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

Matt Wasserman; Ruth Chapman; Rotem Lapidot; Kelly Sutton; Desmond Dillon-Murphy; Shreeya Patel; Erica Chilson; Vincenza Snow; Raymond Farkouh; Stephen Pelton

Disclosures

Emerging Infectious Diseases. 2021;27(6):1627-1636. 

In This Article

Discussion

Vaccines, especially PCVs, are lifesaving and cost-effective public health interventions. At the time PCV7 was introduced in the United States, pneumococcal disease caused high rates of death and disease among infants. Despite conservative findings from the clinical trials,[8] public health officials and healthcare professionals were optimistic about the potential of PCVs to prevent pneumococcal disease. We conducted a literature review and modeling analysis to quantify the effects of PCVs on pneumococcal disease incidence among children <5 years of age, a population at higher risk for IPD and therefore the focus of IPD prevention efforts.[36] Our analysis demonstrated that PCVs have averted >282,000 cases of IPD and 2,780 associated deaths, with reductions across various IPD syndromes. Since their introduction in 2000, PCVs have averted >430,000 pneumonia hospitalizations and >97,000,000 OM-related healthcare visits.

We could not find data on all OM cases; our analysis instead measured ambulatory care visits using input data from Zhou et al..[23] However, because not all children with OM receive treatment through ambulatory care visits, our findings probably underestimate the true effects of PCVs on OM incidence. The annual number of OM visits declined from 78 visits/100 to 46 visits/100 children from the pre-PCV era (1997–1999) to PCV13 era (2010–2019); this 41% decline exceeds the original predictions based on early clinical trial data.[8] Vaccination is probably the main direct contributor to this reduction; however, vaccination also might have had indirect effects such as changes in the disease definition or clinical coding of OM, as well as changes in prescribing patterns of antimicrobial drugs, which might affect healthcare use. Although not all cases of OM prompt healthcare visits, even mild illnesses might require family members to take time from work to care for their children, further reducing productivity and quality of life in ways not reflected by this metric.[37]

Because we could not find data on noninvasive pneumonia, we combined multiple data sources to compare pneumonia hospitalizations during the study period. These data are probably underestimates of the true effect of PCVs because most pneumonia cases among children <5 years of age do not require hospitalization.

The overall findings are impressive but nevertheless conservative. We did not consider the direct benefits of reduced sequelae among children >5 years of age nor adults; we also did not consider indirect benefits such as herd immunity, reduced use of antimicrobial drugs and other healthcare resources, increased educational attainment, or improved parental productivity. In addition, we did not analyze data on common but less resource-intensive manifestations of S. pneumoniae such as conjunctivitis.[38,39] Finally, this analysis does not reflect PCVs' effects on antimicrobial resistance,[17] although preventing infection through vaccination reduces the need for antimicrobial treatment.[40]

In agreement with other studies,[40,41] we found that IPD cases caused by PCV13 serotypes declined while the number of cases caused by non-PCV13 serotypes slightly increased, reflecting modest serotype replacement. PCVs have been used in the United States longer than in any other country. Because of the large quantity of available data, we conducted a literature review to independently identify appropriate references for model inputs and validation. However, although the available data were extensive, it was not comprehensive. As a result, this research was limited by the lack of a single data source for pneumonia and OM incidences during the entire study period, prompting us to impute values for years when no data were available. In addition, because IPD is a notifiable disease but OM and pneumonia are not, we can only estimate PCVs' true effects on OM and pneumonia incidence using alternative metrics such as ambulatory care visits and hospitalizations. Furthermore, healthcare providers do not usually distinguish the causative bacteria of pneumonia and OM cases, which poses difficulties in analyzing serotype distributions. Finally, we could not find alternative national-level IPD data for the validation analysis, prompting us to compare our results with trends from smaller regions.

CDC and the Advisory Committee on Immunization Practices have recommended the use of PCVs in a national infant immunization program since 2000.[1] Our model used available data to quantify the effects of PCV7 and PCV13 on pneumococcal disease burden among children in the United States. Our results demonstrate the effectiveness of PCVs in preventing illness and death among children <5 years of age.

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