Health and economic burden of invasive pneumococcal disease associated with 15-valent pneumococcal conjugate vaccine serotypes in children across eight European countries

Figures & data

Table 1. Year of PCV introduction in European countries.

Country	PCV7	PCV13
UK^11^,^12	2006	2010
France^13	2003	2010
Germany^14^,^15	2006	2009
Italy^16^,^17	2005	2010
Spain^18	2001	2010
Denmark^19^,^20	2007	2010
Norway^21	2006	2011
Switzerland^22	2006	2011

Abbreviation. PCV, pneumococcal conjugate vaccine.

Figure 1. Markov pathway. Abbreviation: IPD, invasive pneumococcal disease.

Table 2. Epidemiological inputs.^a

Country	Age group (years)	IPD serotype-specific incidence rates by age group (per 100,000 person-years)									Case fatality rate meningitis/ bacteremia (%)
		Pre-PCV7			Pre-PCV13			Post-PCV13
		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
UK^6^,^11^,^12	<2	37.0	8.1	1.0	1.9	13.6	2.1	0.2	1.9	1.6	9.6/4.1
	2–4	11.6	2.5	0.3	0.7	4.9	0.7	0.1	0.6	0.5
	5–20	2.1	1.4	0.2	0.3	1.1	0.2	0.0	0.1	0.1
France^6^,^34^,^51^,^55^,^56^,^13	<2	20.5	7.6	0.6	1.1	18.4	0.7	0.8	1.6	1.0	11.0/4.1
	2–4	5.3	2.0	0.2	0.5	7.8	0.3	0.0	0.5	0.3
	5–20	1.1	0.4	0.0	0.1	2.5	0.1	0.4	0.4	0.3
Germany^14^,^47^,^62	<2	13.5	4.0	0.2	2.6	6.1	0.5	0.4	1.9	1.2	7.5/2.0
	2–4	3.6	0.9	0.1	1.8	2.9	0.2	0.1	0.2	0.1
	5–20	0.4	0.5	0.0	0.4	1.1	0.1	0.0	0.3	0.1
Italy^5^,^33^,^48^,^49^,^53^,^54	<1	12.1	5.3	0.5	2.3	6.3	0.4	0.6	0.3	0.2	4.8–12.9/ 0.0–2.90^b
	1–4	9.4	4.1	0.4	1.0	2.8	0.2	0.2	0.1	0.1
	5–9	2.3	1.0	0.1	0.3	0.7	0.0	0.0	0.0	0.0
	10–20	2.3	1.0	0.1	0.1	0.3	0.0	0.0	0.0	0.0
Spain^3^,^30^,^50^,^52	<2	45.3	12.7	1.2	13.2	30.0	0.1	6.5	10.4	0.7	5.6/2.0
	2–4	20.2	5.7	0.5	4.2	27.4	0.0	2.1	7.0	0.2
	5–20	6.3	1.7	0.2	1.7	5.6	0.1	0.9	2.3	0.2
Denmark^31^,^32^,^19^,^20^,^57^,^58^,^63	< 2	34.2	14.6	0.6	2.4	18.8	1.2	0.0	1.2	1.2	8.0/1.0
	2–4	5.2	2.2	0.1	1.0	7.6	0.5	0.0	0.6	0.3
	5–20	0.8	1.0	0.1	0.2	1.4	0.1	0.0	1.4	0.3
Norway^32^,^21^,^59^,^63	< 2	48.4	11.2	0.6	0.6	11.7	2.2	0.0	1.7	1.7	8.0/1.0
	2–4	12.6	2.9	0.2	0.8	2.3	0.9	0.5	0.9	1.4
	5–20	1.9	0.8	0.2	0.1	0.4	0.2	0.3	1.4	2.1
Switzerland^60^,^61^,^64^,^65 ^c	< 2	25.8	2.3	0.0	1.9	12.3	0.0	1.0	0.0	2.0	9.0/1.0
	2–4	4.7	5.2	0.0	2.6	5.9	0.5	0.5	2.5	0.0
	5–20	1.8	1.2	0.0	0.9	1.7	0.2	0.2	0.2	0.0

^aThe 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.

^bCase fatality rates varied by age in Italy.

^cData on IPD incidence from private communication with the Swiss Ministry of Health.

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

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

Table 3. Cost inputs (2018 Euros).^a

Country	Manifestation	Direct medical cost (per episode)	Indirect cost (per episode)^b
UK^66	Meningitis	€9,780	€1,262
	Bacteremia	€8,194	€742
France^66–68^,^69^,^70	Meningitis	€6,089	€954
	Bacteremia	€2,422	€561
Germany^62	Meningitis	€7,162	€459
	Bacteremia	€6,897	€459
Italy^5^,^66^,^71^,^72	Meningitis	€8,228	€971
	Bacteremia	€3,239	€571
Spain^66^,^73–75^c	Meningitis	€10,874–€11,789	€687
	Bacteremia	€3,786–€4,039	€404
Denmark^59^,^63^,^76^,^77	Meningitis	€12,245	€606
	Bacteremia	€8,258	€493
Norway^59^,^78^,^77	Meningitis	€19,862	€834
	Bacteremia	€18,054	€679
Switzerland^59^,^61^,^79^,^80	Meningitis	€10,675	€1,014
	Bacteremia	€4,887	€592

^aCosts were inflated to 2018 Euros using consumer price indices for healthcare^81–88; exchange rates were obtained from the Federal Reserve Bank of St Louis (https://www.federalreserve.gov/releases/g5a/current/).

^bIndirect costs were calculated by multiplying the episode length from the source reference for each country with the daily lost wage (calculated using earnings and labor force participation data for each country from the references indicated).

^cDirect medical costs in Spain varied by age.

Table 4. 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	3,374 (73)	566 (17)	228 (24)
ST18C	376 (8)	76 (2)	15 (2)
ST4	239 (5)	49 (2)	12 (1)
ST6B	612 (13)	65 (2)	18 (2)
ST9V	242 (5)	60 (2)	14 (1)
ST14	1,065 (23)	179 (6)	61 (6)
ST19F	480 (10)	99 (3)	102 (11)
ST23F	360 (8)	39 (1)	7 (1)
PCV13, but not PCV7 serotypes	1,170 (25)	2,544 (78)	546 (57)
ST3	115 (2)	232 (7)	185 (19)
ST19A	250 (5)	625 (19)	94 (10)
ST6A	182 (4)	84 (3)	43 (4)
ST1	337 (7)	882 (27)	136 (14)
ST5	76 (2)	87 (3)	13 (1)
ST7F	210 (5)	633 (19)	76 (8)
ST22F and 33 F (V114, but not PCV13 serotypes)	106 (2)	137 (4)	184 (19)
Total V114 serotypes	4,649	3,248	958

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

Table 5. 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	80 (73)	49 (72)	129 (72)	11 (15)	7 (17)	19 (15)	5 (24)	3 (24)	8 (24)
PCV13, but not PCV7 serotypes	27 (25)	17 (26)	45 (25)	63 (80)	34 (79)	97 (80)	11 (55)	7 (49)	18 (53)
ST3	3 (3)	2 (3)	5 (3)	5 (7)	3 (8)	9 (7)	4 (21)	3 (24)	8 (23)
ST19A	6 (6)	4 (6)	10 (6)	16 (21)	9 (20)	25 (20)	2 (10)	1 (10)	3 (10)
ST6A	4 (4)	2 (4)	7 (4)	2 (2)	1 (2)	3 (2)	1 (4)	0 (2)	1 (3)
ST1	8 (8)	5 (7)	13 (7)	21 (27)	10 (24)	32 (26)	3 (13)	1 (7)	4 (10)
ST5	1 (1)	1 (1)	2 (1)	2 (2)	1 (2)	3 (2)	0 (1)	0 (1)	0 (1)
ST7F	4 (4)	3 (5)	8 (4)	17 (21)	9 (22)	26 (21)	1 (7)	1 (5)	2 (6)
ST22F and 33 F (V114, but not PCV13 serotypes)	3 (2)	1 (2)	4 (2)	4 (5)	2 (4)	6 (5)	4 (20)	4 (27)	8 (23)
Total V114 serotypes	110 (100)	67 (100)	178 (100)	78 (100)	43 (100)	121 (100)	20 (100)	14 (100)	34 (100)

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

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

Table 6. Discounted direct medical costs and indirect costs (including productivity losses due to premature death) attributed to IPD in the pre-PCV7, pre-PCV13, and post-PCV13 periods (2018 Euros).

€ millions (%)	Pre-PCV7 period				Pre-PCV13 period				Post-PCV13 period
	Direct medical costs	All indirect costs	Prod. loss due to premature death^a	Total costs	Direct medical costs	All indirect costs	Prod. loss due to premature death^a	Total costs	Direct medical costs	All indirect costs	Prod. loss due to premature death^a	Total costs
PCV7 serotypes	18.5 (74)	61.0 (73)	59.1 (73)	79.4 (73)	2.8 (18)	8.1 (16)	7.8 (16)	10.8 (16)	0.9 (20)	3.1 (22)	3.0 (22)	4.0 (21)
PCV13 but not PCV7 serotypes	6.0 (24)	21.2 (25)	20.6 (25)	27.3 (25)	11.4 (76)	39.7 (78)	38.4 (78)	51.1 (78)	2.5 (56)	7.3 (52)	7.1 (52)	9.8 (53)
ST3	0.7 (3)	2.5 (3)	2.4 (3)	3.2 (3)	1.1 (7)	4.0 (8)	3.9 (8)	5.1 (8)	0.9 (19)	3.3 (23)	3.2 (23)	4.1 (22)
ST19A	1.2 (5)	4.5 (5)	4.3 (5)	5.6 (5)	2.9 (19)	10.0 (20)	9.6 (20)	12.8 (20)	0.5 (11)	1.5 (11)	1.5 (11)	2.0 (11)
ST6A	1.0 (4)	3.0 (4)	2.9 (4)	4.0 (4)	0.5 (3)	1.2 (2)	1.2 (2)	1.7 (3)	0.2 (5)	0.4 (3)	0.4 (3)	0.6 (3)
ST1	1.8 (7)	6.6 (8)	6.4 (8)	8.4 (8)	3.6 (24)	12.5 (25)	12.1 (25)	16.1 (25)	0.5 (12)	1.3 (9)	1.2 (9)	1.8 (10)
ST5	0.3 (1)	0.8 (1)	0.8 (1)	1.1 (1)	0.4 (2)	1.0 (2)	1.0 (2)	1.4 (2)	0.1 (1)	0.1 (1)	0.1 (1)	0.2 (1)
ST7F	1.2 (5)	3.9 (5)	3.8 (5)	5.1 (5)	3.0 (20)	11.0 (22)	10.6 (22)	14.0 (21)	0.4 (8)	0.8 (6)	0.8 (6)	1.2 (6)
ST22F and 33 F (V114, but not PCV13 serotypes)	0.6 (2)	1.9 (2)	1.8 (2)	2.5 (2)	0.8 (6)	2.9 (6)	2.9 (6)	3.8 (6)	1.1 (25)	3.7 (26)	3.6 (26)	4.8 (26)
Total V114 serotypes	25.1 (100)	84.1 (100)	81.6 (100)	109.1 (100)	15.0 (100)	50.7 (100)	49.1 (100)	65.7 (100)	4.5 (100)	14.1 (100)	13.7 (100)	18.7 (100)

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

^aProductivity losses due to premature death are included in all indirect costs.

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

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

€millions (% change from base cost)	PCV7 serotypes		PCV13 but not PCV7 serotypes		V114 but not PCV13 serotypes
	Discounted indirect costs due to premature death	Discounted total costs	Discounted indirect costs due to premature death	Discounted total costs	Discounted indirect costs due to premature death	Discounted total costs
Base case	59.1	79.4	20.6	27.3	1.8	2.4
Incidence −20%	47.3 (−20)	63.5 (−20)	16.5 (−20)	21.8 (−20)	1.5 (−20)	2.0 (−20)
Incidence +20%	71.0 (20)	95.3 (20)	24.7 (20)	32.7 (20)	2.2 (20)	2.9 (20)
CFR −20%	47.3 (−20)	67.6 (−15)	16.5 (−20)	23.1 (−15)	1.5 (−20)	2.1 (−15)
CFR +20%	71.0 (20)	91.3 (15)	24.7 (20)	31.4 (15)	2.2 (20)	2.8 (15)
Cost −20%	59.1 (0)	75.4 (−5)	20.6 (0)	25.9 (−5)	1.8 (0)	2.3 (−5)
Cost +20%	59.1 (0)	83.1 (5)	20.6 (0)	28.5 (4)	1.8 (0)	2.6 (4)
Discount factor 0%	239.9 (306)	262.8 (231)	83.4 (305)	91.2 (235)	7.6 (311)	8.3 (238)
Discount factor 5%	26.9 (−54)	46.0 (−42)	9.4 (−54)	15.5 (−43)	0.8 (−55)	1.4 (−43)

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

Abbreviations. CFR, case fatality rate, OWSA, one-way sensitivity analysis; PCV, pneumococcal conjugate vaccine.

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