Population at risk

Over the time frame of the study, an average of 7.1 million commercially insured children contributed 5.8 million PY at risk each year (Supplemental Table 3 [Additional File 1]), and 4.3 million Medicaid-insured children contributed 3.5 million PY at risk (Supplemental Table 4 [Additional File 1]). The demographic characteristics for the populations at risk by study period and insurance type are shown in Supplemental Table 5 (Additional File 1). Over time, the mean age of commercially insured patients decreased slightly from 9.36 (SD 5.13) in the pre-PCV period to 9.18 (SD 5.16) years in the late PCV13 period. There was a slight increase in the proportion of patients aged < 2 years, and a corresponding slight decrease in the proportion of patients age 2–4 and 5–17 years, respectively. Moreover, there was an increase between the pre-PCV7 and late PCV13 periods in the proportion of patients living in the Northeast (from 15.5% to 17.9%) and West (from 6.0% to 18.7%), and a decrease of patients living in urban areas (from 221.% to 11.4%). Finally, declines in the proportion of patients with fee-for-service (FFS) plans (33.2% to 1.6%) and point-of-service (POS) plans (from 31.3% to 6.9%) was accompanied by increases in the proportions of patients with all other types of plans, including managed care and consumer directed/high deductible health plans. In the Medicaid population, average age increased between the early PCV7 and late PCV13 periods, from 7.90 (SD 5.24) to 8.58 (SD 5.16) years, due to a decline in the proportions of patients < 2 and 2–4 years, respectively. In this population, the substantial declines in the proportions of patients with FFS plans (from 42.7% to 34.5%) and POS plans (from 30.6% to 0.0%) was accompanied by a rise in the proportion of patients with health maintenance organization (HMO) plans (from 26.7% to 65.3%).

Patient populationDemographic characteristics

The demographic characteristics for the commercially insured patient population with ACP across PCV periods are shown in Table 1. The mean age of patients slightly increased over time, from 6.0 years in the early PCV7 period to 6.4 years in the late PCV13 period, while the proportion aged < 2 years decreased over the same timeframe, from 21.6% to 15.7%. Approximately half of patients were male across all periods (i.e., 54.9% in the pre-PCV7 period to 53.0% in the late PCV13 period). The largest proportions of patients were located in the US South (33.5% to 46.8% across all periods) and in urban areas (67.5% to 85.8% across all periods), which is partially a reflection of the health plans whose data are captured in the MarketScan database. While a variety of plan types were represented in the patient sample, in the late PCV13 period more than half of children (56.0%) were covered under Preferred Provider Organization plans.

Table 1 Demographic characteristicsa of commercially insured patients with ACP by vaccine period (1998–2018)

Demographic characteristics for the Medicaid population with ACP are shown in Supplemental Table 6 (Additional File 1). Medicaid patients were qualitatively younger than commercially insured children and were covered almost exclusively under Health Maintenance Organization or fee-for-service plans in the late PCV13 period.

Risk factors

Risk factors for pneumococcal disease among the ACP patients with commercial insurance and Medicaid are shown in Supplemental Tables 7 and 8 (Additional File 1), respectively. The most common risk factors among both commercially insured and Medicaid patients were chronic lung disease including asthma (7.1%-8.4% and 14.3%-16.1%, respectively, across all periods) and cancer and iatrogenic immunosuppression (1.6%-3.3% and 2.3%-9.8%, respectively, across all periods).

Crude IRs of ACPOverall episodes

The annual IRs for ACP episodes among commercially insured children are presented graphically by age group in Fig. 1a-d, overall and by setting. Average annual IRs by study period and 95% CIs are also presented in Table 2. Among children of all ages, ACP IRs decreased slightly from 2,074 to 1,986 per 100,000 PY between the pre-PCV7 and the late PCV13 period. IRs were highest in the subgroup aged < 2 years and decreased from 5,322 to 3,471 episodes per 100,000 PY from the pre-PCV7 to the late PCV13 period. IRs also decreased slightly in the 2–4-year-old subgroup, from 4,012 to 3,794 episodes per 100,000 PY from the pre-PCV7 to the late PCV13 period. IRs were lowest among the subgroup aged 5–17 years and increased slightly from 1,383 to 1,475 episodes per 100,000 PY in the pre-PCV7 period to the late PCV13 periods, respectively.

Fig. 1

Trends in annual IRs of ACP episodes per 100,000 PY among commercially insured children aged < 18 years (1998–2018). Notes: Average IRs for total ACP episodes are shown for each PCV period. All patients' month and day of birth was imputed as July 1st. Age at onset was calculated as the difference between condition start date and imputed birth date. Patients with negative age at onset were included in the age 0–1 year cohort. Abbreviations: ACP, all-cause pneumonia; IP, inpatient; IR, incidence rate; OP, outpatient; PCV, pneumococcal conjugate vaccine, PY, person-years

Table 2 ACP episode IRs and 95% CIs by setting and study period for commercially insured children, in episodes per 100,000 PY, and percent change from prior period (1998–2018)

The annual IRs for ACP episodes among children with Medicaid are presented in Fig. 2a-d. Average rates by study period and associated 95% CIs, as well as percent changes from the prior period, are shown in Supplemental Table 9 (Additional File 1). In general, overall IRs were qualitatively higher in Medicaid children compared to commercially insured children, except for the late PCV13 period. Substantial reductions in IRs were observed over the entire study timeframe among Medicaid enrollees of all age groups, including older children. Specifically, ACP IRs decreased between the PCV7 and late PCV13 periods from 7,267 to 4,549 episodes per 100,000 PY among children aged < 2 years, from 4,346 to 3,231 episodes per 100,000 PY among children aged 2–4 years, and from 1,470 to 1,175 episodes per 100,000 PY among children aged 5–17 years. While inpatient episode IRs declined steadily, they remained higher than those in commercially insured children throughout the study timeframe. However, outpatient episode IRs declined rapidly in older Medicaid children, leading to lower levels in the early and late PCV13 periods among the 2–4 and 5–17 year-old groups.

Fig. 2

Trends in annual IRs of ACP episodes per 100,000 PY among Medicaid-insured children aged < 18 years (2001–2018). Notes: Average IRs for total ACP episodes are shown for each PCV period. All patients' month and day of birth was imputed as July 1st. Age at onset was calculated as the difference between condition start date and imputed birth date. Patients with negative age at onset were included in the age 0–1 year cohort. Abbreviations: IP, inpatient; IR, incidence rate; OP, outpatient; PCV, pneumococcal conjugate vaccine; PY, person-years

Annual IRs of pneumococcal pneumonia for the commercially insured and Medicaid populations are shown in Supplemental Fig. 1 and Supplemental Fig. 2 (Additional File 1), respectively. Annual IRs of unspecified pneumonia for the commercially insured and Medicaid populations are shown in Supplemental Fig. 3 and Supplemental Fig. 4 (Additional File 1), respectively.

Inpatient and outpatient episodes

The annual and period-specific IRs of outpatient and inpatient ACP episodes are also shown by age group in Fig. 1a-d, with 95% CIs shown in Table 2. In children of all ages, outpatient episodes comprised more than 80% of ACP episodes among both commercially insured and Medicaid children, and the rates of outpatient episodes exhibited a slight numerical increase over time. When stratified by age groups, outpatient pneumonia IRs decreased substantially in children ages < 2 years, changed little in children aged 2–4 years, and increased in children aged 5–17 years. In contrast, inpatient IRs declined from the pre-PCV period to the late PCV13 period across all age groups. In general, proportions of inpatient episodes among total ACP episodes were numerically higher for younger children compared to older children (results not shown).

Annual and period-specific IRs of outpatient and inpatient pneumonia are shown in Fig. 1a-d for the commercially insured children, and in Fig. 2a-d (with 95% CIs shown in Supplemental Table 9 [Additional File 1]) for Medicaid enrollees. In contrast to the commercially insured population, rates of both outpatient and inpatient episodes decreased over the study timeframe among Medicaid enrollees in all age groups. Despite the downward trends, however, inpatient and outpatient ACP IRs in Medicaid were numerically higher than those in commercially insured children throughout the timeframe of the study, except for the early and late PCV13 periods in older children.

National IR estimates of ACP

The national estimates of annual IRs of ACP for the overall US population and by age group, along with 95% CIs, are shown in Table 3. The IR for children of all ages decreased from 2,329 to 1,894 episodes per 100,000 PY from 2001 to 2018. By age group, the IRs decreased from 5,761 to 3,649 episodes per 100,000 among children aged < 2 years; from 3,841 to 3,365 episodes per 100,000 PY among those aged 2–4 years; and from 1,452 to 1,284 episodes per 100,000 PY in those aged 5–17 years between 2001 and 2018. Despite the overall decrease in IRs for all age groups, fluctuations in IRs were observed over the course of the study, and IRs peaked in 2009 in all subgroups and in the overall population.

Table 3 National estimates for IRs and 95% CIs of ACP, in episodes per 100,000 PY (2001–2018)Results of ITS analyses

The estimated IRRs from the ITS analyses of the commercially insured children are shown in Supplemental Table 10, and the monthly predicted IRs of ACP episodes are shown in Supplemental Fig. 1a-d (Additional File 1).

In children aged < 2 years, there was a 52% decrease in monthly ACP IRs by the end of the early PCV7 period (IRR 0.48, 95%CI [0.26, 0.90]), while no statistically significant changes occurred in older children (Table 4). The IRs were relatively unchanged during the late PCV7, such that there was still an overall decline by the end of this period compared to the end of the pre-PCV7 period (IRR 0.53, 95% CI [0.28, 0.99]). The decline resumed during the early PCV13 period (IRR 0.75, 95% CI [0.65, 0.87]), but the IRs stabilized again during the late PCV13 period, with an overall decline of 52% by the end of this period compared to the pre-PCV7 period (IRR 0.48, 95%CI [0.24, 0.94]).

In children aged 2–4 years, the decrease in the early PCV7 period was not statistically significant, and during the late PCV7 period rates were also relatively unchanged. During the early PCV13 period, there was a 20% decline in IRs (IRR 0.80, 95% CI [0.69, 0.92]), with rates down 51% overall since the end of the pre-PCV7 period (IRR 0.49, 95% CI [0.26, 0.91]). Rates increased 31% during the late PCV13 period (IRR 1.31, 95% CI [1.00, 1.75]), and thus the overall change was statistically insignificant compared to the end of the pre-PCV7 period (Table 4).

Table 4 Estimated changes in ACP IRs at the end of each PCV study period vs. prior period and pre-PCV7 period among commercially insured children aged 0–17 years (1998–2018)

In children aged 5–17 years, rates did not change significantly during the early PCV7 period, and then increased by 58% during the late PCV7 period (IRR 1.58, 95% CI [1.30, 1.92]). However, IRs declined by 42% during the early PCV13 period (IRR 0.58, 95% CI [0.48, 0.71]). They then increased sharply by 68% during the late PCV13 period (IRR 1.68, 95% CI [1.14, 2.46]), resulting in an insignificant overall change between the end of the pre-PCV7 period and the end of the late PCV13 period.

In the Medicaid population, the findings were qualitatively similar to those in the commercially insured during the early PCV13 period, showing overall declines in monthly ACP IRs in all age groups (Table 5). Specifically, rates declined by 30% among children aged < 2 years (IRR 0.70, 95% CI [0.61, 0.80]), 37% among children aged 2–4 years IRR 0.63, 95% CI [0.54, 0.74]), and 50% among children aged 5–17 years (IRR 0.50, 95% CI [0.40, 0.64]). A key difference, however, is the significant decrease in IRs during the late PCV13 period among all age groups (though only statistically significant among children aged 5–17 years, IRR 0.50, 95% CI [0.32, 0.77]), in contrast to the stabilization or increase in ACP IRs during this period among commercially insured children. The estimates from the ITS models for the Medicaid population are shown in Supplemental Table 11 and the predicted monthly IRs are show in Supplemental Fig. 2 [Additional File 1]).

Table 5 Estimated changes in ACP IRs at the end of each PCV study period compared to the prior period and the pre-PCV7 period among Medicaid-insured children aged 0–17 years (2001–2018)Inpatient CFRs

Over the timeframe of the study, inpatient CFRs for commercially insured children with ACP varied between 0.29% and 0.42% in the 0–4 years age group, and between 0.46% and 0.89% in the 5–17 years age group (Table 6). Among Medicaid children, rates were higher, varying between 0.46% and 0.63% for patients 0–4 years old, and between 0.60% and 0.78% for patients 5–17 years old.

Table 6 Inpatient CFR and 95% CIs by age group for commercially and Medicaid- insured children aged < 18 years with ACP, by age group (1998–2018)Exploratory analyses of pneumococcal and unspecified pneumonia

In addition to the more comprehensive, but less specific definition of ACP, we also conducted descriptive exploratory analyses of pneumococcal and unspecified pneumonia IRs. More dramatic declines in the IRs of pneumococcal pneumonia were observed both in commercially insured and Medicaid children across all age groups (Supplemental Figs. 3 and 4 [Additional File 1]). Between 2001 and 2018, pneumococcal pneumonia IRs decreased by approximately 85.4% overall, with the most substantial reduction occurring in children aged < 2 years.

The results of the exploratory analyses on unspecified pneumonia were very similar to theACP results (Supplemental Figs. 5 and 6, respectively [Additional File 1]), suggesting more modest declines over time which occurred mainly in the early PCV13 period and were concentrated largely among younger children.