Public health impact of herpes zoster vaccination on older adults in Singapore: a modeling study

Figures & data

Table 1. Model inputs for demographic, epidemiology, and vaccination parameters.

	Age (years)	Base value	Range^a
			Lower limit	Upper limit
Demographics
Population size (n)^Citation15	50–59	584,188	N/A	N/A
	60–64	282,612	N/A	N/A
	65–69	235,391	N/A	N/A
	70–79	272,304	N/A	N/A
	≥80	131,313	N/A	N/A
Epidemiology^b
Incidence (probability 0–1)
HZ^c, Citation49	50–59	0.008	0.007	0.010
	60–64	0.011	0.009	0.013
	65–69	0.011	0.009	0.013
	70–79	0.012	0.010	0.015
	≥80	0.010	0.008	0.012
Proportion (%) of HZ cases with
PHN^d, Citation17,Citation50,Citation51	50–59	7.000	0.063	0.390
	60–64	14.450	0.063	0.390
	65–69	14.450	0.063	0.390
	70–79	14.450	0.063	0.390
	≥80	25.610	0.063	0.390
Ocular complications^e, Citation17,Citation52	50–59	2.870	1.000	11.000
	60–64	4.230	1.000	11.000
	65–69	4.230	1.000	11.000
	70–79	4.530	1.000	11.000
	≥80	6.910	1.000	11.000
Neurological complications^Citation52	50–59	2.230	0.600	3.860
	60–64	3.170	1.000	5.210
	65–69	3.170	1.000	5.210
	70–79	5.920	1.000	8.650
	≥80	4.880	1.000	7.570
Cutaneous complications^Citation52	50–59	1.590	0.210	2.980
	60–64	1.060	0.000	2.250
	65–69	1.060	0.000	2.250
	70–79	2.090	0.440	3.750
	≥80	2.850	0.770	4.920
Other non-pain complications^Citation52	50–59	1.590	0.210	2.980
	60–64	1.410	0.040	2.780
	65–69	1.410	0.040	2.780
	70–79	2.090	0.440	3.750
	≥80	2.850	0.770	4.920
Hospital resource utilization, mean number per case of HZ
Hospitalizations^Citation53	50–59	0.018	N/A	N/A
	60–64	0.018	N/A	N/A
	65–69	0.029	N/A	N/A
	70–79	0.048	N/A	N/A
	≥80	0.066	N/A	N/A
Mortality
All-cause mortality (probability 0–1)^f, Citation15	50–54	0.002	N/A	N/A
	55–59	0.004	N/A	N/A
	60–64	0.006	N/A	N/A
	65–69	0.010	N/A	N/A
	70–74	0.016	N/A	N/A
	75–79	0.028	N/A	N/A
	80–84	0.049	N/A	N/A
	85–89	0.089	N/A	N/A
	90–94	0.152	N/A	N/A
	95–99	0.167	N/A	N/A
	≥100	0.181	N/A	N/A
HZ-related mortality (proportion of HZ cases, %)^Citation54	50–54	0.001	N/A	N/A
	55–59	0.001	N/A	N/A
	60–64	0.002	N/A	N/A
	65–69	0.002	N/A	N/A
	70–74	0.006	N/A	N/A
	75–79	0.006	N/A	N/A
	80–84	0.024	N/A	N/A
	85–89	0.073	N/A	N/A
	90–94	0.073	N/A	N/A
	95–99	0.073	N/A	N/A
	≥100	0.073	N/A	N/A
Vaccination parameters
Initial vaccine efficacy (%) against HZ
RZV (one dose)^Citation33,Citation34	50–69	90.100	58.900	98.900
	≥70	69.500	24.900	89.100
RZV (two doses)^Citation33,Citation34	50–69	98.900	94.000	100.000
	≥70	95.400	89.700	100.000
ZVL^Citation35–37	50–59	69.800	54.100	80.600
	60–64	63.900	56.000	71.000
	65–69	63.900	56.000	71.000
	70–79	40.900	28.000	52.000
	≥80	18.300	0.000	48.000
Initial vaccine efficacy (%) against PHN
RZV (one dose)^Citation33,Citation34	50–69	90.100	58.900	98.900
	≥70	69.500	24.900	89.100
RZV (two doses)^Citation33,Citation34	50–69	98.900	94.000	100.000
	≥70	95.400	89.700	100.000
ZVL^Citation35–37	50–59	69.800	30.800	89.600
	60–64	65.700	25.400	84.200
	65–69	65.700	25.400	84.200
	70–79	73.400	51.600	85.800
	≥80	39.500	0.000	73.800
Annual waning of vaccine efficacy (%)
RZV (one dose)^g, ^Citation35–37	All ages, Years 1–4 post-vaccination	5.400	1.000	7.400
	All ages, Years ≥ 4 post-vaccination	5.100	3.600	6.900
RZV (two doses)^Citation45	50–69	1.500	0.000	3.400
	≥70	2.300	0.300	4.400
ZVL^Citation35–37	All ages, Years 1–4 post-vaccination	5.400	4.500	6.400
	All ages, Years ≥ 4 post-vaccination	5.100	4.100	6.000
Vaccine coverage (%)^Citation55,Citation56	All ages	30.000	N/A	N/A
Second-dose compliance (%)^Citation33,Citation34,Citation57	All ages	82.500	70.000	95.000

^aParameters indicated as ‘N/A’ were not varied in scenario or sensitivity analysis. ^bThe incidences of HZ and PHN were gender-weighted and combined. ^cThe incidences of initial HZ and recurrent HZ were assumed to be the same; the lower and upper bound values of the range of HZ incidence were calculated as a 20% reduction and increase from the base values. ^dThe proportions (%) of initial cases and recurrent cases of HZ with PHN were assumed to be the same, given that the incidence of initial HZ was assumed to be the same as recurrent HZ; the lower and upper bound values of the range of PHN incidence were obtained from Chen et al.¹⁷ (2015) and Goh et al.⁵¹ (1997), respectively. ^eThe upper bound value of the range of ocular complications (as a proportion of HZ cases) was obtained from Chen et al.¹⁷ (2015). ^fAll-cause mortality rates from SingStat¹⁵ were transformed to probabilities. The probability of all-cause mortality for the 95–99 YOA and ≥ 100 YOA age groups are based on an exponential smoothing forecast performed in Microsoft Excel. ^gNo clinical trials have been conducted to assess the vaccine efficacy of a single dose of RZV; the efficacy of one dose of RZV was thus derived based on a post-hoc analysis of patients from the ZOE-50 and ZOE-70 trials who had received one dose of RZV (including those who went on to receive the second dose and those who received only the first dose). HZ: herpes zoster; N/A: not applicable; PHN: post-herpetic neuralgia; RZV: recombinant zoster vaccine; YOA: years of age; ZVL: zoster vaccine live.

Table 2. Base case results in the mass vaccination setting (30% coverage).

Outcome of interest	No vaccination (control)	RZV vaccination		ZVL vaccination		RZV versus ZVL
	Cases (n)	Cases (n)	Cases avoided (n)	Cases (n)	Cases avoided (n)	Cases avoided (n)
HZ	406,513	333,384	73,129	388,948	17,565	55,564
PHN	68,264	57,170	11,094	65,483	2,781	8,312
Other complications	54,949	45,745	9,205	53,116	1,834	7,371
Ocular	20,103	16,756	3,347	19,430	672	2,675
Neurological	18,303	15,186	3,117	17,696	607	2,510
Cutaneous	8,093	6,762	1,330	7,828	265	1,065
Other non-pain	8,451	7,041	1,410	8,162	289	1,121
Hospitalizations	17,762	14,935	2,827	17,278	484	2,343
HZ-related deaths	72	64	8	71	1	8

Data were rounded to the nearest whole and slight discrepancies may be present. The base case referred to the 2021 population of Singapore adults ≥ 50 YOA, comprising a total of 1.51 million adults, modeled from the year of vaccination over their remaining lifetime. With 30% coverage in the mass vaccination setting, the total vaccinated cohort of adults ≥ 50 YOA was 451,742. HZ: herpes zoster; PHN: post-herpetic neuralgia; RZV: recombinant zoster vaccine; YOA: years of age; ZVL: zoster vaccine live.

Figure 1. Number of cases of (a) HZ, (b) PHN, (c) other complications avoided in the mass vaccination setting (30% coverage), by age cohort.

HZ: herpes zoster; PHN: post-herpetic neuralgia; RZV: recombinant zoster vaccine; ZVL: zoster vaccine live.

Figure 2. NNV to prevent one case of (a) HZ, (b) PHN, by age cohort.

HZ: herpes zoster; PHN: post-herpetic neuralgia; NNV: number needed to vaccinate; RZV: recombinant zoster vaccine; ZVL: zoster vaccine live.

Table 3. Base case results for hospitalizations in the mass vaccination setting (30% coverage), by age cohort.

Outcome of interest	Age (years)	No vaccination (control)	RZV vaccination		ZVL vaccination		RZV versus ZVL
		Cases (n)	Cases (n)	Cases avoided (n)	Cases (n)	Cases avoided (n)	Cases avoided (n)
Hospitalizations	50–59	7,793	6,751	1,042	7,664	130	913
	60–64	3,462	2,890	572	3,358	104	468
	65–69	2,742	2,241	502	2,607	135	366
	70–79	2,889	2,363	526	2,790	100	426
	≥80	875	690	185	860	15	169
	Total ≥50	17,762	14,935	2,827	17,278	484	2,343

Data were rounded to the nearest whole and slight discrepancies may be present. The base case referred to the 2021 population of Singapore adults ≥ 50 YOA, comprising a total of 1.51 million adults, modeled from the year of vaccination over their remaining lifetime. With 30% coverage in the mass vaccination setting, the total vaccinated cohort of adults ≥ 50 YOA was 451,742. RZV: recombinant zoster vaccine; YOA: years of age; ZVL: zoster vaccine live.

Table 4. Scenario analysis results in the aggregated cohort of adults ≥ 65 YOA, under the mass vaccination setting (30% coverage).

Outcome of interest	No vaccination (control)	RZV vaccination		ZVL vaccination		RZV versus ZVL
	Cases (n)	Cases (n)	Cases avoided (n)	Cases (n)	Cases avoided (n)	Cases avoided (n)
HZ	283,835	228,168	55,667	269,720	14,115	41,552
PHN	55,078	44,932	10,146	51,400	3,678	6,468
Other complications	43,716	35,421	8,295	41,880	1,835	6,460
Ocular	15,768	12,823	2,945	15,131	637	2,309
Neurological	14,683	11,806	2,877	13,995	688	2,188
Cutaneous	6,580	5,358	1,222	6,335	246	976
Other non-pain	6,684	5,434	1,251	6,420	264	987
Hospitalizations	15,333	12,476	2,857	14,743	589	2,267
HZ-related deaths	74	63	11	73	1	10

Data were rounded to the nearest whole and slight discrepancies may be present. This scenario analysis was conducted in a subgroup of the 2021 population of Singapore adults ≥ 65 YOA, comprising a total of 639,008 adults, modeled from the year of vaccination over their remaining lifetime. With 30% coverage in the mass vaccination setting, the vaccinated cohort of adults ≥ 65 YOA was 191,702. HZ: herpes zoster; PHN: post-herpetic neuralgia; RZV: recombinant zoster vaccine; YOA: years of age; ZVL: zoster vaccine live.

Table 5. Scenario analysis results for hospitalizations in the aggregated cohort of adults ≥ 65 YOA, under the mass vaccination setting (30% coverage), by age cohort.

Outcome of interest	Age (years)	No vaccination (control)	RZV vaccination		ZVL vaccination		RZV versus ZVL
		Cases (n)	Cases (n)	Cases avoided (n)	Cases (n)	Cases avoided (n)	Cases avoided (n)
Hospitalizations	65–69	6,462	5,280	1,182	6,143	319	864
	70–79	6,809	5,569	1,239	6,574	235	1,005
	≥80	2,062	1,627	435	2,026	36	399
	Total ≥65	15,333	12,476	2,857	14,743	589	2,267

Data were rounded to the nearest whole and slight discrepancies may be present. This scenario analysis was conducted in a subgroup of the 2021 population of Singapore adults ≥ 65 YOA, comprising a total of 639,008 adults, modeled from the year of vaccination over their remaining lifetime. With 30% coverage in the mass vaccination setting, the vaccinated cohort of adults ≥ 65 YOA was 191,702. RZV: recombinant zoster vaccine; YOA: years of age; ZVL: zoster vaccine live.

Figure 3. DSA on cases of HZ avoided with RZV vaccination versus no vaccination, in the mass vaccination setting (30% coverage).

Note: Number of HZ cases avoided with RZV vaccination (versus no vaccination) in the base case: 73,129. DSA: deterministic sensitivity analysis; HZ: herpes zoster; RZV: recombinant zoster vaccine; YOA: years of age.

Department of Statistics Singapore, SingStat. Population and population structure; 2022 [accessed 2023 Apr]. https://tablebuilder.singstat.gov.sg/statistical-tables/downloadMultiple/zX5lZdqFrk-29wjZN4FFXw.

 Google Scholar

Lin YH, Huang LM, Chang IS, Tsai FY, Lu CY, Shao PL, Chang LY. Varicella-Zoster Working Group, Advisory Committee on Immunization Practices Taiwan. Disease burden and epidemiology of herpes zoster in pre-vaccine Taiwan. Vaccine. 2010;28(5):1217–20. doi:10.1016/j.vaccine.2009.11.029.

 PubMed Web of Science ®Google Scholar

Chen Q, Hsu T-Y, Chan R, Kawai K, Acosta CJ, Walia A, Pan JY. Clinical and economic burden of herpes zoster and postherpetic neuralgia in patients from the National Skin Centre, Singapore. Dermatol Sin. 2015;33(4):201–5. doi:10.1016/j.dsi.2015.04.002.

 Web of Science ®Google Scholar

Jih JS, Chen YJ, Lin MW, Chen YC, Chen TJ, Huang YL, Chen CC, Lee DD, Chang YT, Wang WJ. et al. Epidemiological features and costs of herpes zoster in Taiwan: a national study 2000 to 2006. Acta Derm Venereol. 2009;89(6):612–6. doi:10.2340/00015555-0729.

 PubMed Web of Science ®Google Scholar

Goh CL, Khoo L. A retrospective study of the clinical presentation and outcome of herpes zoster in a tertiary dermatology outpatient referral clinic. Int J Dermatol. 1997;36(9):667–72. doi:10.1046/j.1365-4362.1997.00241.x.

 PubMed Web of Science ®Google Scholar

Yawn B, Saddier P, Wollan PC, St. Sauver JL, Kurland MJ, Sy LS. A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction. Mayo Clinic Proc. 2007;82(11):1341–9. doi:10.4065/82.11.1341.

 PubMed Web of Science ®Google Scholar

Lu WH, Lin CW, Wang CY, Chen LK, Hsiao FY. Epidemiology and long-term disease burden of herpes zoster and postherpetic neuralgia in Taiwan: a population-based, propensity score-matched cohort study. BMC Public Health. 2018;18(1):369. doi:10.1186/s12889-018-5247-6.

 PubMed Web of Science ®Google Scholar

Le P, Rothberg MB. Cost-effectiveness of herpes zoster vaccine for persons aged 50 years. Ann Intern Med. 2015;163(7):489–97. doi:10.7326/M15-0093.

 PubMed Web of Science ®Google Scholar

Lal H, Cunningham AL, Godeaux O, Chlibek R, Diez-Domingo J, Hwang SJ, Levin MJ, McElhaney JE, Poder A, Puig-Barbera J. et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015;372(22):2087–96. doi:10.1056/NEJMoa1501184.

 PubMed Web of Science ®Google Scholar

Cunningham AL, Lal H, Kovac M, Chlibek R, Hwang SJ, Diez-Domingo J, Godeaux O, Levin MJ, McElhaney JE, Puig-Barbera J. et al. Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older. N Engl J Med. 2016;375(11):1019–32. doi:10.1056/NEJMoa1603800.

 PubMed Web of Science ®Google Scholar

Curran D, Van Oorschot D, Matthews S, Hain J, Salem AE, Schwarz M. Long-term efficacy data for the recombinant zoster vaccine: impact on public health and cost effectiveness in Germany. Hum Vaccin Immunother. 2021;17(12):5296–303. doi:10.1080/21645515.2021.2002085.

 PubMed Web of Science ®Google Scholar

HealthyPeople.gov, U.S. Department of Health and Human Services. Immunization and infectious diseases data details; 2020 [accessed 2023 Apr]. https://wayback.archive-it.org/5774/20210211114047/https://www.healthypeople.gov/node/3527/data-details.

 Google Scholar

Wick JY. Pharmacy Times. HP2020 herpes zoster immunization goal has been met; 2020 [accessed 2023 Apr]. https://www.pharmacytimes.com/view/hp2020-herpes-zoster-immunization-goal-has-been-met.

 Google Scholar

LaMori J, Feng X, Pericone CD, Mesa-Frias M, Sogbetun O, Kulczycki A. Real-world evidence on adherence and completion of the two-dose recombinant zoster vaccine and associated factors in U.S. adults, 2017–2021. Vaccine. 2022;40(15):2266–73. doi:10.1016/j.vaccine.2022.03.006.

 PubMed Web of Science ®Google Scholar