Health and economic burden associated with 15-valent pneumococcal conjugate vaccine serotypes in children in the United States

Figures & data

Figure 1. Markov pathway. Abbreviations. AOM, acute otitis media; IPD, invasive pneumococcal disease.

Table 1. Epidemiological inputs^†.

	Age group^‡ (years)	Pre-PCV7 period			Pre-PCV13 period			Post-PCV13 period
		PCV7 serotypes	PCV13 not PCV7 serotypes	V114 not PCV13 serotypes	PCV7 serotypes	PCV13 not PCV7 serotypes	V114 not PCV13 serotypes	PCV7 serotypes	PCV13 not PCV7 serotypes	V114 not PCV13 serotypes
IPD incidence rate (100,000 person-years)^39	<1	138.9	6.9	2.4	0.4	25.7	4.5	0.5	2.0	1.4
	1	175.4	8.7	3.1	0.3	22.2	3.9	0.3	1.4	1.0
	2–4	25.8	2.6	0.5	0.3	9.6	1.2	0.5	1.1	0.7
	5–20	2.5	0.9	0.1	0.1	2.3	0.2	0.2	0.3	0.1
Pneumococcal AOM incidence rate (100,000 person-years)^12^,^16^,^31^,^38^†	<2	24,381.7	5,257.3	304.8	562.1	12,647.7		81.3	975.2	325.1
	2–4	7,822.2	1,686.7	97.8	198.3	4,462.7		32.1	385.6	128.5
	5–20	2,538.5	547.4	31.7	74.3	1,670.9		11.6	138.6	46.2

† The IPD serotype-specific incidence rate was calculated by multiplying incidence with serotype distribution data in the reference in pre-PCV7, pre-PCV13, and post-PCV periods. The pneumococcal AOM serotype-specific incidence was calculated by multiplying the proportion of Streptococcus pneumoniae among AOM incidence and serotype distribution data in the reference in pre-PCV7, pre-PCV13, and post-PCV periods. ^‡Age groups are different for IPD and AOM due to different methodologies used in the literature.

PCV7 serotypes are 4, 6B, 9V, 14, 18C, 19F, and 23F; PCV13 not PCV7 serotypes are 1, 3, 5, 6A, 7F, and 19A; V114 not PCV13 serotypes are 22F and 33F.

Abbreviations. AOM, acute otitis media; IPD, invasive pneumococcal disease; PCV, pneumococcal conjugate vaccine.

Table 2. Cost inputs (2018 US dollars).

	Medical cost per episode^†	Indirect cost per episode‡
Meningitis	$22,703^32	$1,170^29
Bacteremia	$4,332^32	$745^35
AOM	$135^32	$106^47

^†Costs from Rubin et al. 2010 were inflated to 2018 dollars using the consumer price index for medical care (https://fred.stlouisfed.org/series/CPIMEDSL). ‡The indirect cost was calculated by multiplying the episode length from the source reference indicated, with the daily lost wage (calculated by multiplying $907 [2017 August Weekly earnings from https://www.bls.gov/news.release/archives/empsit_09012017.pdf] by 80.5% [men and women labor force participation] divided by 7).

Abbreviation. AOM, acute otitis media.

Table 3. IPD cases attributable to V114 serotypes in the pre-PCV7, pre-PCV13, and post-PCV13 periods.

Cases, n (%)	Pre-PCV7 period	Pre-PCV13 period	Post-PCV13 period
PCV7 serotypes	16,321 (86)	147 (3)	224 (24)
ST18C	1,863 (10)	41 (1)	11 (1)
ST4	1,421 (7)	9 (0)
ST6B	1,960 (10)
ST9V	1,343 (7)	19 (0)
ST14	6,326 (33)	27 (1)
ST19F	2,156 (11)	42 (1)	214 (23)
ST23F	1,252 (7)	9 (0)
PCV13, but not PCV7 serotypes	2,338 (12)	4,009 (85)	427 (45)
ST3	147 (1)	226 (5)	202 (21)
ST19A	514 (3)	2,081 (44)	214 (23)
ST6A	1,056 (6)	27 (1)
ST1	358 (2)	243 (5)
ST5	17 (0)	32 (1)
ST7F	246 (1)	1,400 (30)	11 (1)
V114, but not PCV13 serotypes	324 (2)	545 (12)	298 (31)
ST22F	185 (1)	229 (5)	181 (19)
ST33F	139 (1)	315 (7)	116 (12)
Total V114 serotypes	18,983 (100)	4,697 (100)	948 (100)

Abbreviations. IPD, invasive pneumococcal disease; PCV, pneumococcal conjugate vaccine; ST, serotype.

Table 4. IPD deaths attributable to V114 serotypes in the pre-PCV7, pre-PCV13, and post-PCV13 periods.

Deaths, n (%)	Pre-PCV7 period			Pre-PCV13 period			Post-PCV13 period
	Bacteremia	Meningitis	Total	Bacteremia	Meningitis	Total	Bacteremia	Meningitis	Total
PCV7 serotypes	418 (87)	240 (83)	657 (85)	4 (3)	1 (3)	5 (3)	6 (24)	3 (24)	9 (24)
PCV13, but not PCV7 serotypes	60 (12)	34 (12)	94 (12)	109 (85)	38 (85)	147 (85)	5 (45)	3 (45)	17 (45)
ST5	0 (0)	0 (0)	1 (0)	1 (1)	0 (1)	1 (1)	0 (0)	0 (3)	0 (0)
ST3	4 (1)	2 (1)	6 (1)	6 (5)	2 (5)	8 (5)	6 (21)	3 (21)	8 (21)
ST7F	6 (1)	4 (1)	10 (1)	38 (30)	13 (30)	51 (30)	0 (0)	0 (1)	0 (0)
ST1	9 (2)	5 (2)	14 (2)	7 (5)	2 (5)	9 (5)	0 (0)	0 (0)	0 (0)
ST19A	13 (3)	8 (3)	21 (3)	57 (44)	20 (44)	76 (44)	8 (23)	3 (23)	6 (23)
ST6A	27 (6)	16 (5)	43 (6)	1 (1)	0 (1)	1 (1)	0 (0)	0 (0)	0 (0)
V114, but not PCV13 serotypes (ST22F and ST33F)	5 (1)	13 (5)	18 (2)	15 (12)	5 (12)	20 (12)	8 (31)	4 (31)	12 (31)
Total V114 serotypes	482 (100)	287 (100)	769 (100)	128 (100)	44 (100)	172 (100)	25 (100)	12 (100)	37 (100)

PCV7 serotypes are 4, 6B, 9V, 14, 18C, 19F, and 23F.

Abbreviations. IPD, invasive pneumococcal disease; PCV, pneumococcal conjugate vaccine; ST, serotype.

Table 5. AOM cases attributable to V114 serotypes in the pre-PCV7, pre-PCV13, and post-PCV13 periods.

Cases, n (%)	Pre-PCV7 period	Pre-PCV13 period	Post-PCV13 period
PCV7 serotypes	4,572,053 (85)	109,613 (4)	16,728 (8)
ST18C
ST4
ST6B	844,392 (16)
ST9V	350,115 (7)
ST14	1,132,697 (21)
ST19F	1,441,644 (27)	109,613 (4)	16,728 (8)
ST23F	803,205 (15)
PCV13, but not PCV7 serotypes	782,613 (15)	2,849,930 (96)	133,822 (62)
ST3	164,761 (3)	274,034 (9)	66,911 (31)
ST19A	226,546 (4)	2,192,250 (74)	66,911 (31)
ST6A	391,306 (7)	383,647 (13)
ST1
ST5
ST7F
V114, but not PCV13 serotypes			66,911 (31)
ST22F
ST33F			66,911 (31)
Total V114 serotypes	5,354,666 (100)	2,959,544 (100)	217,461 (100)

Abbreviations. AOM, acute otitis media; PCV, pneumococcal conjugate vaccine; ST, serotype.

Table 6. Discounted direct and indirect costs due to IPD and AOM in the pre-PCV7, pre-PCV13, and post-PCV13 periods (2018 US dollars).

$ in millions (%)	Pre-PCV7 period			Pre-PCV13 period			Post-PCV13 period
	Direct costs	Indirect costs	Total costs	Direct costs	Indirect costs	Total costs	Direct costs	Indirect costs	Total costs
PCV7 serotypes	647.2 (86)	766.1 (86)	1,413.3 (86)	13.4 (4)	12.9 (4)	26.3 (4)	3.2 (10)	6.4 (15)	9.6 (13)
PCV13, but not PCV7 serotypes	106.8 (14)	121.7 (141)	228.5 (14)	351.3 (96)	338.9 (94)	690.2 (95)	17.8 (58)	23.9 (54)	41.8 (56)
ST5	0.1 (0)	0.4 (0)	0.5 (0)	0.2 (0)	0.6 (0)	0.8 (0)	0.0 (0)	0.0 (0)	0.0 (0)
ST3	20.3 (3)	18.5 (2)	38.8 (2)	32.9 (9)	29.6 (8)	62.5 (9)	8.9 (29)	11.8 (27)	20.6 (28)
ST7F	1.5 (0)	5.1 (1)	6.5 (0)	7.0 (2)	26.1 (7)	33.1 (5)	0.1 (0)	0.2 (0)	0.3 (0)
ST1	2.0 (0)	7.3 (1)	9.3 (1)	1.1 (0)	4.5 (1)	5.7 (1)	0.0 (0)	0.0 (0)	0.0 (0)
ST19A	29.9 (4)	31.9 (4)	61.8 (4)	265.5 (72)	242.0 (67)	507.5 (70)	8.9 (29)	12.0 (27)	20.9 (28)
ST6A	53.1 (7)	58.6 (7)	111.8 (7)	44.5 (12)	36.0 (10)	80.6 (11)	0.0 (0)	0.0 (0)	0.0 (0)
V114, but not PCV13 serotypes (22 F and 33 F)	2.1 (0)	6.7 (1)	8.8 (1)	3.1 (1)	10.2 (3)	13.3 (2)	9.5 (31)	13.7 (31)	23.2 (31)
Total V114 serotypes	756.1 (100)	894.5 (100)	1,650.6 (100)	367.7 (100)	362.0 (100)	729.8 (100)	30.5 (100)	44.0 (100)	74.5 (100)

PCV7 serotypes are 4, 6B, 9V, 14, 18C, 19F, and 23F.

Abbreviations. AOM, acute otitis media; IPD, invasive pneumococcal disease; PCV, pneumococcal conjugate vaccine; ST, serotype; US, United States.

Table 7. One-way sensitivity analyses results (2018 US dollars).

$ in millions (% change from base cost)	Discounted total costs
	PCV7 serotypes	PCV13, but not PCV7 serotypes	V114, but not PCV13 serotypes
Base case	1,413	229	9
Incidence −20%	1,131 (−20%)	183 (−20%)	7 (−20%)
Incidence +20%	1,696 (20%)	274 (20%)	11 (20%)
CFR −20%	1,349 (−5%)	219 (−4%)	7 (−15%)
CFR +20%	1,478 (5%)	238 (4%)	10 (15%)
Cost −20%	1,195 (−15%)	192 (−16%)	8 (−5%)
Cost +20%	1,631 (15%)	265 (16%)	9 (5%)
Discount factor 0%	2,393 (69%)	374 (64%)	25 (189%)
Discount factor 5%	1,166 (−18%)	191 (−17%)	5 (−40%)

PCV7 serotypes are 4, 6B, 9V, 14, 18C, 19F, and 23F; PCV13, but not PCV7 serotypes are 1, 3, 5, 6A, 7F, and 19A; V114, but not PCV13 serotypes are 22F and 33F.

Abbreviations. CFR, case fatality rate; PCV, pneumococcal conjugate vaccine; US, United States.

Centers for Disease Control and Prevention [Internet]. Active bacterial core surveillance (ABCs): surveillance reports. Atlanta (GA): CDC; 2019 [2019 September 18]. Available from: https://www.cdc.gov/abcs/index.html

 Google Scholar

Kawai K, Adil EA, Barrett D, et al. Ambulatory visits for otitis media before and after the introduction of pneumococcal conjugate vaccination. J Pediatr. 2018;201:122–127.

 PubMed Web of Science ®Google Scholar

Pichichero M, Kaur R, Scott DA, et al. Effectiveness of 13-valent pneumococcal conjugate vaccination for protection against acute otitis media caused by Streptococcus pneumoniae in healthy young children: a prospective observational study. Lancet Child Adolesc Health. 2018;2(8):561–568.

 PubMedGoogle Scholar

Kaur R, Morris M, Pichichero ME. Epidemiology of acute otitis media in the postpneumococcal conjugate vaccine era. Pediatrics. 2017;140(3):e20170181.

 PubMed Web of Science ®Google Scholar

Joloba ML, Windau A, Bajaksouzian S, et al. Pneumococcal conjugate vaccine serotypes of Streptococcus pneumoniae isolates and the antimicrobial susceptibility of such isolates in children with otitis media. Clin Infect Dis. 2001;33(9):1489–1494.

 PubMed Web of Science ®Google Scholar

Rubin JL, McGarry LJ, Strutton DR, et al. Public health and economic impact of the 13-valent pneumococcal conjugate vaccine (PCV13) in the United States. Vaccine. 2010;28(48):7634–7643.

 PubMed Web of Science ®Google Scholar

Olarte L, Barson WJ, Barson RM, et al. Impact of the 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis in US children. Clin Infect Dis. 2015;61(5):767–775.

 PubMed Web of Science ®Google Scholar

Myers AL, Hall M, Williams DJ, et al. Prevalence of bacteremia in hospitalized pediatric patients with community-acquired pneumonia. Pediatr Infect Dis J. 2013;32(7):736–740.

 PubMed Web of Science ®Google Scholar

Delgleize E, Leeuwenkamp O, Theodorou E, et al. Cost-effectiveness analysis of routine pneumococcal vaccination in the UK: a comparison of the PHiD-CV vaccine and the PCV-13 vaccine using a Markov model. BMJ Open. 2016;6(11):e010776.

 PubMed Web of Science ®Google Scholar