Global impact of varicella vaccination programs

Figures & data

Table 1. Countries who have Universal Varicella Vaccination.^14–16

Americas	Country	Vaccine	Funded dosis	1st and 2nd dose introduction (year)	Schedule (1st; 2nd dose)
	Argentina	Varicella	1	2015	15 m;
	Bahamas (the)	Varicella	2	2012	12 m; 4–5 y;
	Barbados	Varicella	1	2012	12 m;
	Brazil	MMRV, Varicella	2	2013, 2017	15 m; 4 y
	Canada	MMRV or Varicella	2	2001, 2012	12–15 m;18 m-6 y
	Colombia	Varicella	1	2015	12 m
	Costa Rica	Varicella	1	2007	15 m
	Ecuador	Varicella	1	2011	15 −23 m
	Panama	Varicella	2	2013	15 m – 4 y;
	Paraguay	Varicella	1	2013	15 m;
	Puerto Rico	Varicella	2	1997	12 m; 4–5 y
	United States of America (the)	Varicella	2	1995, 2006	> 12 m; 4 y
	Uruguay	Varicella	2	1999	12 m; 5 y
Eastern Mediterranean	Bahrain	Varicella	2	no data	12 m; 3 y
	Kuwait	MMRV	2	2017	12, 24 m; 12 y
	Oman	Varicella	1	2010	12 m;
	Qatar	Varicella	2	2002	12 m; 4–6 y
	Saudi Arabia	Varicella	2	1998, mandatory sincce 2008	18 m; 6 y
	United Arab Emirates (the)	Varicella	2	2012	12 m; 5–6 y
Europe	Andorra	Varicella	2	no data	15 m; 3 y
	Finland	Varicella	2	2017	18 m; 6 y
	Germany	MMRV, Varicella	2	2004, 2009	11–14 m;15–23 m
	Greece	MMRV, Varicella	2	2006, 2009	12–15 m; 4–6 y
	Israel	MMRV, Varicella	2	2008	12 m; 6 y
	Italy	MMRV or Varicella	2		13–15 months; 5–6 years;
	Sicily			2003	2y
	Veneto			2005	15 months, 3y
	Puglia			2006	13 months; 5-6y
	Toscana			2008	13–15 months; 5-6y
	Basilicata			2010	13 months; 6y
	Calabria			2010	13–15 months; 5-6y
	Sardinia			2011	13 months; 6y
	Friuli-Venezia-Giulia			2013	13 months; 6y
	Latvia	Varicella	1	2008	12–15 m
	Luxembourg	MMRV	2	2010	12, 15–23 m
	San Marino	Varicella	2	no data	15 m; 10 y
	Spain	Varicella	2	2016	15 m; 3–4 y
	Madrid	Program withdrawn nov/2013		2006	15 m
	Navarre			2007	15 m, 3y
	Ceuta			2009	18 m, 24 m
	Melila			2009	15 m, 24 m
	Switzerland	Varicella	1	no data	11–15 y;
	Turkey	Varicella	1	2013	12 m
Western Pacific	Australia	MMRV, Varicella	2	2005	18 m; 10–15 y
	Japan	Varicella	2	2014	12; 18 m
	New Zealand	Varicella	1	2017	15 m
	Niue	Varicella	1	2017	15 m
	Republic of Korea (the)	Varicella	1	2005	12–15 m
	Taiwan	Varicella	1	2004	12–18 m

Table 2. Impact of universal varicella vaccination on Varicella incidence.

Country/ region	Studies (First author/year)	Design of studies/Period	Years after introduction and population evaluated (years of age)	Incidence Before VV (cases/100.000/year)	Vaccination coverage	% reduction after 1 dose (CI95%)	% Incidence change after 2 doses (CI95%) from pre-vaccine period	Impact in HZ	Evidence of indirect effect and age**
Uruguay	Quian, 2008^Citation24	Retrospective (1997–2005)	6 years, 0–14 years	105,1	88–96%	Medical visits reduction of 87% over all groups (< 15y)(P < 0,001), 97% in 1–4y)(P < 0,001)	#	No data	Incidence reduction 80% in < 1 year (P < 0,001), 81% in 5–9 years (P < 0,001), and 65% in10–14 years (P < 0,001),
Costa Rica	Avila-Aguero, 2016^Citation25	National database retrospective review (2007–2015)	8 years, all ages	301–437	76–95%	79,1% (< 5y),		No data	Incidence reduction of 73,8% (all ages)
Brazil	Andrade, 2018^Citation26	Case-control	5–32 months of age	-	-	VE for any severity: 86% (95% CI 72–92%) VE for moderate/severe disease: 93% (95% CI 82–97%)	#	No data
Canada	Wormsbecker, 2015^Citation27	Retrospective health care administrative data (1992–2011)	10 years, 0–17 years	1756,77 (OV) and 158,8 (ED)	Not available	71% for office visits (p < 0.001), 71% for emergency visits (p < 0.001)	#	Decrease in OV (p < 0.001), increase in ED (p < 0.001) for 5–17 years	Shift to older ages (~ 11 months) for OV
U.S.A. Antelope Valley (AV), West Philadelphia (WP)	Bialek, 2013^Citation22	Active surveillance data analyzes (1995–2010)	9 years, all ages	AV: 1030 WP: 410	For one-dose AV: 90.5% to 95.1% WP: 92.7% to 94.6%	89% in AV (~ 100) 90% in WP (~ 40)	76.3% in WP (P < 0.001) and 67.1% in AV (P < 0.001)	No data	Decrease of 81.3% (p < 0.001) in individuals > 20 years
U.S.A.	Lopez, 2016^Citation21	Nationwide rates from passive surveillance data (2005–2014)	19 years, all ages	No data	No data	72%, 25.4 per 100,000 population (2005–06)	84.6% 3.9 per 100,000 (2013–17), (p < 0.001).	No data	Mild disease was more frequent among vaccinated patients (76.8%) than unvaccinated (23.2%) (p < 0.001).
U.S.A.	Baxter, 2014^Citation28	Serial cross-sectional survey (1995–2009)	14 years, 0–29 years of age	10310 (5–9y) 1940 (10–14y) 1230 (15–19y)	> 90% for one-dose, 40% for two-dose	90,2% (5–9y) 72,7% (10–14y) 92,7% (15-19y)	95,5% (5–9y) 90,7% (10–14y) 94,3% (15-19y)	No data	No shift to older age group
U.S.A.	Leung, 2016^Citation20	Retrospective cohort (1994–2012)	17 years, 0–49 years	215 (OV)	Not available	78%	84% (p = < 0,001) in 1–9 years;	No data	Incidence decline 60% (p = < 0,001) in all ages, O.F. decline 95% in < 1year with 35% reduction during 2nd dose (p = < 0,001); 84% all ages (0–49y)
Australia	Kelly, 2014^Citation29	Ecologic(1998–2012)	7 years, all ages	430	~ 83%	53% in 0–4 years-old (p < 0.05) 47% in 5–9 years-old (p < 0.05)	-	Grow incidence in < 70 years-old (p < 0.05), no change in those > 70 years-old	Significant decrease for all age groups < 50 years (p < 0.01), ≥ 50 years (p = 0.02)
Taiwan	Chang, 2011^Citation14	National health insurance database (2000–2008)	4 years, < 20 years	6600 in 4–5 years-old	93–97%	Significant reduction in individuals < 7 years (p < 0.01);	-	No data	Shift to older ages (p < 0.001)
Taiwan	Chao, 2012^Citation30	National health insurance database (2000–2008)	4 years, all ages	829	> 90%	56% in 0–4 years-old	-	Increase,but it was not vaccine attributed	29% decline in those > 20 years-old
Saudi Arabia	Al-Tawfiq, 2013^Citation31	Retrospective health insurance database (1994–2011)	3 years, all ages	739.8	No data	-	60% in 1–4 years (p < 0.0001)	No data	Reduction of incidence in < 1 year-old (p < 0.0001), and all ages (p < 0.0001) The peak age shif from < 5 years to 5–9 years
Italy (Veneto)	Pozza, 2011^Citation32	Ecologic (2000–2008)	4 years, all ages	All ages: 289.2–325.6 (all ages) 0–14 years-old: 1939.3–2211.4 (RDP system), 6136.8–7712.7 (SPES system)	78.6% in 2008	-	Reduction in individuals between 0–14 years-old: 28.6% (RDP system) 34,7% (SPES system)	Not available
Italy	Bechini, 2015^Citation33	Ecologic (2003–2012)	9 years, not informed	130–218	84%-95%	-	75.3%	No data
Italy (Sicily)	Amodio, 2015^Citation34	Regional administrative/clinical data (2003–2012)	10 years, all ages	110	~ 85%	90%	95% (p < 0.001).	No data
Germany (Bavaria)	Streng, 2013^Citation35	Population based surveillance (2006–2011)	7 years, < 17 years	660 (95%CI 610–700) in 2006–2007, two years after vaccine introduction	1st dose 38–68%, 2nd dose 59%	65.2% (95%CI 200–260) in 2009–2010	67%(95%CI 190–250) (< 17 years)	No data	71% decrease in children beloow 1 years of age, and 63% in older children and adolecents.
Germany	Rieck, 2017^Citation36	Health Insurance based study (2006–2015)	11 years, -	Not available	> 80%	VE of 81.9% (95% CI: 81.4–82.5),	VE of 94.4% (95% CI: 94.2–94.6)	No data	No association of VE with vaccination age, time since vaccination, or vaccine type. Unvaccinated individual had benefit from herd immunity
Spain (Navarra)	Cenoz, 2011^Citation37	Regional population data information (2006–2010)	3 years, all ages	804	88% one-doe 81% two-doses	-	96.3% in 1–6 years of age 96.3% in 10–14 years of age 85% in 15-19 years (vaccinated individuals)	No data	93% (p < 0,0001) in all ages Decline in no vaccinated groups of 88.2% (< 1 year), 73.3% (7–9 years) and 84.6% (> 20 years)
Spain (Navarra)	Cenoz, 2013^Citation38	Cohort (2006–2012)	5 years, all ages	804 (all ages) 5010 (0–14 years)	95% one-doe 89% two-dose	VE 96.8% (95% CI: 96.3–97.2%)	98.5% (p < 0.0001) in the vaccinated cohort Incidence decrease 97.3% in all ages (p < 0.0001)	No data	Significant herd protection among < 1 year, 22–44 years (p < 0.0001) and 45–64 years (p = 0.0015) Shift from 3 years-old to two peaks in individuals < 15 months and 9 years-old
Spain (Navarra)	Cenoz, 2013^Citation39	Case-control (2010–2012)	5 years, 15 months to 10 years of age	-	95% one-dose 89% two-dose	87% (95% CI: 60% – 97%) (p < 0.001)	97% (95% CI: 80% −100%) (p < 0.001)	No data
Spain (Madrid)	Latasa, 2018^Citation40	Population-based follow-up (2001–2015)	7 years (vaccine available between Nov 2006 and Jan 2014), all ages	8439.61 (0–4 years) 2906.96 (5–9 years) 672.79 (10–14 years) 114.53 (> 14 years)	> 90%	95.8% RR 0.04 (0.03 to 0.05) (0–4 years) 78.6% RR 0.21 (0.18 to 0.25) (5–9 years)	-	No data	VE of 93.1% (95% CI: 90.9 to 94.8) Incidence decrease: 80.1% RR 0.20 (0.14 to 0.29) (10–14 years) and 80.4% RR 0.20 (0.15 to 0.25) (> 14 years)
Spain (Madrid)	Comas, 2018^Citation41	Observational descriptive (2001–2015)	7 years (vaccine available between Nov 2006 and Jan 2014), all ages	1494.29 (all ages) 8792.65 (0–4 years) 3354.38 (5–9 years) 751.27 (10–14 years) 128.24 (> 14 years)	93,7%	88.9% RR (IC 95%: 0,09–0,13) (0–4 years) 76% RR IC 95%: 0,20–0,29) (5–9 years)	-		Incidence reduction of 94% RR (IC 95%): 0,05–0,07 (all ages), 61% RR (IC 95%): 0,28–0,54 (10–14 years) 88.8% (IC 95%: 0,06–0,19) (> 14 years)
Europe (Czech Republic, Greece, Italy, Lithuania, Norway, Poland, Romania, Russian Federation, Slovakia and Sweden)	Henry, 2018^Citation42	Multicenter phase A cohort, observer-blind, controlled Study (2009–2015)	6.4 years, included children aged 12–22 months	-	-	VE 67.0% (95% CI: 61.8–71.4) for all and moderate cases VE 90.3% (95% CI: 86.9–92.8) for severe cases	VE 95.0% (95% CI: 93.6–96.2) for moderate cases VE: 99.0% (95% CI: 97.7–99.6) for severe cases	Four confirmedcases, all mild and three positive for wild-type virus	96.6% to 99.8% seropositivity after 6 years of vaccination

*Comparing with pre-vaccination period.** Limit of age where effect was found #implemented after the study period

ED = emergency department; OV = Office visits, VE = vaccine effectiveness; CI = confident interval; U.S.A. = (The) United States of America, HZ = herpes-zoster

Table 3. Impact of universal varicella vaccination on hospitalization due to Varicella.

Country/region	Studies (First author/year)	Design of studies/Period	Years after introduction and population evaluated (years of age)	Incidence of hospitalizations due to Varicella Before Universal VV (rate per100.000)	Vaccination coverage	% Change on incidence after one-dose	% Change on incidence after two-doses from pre-vaccine period	Impact in HZ	Evidence of indirect effect and age**
Uruguay	Quian, 2008^Citation24	Retrospective (1997–2005)	6 years, < 15 years	101 total cases in 1998	88–96%	81% all ages (p < 0,001) 94% in 1–4y (p < 0,001) 73% in 5-9y (p < 0,001)	#	No data	Hospitalization reduced by 63% in < 1 year (p < 0.001), 62% in 10–14 years (p = 0.044)
Brazil	Scotta, 2018^Citation43	Ecologic (2003–2016)	3 years, < 20 years	27,33	60%	47.6% (p < 0.001) in 1–4 years	#	No data	Not significant in other age groups
Costa Rica	Avila-Aguero, 2017^Citation25	National database retrospective review (2007–2015)	8 years, all ages	~ 100–160	76–95%	85,9% (all ages), 87% (< 5y)	#	No data	98% less cases complication
U.S.A.	Shah, 2010^Citation18	National health care survey data (1993–2004)	9 years, < 45 years	30.9	No data	53%, (P < 0.001) in < 14 years	#	No data	65.8% reduction in ambulatory discharges (p < 0.001) < 45 years, 98% reduction among 0–4 years
U.S.A.	Lopez, 2011^Citation19	National health care survey data (1988–1995 vs 2000–2006)	11 years, all ages	4,2	≥ 65% (89% in 2006)	> 70% (p < 0,001) in those < 20 years	#	No data	~ 65% hospitalization reduction in those > 20 years, p < 0,001
U.S.A.	Baxter, 2014^Citation28	Cross-Sectional Series (1995–2009)	14 years, 0–29 years	2,13	> 90%, 40% for 2nd dose	77,1%	~ 90%	No data	Annual decreased in all ages of 13% (p < 0.001)
U.S.A.	Leung, 2016^Citation20	Retrospective cohort (1994–2012)	17 years, 0–49 years	2,35	No data	89% (p < 0.001)	99% for infants < 1 years, and 86–96¨% (p = < 0.001), in all ages	No data	Additional 10% decline for those 20–49 years-old during the 2-dose period
Canadá (Ontario)	Wormsbecker, 2015^Citation27	Retrospective health care administrative data analyzes (1992–2011)	10 years, 0–17 years	7,6 (< 1 year)	Not available	59% (95%CI: 0.10-1.69)	#	No change (< 18year)	Decrease in ICU admissions in < 1 year (p < 0.05), 69% decline in SSTI among < 12 years (p < 0.001)
Australia	Carville, 2010^Citation44	Ecologic (1995–2007)	8 years privately available and 2 years funded, all ages	4 (all ages) 21 (0–4 years) 7.7 (5-9 years)	69% private available 98–102% publicly available	38% (p < 0.05) in 0–4 years-old	-	5% increase per years (95% CI 3–6%) in HZ hospitalization in all ages	22.5% less hospitalization in all ages (p < 0.05)
Australia	Heywood, 2014^Citation45	Ecologic (1998–2010)	4 years of funded vaccination, all ages	~ 30 in 18–59 months	> 80%	72.5% (95% CI: 68.8–75.7) in 1–4 years-old	-	HZ hospitalization decline 0.57% (95% CI: 0.24–0.91) per year, age-standardized	Significant Decline in < 40 years (p < 0.001) And 62,1% (95% CI: 54.7–68.3) in individuals < 1 year
Taiwan	Chang, 2011^Citation14	National heal insurance database (2000–2008)	4 years, < 20 years	~ 80 in < 1 year ~ 65 in < 6 years	93–97%	Significant decrease in individuals < 6 years (p < 0.01)	-	No data
Israel	Elbaz, 2016^Citation46	Retrospective chart review (2004–2012)	4 years, ≤ 18 years	389 (≤ 18 years) 1100 (1–6 years)	Not available	-	75% decline in individuals 1–6 years, (p < 0.001)		Decline 63% (p < 0.5) in < 18 years
Spain (Navarra)	Cenoz, 2011^Citation37	Regional population data information (2006–2010)	3 years, all ages	25 total cases	88% one-dose 81% two-doses	-	73% (p < 0.0001)	No data	Complicated hospitalizations were 40% in 2006 and 42.9% in 2009
Spain (Navarra)	Cenoz, 2013^Citation38	Cohort (2006–2010)	5 years, all ages	4.2 (all ages) 20.9 (< 15 years)	95% for one-doe 89% fro two-dose	-	95% (p < 0.0001) in individuals < 15 years	No data	89% (p < 0.0001) in all ages
Spain (Madrid)	Latasa, 2018^Citation40	Population-based follow-up (2001–2015)	7 years (vaccine available between november 2006 and January 2014), all ages	60.91 (0–4 years) 10.36 (5-9 years) 2.59 (10–14 years) 2.57 (> 14 years)	> 90%	93.7% RR, RR (CI 95%): 0.05–0.09 (0-4 years) 76.4% RR, RR (CI 95%): 0.15–0.36 (5-9 years)	-	No data	Incidence decrease (not vaccinated):83.0%, RR (CI 95%): 0.06–0.48 (10-14 years) 69.6%, RR (CI 95%): 0.25–0.37 (> 14 years)
Spain (Madrid)	Comas, 2018^Citation41	Observational descriptive (2001–2015)	7 years (vaccine available Nov 2006 to Jan 2014), all ages	5,99 all ages	93.7%	80.8% (RR CI 95%: 0,16–0,23)	-	No data	80.4% decline among individuals < 1 year, RR (CI 95%): 0,09–0,37
Italy (Veneto)	Pozza, 2011^Citation32	Ecologic (2000–2008)	4 years, all ages	4.1 (all ages) 18.7 (0-14 years-old) 44.3 (1-4 years-old)	78.6%	-	73.6% (1-4 years-old), informed as statistically significant	Not available	55.1% (0-14 years)
Italy	Bechini, 2015^Citation33	Ecologic, (2003–2012)	9 years, not informed	3.0–3.8	84%–95%	-	~ 75%	No data	Hospitalization costs reduction per region Apulia (86%), Sicily (83%), Tuscany (77%), Veneto (75%), Basilicata (71%), Friuli Venezia Giulia (10%)
Italy (Sicily)	Amodio, 2015^Citation34	Regional administrative/clinical data (2003–2012)	10 years, all ages	4.8	~ 85%	62.5%	83.3% (p < 0.001)
Germany (Bavaria)	Streng, 2013^Citation35	Population based surveillance (2006–2011)	7 years, < 17 years	7.6–12.1 (< 17 years) 15.2–21.0 (< 5 years) 60.8 (< 1 year)	1st dose 38–68%, 2nd dose 59%	-	43% (< 17 years) 78% (< 5 years) 76.6% (< 1 year)	No data	Incidence hospitalization decline 76.6% in non-vaccinated group < 1 years-old (2005 vs 2009)

*Comparing with pre-vaccination period.** Limit of age where effect was found #implemented after the study period

SSTI = skin and soft tissue infection; CI = confident interval; U.S.A. = (The) United States of America, ICU = Intensive care unit, HZ = herpes-zoster

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