A review of the value of quadrivalent influenza vaccines and their potential contribution to influenza control

Figures & data

Figure 1. The evaluation of influenza viruses and vaccine development. Information from Hannoun et al.⁸ and McCullers et al.⁹⁷ *Asian influenza pandemic caused by the shifted A/H2N2 strain and Hong Kong influenza pandemic caused by the shifted A/H3N2 strain: both examples of A-strain shift through reassortment (sharing) of genetic material. LAIV = live-attenuated trivalent influenza vaccine; TIV = trivalent influenza vaccine; QIV = quadrivalent influenza vaccine; WHO = World Health Organization.

Figure 2. Results of the literature search (30 October 2016). Search string: “(Quadrivalent OR tetravalent) (influenza vaccine OR flu vaccine) (cost OR burden OR epidemiology OR death OR mortality OR illness OR hospitalisation OR hospitalization)” No limits applied.

Table 1. Summary of QIV modeling data in different countries: results from a review of the literature.

	Model	Vaccinated		Time	Influenza vaccine	Illness averted by QIVs compared with TIVs
	framework	population	Population size	horizon	coverage (%)	Total Cases	Total hospitalisations	Total Deaths
North America
US ^58	Static	All ages	270–304 million	10 y	18–30^*	2,741,575 (Range 2200–970,000)	21,440 (Range 14–8,200)	1371 (Range 1–485)
US ^59	Static	All ages	311.6 million	1 y	21.3–66.6^**	30,251	3,512	722
US ^60	Static	≥ 65 y	41.5 million	1 y	67	26,701	1,345	211
US ^61	Static	≥ 65 y	44,704,074	10 months	64.7	39,136	1,648	458
US ^65	Dynamic	All ages	US population	10 y	∼25–60^**	1,973,849 annually	—	1,396 annually
US ^64	Dynamic	All ages	313.9 million	1 y	46.2	1,382,509	18,354	2,981
US ^62	Dynamic	All ages	US population without immigration	13 y	Weekly age-based from CDC	6,267,800 (Average 482,000 annually)	—	—
US ^63	Dynamic	All ages	US population	20 y	Weekly age-based from CDC	16 million	137,645	16,199
Canada ^68	Dynamic	All ages	34.8 million	10 y	16.1–64.4^**	135,538 annually	1876 annually	328 annually
Ontario, Canada^67	Static	All ages	12.8 million	2000–2008	27–81^**	2,516 annually	27 annually	5 annually
Europe
UK ^68	Dynamic	All ages	62.8 million	10 y	17.6–71.1^**	88,755 annually	1050 annually	230 annually
UK ^71	Static	≥ 65 and risk groups	63.7 million	100 y	34.07–100^**	1.4 million	41,780	19,906
				10 y		183,844	4,871	2,142
Germany ^73	Dynamic	0–15 y	Approx. 80 million	20 y	26.8–33.4^*	79,000 annually	—	—
		16–60 y				223,000 annually	—	—
		≥ 61 y				93,000 annually	—	—
		All ages				395,000 annually	—	—
Germany ^74	Dynamic	All ages	81.3 million	20 y	Not given	276,505 annually	5,690 annually	262 annually
Finland ^75	Dynamic	All ages	Finnish population	20 y	∼10–75^**	40,500 annually†	360 annually†	54 annually†
Belgium ^76	Dynamic	2–17 y^††	11.16–11.63 million	10 y	50	2,953,995	16,968	1,455
Spain^77	Static	≥ 65 y, at risk ≥ 3y	46,727,891	100 y	0–72.47^**	18,565 in the first year	407 in the first year	181 in the first year
Italy^78	Static	All ages at risk, ≥ 65y	17,420,318	2014–2015	9% QIV, 31.02 total	2,632	100	—
France^79	Static	All ages	French population	2003–2012	Not reported	6,214 consultations	614	372
5 countries in Europe^80	Static	6 m-2 y		2002–2013	6.1–19.2	28,877	140	0
		2–17 y			4.1–14.0	219,163	348	4
		18–49 y high risk			30.9–52.0	83,635	389	79
		18–49 y low risk			6.5–12.0	133,656	110	0
		50–64 y high risk			30.9–52.0	89,908	1,801	325
		50–64 y low risk			14.9–25.3	86,216	515	0
		65+			48.6–69.2	393,270	21,151	9,391
		All ages				1,034,727	24,453	9,799
		All ages	Extrapolated to 27-EU			1,624,533	37,317	14,866
Asia-Pacific and Western Pacific
Hong Kong ^83	Static	All ages	7.2 million	1 y	11.0–39.1^**	91/100,000	1.8/100,000	0.046/100,000
Hong Kong ^98,99	Static	≥ 65 y	747,000–924,000	2001–2010	39.1	191.3/100,000	—	—
		65–79 y	601,000–666,000			104.8/100,000	0–2.4/100,000	0–0.14/100,000
		≥ 80 y	146,000–258,000			451.4/100,000	0–13.1/100,000	0–0.77/100,000
		All ages	Not reported			25.6/100,000	—	—
Albany, Australia ^85	Static	All ages	ABS CCD	2003–2013	2–20 (selected range)	0.1/100,000 (3.8% reduction)	2.0/100,000 (2.2% reduction)	0.1/100,000 (2.1% reduction)
Australia ^86	Static	6–59 months	173,778	2002–2012	41.3	4,153	23	0
		5–17 y	509,239		41.3	11,824	11	0
		18–49 y	2,223,249		36.2	10,240	86	1
		50–64 y	1,296,098		36.2	5,731	143	6
		65+ y	3,221,312		74.6	36,322	3,257	675
		Total	7,423,676 at risk		—	68,271	3,522	683
Thailand ^100	Static	All ages	66–68 million	2007–2012	3–12^*	21, 974	698	7
Taiwan ^101	Static	All ages	Not reported	100 y	0–39.49^**	529,874	8,126	3,590
Africa
Agincourt, South Africa ^85	Static	All ages	40,383	2003–2013	2–20 (selected range)	0.3/100,000 (12.0% reduction)	4.8/100,000 (18.6% reduction)	2.0/100,000 (17.6% reduction)

* Coverage across seasons

** coverage across age ranges, ^††this study evaluated immunisation of 2–17 y olds with QIV vs. the baseline scenario of TIV vaccination of at-risk groups, †switching from TIV to Q-LAIV in 2–18 y olds (with QIV in other age groups) was estimated to prevent an additional 76,100 infections, 540 hospitalizations, and 72 deaths compared with TIV

ABS CCD = Australian Bureau of Statistics Census Collection Districts; CDC = Centers for Disease Control and Prevention in the United States; ONS = Office of National Statistics; QIV = quadrivalent influenza vaccine; TIV = trivalent influenza vaccine; US = United States; UK = United Kingdom; y = years

Table 2. Current recommendations for influenza vaccination using quadrivalent seasonal influenza vaccines (QIVs).

Countries/authorities with permissive recommendations for QIVs use	Year recommended	Age/group indicated for QIVs
World Health Organization ^102	2012	Pregnant women, Children <5 y, Health care workers, Elderly >65 y, Chronic conditions
Germany ^103	2013	Pregnant women, Children <5 y, Health care workers, Elderly >65 y, Chronic conditions
United States ^104	2013	Children (≥6 months) & Adults
Hong Kong ^105	2013	Children (≥ 3 y) & Adults
Canada ^106	2014	From 6 months of age
Italy ^107	2014	Children (≥ 3 y) & Adults
France ^108	2014	Children (≥ 3 y) & Adults
Belgium ^109	2015	From age 2 y
Brazil ^110	2014	Elderly 60+ y
Countries preferentially recommending QIVs
United Kingdom ^111	2013	Children 2–7 y and children at risk 2–18 y.
Germany ^112	2014	All long-distance travelers
Brazil ^110	2015	Elderly
Australia ^113	2015	From 6 months of age

QIV = quadrivalent seasonal influenza vaccine (LAIV or IIV4)

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