The global burden of varicella and herpes zoster in adults aged 65 years and older: a comprehensive analysis based on the global burden of disease 2021

Abstract

Background

The global population is aging at an accelerated rate. There is a lack of data on the burden of varicella and herpes zoster in adults aged 65 years and older.

Objective

This study assesses the global burden of varicella and herpes zoster among adults aged 65 and older from 1992 to 2021.

Methods

We used Global Burden of Disease (GBD) 2021 to identify the number and rates of incidence and disability-adjusted life years (DALYs) of varicella and herpes zoster in adults aged 65 and older.

Results

From 1992 to 2021, The age-standardized incidence rate (ASIR) of varicella and herpes zoster increased among adults aged 65 years and older, while the age-standardized death rate (ASDR) decreased. There were differences in the burden of varicella-zoster among adults aged 65 years and older by among sexes, ages, and regions. The health inequalities analysis showed an improvement among countries.

Conclusion

From 1992 to 2021, the global burden of varicella zoster among adults aged 65 and older has changed significantly. The ASIR of varicella and herpes zoster increased, but ASDR decreased. Despite the notable advancement in health equity across countries, the burden persists disproportionately among populations in low-SDI regions.

Highlights

What is already known about this topic?

Herpes zoster is a common dermatological disease in adults aged 65 years and older. Few studies have assessed the global burden of varicella and herpes zoster in adults aged 65 years and older.

What does this study add?

This study shows that the global incidence of varicella and herpes zoster increased, and DALYs decreased in adults aged 65 years and older from 1992 to 2021. The burden persists disproportionately among populations in low SDI regions.

Introduction

Varicella and herpes zoster are two diseases caused by infection with the varicella and herpes zoster virus [1]. Varicella is a highly contagious disease that occurs mainly in early childhood. Its clinical manifestations are a generalized vesicular rash accompanied by fever and general malaise [2, 3]. After the initial varicella-zoster virus infection, the virus lurks in the surrounding nerve cells. If the body’s immunity weakens, the virus can reactivate and cause herpes zoster [4, 5]. Herpes zoster presents as a unilateral vesicular itchy rash with pain. Herpes zoster can be misdiagnosed as other diseases before the appearance of the vesicular rash. The adults aged 65 years and older are at high risk of developing herpes zoster, and post-herpetic neuralgia has a profound impact on the quality of life of the adults aged 65 years and older [6, 7].

With the increasing aging of the global population, the associated diseases of the elderly have also come to the fore. More data on global varicella-zoster disease must be available in adults aged 65 years and older [8, 9]. At the same time, after the COVID-19 global pandemic, we need to analyze varicella and herpes zoster infections in the elderly as a reference for developing global prevention and control strategies.

Methods

Data sources

Our data was from the 2021 GBD, available at http://ghdx.healthdata.org/gbd-results-tool. The GBD database was a global disease database developed and maintained by the Institute for Health Metrics and Evaluation (IHME). The IHME was a global disease database developed and maintained by the University of Washington. The database assesses diseases, injuries, and risk factors in the global socio-demographic index (SDI) regions and 204 countries. SDI is a way of measuring the link between social development and health outcomes. We selected the number, percentage, and rate of varicella-zoster incidence and disability-adjusted life years (DALYs) in adults aged 65 and older from 1992 to 2021. The database was divided into five levels according to SDI: high SDI, high-middle SDI, middle SDI, low-middle SDI, and low SDI. The supplementary figures and tables were in data.mendeley.com/datasets/shchv9hcgy/1.

We used ASR and EAPC to compare the varicella and herpes zoster burden in each region. This was how we did it [10]:

Age standardised rate =

a_i was the age proportion of the i-th age group; wi was the number of people in the corresponding i-th age subgroup in a specific reference population; A was the upper age limit.

EAPC was an indicator that describes the trend of ASR changes and is calculated as follows (10):

y = α + βx + ε.

EAPC = 100×[exp(β)-1]

y is the logarithm of ASR, and x corresponds to the year. A linear regression model was used to estimate EAPC and the 95% confidence interval (CI). The results are as follows: (1) EAPC and 95% CI > 0, indicating an upward trend in ASR; (2) EAPC and 95% CI < 0, indicating a downward trend in ASR; (3) otherwise, ASR is relatively stable.

Cross-country inequality analysis

In order to assess distributional differences among countries, we selected the Slope Index of Inequality (SII) and the Concentration Index [11]. The algorithm employed for the SII regresses the rate of DALYs on the SDI, utilizing the midpoints of the cumulative population distributions, which the SDI has sorted. To control for bias and heterogeneity, we employed a robust regression model (rlm) instead of a standard linear regression model (lm) to reduce sensitivity to outliers.

Statistical analysis

This statistical analysis and mapping were performed using R 4.4.1 software, and the world map data comes from the Resource and Environmental Science Data Platform(https://www.resdc.cn/). Missing values were imputed using multiple imputation methods. For outlier handling, we employed a dual approach combining domain expertise with statistical analytical methods, including identification and processing of outliers through boxplot analysis.

Results

Global change in ASR and number of varicella and herpes Zoster in adults aged 65 and older

From 1992 to 2021, the global incidence of varicella and herpes zoster in adults aged 65 and older increased from 2.83 million to 6.52 million, and the number of DALYs increased from 90,000 to 140,000 (supplementary Table 1). ASIR increased from 841.78 to 855.91 (95% CI: 0.09, 0.05 to 0.14), while ASDR decreased from 30.80 to 19.55 (95% CI: -1.68, -1.74 to -1.61) (Table 1).

Table 1. ASR of global incidence and dalys for varicella and herpes Zoster for 1992 and 2021, and the 1992–2021 EAPC. (ASR, age-standardized rates; dalys, disability-adjusted life years; UI, uncertainty intervals; CI, confidential interval; SDI, socio-demographic index)

	Incidence			DALYs
	ASR No.×10 − 5 (95%UI)		EAPC(95%CI)	ASR No.×10 − 5 (95%UI)		EAPC(95%CI)
	1992	2021	1992–2021	1992	2021	1992–2021
Global	841.78(584.94-1173.37)	855.91(585.28-1206.09)	0.09(0.05–0.14)	30.80(25.26–37.28)	19.55(14.93–25.43)	-1.68(-1.74–1.61)
Sex
Female	881.46(613.75-1226.93)	899.37(615.09-1265.40)	0.12(0.07–0.16)	29.12(23.09–36.10)	19.53(14.46–25.88)	-1.47(-1.53–1.40)
Male	786.33(541.96-1098.99)	802.20(544.53-1130.18)	0.09(0.05–0.13)	33.68(27.42–41.41)	19.72(15.19–25.42)	-1.98(-2.05–1.91)
SDI
High SDI	912.16(652.84-1247.73)	913.80(626.22-1284.27)	0.22(0.12–0.33)	16.56(12.03–22.46)	15.14(10.37–21.07)	-2.09(-2.23–1.96)
High-middle SDI	741.20(505.60-1044.38)	767.45(520.11-1079.32)	0.21(0.12–0.30)	16.10(11.32–22.32)	10.36(6.45–15.76)	-1.83(-1.98–1.68)
Middle SDI	896.75(610.44-1265.94)	800.31(543.47-1126.59)	-0.08(-0.18-0.02)	40.22(31.55–50.39)	17.54(12.80-23.88)	-1.80(-1.89–1.71)
Low-middle SDI	798.16(542.33-1123.05)	800.82(546.49-1128.05)	0.00(0.00-0.01)	63.9s6(48.83–83.11)	38.74(29.42–50.31)	-2.34(-2.67–2.01)
Low SDI	763.82(517.63-1075.06)	894.95(608.89-1263.46)	0.02(0.02–0.02)	112.39(87.75–139.40)	69.33(54.01–87.90)	-3.47(-3.57–3.38)
Region
High-income Asia Pacific	933.24(644.09-1302.05)	1005.46(684.65-1410.72)	0.48(0.39–0.57)	13.23(8.37–19.46)	11.68(6.77–18.06)	-0.13(-0.35-0.10)
Central Asia	458.08(310.78-640.77)	456.14(309.66-639.41)	-0.02(-0.02–0.01)	12.84(6.90-21.56)	7.29(4.29–11.36)	-2.20(-2.37–2.03)
East Asia	963.23(654.65-1365.08)	961.18(649.70-1366.74)	-0.17(-0.39-0.05)	39.34(28.99–51.52)	13.26(8.44–19.95)	-4.08(-4.34–3.83)
South Asia	775.62(523.78-1096.42)	779.22(526.87-1101.66)	0.02(0.02–0.02)	64.43(47.31–86.06)	39.66(29.95–51.64)	-1.79(-1.91–1.67)
Southeast Asia	1039.92(700.05-1467.77)	1040.92(700.83-1470.58)	0.00(0.00–0.00)	52.38(37.13–71.82)	29.49(21.41–39.47)	-2.09(-2.23–1.96)
Australasia	456.84(367.19-570.81)	571.96(390.41-812.28)	0.64(0.23–1.06)	12.86(9.30-17.34)	18.36(12.79–25.34)	0.77(0.32–1.21)
Caribbean	747.15(504.18-1051.10)	748.95(505.52-1053.22)	0.01(0.01–0.01)	31.63(18.47–51.58)	20.09(12.27–31.14)	-1.52(-1.67–1.36)
Central Europe	432.22(291.42-613.36)	435.28(293.88-617.73)	0.44(0.18–0.69)	8.23(5.51–11.92)	5.34(3.17–8.37)	-1.27(-1.47–1.08)
Eastern Europe	483.95(321.99-688.72)	481.71(321.30-685.28)	-0.02(-0.02–0.01)	4.92(2.63–8.11)	5.15(2.83–8.41)	0.15(0.13–0.17)
Western Europe	917.16(663.04-1246.28)	941.97(645.48-1322.14)	0.04(-0.01-0.10)	17.81(12.92–23.72)	16.90(11.77–23.62)	-0.32(-0.44–0.19)
Andean Latin America	746.28(503.48-1049.68)	747.22(504.11-1050.98)	0.00(0.00–0.00)	52.36(22.89–97.04)	19.16(10.84–31.40)	-3.47(-3.64–3.30)
Central Latin America	764.58(517.96-1076.56)	766.41(519.20-1078.75)	0.01(0.01–0.01)	25.52(19.78–33.45)	14.10(10.23–19.54)	-2.52(-2.70–2.35)
Southern Latin America	821.57(556.35-1159.58)	840.78(569.28-1190.26)	0.11(0.09–0.14)	9.89(5.96–15.95)	9.72(5.63–15.64)	0.01(-0.03-0.05)
Tropical Latin America	784.42(528.60-1111.17)	786.10(529.84-1113.90)	0.01(0.01–0.01)	12.04(7.96–17.91)	13.31(9.34–18.73)	0.56(0.32–0.80)
North Africa and Middle East	749.79(507.18-1053.78)	751.96(508.67-1056.79)	0.01(0.01–0.01)	48.70(33.45–68.77)	18.92(13.35–26.16)	-3.47(-3.57–3.38)
High-income North America	989.04(688.03-1371.11)	904.24(607.28-1280.56)	0.31(0.02–0.61)	15.01(10.37–21.53)	15.28(10.58–21.17)	0.31(0.18–0.43)
Oceania	1009.20(674.03-1418.58)	1008.38(673.64-1417.22)	-0.01(-0.01-0.00)	75.42(39.62–132.50)	57.08(27.65-107.77)	-0.96(-1.02–0.90)
Central Sub-Saharan Africa	747.27(504.23-1051.20)	752.50(506.99-1059.55)	0.02(0.02–0.03)	134.15(60.66-255.37)	79.94(34.52-157.47)	-1.83(-1.98–1.68)
Eastern Sub-Saharan Africa	758.04(513.81-1066.19)	763.70(517.57-1073.59)	0.03(0.02–0.03)	126.32(90.29-171.23)	70.20(51.43–91.74)	-2.04(-2.11–1.98)
Southern Sub-Saharan Africa	781.85(530.02-1102.82)	785.54(532.57-1109.39)	0.02(0.01–0.02)	52.82(36.04–74.24)	32.38(22.35–44.96)	-2.34(-2.67–2.01)
Western Sub-Saharan Africa	765.90(518.25-1078.18)	763.51(517.15-1073.96)	-0.01(-0.02–0.01)	106.78(84.09-132.05)	64.75(50.70-81.78)	-1.80(-1.89–1.71)

Global trends in varicella and herpes Zoster in adults aged 65 and older by gender and age

From 1992 to 2021, the number of incidence of varicella and herpes zoster, and ASIR in males and females in adults aged 65 and older increased. The number of males increased from 1.13 million to 2.74 million, while the number of females increased from 1.7 million to 3.78 million. The ASIR of females was higher than males (male: 786.33 to 802.20; female: 881.46 to 899.37), and the ASIR of females increased more (EAPC male 0.09 vs. female 0.12). The number of DALYs increased in both males and females, from 40,000 to 60,000 in males and from 50,000 to 80,000 in females. There was a notable decline in ASIR across both sexes, with a more pronounced reduction observed in males (33.68 to 19.72) compared to females (29.12 to 19.53). The decline in ASIR was more rapid in males (EAPC male − 1.98 vs. female − 1.47)(Table 1, Supplementary Table 1, Supplementary Fig. 1, Supplementary Fig. 2).

Supplementary Fig. 1 and Supplementary Fig. 2 show the number and ASR of incidence and DALYs of varicella and herpes zoster in different age groups in 1992 and 2021. The 65-69-year-old group had the highest number of incidence and DALYs in 1992 and 2021. As age increases, the ASIR and ASDR of varicella and herpes zoster also increase. Furthermore, the 95 + age group has the highest ASID and ASDR of varicella and herpes zoster.

Global trends of varicella and herpes Zoster in adults aged 65 and older in SDI regions

From 1992 to 2021, there was a notable decline in the global ASIR of middle SDI varicella and herpes zoster among adults aged 65 and older. Conversely, there was an increase observed in other SDI regions, particularly in the high SDI (EAPC: 0.22, 0.12–0.33) (Table 1, Supplementary Fig. 3, Supplementary Fig. 4). In 2021, the ASIR of the highest SDI was recorded at 912.16 (95% UI 626.22-1284.27). Concurrently, the ASDR declined across various SDI regions, with the lowest SDI experiencing the most pronounced reduction (EAPC: -3.08, -3.18 to -2.98). In 2021, the highest level of ASDR was observed in high middle SDI (69.33, 95% UI: 54.01–87.90).

Global trends of varicella and herpes Zoster in adults aged 65 and older in different regions

Table 1, Supplementary Tables 1, and Fig. 1 showed the burden of varicella and herpes zoster in 21 regions. In 2021, Southeast Asia had the highest ASIR of varicella and herpes zoster (1040.92:700.83-1470.58), Central Sub-Saharan Africa had the highest ASDR of varicella and herpes zoster (79.94: 34.52-157.47). Different regions showed the changes of varicella and herpes zoster different burdens. In Australasia, ASIR (EAPC: 0.64, 0.23–1.06) and ASDR(EAPC: 0.77, 0.32–1.21) exhibited the most significant increases, while the ASIR(EAPC: -0.17, -0.39-0.05) and ASDR(EAPC: -4.08, -4.34-3.83) had most significant decreases in East Asia.

[See PDF for image]

Fig. 1

The ASIR and ASDR of varicella and herpes zoster in adults aged 65 and older across by SDI 2021. (A) The ASDR. (B) The ASIR

Global trends of varicella and herpes Zoster in ASR and EAPC in adults aged 65 and older in 204 countries

From 1992 to 2021, at both national and regional levels, Slovenia exhibited the highest increase in ASIR(EAPC: 1.30, 0.87–1.73) for varicella and herpes zoster among adults aged 65 and older (Supplementary Table 1, Supplementary Table 2, Fig. 2). The most significant decline was observed in Taiwan, China (EAPC: -0.22, -0.37-0.08), while the most significant increase was seen in Equatorial Guinea (EAPC: 5.56, 5.88 to 5.24). Concerning the EAPC of ASDR, all countries exhibited a declining trend for adults aged 65 and older. The most significant reduction was observed in Equatorial Guinea (EAPC: -5.56, -5.88- -5.24), while Norway reported the most significant increase (EAPC: 3.32, 3.06–3.58).

[See PDF for image]

Fig. 2

The EAPC of varicella and herpes zoster in adults aged 65 and older in 204 countries 1992–2021. (A) The EAPC in ASIR. (B) The EAPC in ASDR

Supplementary Fig. 5 showed global health inequities in varicella and herpes zoster across countries, focusing on ASIR and ASDR. The Slope Index of Inequality(SII) had a modest increase in ASIR from 60 to 71 per 100,000 between 1992 and 2021, particularly in regions with a higher Socio-Demographic Index (SDI). The SII had a reduction in ASDR from 131 to 58 per 100,000, indicative of enhanced health outcomes over time. The Concentration Index for incidence slightly increased from 0.01 (95% CI: -0.01, 0.02) in 1992 to 0.02 (95% CI: 0.01, 0.03) in 2021, indicating a marginal rise in inequity. Concerning DALYs, the Concentration Index improved, shifting from − 0.38 (95% CI: -0.42, -0.33) in 1992 to -0.28 (95% CI: -0.32, -0.23) in 2021. This suggests a reduction in inequity, although it is notable that the burden remains higher in low SDI populations. These findings highlight the necessity for targeted interventions to address persistent disparities.

Discussion

This study aimed to analyze the global incidence and DALYs of varicella and herpes zoster in adults aged 65 and older from 1992 to 2021. From 1992 to 2021, the global incidence number of varicella and herpes zoster in adults aged 65 and older increased from 2.83 million to 6.52 million. The ASIR exhibits an upward trend, whereas the ASDR demonstrated a downward trend. This indicates that the incidence of varicella and herpes zoster in adults aged 65 and older is still increasing. Additionally, the clinical presentation of varicella and herpes zoster varies, with pain being the primary symptom of diagnosis. In some cases, the late appearance of a blister-like rash or the absence of a blister-like rash can lead to misdiagnosis by medical personnel, resulting in unnecessary examinations and treatments and an increased burden on patients.Meanwhile, this may also lead to underreporting of varicella and herpes zoster (VHZ) incidence data, resulting in underestimated VHZ incidence rates. This issue is particularly pronounced in low-SDI regions, where limited healthcare infrastructure and lower-quality health services contribute to missing epidemiological data or lower reporting rates for VHZ. Notably, some countries’ data are estimated based on neighboring countries’ surveillance results [12, 13].In light of the findings presented in this report, global attention must be directed toward the health issues confronting varicella and herpes zoster patients in adults aged 65 and older. Health resources must be allocated appropriately and targeted strategies formulated, such as strengthening education, promoting health campaigns, and improving varicella zoster vaccination [14, 15–16].

From 1992 to 2021, the global incidence of varicella and herpes zoster increased in adults aged 65 and older of different genders; the incidence was higher in females than in males, and the ASDR decreased significantly, with a faster decline in males. These findings indicate that females are more likely to suffer from varicella and herpes zoster and that the disability loss caused by varicella and herpes zoster is also decreasing. The 65-69-year-old group has the highest incidence, and DALYs, the 95 + age group, had the highest ASID and ASDR of varicella and herpes zoster.

A study analyzing the burden of herpes zoster among the Chinese population aged ≥ 50 years from 2010 to 2012 reports that the cumulative incidence and annual average incidence rates are higher in females than in males, with the highest cumulative incidence observed in individuals aged ≥ 80 years [17]. Similarly, an analysis of herpes zoster and postherpetic neuralgia in the United States from 1994 to 2018 demonstrates that females constituted 59.8% of cases [18]aligning with our findings. However, a study in South Korea using a nationwide population-based database on chronic herpes zoster found that the incidence generally increased with age, typically at 60–64 or 65–69 years, with similar rates in males and females. This discrepancy may reflect geographic differences [19].

In the analysis across different Socio-Demographic Index (SDI) regions, we observe a decrease in ASIR of varicella and herpes zoster among adults aged 65 and older in low-SDI regions. At the same time, the ASIR increased in all other SDI regions. However, the ASIR remained highest in the low SDI region in 2021. The ASDR decreases in all SDI regions, with the middle SDI regions having the highest ASDR in 2021. These findings highlight regional disparities in the burden of varicella and herpes zoster; however, the overall burden of disability associated with varicella and herpes zoster has decreased. The 2019 Global Burden of Disease (GBD) study reports the highest ASIR in high-SDI regions and the lowest EAPC for ASDR, which differs from our findings and may be due to differences in sampling statistics [20, 21]. Differences in ASIR and ASDR are evident at both regional and national levels. Although there has been some improvement in health inequalities between countries, disparities remain, particularly for populations in regions with low SDIs. Differences may influence these inequalities in economic development and investment in health systems among countries [22, 23].

Limitations

The data in this study were sourced from GBD 2021. Model-based estimates from the database may introduce potential biases. Variations exist in case definitions for herpes zoster infection across different regions, and underreporting of herpes zoster data may occur particularly in low-SDI regions. Diagnostic confirmation often relies on clinical diagnosis without virological confirmation in these areas. Additionally, herpes zoster vaccination does not cover entire populations, and longitudinal data for assessing causal relationships are lacking. In future research, it is essential to integrate epidemiological data from multiple countries and regions and to conduct ongoing longitudinal surveillance. Such efforts will provide more robust evidence to inform health system policy development.

Conclusions

from 1992 to 2021, the global burden of varicella and herpes zoster in adults aged 65 years and older has changed dynamically. Differences exist between sexes, age groups, SDI regions, regions, and countries. Health inequalities between countries have improved. Targeted public health interventions are also needed to address differences in health outcomes among different socio-demographic groups.At the same time, targeting low-SDI regions, integrating VHZ screening into elderly care.

Acknowledgements

We want to thank all Global Burden of Disease Study 2021 participants.

Author contributions

Research design: Jiang Li, Zhaofeng Jin, Jun Niu; Data analysis: Jiang Li, Zhaofeng Jin, Wei Yang; Draft Writing and Revision: Jiang Li, Wei Yang, Jun Niu.

Funding

Liaoning Province Technological Innovation Planned Project (Grant number 2022JH2/101500012).

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics statement

These data are obtained from publicly available databases and do not require additional ethical approvals. Ethical approvals and informed consent of participants were obtained in all original studies.

Patient consent

Not applicable.

Competing interests

The authors declare no competing interests.

Conflicts of interest

None declared.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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