Public health and economic impact of seasonal influenza vaccination with quadrivalent influenza vaccines compared to trivalent influenza vaccines in Europe

Figures & data

Table 5. Proportions (%) of influenza A and B (B Victoria and B Yamagata) strains circulating in the 5-EU countries by influenza season between 2002 and 2013. For France, Germany, Italy and Spain, data from came from ref. ⁴² for the 2002–03 season, from ref. ⁴³ for the 2012–13 season and from ref. ¹ for all other seasons. For UK, data came from ref. ²⁶ for the 2003–03 to 2008–09 seasons, from ref. ¹ for the 2010–11 and 2011–12 seasons and from ref. ⁴³ for the 2012–13 season.

	France			Germany			Italy			Spain			UK
Year	A	B/Vic.	B/Yag.	A	B/Vic.	B/Yag.	A	B/Vic.	B/Yag.	A	B/Vic.	B/Yag.	A	B/Vic.	B/Yag.
2002–03	34.0	76.0	0.0	86.0	14.0	0.0	89.0	11.0	0.0	30.0	70.0	0.0	51.1	48.9	0.0
2003–04	99.0	0.2	0.8	99.0	0.2	0.8	99.0	0.2	0.8	99.0	0.2	0.8	99.6	0.0	0.4
2004–05	83.5	7.3	9.2	83.5	7.3	9.2	83.5	7.3	9.2	83.5	7.3	9.2	85.1	2.5	12.4
2005–06	40.2	54.4	5.4	40.2	54.4	5.4	40.2	54.4	5.4	40.2	54.4	5.4	29.7	69.5	0.8
2006–07	97.9	1.2	0.9	97.9	1.2	0.9	97.9	1.2	0.9	97.9	1.2	0.9	98.8	0.4	0.8
2007–08	61.4	0.4	38.2	61.4	0.4	38.2	61.4	0.4	38.2	61.4	0.4	38.2	64.3	0.0	35.7
2008–09	83.1	16.4	0.5	83.1	16.4	0.5	83.1	16.4	0.5	83.1	16.4	0.5	89.7	9.7	0.6
2010–11	98.7	1.2	0.1	98.7	1.2	0.1	98.7	1.2	0.1	98.7	1.2	0.1	98.7	1.2	0.1
2011–12	71.2	26.5	2.3	71.2	26.5	2.3	71.2	26.5	2.3	71.2	26.5	2.3	71.2	26.5	2.3
2012–13	61.2	7.4	31.4	61.2	7.4	31.4	61.2	7.4	31.4	61.2	7.4	31.4	61.2	7.4	31.4

Table 6. Influenza vaccination coverage (%) by country, age and risk group for EU-5.

Risk Group	France	Germany	Italy	Spain	UK
6 m – < 2 yrs	9.9 [6.8–14.2]	19.2 [9.0–28.0]	6.1 [3.0–24.5 ]	11.1 [5.0–17.0]	13.4 [8.0–20.0]
2–17 yrs	6.5 [4.0–10.3]	13.7 [8.7–18.7]	5.1 [2.5–11.7]	14.0 [9.0–19.0]	4.1 [2.1–6.1]
18–49 yrs Low risk	6.5 [1.5–11.5]	9.5 [4.5–14.5]	8.7 [3.7–13.7]	12.0 [7.0–17.0]	10.2 [5.2–15.2]
50–64 yrs Low risk	15.6 [10.6–20.6]	25.3 [20.3–30.3]	14.9 [9.9–19.9]	17.4 [12.4–22.4]	23.8 [18.8–28.8]
18–49 yrs High risk	30.9 [25.0–38.0]	34.7 [30.0–49.0]	42.4 [37.0–51.0]	38.5 [11.0–46.0]	52.0 [45.0–59.0]
50–64 yrs High risk	30.9 [25.0–38.0]	34.7 [30.0–49.0]	42.4 [37.0–51.0]	38.5 [33.0–60.0]	52.0 [45.0–59.0]
65+	63.5 [58.0–70.0]	48.6 [41.0–59.0]	56.1[51.0–66.0]	64.7 [57.0–70.0]	69.2 [64.0–78.0]

Table 7. Vaccination efficacy/effectiveness against influenza A, matched influenza B and mismatched influenza B used in the model. The lower and upper bound correspond to a variation of +/−20% in vaccine effectiveness. Cross protection was included in the model by considering that VE against mismatched B was 67% of the VE against matched B.

		Influenza A		Matched influenza B		Mismatched influenza B
Age group	Risk group	VE against A	Range for the sensitivity analysis	VE against matched B	Range for the sensitivity analysis	VE against mismatched B	Range for the sensitivity analysis
6 m – <2 yrs		59.0%	47.2%–70.8%	66.0%	52.8%–79.2%	44.0%	35.2%–52.8%
2–17 yrs		59.0%	47.2%–70.8%	66.0%	52.8%–79.2%	44.0%	35.2%–52.8%
18–49 yrs	Low risk	61.0%	48.8%–73.2%	77.0%	61.6%–92.4%	52.0%	41.6%–62.4%
	High risk	61.0%	48.8%–73.2%	77.0%	61.6%–92.4%	52.0%	41.6%–62.4%
50–64 yrs	Low risk	61.0%	48.8%–73.2%	73.0%	58.4%–87.6%	49.0%	39.2%–58.8%
	High risk	61.0%	48.8%–73.2%	73.0%	58.4%–87.6%	49.0%	39.2%–58.8%
65+		58.0%	46.4%–69.6	66.0%	52.8%–79.2%	44.0%	35.2%–52.8%

* VE is assumed the same across all seasons.

Table 1. Absolute number and incidence per 100,000 inhabitants of influenza cases, GP consultations, workdays lost, hospitalizations and deaths due to influenza avoided for the 5 EU countries for the 2002–03 to 2012–13 influenza seasons. Epidemiological burden avoided are presented with the lower and upper bound corresponding to a variation of +/−20% in vaccine effectiveness.

Country	Cases avoided	GP Consultations avoided	Workdays lost avoided	Hospitalizations avoided	Deaths avoided
Absolute numbers
France	200,080 [160,064;240,096]	155,782 [119,877;195,030]	196,943 [154,275;241,551]	4,379 [3,271;5,662]	1,308 [972;1,699]
Germany	224,760 [179,808;269,712]	130,723 [101,570;161,737]	249,054 [193,689;307,794]	4,748 [3,618;5,996]	1,476 [1,120;1,871]
Italy	231,133 [184,906;277,359]	75,640 [58099;94874]	95,820 [74,827;117,919]	5,344 [3,976;6,938]	1,550 [1,150;2,020]
Spain	150,964 [120,771;181,157]	13,181 [10,144;16,498]	18,546 [14,487;22,816]	4,042 [3,006;5,249]	1,511 [1,121;1,968]
UK	227,790 [182,232;273,348]	78,637 [59,220;100,823]	112,089 [85,762;141,124]	5,940 [4,389;7,776]	3,955 [2,912;5196]
Total EU-5	1,034,727 [827,781;1,241,672]	453,963 [348,910;568,962]	672,452 [523,040;831,204]	24,453 [18,260;31,620]	9,799 [7,275;12,753]
Total EU-27	1,624,533 [1,299,626;1,949,440]	715,826 [550,507;896,552]	1,081,255 [840,994;1,336,546]	37,317 [27,873;48,240]	14,866 [11,037;19,345]
Incidence per 100,000 inhabitants
France	308.2 [246.5;369.8]	239.9 [184.6;300.4]	303.3 [237.6;372.0]	6.7 [5.0;8.7]	2.0 [1.5;2.6]
Germany	275.7 [220.6;330.9]	160.4 [124.6;198.4]	305.5 [237.6;377.6]	5.8 [4.4;7.4]	1.8 [1.4;2.3]
Italy	381.7 [305.4;458.1]	124.9 [96.0;156.7]	158.3 [123.6;194.8]	8.8 [6.6;11.5]	2.6 [1.9;3.3]
Spain	330.1 [264.1;396.2]	28.8 [22.2;36.1]	40.6 [31.7;49.9]	8.8 [6.6;11.5]	3.3 [2.5;4.3]
UK	362.5 [290.0;435.0]	125.1 [94.2;160.4]	178.4 [136.5;224.6]	9.5 [7.0;12.4]	6.3 [4.6;8.3]
Total EU-5	327.9 [262.3;393.5]	143.9 [110.6;180.3]	213.1 [165.8;263.4]	7.7 [5.8;10.0]	3.1 [2.3;4.0]
Total EU-27	324.1 [259.3;388.9]	142.8 [109.8;178.8]	215.7 [167.8;266.6]	7.4 [5.6;9.6]	3.0 [2.2;3.9]

Table 2. Epidemiological burden averted (absolute numbers and incidence per 100,000 inhabitants) by age-group for the 5 EU countries for the 2002–03 to 2012–13 influenza seasons. Epidemiological burden avoided are presented with the lower and upper bound corresponding to a variation of +/−20% in vaccine effectiveness.

Age group	Risk Group	Cases avoided	GP consultations avoided	Workdays lost avoided	Hospitalizations avoided	Deaths avoided
Absolute numbers
6 m – <2 yrs		28,877 [23,102;34,653]	11,223 [8,855;13,658]	10,999 [8,678;13,385]	140 [110;170]	0 [0;0]
2–17 yrs		219,163 [175,331;262,996]	80,450 [63,728;97,510]	78,841 [62,453;95,560]	348 [275;422]	4 [3;4]
18–49 yrs	Low-risk	133,656 [106,925;160,387]	59,665 [47,241;72,351]	156,472 [123,895;189,732]	110 [87;134]	0 [0;0]
	High-risk	83,635 [66,908;100,362]	53,355 [40,809;67,129]	143,054 [109,408;180,003]	389 [297;491]	79 [60;101]
50–64 yrs	Low-risk	86,216 [68,973;103,460]	48,601 [37,946;59,799]	129,277 [100,907;159,108]	515 [402;634]	0 [0;0]
	High-risk	89,908 [71,926;107,890]	57,767 [44,210;72,633]	153,808 [117,698;193,416]	1801 [1372; 2275]	325 [247;413]
65+		393,270 [314,616;471,924]	142,902 [106,121;185,882]	0 [0;0]	21,151 [15,717;27,495]	9,391 [6,965;12,235]
Total EU-5		1,034,727 [827,781;1,241,672]	453,963 [348,910;568,962]	672,452 [523,040;831,204]	24,453 [18,260;31,620]	9,799 [7,275;12,753]
Incidence per 100,000 inhabitants
6 m – <2 yrs		604.0 [483.2;724.8]	234.8 [185.2;285.7]	230.1 [181.5;280.0]	2.9 [2.3;3.6]	0.0 [0.0;0.0]
2–17 yrs		413.6 [330.9;496.3]	151.8 [120.3;184.0]	148.8 [117.9;180.3]	0.7 [0.5;0.8]	0.0 [0.0;0.0]
18–49 yrs	Low-risk	115.1 [92.1;138.1]	51.4 [40.7;62.3]	134.8 [106.7;163.4]	0.1 [0.1;0.1]	0.0 [0.0;0.0]
	High-risk	394.0 [315.2;472.8]	251.4 [192.3;316.2]	673.9 [515.4;848.0]	1.8 [1.4;2.3]	0.4 [0.3;0.5]
50–64 yrs	Low-risk	223.7 [178.9;268.4]	126.1 [98.4;155.1]	335.4 [261.8;412.8]	1.3 [1.0;1.6]	0.0 [0.0;0.0]
	High-risk	398.0 [318.4;477.6]	255.7 [195.7;321.6]	680.9 [521.1;856.3]	8.0 [6.1;10.1]	1.4 [1.1;1.8]
65+		663.1 [530.4;795.7]	240.9 [178.9;313.4]	0.0 [0.0;0.0]	35.7 [26.5;46.4]	15.8 [11.7;20.6]
Total EU-5		327.9 [262.3;393.5]	143.9 [110.6;180.3]	213.1 [165.8;263.4]	7.7 [5.8;10.0]	3.1 [2.3;4.0]

Figure 1. Influenza cases avoided per season for the 5 EU countries if QIV vaccine was used instead of a TIV vaccine during the 2002–03 to 2012–13 influenza seasons.

Table 3. Total costs for GP, hospitalizations and workdays lost avoided for the 5 EU countries for the 2002–03 to 2012–13 influenza seasons.

	Tax-Payer Perspective (TPP)		Societal Perspective (SP)
Country	Total GP costs avoided	Total hospitalization costs avoided	Total GP costs avoided	Total hospitalization costs avoided	Costs savings from workdays lost avoided
France (Euros)	€2,397,405 [€1,845,982;€2,999,447]	€12,304,338 [€9,184,791;€15,914,216]	€3,599,220 [€2,770,057;€4,505,349]	€15,019,057 [€11,210,050;€19,427,754]	€47,148,159 [€36,933,444;€57,827,416]
Germany (Euros)	€4,987,066 [€3,874,890;€6,170,277]	€13,623,017[ €10,381,417;€17,207,801]	€4,987,066 [€3,874,890;€6,170,277]	€13,955,346 [€10,634,703;€17,627,519]	€60,570,026 [€47,105,222;€74,855,443]
Italy (Euros)	€1,562,728 [€1,200,319;€1,960,104]	€16,256,102 [€12,094,563;€21,104,281]	€1,562,728 [€1,200,319;€1,960,104]	€16,256,102 [€12,094,563;€21,104,281]	€21,003,822 [€16,402,017;€25,847,758]
Spain (Euros)	€520,659 [€400,688;€651,681]	€20,860,508 [€15,511,600;€27,097,312]	€520,659 [€400,688;€651,681]	€20,860,508 [€15,511,600;€27,097,312]	€3,115,701 [€2,433,790;€3,833,078]
UK (Euros)	€4,071,053 [€3,065,832;€5,219,602]	€10,538,606 [€7,786,283;€13,793,457]	€4,071,053 [€3,065,832;€5,219,602]	€10,538,606 [€7,786,283;€13,793,457]	€18,158,275 [€13,893,491;€22,862,118]
Total EU-5 (millions of Euros)	13.539 [10.388;17.001]	73.583 [54.959;95.117]	14.741 [11.312;18.507]	76.630 [57.237;99.050]	149.996 [116.768;185.226]
Total EU-27 (millions of Euros)	21.367 [16.403;26.814]	112.213 [83.833;145.012]	23.254 [17.855;29.176]	116.856 [87.306;151.004]	241.173 [187.743;297.824]

Table 4. Total costs avoided for the 5 EU countries according to age and risk groups, and perspectives in million Euros for the 2002–03 to 2012–13 influenza seasons.

		Perspective
Age group	Risk Group	Tax-Payer Perspective (TPP)	Societal Perspective (SP)
6 m – <2 yrs		€0.696 [€0.549;€0.847]	€3.248 [€2.562;€3.953]
2–17 yrs		€3.164 [€2.503;€3.839]	€21.676 [€17.168;€26.276
18–49 yrs	Low risk	€2.091 [€1.654;€2.536]	€36.802 [€29.144;€44.619]
	High-risk	€2.855 [€2.178;€3.601]	€34.612 [€26.506;€43.485]
50–64 yrs	Low risk	€2.991 [€2.333;€3.684]	€32.202 [€25.135;€39.633]
	High-risk	€6.781 [€5.177;€8.548]	€41.111 [€31.492;€51.638]
65+		€68.545 [€50.952;€86.063]	€71.715 [€53.310;€93.178]
Total		€87.121 [€65.346;€112.118]	€241.366 [€185.317;€302.783]

Figure 2. Total costs avoided if QIV vaccine was used instead of a TIV vaccine according to TPP and SP perspectives for the 5 EU countries for the 2002–03 to 2012–13 influenza seasons.

Figure 3. Deterministic sensitivity analysis represented by tornado charts reports the impact of the parameters on the number of influenza cases per season in EU-5.

Figure 4. Deterministic sensitivity analysis represented by tornado charts reports the effect of varying various parameters on the average cost savings per season according to TPP and SP for the 5 EU countries during the 2002–03 to 2012–13 influenza seasons.

European Centre for Disease Prevention and Control. European Influenza Surveillance Network (EISN). Available at: http://ecdc.europa.eu/en/healthtopics/influenza/EISN/Pages/index.aspx. (Last access: 11/24/2015).

 Google Scholar

European Centre for Disease Prevention and Control. Influenza virus characterisation, May 2013. Available at: http://ecdc.europa.eu/en/publications/Publications/influenza-virus-characterisation-may-2013.pdf. (Last access: 03/12/2014).

 Google Scholar

Ambrose CS, Levin MJ. The rationale for quadrivalent influenza vaccines. Hum Vaccin Immunother 2012; 8:81-8; PMID:22252006; http://dx.doi.org/10.4161/hv.8.1.17623

 PubMed Web of Science ®Google Scholar

Reingold L. Proposed Revisions to the 2005 WHO Position Paper on Influenza Vaccines. 2012.

 Google Scholar