
Despite the large fall in disease caused by vaccine serotypes after PCV7 was introduced, disease caused by non-vaccine serotypes soon began to increase.5, 6 For example, sharp decreases in invasive pneumococcal disease caused by PCV7 serotypes were offset by increases of disease caused by replacement serotypes—mostly 19A—leaving the overall incidence stable since around 2005, at roughly 20% of the pre-PCV7 incidence.2 Serotype 19A is associated with widespread and high-level resistance to antimicrobial drugs in the USA5, 7, 8 and is now a major cause of difficult-to-treat ear infections.9 The prevalence of the previously unrecognised serotype 6C has also increased.10
All-cause pneumonia in children became less common soon after the introduction of PCV7 and then plateaued,11 but rates of empyema increased during the 2000s in children of all ages.12 Although most of this increase was attributed to nonspecific empyema,12 many cases of empyema in children younger than age 5 years are caused by pneumococcus, particularly the non-PCV7 serotypes 1, 3, 7F, and 19A.13 Surveillance and observational studies cannot rule out the role of chance in serotype replacement, but one randomised controlled trial has linked PCV7 vaccination with 19A replacement in young children.14
Concern about serotype replacement motivated the development of PCV13, which included six additional pneumococcal serotypes: 1, 3, 5, 7F, 19A, and 6A (which induces protective antibodies against serotype 6C).15 The introduction of PCV13 in the USA in March 2010 came with a recommendation for catch-up immunisation of all children aged up to 5 years, including those previously immunised with PCV7.16
Early evidence about the effect of PCV13 on hospital admissions related to pneumococcal infection in the USA would help inform other countries considering the addition of PCV13 to their routine vaccination schedules. However, data from the US Agency for Healthcare Research and Quality are only available after a delay of at least 2 years. We have therefore used a large private database where data become available after 2 months to make an early assessment of the effect of the introduction of PCV13.
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Study design and data sources
We did this retrospective time series analysis with data from the IMS Charge Data Master hospital database (IMS Health, Plymouth Meeting, PA, USA). This database contains deidentified data for discharge diagnoses coded by International Classification of Diseases 9 (ICD9).17 Data are taken from a convenience sample of roughly 500 non-federal, short-stay US hospitals (federally operated facilities, including Veteran's Association hospitals, are excluded), capturing roughly 20% of all admissions
Results
Figure 2 shows unadjusted trends in hospital admission rates before and after the introduction of PCV13. Decreases for 2011–12 are generally greater than those noted for 2010–11, suggesting a dose-response effect.
The unadjusted rates of hospital admission for invasive pulmonary disease and non-invasive pneumococcal or lobar pneumonia fell for all age groups between baseline and the 2011–12 season, 2 years after the programme began (table 1). However, few cases of pneumonia (1–6%) were coded
Discussion
Our findings suggest that after only 2 years, PCV13 significantly reduced hospital admissions for residual invasive and non-invasive pneumococcal pneumonia in both children and adults. Assessment of the benefit of pneumococcal vaccines for the total population is difficult in post-licensure studies, partly because much of the benefit results from herd protection of unvaccinated adults.2, 4 Case-control and prospective cohort studies can measure direct benefits, but cannot assess indirect (herd)
References (28)
- et al.
Decline in pneumonia admissions after routine childhood immunisation with pneumococcal conjugate vaccine in the USA: a time-series analysis
Lancet
(2007) - et al.
Serotype replacement in disease after pneumococcal vaccination
Lancet
(2011) - et al.
The 13-valent pneumococcal conjugate vaccine (PCV13) elicits cross-functional opsonophagocytic killing responses in humans to Streptococcus pneumoniae serotypes 6C and 7A
Vaccine
(2011) - et al.
Use of near-real-time medical claims data to generate timely vaccine coverage estimates in the US: the dynamics of PCV13 vaccine uptake
Vaccine
(2013) - et al.
Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine
N Engl J Med
(2003) - et al.
Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine
J Infect Dis
(2010) - et al.
Impact of pneumococcal conjugate vaccination of infants on pneumonia and influenza hospitalization and mortality in all age groups in the United States
MBio
(2011) - et al.
Population snapshot of emergent Streptococcus pneumoniae serotype 19A in the United States, 2005
J Infect Dis
(2008) - et al.
Increased penicillin nonsusceptibility of nonvaccine-serotype invasive pneumococci other than serotypes 19A and 6A in post-7-valent conjugate vaccine era
J Infect Dis
(2010) - et al.
Outpatient antibiotic prescribing and nonsusceptible Streptococcus pneumoniae in the United States, 1996–2003
Clin Infect Dis
(2011)