Table 2.
Vaccine efficacy and effectiveness of influenza vaccination in healthy children under 5 years of age.
| Vaccine strains | Age (no. of participants) | Outcomes | Effect sizes (95%CI) | First author, year (region) |
|---|---|---|---|---|
| RCTs | ||||
| Seasonal TIV 1995–1996 NH, F | <6 years (n = 476) | Influenza RR ILI RR |
0.61 (0.34–1.08) 0.39 (0.21–0.69) |
Colombo, 2001; Clover, 1991; and Gruber, 1990 (132–135) (Italy and USA) |
| Seasonal TIV 1999–2000 N and 2000–2001 NH, H | <2 years (n = 786) | Influenza risk ratio | 0.55 (0.18–1.69) | Hoberman, 2003 (135, 136) (Netherlands, two studies) |
| Seasonal TIV 1999–2000 and 2000–2001 NH subvirion, H | 6–24 months (n = 786) Groups (first cohort: 411; second cohort: 375) |
Efficacy against culture-confirmed influenza | First cohort: 66% (34–82) Second cohort: −7% (−247 to 67) |
Hoberman, 2003 (136) (USA) |
| TIV 2003–2004, 2004–2005, and 2005–2006 N | 18–72 months with H/O RTI (n = 579) | Efficacy against PCR-confirmed influenza | 51% (3–75) despite substantial strain mismatch | Jansen, 2008 (137) (Netherlands) |
| Seasonal TIV 2007–2009 NH (MF59 emulsion adjuvant or subunit non-adjuvanted), F | 6–72 months (n = 4,707) | Efficacy against all PCR-confirmed influenza strains for adjuvanted and non-adjuvanted TIV | 86% (74–93) and 43% (15–61) | Vesikari, 2011 (59) (Finland and Germany) |
| Seasonal QIV 2010–2011, F | 3–4 years (n = 80) | Efficacy against all PCR-confirmed influenza, any severity | 35.3% (−1.3 to 58.6) | Jain, 2013 (138) (15 centers in Bangladesh, the Dominican Republic, Honduras, Lebanon, Panama, the Philippines, Thailand, and Turkey) |
| Seasonal TIV 2010–2014 SH, H | 6–23 months (n = 4,081) | Efficacy against PCR-confirmed influenza | 31% (18–42) | Rolfes, 2017 (139) (Bangladesh) |
| Five seasonal QIV formulations, F | 6–35 months (n = 6,006 in QIV and n = 6,012 in control) | Efficacy against moderate-to-severe influenza and all influenza in total vaccinated cohorts | 64% (53–73) 50% (42–57) |
Claeys, 2018 (123) (13 countries in Europe, Central America, and Asia) |
| Seasonal 2008–2009 TIV NH | 6 months to 10 years (n = 3,918 in TIV and n = 3,848 in control) | Adjusted VE in 6- to 35-month-olds and in 3- to 5-year-olds in preventing A/H3N2 and A/H1N1pdm09 | 20.6% (−16.3 to 45.8) and 57.7% (34.7–72.7); −30.8% (−128.3 to 25.0), and −56.2% (−238.2 to 27.8) | Diallo, 2019 (140) (Senegal) |
| Thimerosal-free, split-virion seasonal QIV NH (2014–2015 and 2015–2016) and SH (2014 and 2015) F; TIV, F | 6–35 months (n = 4,980) | LCI caused by any influenza A or B strain and vaccine-similar strains | 50.98% (37.36–61.86) and 68.40% (47.07–81.92) | Pepin, 2019 (37) (13 countries in Europe, Central America, and Asia) |
| Seasonal TIV 2009–2012 NH, H | 6–35 months (n = 807) | Efficacy against PCR-confirmed influenza in 2011–2012 | 70.5% (24.2–88.5) | Sullender, 2019 (141) (India) |
| Cohort studies | ||||
| Seasonal 1998–1999 TIV NH subvirion | 7–50 months (187 vaccinees and 187 controls) | Reduction in incidence of acute otitis media associated with influenza A | 83% (58–93) | Heikkinen, 1991 (142) (Finland) |
| Five influenza seasons (from 2004–2005 to 2008–2009) | All aged 6–23 months (n = 919,021), full-term children (n = 847,294) and preterm children (n = 71,727) | Influenza-coded ambulatory visits VE in all children, full-term and preterm children (full and partial vaccination with an unvaccinated reference group) | 19% (3–32) and 2% (−12 to 15) 18% (1–32) and 1% (−13 to 15) 28% (−29 to 60) and 4% (−50 to 38) |
Shen, 2013 (30) (Canada) |
| Seasonal 2015–2018 TIV NH | 2 years (n = 60,088 in 2015–2016, n = 60,860 in 2016–2017, n = 60,345 in 2017–2018) | VE against LCI caused by influenza strains (any, A and B) in 2015–2016, 2016–2017, and 2017–2018 | 77.2% (48.9–89.8), 90.3% (60.9–97.6), and 34.6% (−79.5 to 76.1); 24.5% (−29.8 to 56.1), 23.1% (−32.3 to 55.3), and NA; −20.1% (−61.5 to 10.7), −42.0% (−110.6 to 4.2), and −0.2% (−55.9 to 35.6) | Baum, 2020 (143) (Finland) |
| Classic case–control studies | ||||
| Seasonal TIV 1999–2006 | 6–59 months (15 fully vaccinated and 75 unvaccinated) | VE against LCI | 86% (29–97) | Joshi, 2009 (36, 144) (USA) |
| Seasonal 2007–2008 TIV NH, F | 9 months to 3 years (n = 340; 84 vaccinated and 256 unvaccinated) | VE against influenza A VE against influenza B VE any influenza |
85% (37–96) 48% (−38 to 81) 72% (35–88) |
Heinonen, 2011 (145) (Finland) |
| Test-negative designc | ||||
| 2003–2005 IIV, F | 6–59 months (n = 2,474) | VE against LCI in 2003–2004 (two and one dose) VE against LCI in 2004–2005 (two and one dose) |
44% (−42 to 78) and 43% (−3 to 68) 57% (28–74) and 11% (−35 to 41) |
Eisenberg, 2008 (125) (USA) |
| Adjuvanted pandemic 2009 H1N1 influenza vaccine, H | 6–59 months (n = 53) | VE against LCI | 100% (44.0–100) | Van Buynder, 2010 (130) (Canada) |
| Seasonal 2007–2008 TIV NH | 6–59 months (n = 412) | VE against LCI | 39% (2–62) | Belongia, 2011 (129) (USA) |
| Seasonal 2008 TIV SH, H (<3 years old) and F (3–5 years old) | 6–59 months (n = 289) | Adjusted VE against LCI using all controls | 58% (9–81) | Kelly, 2011 (128) (Australia) |
| Seasonal 2005–2007 TIV NH, F | 6–59 months (n = 528) | VE against LCI for 6- to 59-month-olds Subgroups: 6–23 months and 24–59 months old |
56% (25–74) 61% (16–82) and 56% (3–80) |
Staat, 2011 (29) (Canada) |
| Seasonal 2008–2012 TIV | 6–59 months (n = 1,514) | VE against LCI against influenza A Against influenza B |
79.6% (41.6–92.9) 47.8% (−12.4 to 75.8) |
Blyth, 2014 (126) (USA) |
| Seasonal 2009–2013 TIV a | ≤2 years (n = 2,881) 3–5 years (n = 1,481) |
VE against influenza A and B | 34.1% (−27.3 to 65.9) 70.4% (36.3–86.3) |
Cowling, 2014 (127) (Hong Kong) |
| Seasonal 2012-13 TIV a | 6 months to 5 years (n = 334) | Adjusted VE against LCI hospitalizations | 75% (−100 to 97) | Turner, 2014 (146) (New Zealand) |
| Seasonal 2013–2015 TIV NH b | 6 months to 5 years (n = 665) | Adjusted VE against LCI hospitalizations | 81.2% (−52.3 to 97.7) | Qin, 2016 (147) (China) |
| Seasonal 2015–2016 TIV NH b | <5 years (n = 832) | Adjusted VE against LCI hospitalizations | −63.7% (−423.6 to 48.9%) | Zhang, 2017 (148) (China) |
| Seasonal 2011–2015 TIV or QIV a | 0.5–2 years (n = 12,516 fully vs. n = 11,949 partially vaccinated) 3–5 years (n = 7,295 fully vs. n = 6,467 partially vaccinated) |
Adjusted VE against influenza A and B hospitalizations | 74% (64–81%) vs. 18% (−20 to 43) 74% (68–80) vs. 47% (13–67) |
Chua, 2019 (149) (Hong Kong) |
| Seasonal 2015–2018 TIV | 6–24 months (n = 246 fully vs. n = 436 partially vaccinated) (n = 1,228 unvaccinated) | Adjusted VE against LCI hospitalizations for fully and partially vaccinated children | 48.1% (8.3–72.6) and 9.3% (−27.1 to 40.9) | Segaloff, 2019 (150) (Israel) |
| Seasonal 2013–2017 TIV SH | 6–24 months (n = 2,389) | Adjusted VE against LCI hospitalizations for fully and partially vaccinated children | 43% (33–51) and 20% (−16 to 45) | Arriola, 2019 (151) (Argentina, Brazil, Chile, Colombia, and Paraguay) |
Children 6 months to 5 years old require two doses as a prime–boost regime to ensure adequate seroprotection against influenza. Thereafter, only one annual dose is required. Fully vaccinated children received either two doses of IIV, or one dose in primed children and two doses in unprimed children, unless otherwise stated.
RCTs, randomized controlled trials; F, full dose (0.5 ml); H, half dose (0.25 ml); BIV, bivalent influenza vaccine; TIV, trivalent influenza vaccine; QIV, quadrivalent influenza vaccine; NH, WHO Northern Hemisphere recommended strains; RR, risk ratio; ILI, influenza-like illness; VE, vaccine effectiveness; LCI, laboratory-confirmed influenza; VA, vaccine arm; CA, control arm; RTI, respiratory tract infection.
a
Estimates in 2009–2010 were also adjusted for receipt of the monovalent A(H1N1)pdm09 vaccine.
b
Recruited patients who received at least one dose of influenza vaccine were identified as vaccinated.
c
Test-negative design (117) used to evaluate influenza vaccine effectiveness.