Influenza vaccine effectiveness among high-risk groups: A systematic literature review and meta-analysis of case-control and cohort studies

Figures & data

Figure 1. Flowchart of the systematic literature review process about influenza vaccine effectiveness among high risk groups.

Table 1. Characteristics of included studies on anti-influenza vaccine effectiveness among at risk-group.

Reference article	At risk-group	Outcome	Publication year	Influenza season	Age range	Sample size	Country	Influenza vaccine type	Influenza virus diagnsosis among cases	Vaccine status	Study design	Qualitative/Quantitative analysis
Szilagyi PG^22	children	outpatient visit	2008	from 2003–2004 to 2004–2005	from 6 months to 6 years	10,906	US	trivalent inactivated	A(H3N2)	Confirmed	Cohort	Qualitative
Ridenhour BJ^23	older	hospitalization/ deaths	2013	from 1993–1994 to 2007–2008	≥ 65 years	21,180,919	Canada	N.A.	N.A.	Confirmed	Cohort	Qualitative
Andrews N^28	comorbidity	outpatient visit	2011	2009–2012	<5 and ≥ 65 years	2,153	UK	adiuvated pH1N1	A(H1N1)	Confirmed	Case-control	Qualitative
Emborg HD^29	comorbidity	outpatient visit / hospitalization	2011	2009–2010	<65 years	388,069	Denmark	adiuvated pH1N1	A(H1N1)	Confirmed	Cohort	Qualitative
MacIntyre CR^25	comorbidity	hospitalization	2013	from 2008 to 2010	≥ 18 years	599	Australia	trivalent inactivated	A and B	Confirmed	Cohort	Qualitative
Perez-Romero P^30	comorbidity	hospitalization	2012	2010–2011	>16 years	64	Spain	trivalent inactivated	A(H1N1), A(H3N2) and B	Confirmed	Cohort	Qualitative
Steens A^27	comorbidity	hospitalization	2011	2009–2011	from 1 to 84 years	10,968	Netherlands	adiuvated pH1N1	A(H1N1)	Confirmed	Case-control	Qualitative
Thompson MG^31	pregnant women	outpatient visit	2013	2010–2011 and 2011–2012	from 22 to 38 years	492	US	trivalent inactivated	A(H1N1)	Confirmed	Case-control	Qualitative
Regan AK^32	pregnant women	outpatient visit / hospitalization	2016	2012–2013	≥ 18 years	2,962,374	Australia	trivalent inactivated	A(H1N1)	Confirmed	Cohort	Qualitative
Costa JT^33	health care workers	outpatient visit	2012	2009–2010	≥ 18 years	245	Portugal	adiuvated pH1N1	A(H1N1)	Confirmed	Case-control	Qualitative
Igari H^34	health care workers	hospitalization	2011	2009–2013	≥ 20 years	1,817	Japan	adiuvated pH1N1	A(H1N1)	Confirmed	Cohort	Qualitative
Blyth CC^71	children	outpatient visit	2016	2008 and from 2010 to 2013	from 6 months to 18 years	2,205	Australia	trivalent inactivated	A(H1N1), A(H3N2) and B	Confirmed	Case-control	Quantitative
Sullivan SG^48	children and older	outpatient visit	2014	2012	< 18 and >65 years	488	Australia	trivalent inactivated	A(H1N1), A(H3N2) and B	Not confirmed	Case-control	Quantitative
Mc Lean HK^72	children and older	outpatient visit	2014	2012–2013	from 6 months to 17 y and ≥ 65 years	3,145	US	trivalent inactivated, adiuvated and live attenuated	A(H1N1), A(H3N2) and B	Confirmed	Case-control	Quantitative
Belongia EA^73	children	outpatient visit	2011	2007–2008	from 6 months to 6 years	412	US	trivalent inactivated	A(H3N2) and B Yamagata	Confirmed	Case-control	Quantitative
Joshi AY^74	children	outpatient visit	2009	from 1999–2000 to 2006–2007	from 6 months to 6 years	206	US	trivalent inactivated	A(H1N1), A(H3N2) and B Victoria	Confirmed	Case-control	Quantitative
Eisenberg KW^50	children	outpatient visit	2008	from 2003–2004 to 2004–2005	from 6 months to 6 years	2,534	US	trivalent inactivated	N.A.	Confirmed	Case-control	Quantitative
Shuler CM^75	children	outpatient visit	2007	2003–2004	from 6 months to 6 years	870	US	trivalent inactivated	N.A.	Confirmed	Case-control	Quantitative
Chiu SS^76	children	hospitalization	2016	from 2009–2010 to 2013–2014	from 6 months to 17 years	6,257	Hong Kong	trivalent inactivated	B Yamagata and B Victoria	Not confirmed	Case-control	Quantitative
Blith CC^54	children	hospitalization	2015	2009 and from 2010 to 2014	from 6 months to 6 years	712	Australia	trivalent inactivated	A(H1N1), A(H3N2) and B	Confirmed	Case-control	Quantitative
Grijalva CC^77	children and older	hospitalization	2015	from 2009–2010 to 2011–2012	from 6 months to 17 y and ≥ 65 years	1,806	US	pandemic, trivalent inactivated and live attenuated	A(H1N1), A(H3N2) and B	Confirmed	Case-control	Quantitative
Cowling BJ^78	children	hospitalization	2014	from 2009–2010 to 2012–2013	from 6 months to 17 years	5,399	Hong Kong	pandemic and trivalent inactivated	A(H1N1), A(H3N2) and B	Not confirmed	Case-control	Quantitative
Ferdinands JM^79	children	hospitalization	2014	from 2010–2011 to 2011–2012	from 6 months to 17 years	309	US	N.A.	A(H1N1), A(H3N2) and B	Confirmed	Case-control	Quantitative
Gilca R^80	children	hospitalization	2011	2009–2010	from 6 months to 9 years	884	Canada	adiuvated pH1N1	pH1N1	Confirmed	Case-control	Quantitative
Griffin MR^81	children	hospitalization	2011	2009–2010	from 6 months to 9 years	2,168	US	live attenuated and inactivated pH1N1	pH1N1	Confirmed	Case-control	Quantitative
Dixon GA^53	children	hospitalization	2010	2008	from 6 months to 6 years	76	Australia	trivalent inactivated	A(H1N1), A(H3N2) and B	Confirmed	Case-control	Quantitative
Orellano PW^59	children and older	hospitalization	2010	2009	<5 y and >65 years	1,115	Argentina	trivalent inactivated	pH1N1	Confirmed	Case-control	Quantitative
Chen Q^82	older	outpatient visit	2014	from 2006–2007 to 2008–2009, from 2010–2011 to 2011–2012	≥ 65 years	927	US	trivalent inactivated	A(H1N1), A(H3N2) and B	Confirmed	Case-control	Quantitative
Havers F^83	older	hospitalization	2016	2010–2011	>50 years	1,141	US	trivalent inactivated	A(H1N1), A(H3N2) and B	Not confirmed	Case-control	Quantitative
Cheng AC^24	older and comorbidity	hospitalization	2015	2014	>65 y and ≥ 16 y for comorbidity	3,217	Australia	trivalent inactivated	A(H1N1), A(H3N2) and B	Not confirmed	Case-control	Quantitative
Gilca R^60	older	hospitalization	2015	2014–2015	≥ 65 years	314	Canada	adiuvated trivalent inactivated	A(H3N2)	Not confirmed	Case-control	Quantitative
Puig-Barberà J^84	older	hospitalization	2015	2014–2015	≥ 65 years	1,108	Spain	trivalent inactivated	A(H3N2)	Confirmed	Case-control	Quantitative
Castilla J^85	older	hospitalization	2014	2013–2014	>65 years	239	Spain	trivalent inactivated	A(H1N1) and A(H3N2)	Confirmed	Case-control	Quantitative
Kwong JC^86	older	hospitalization	2013	2010–2011	>65 years	2,230	Canada	trivalent inactivated	A(H1N1), A(H3N2) and B	Confirmed	Case-control	Quantitative
Puig-Barberà J^26	older and comorbidity	hospitalization	2012	2010–2011	>60 y and ≥ 18 y for comorbidity	379	Spain	adiuvated trivalent inactivated	A(H1N1), A(H3N2) and B	Confirmed	Case-control	Quantitative
Van Vuuren A^87	older	hospitalization	2008	2004–2005	≥ 65 years	6,410	South Africa	trivalent inactivated	A(H1N1), A(H3N2) and B	Confirmed	Case-control	Quantitative

Figure 2. Forest plot of influenza visits and hospitalization vaccine effectiveness (1-Odds ratio) among children from 6 months to 18 year old.

Figure 3. Forest plot of influenza visits and hospitalization vaccine effectiveness (1-Odds ratio) among elderly subjects.

Table 2. Analysis for funnel plot asymmetry of studies reporting vaccine effectiveness, estimated by Egger's regression test.

	No. studies	coefficient	95% CI		p-value
Vaccine effectiveness on influenza visits among children	9	−0.78	−3.51	1.94	0.520
Vaccine effectiveness on influenza hospitalization among children	10	−3.05	−5.93	−0.18	0.040
Vaccine effectiveness on influenza visits among elderly subjects	3	−1.06	−16.41	14.29	0.541
Vaccine effectiveness on influenza hospitalization among elderly subjects	10	−0.52	−2.35	1.31	0.531

Szilagyi PG, Fairbrother G, Griffin MR, Hornung RW, Donauer S, Morrow A, Altaye M, Zhu Y, Ambrose S, Edwards KM, et al. Influenza vaccine effectiveness among children 6 to 59 months of age during 2 influenza seasons: a case-cohort study. Arch Pediatr Adolesc Med 2008; 162(10):943-51; PMID:18838647; https://doi.org/10.1001/archpedi.162.10.943

 PubMedGoogle Scholar

Ridenhour BJ, Campitelli MA, Kwong JC, Rosella LC, Armstrong BG, Mangtani P, Calzavara AJ, Shay DK. Effectiveness of inactivated influenza vaccines in preventing influenza-associated deaths and hospitalizations among Ontario residents aged ≥ 65 years: estimates with generalized linear models accounting for healthy vaccinee effects. PLoS One 2013; 8(10):e76318; PMID:24146855; https://doi.org/10.1371/journal.pone.0076318

 PubMed Web of Science ®Google Scholar

Emborg HD, Krause TG, Hviid A, Simonsen J, Mølbak K. Effectiveness of vaccine against pandemic influenza A/H1N1 among people with underlying chronic diseases: cohort study, Denmark, 2009–10. BMJ 2011; 344:d7901; PMID:22277542; https://doi.org/10.1136/bmj.d7901

 PubMed Web of Science ®Google Scholar

MacIntyre CR, Heywood AE, Kovoor P, Ridda I, Seale H, Tan T, Gao Z, Katelaris AL, Siu HW, Lo V, et al. I schaemic heart disease, influenza and influenza vaccination: a prospective case control study. Heart 2013; 99(24):1843-8; PMID:23966030; https://doi.org/10.1136/heartjnl-2013-304320

 PubMed Web of Science ®Google Scholar

Thompson MG, Li DK, Shifflett P, Sokolow LZ, Ferber JR, Kurosky S, Bozeman S, Reynolds SB, Odouli R, Henninger ML, et al. Effectiveness of seasonal trivalent influenza vaccine for preventing influenza virus illness among pregnant women: a population-based case-control study during the 2010–2011 and 2011–2012 influenza seasons. Clin Infect Dis 2014; 58(4):449-57; PMID:24280090; https://doi.org/10.1093/cid/cit750

 PubMed Web of Science ®Google Scholar

Regan AK, Klerk Nd, Moore HC, Omer SB, Shellam G, Effler PV. Effectiveness of seasonal trivalent influenza vaccination against hospital-attended acute respiratory infections in pregnant women: A retrospective cohort study. Vaccine 2016; 34(32):3649-56; PMID:27216758; https://doi.org/10.1016/j.vaccine.2016.05.032

 PubMed Web of Science ®Google Scholar

Costa JT, Silva R, Tavares M, Nienhaus A. High effectiveness of pandemic influenza A (H1N1) vaccination in healthcare workers from a Portuguese hospital. Int Arch Occup Environ Health 2012; 85(7):747-52; PMID:22045387; https://doi.org/10.1007/s00420-011-0714-8

 PubMed Web of Science ®Google Scholar

Blyth CC, Jacoby P, Effler PV, Kelly H, Smith DW, Borland ML, Willis GA, Levy A, Keil AD, Richmond PC, et al. Influenza vaccine effectiveness and uptake in children at risk of severe disease. Pediatr Infect Dis J 2016; 35(3):309-15; PMID:26646548; https://doi.org/10.1097/INF.0000000000000999

 PubMed Web of Science ®Google Scholar

Sullivan SG, Chilver MB, Higgins G, Cheng AC, Stocks NP. Influenza vaccine effectiveness in Australia: results from the Australian Sentinel Practices Research Network. Med J Aust 2014; 201(2):109-11; PMID:25045991

 PubMed Web of Science ®Google Scholar

McLean HQ, Thompson MG, Sundaram ME, Kieke BA, Gaglani M, Murthy K, Piedra PA, Zimmerman RK, Nowalk MP, Raviotta JM, et al. Influenza vaccine effectiveness in the United States during 2012–2013: variable protection by age and virus type. J Infect Dis 2015; 211(10):1529-40; PMID:25406334; https://doi.org/10.1093/infdis/jiu647

 PubMed Web of Science ®Google Scholar

Belongia EA, Kieke BA, Donahue JG, Coleman LA, Irving SA, Meece JK, Vandermause M, Lindstrom S, Gargiullo P, Shay DK. Influenza vaccine effectiveness in Wisconsin during the 2007–08 season: comparison of interim and final results. Vaccine 2011; 29(38):655; https://doi.org/10.1016/j.vaccine.2011.07.002

 Web of Science ®Google Scholar

Joshi AY, Iyer VN, St Sauver JL, Jacobson RM, Boyce TG. Effectiveness of inactivated influenza vaccine in children less than 5 years of age over multiple influenza seasons: a case-control study. Vaccine 2009; 27(33):4457-61; PMID:19490957; https://doi.org/10.1016/j.vaccine.2009.05.038

 PubMed Web of Science ®Google Scholar

Shuler CM, Iwamoto M, Bridges CB, Marin M, Neeman R, Gargiullo P, Yoder TA, Keyserling HL, Terebuh PD. Vaccine effectiveness against medically attended, laboratory-confirmed influenza among children aged 6 to 59 months, 2003–2004. Pediatrics 2007; 119(3):e587-95; PMID:17332179; https://doi.org/10.1542/peds.2006-1878

 PubMed Web of Science ®Google Scholar

Chiu SS, Feng S, Chan KH, Lo JY, Chan EL, So LY, Cowling BJ, Peiris JS. Hospital-based vaccine effectiveness against influenza B lineages, Hong Kong, 2009–14. Vaccine 2016; 34(19):2164-9; PMID:27013437; https://doi.org/10.1016/j.vaccine.2016.03.032

 PubMed Web of Science ®Google Scholar

Blyth CC, Cheng AC, Finucane C, Jacoby P, Effler PV, Smith DW, Kelly H, Macartney KK, Richmond PC. The effectiveness of influenza vaccination in preventing hospitalisation in children in Western Australia. Vaccine 2015; 33(51):7239-44; PMID:26549359

 PubMed Web of Science ®Google Scholar

Grijalva CG, Zhu Y, Williams DJ, Self WH, Ampofo K, Pavia AT, Stockmann CR, McCullers J, Arnold SR, Wunderink RG, et al. Association Between Hospitalization With Community-Acquired Laboratory-Confirmed Influenza Pneumonia and Prior Receipt of Influenza Vaccination. JAMA 2015; 314(14):1488-97; PMID:26436611; https://doi.org/10.1001/jama.2015.12160

 PubMed Web of Science ®Google Scholar

Cowling BJ, Chan KH, Feng S, Chan EL, Lo JY, Peiris JS, Chiu SS. The effectiveness of influenza vaccination in preventing hospitalizations in children in Hong Kong, 2009–2013. Vaccine 2014; 32(41):5278-84; PMID:25092636; https://doi.org/10.1016/j.vaccine.2014.07.084

 PubMed Web of Science ®Google Scholar

Ferdinands JM, Olsho LE, Agan AA, Bhat N, Sullivan RM, Hall M, Mourani PM, Thompson M, Randolph AG, Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Effectiveness of influenza vaccine against life-threatening RT-PCR-confirmed influenza illness in US children, 2010–2012. J Infect Dis 2014; 210(5):674-83; PMID:24676207; https://doi.org/10.1093/infdis/jiu185

 PubMed Web of Science ®Google Scholar

Griffin MR, Monto AS, Belongia EA, Treanor JJ, Chen Q, Chen J, Talbot HK, Ohmit SE, Coleman LA, Lofthus G, et al. Effectiveness of non-adjuvanted pandemic influenza A vaccines for preventing pandemic influenza acute respiratory illness visits in 4 U.S. communities. PLoS One 2011; 6(8):e23085; PMID:21857999; https://doi.org/10.1371/journal.pone.0023085

 PubMed Web of Science ®Google Scholar

Dixon GA, Moore HC, Kelly H, Jacoby P, Carcione D, Williams S, Smith D, Keil AD, Van Buynder P, Richmond PC, et al. Lessons from the first year of the WAIVE study investigating the protective effect of influenza vaccine against laboratory-confirmed influenza in hospitalised children aged 6–59 months. Influenza Other Respir Viruses 2010; 4(4):231-4; PMID:20629773

 PubMed Web of Science ®Google Scholar

Orellano PW, Reynoso JI, Carlino O, Uez O. Protection of trivalent inactivated influenza vaccine against hospitalizations among pandemic influenza A (H1N1) cases in Argentina. Vaccine 2010; 28(32):5288-91

 PubMed Web of Science ®Google Scholar

Cheng AC, Kotsimbos T, Kelly PM, FluCAN Investigators. Influenza vaccine effectiveness against hospitalisation with influenza in adults in Australia in 2014. Vaccine 2015; 33(51):7352-6; PMID:26529066; https://doi.org/10.1016/j.vaccine.2015.10.016

 PubMed Web of Science ®Google Scholar

Kwong JC, Campitelli MA, Gubbay JB, Peci A, Winter AL, Olsha R, Turner R, Rosella LC, Crowcroft NS. Vaccine effectiveness against laboratory-confirmed influenza hospitalizations among elderly adults during the 2010–2011 season. Clin Infect Dis 2013; 57(6); PMID:23788243; https://doi.org/10.1093/cid/cit404

 PubMed Web of Science ®Google Scholar