Changes in empyema among U.S. children in the pneumococcal conjugate vaccine era
Introduction
Parapneumonic empyema, a rare but serious complication of pneumonia, is associated with increased morbidity, mortality and length of hospital stay among patients with pneumonia [1], [2], [3], [4], [5], [6]. Parapneumonic empyema among children <18 years of age in the United States (U.S.) started increasing before the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2000, and continued afterwards [2], [7], [8], [9]. Greater awareness of empyema, improved diagnostics, and more complete coding may have contributed to an apparent increase in empyema [7], [8]. However, the changing ecology of Streptococcus pneumoniae after PCV7 introduction likely contributed to a real increase as well [5], [10].
The serotypes most commonly associated with parapneumonic empyema among children (1, 3, 7F and 19A) were not included in PCV7 [3], [10], [11], [12], [13], [14], [15]. The incidence of pneumococcal pneumonia involving PCV7 serotypes decreased after PCV7 introduction, but with an increasing proportion of pneumococcal pneumonia attributed to non-PCV7 serotypes (such as 1, 7F and 19A) [3], [16], [17], [18]. This increased representation of serotypes historically associated with parapneumonic empyema likely contributed to the increasing incidence of parapneumonic empyema observed after PCV7 introduction [3], [10].
The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in 2010 to reduce further the incidence of invasive pneumococcal disease (IPD) due to non-PCV7 serotypes, and included serotypes 1, 3, 7F and 19A, among others. Vaccination coverage has been high and widespread among young U.S. children as coverage with ⩾3 doses of PCV7 was >90% in 2007–2008 and has been >92% for ⩾3 doses of PCV13 since 2010 [19], [20]. However, little information is available regarding national parapneumonic empyema rates in the U.S. after PCV13 introduction. Therefore, we assessed changes in hospitalizations for parapneumonic empyema among U.S. children after PCV13 introduction.
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Data sources
We used the Nationwide Inpatient Sample (NIS) to obtain national hospitalization data from 1997 to 2013 for all U.S. children <18 years of age. The NIS is the largest publicly available database for all-payer inpatient healthcare in the U.S., representing over 35 million hospitalizations annually from all states that participate in the Healthcare Cost and Utilization Project (HCUP) [21]. Information on each hospitalization includes hospital characteristics, patient demographics, primary and
Results
During the study period, parapneumonic empyema was rare, and accounted for 1.3% of pneumonia hospitalizations among U.S. children <18 years of age. Among all children, the annualized rate of hospitalizations for parapneumonic empyema per 100,000 persons was 2.1 (95% CI: 1.7–2.4) in the pre-PCV7 period, and progressively rose to 3.6 per 100,000 in the late-PCV7 period [RR: 1.70 (95% CI: 1.11–2.60)]. Rates in the post-PCV13 period declined and were similar to rates in the pre-PCV7 period [RR:
Discussion
Rates of hospitalizations for parapneumonic empyema among U.S. children continued increasing and peaked after PCV7 introduction into the U.S. childhood immunization schedule, but decreased to historical low levels after PCV13 introduction. Importantly, rates of hospitalizations for parapneumonic empyema were significantly lower in the post-PCV13 period compared to the pre-PCV7 period among children <2 years, the target population for the pneumococcal conjugate vaccination program. In addition, a
Conclusion
In contrast to the increased incidence of hospitalizations for parapneumonic empyema observed after PCV7 introduction, PCV13 introduction into the U.S. childhood immunization schedule was associated with a substantial reduction of hospitalizations for parapneumonic empyema among U.S. children. The expanded serotype coverage of PCV13 likely contributed to the return of hospitalization rates for parapneumonic empyema closer to historical rates observed prior to PCV7 introduction.
Conflict of interest
Dr. Grijalva has served as consultant for Pfizer Inc. (New York, NY). Dr. Griffin received grant support from MedImmune (Gaithersburg, MD). The other authors have no conflicts of interest relevant to this article to disclose.
Acknowledgements
This work was supported by the Agency for Healthcare Research and Quality – United States (R03HS022342).
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2023, Respiratory MedicineCitation Excerpt :The NIS is the largest publicly available database for all-payer inpatient healthcare in the U.S., including information on patient demographics, hospital characteristics and associated diagnoses for over 35 million hospitalizations annually from all states that participate in the Healthcare Cost and Utilization Project (HCUP) [8]. The NIS further employs trend weighting to account for the sampling design and to allow for the examination of disease trends over time [1,3,8]. We used U.S. census data (2006–2019) to create annual, national age-based population estimates as the denominator for empyema rate calculations.