The health and economic impact of switching vaccines in universal varicella vaccination programs using a dynamic transmission model: An Israel case study

Figures & data

Figure 1. MSEIVR dynamic transmission model diagram with switching vaccines.

M: Maternal-induced immunity. S: Susceptible to VZV infection. V: Vaccinated with varicella vaccine strategy V₁ or V₂ or V₃ for the specified time period. E: Exposed to VZV. I: Infectious with VZV. R: Recovered (after VZV infection). W: Waning zoster immunity. Z: Zoster (VZV reactivation). RZ: Recovered (after zoster). The dashed line reflects exogenous boosting. The bracket reflects the sequence of vaccination strategies used over time in the UVV program, where T_i is the time when the i^th vaccination strategy is introduced.

Table 1. Epidemiological inputs.

Parameters	Values	Source
Varicella
Average waning period of passive immunity	6 months	^Citation23
Average latent period: natural and breakthrough varicella	14 days	^Citation24,Citation25
Average infectious period: natural varicella	7 days	^Citation24,Citation26,Citation27
Average infectious period: breakthrough varicella	4.5 days	^Citation27
Average waning period of herpes zoster immunity following (natural and breakthrough) varicella infection	81.3 years	Modeled from^Citation19
Infectivity of breakthrough varicella relative to natural varicella	50%	^Citation25,Citation28
Herpes zoster
Average duration of herpes zoster outbreak following natural and breakthrough varicella and successful vaccination	28 days	^Citation18,Citation29
Average waning period of vaccine type herpes zoster post successful varicella vaccination	81.3 years	Modeled from^Citation19
Reactivation rate factor on vaccine arms	1/6	^Citation30
Relative infectivity of herpes zoster (compared to natural varicella)	7%	^Citation18
Percentage of contacts leading to exogenous boosting after natural and breakthrough varicella and successful vaccination	33.45%	Modeled from^Citation19

Table 2. Model inputs for direct and indirect costs for varicella and herpes zoster.

Varicella
Vaccine	Primary and booster coverage rate								97%		^Citation36
	MMRV-MSD cost per dose								$86.00		Assumed
	MMRV-GSK cost per dose								$86.00		^Citation37
	Vaccine administration cost								$7.00		Assumed
Outpatient	Proportion of varicella cases requiring outpatient care								90.00%		^Citation38
	Mean number of GP visits per outpatient							<18y	1.15		^Citation38
								≥18y	1.44
	Outpatient visit cost								$61.33		^Citation38
	Outpatient varicella workdays lost							<18y	2.50		^Citation38
								≥18y	5.69
Inpatient	Proportion of varicella cases requiring inpatient care										^Citation39
	0-5y	5-10y		10-15y		15-20y		20-40y	>40y
	0.33%	0.13%		0.41%		0.61%		1.31%	0.87%
	Length of hospital stay (days)							<18y	3.8		^Citation38
								≥18y	5.6
	Varicella hospitalization cost per day								$739.00		^Citation40
	Inpatient varicella workdays lost							<18y	3.75		^Citation38
								≥18y	7.77
Herpes zoster
Uncomplicated Herpes zoster
Proportion of Herpes zoster cases that are uncomplicated	0-15y	15-25y	25-35y	35-45y	45-55y	55-65y	65-75y	75-85y	>85y		Assumed from^Citation34
	99.89%	99.28%	98.19%	97.76%	95.05%	93.25%	88.44%	86.76%	84.57%
Outpatient	Proportion of uncomplicated Herpes zoster cases requiring outpatient care								98.7%		Assumed from^Citation41
	Outpatient visit cost							$194.73			^Citation42
Inpatient	Proportion of uncomplicated Herpes zoster cases requiring inpatient care								1.3%		^Citation41
	Length of hospital stay (days)								7.8		^Citation41
	Uncomplicated Herpes zoster hospitalization cost per day								$739.00		^Citation40
PHN
Proportion of Herpes zoster cases leading to PHN	0-15y	15-25y	25-35y	35-45y	45-55y	55-65y	65-75y	75-85y	>85y		^Citation34
	0.11%	0.72%	1.81%	2.24%	4.95%	6.75%	11.56%	13.24%	15.43%
Average duration of a PHN episode (months)									9		^Citation43
Outpatient	Proportion of PHN cases requiring outpatient care								98.00%		^Citation41
	PHN cost per outpatient case								$290.11		^Citation42
Inpatient	Proportion of PHN cases requiring inpatient care								2.00%		^Citation41
	Length of hospital stay (days)								10.2		^Citation41
	PHN hospitalization cost per day								$739.00		^Citation40
Herpes zoster related workdays lost								<18y		0	^Citation42
								18-65y		12.8
								>65y		0
Cost per workday lost (varicella and HZ related)										$148.71	^Citation44

Figure 2. Total varicella incidence (2022–2072).

Figure 3. Breakthrough varicella incidence* (2022–2072).

* Breakthrough varicella incidence includes varicella cases following the first or second varicella dose.

Table 3. Cumulative varicella and HZ health outcomes over 50 years (2022-2072).

Health Outcome	Remain with MMRV-MSD	Switch to MMRV-GSK	Impact of Switching
			Difference	% Change
Varicella Outcomes
Natural cases	97,283	130,528	33,245	34%
Breakthrough cases	115,639	373,766	258,127	223%
Total cases	212,922	504,294	291,372	137%
Outpatient cases	191,631	453,844	262,213	137%
Hospitalizations	1,065	2,030	965	91%
Deaths	6	7	1	29%
Herpes Zoster Outcomes
Total cases	1,167,745	1,153,210	-14,535	-1%
Deaths	174	174	0	0%

Table 4. Vaccine doses, QALYs lost, and discounted costs per capita (2022–2072).

	Remain with MMRV-MSD	Switch to MMRV-GSK	Impact of Switching
			Difference	% Change
Vaccine doses administered
Primary	5,658,397	5,646,208	−12,188	−0.2%
Booster	5,193,725	4,853,115	−340,609	−6.6%
Total QALYs lost	20,640	20,779	139	0.7%
Cost per capita with price parity
Vaccination costs	$57.77	$55.38	-$2.39	−4.1%
primary dose	$30.34	$30.28	-$0.06	−0.2%
booster dose	$27.43	$25.11	-$2.32	−8.5%
Direct medical costs	$20.64	$21.66	$1.02	4.9%
Indirect costs	$71.04	$76.79	$5.74	8.1%
Total costs (payer)	$78.41	$77.04	-$1.37	−1.7%
Total costs (societal)	$149.46	$153.83	$4.37	2.9%

Figure 4. Tornado plot of incremental cost per capita over 50 years following switch from MMRV-MSD to MMRV-GSK (in USD, societal perspective).

Figure 5. Tornado plot for incremental QALYs lost per capita over 50 years following switch from MMRV-MSD to MMRV-GSK.

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