Abstract
Introduction
This study aims to deliver contemporary, population-based estimates of herpes zoster (HZ) incidence, temporal trends, complications, healthcare utilisation and direct costs among general adults and adults with increased-risk conditions.
Methods
A retrospective cohort study using the Yinzhou Integrated Health Platform (2015–2021; China) was performed. Incident HZ was ascertained after a 1-year washout; increased-risk conditions were pre-specified (immunocompromising/autoimmune). We calculated age-/sex-standardised incidence, assessed trends with joinpoint regression and summarised HZ-related outpatient visits, hospitalisations and direct medical costs [Chinese yuan (¥) and US dollars ($)].
Results
Among 5.42 million person-years, including 790,410 subjects, 25,855 incident HZ events were identified. Overall incidence was 4.77/1000 person-years (PY) [95% confidence interval (CI) 4.71–4.83] and 16.13/1000 PY (95% CI 15.25–17.06) in increased-risk adults [incidence rate ratio (IRR) 3.44 versus in adults without immunocompromising conditions or autoimmune diseases (AIDs)]. Incidence rose with age (peak 70–79 years overall; 60–69 years increased-risk) and was higher in women. Postherpetic neuralgia (PHN) was the most frequent complication (8.96% overall; 10.88% increased-risk). Standardised incidence increased from 4.67 to 7.51/1000 PY during 2015–2021 [annual percentage change (APC) 7.94%], with a steep rise to 2019 and plateau thereafter. Hospitalisation among incident HZ was 1.35%. Mean direct cost per episode was Chinese yuan (¥)625.52 [US dollars ($)94.35] for outpatients and ¥8854.03 ($1335.45) for inpatients; increased-risk outpatients incurred higher mean costs (¥1205.47, $181.82). Across strata, complications – especially PHN – were associated with more visits and higher expenditure.
Conclusions
HZ imposes a rising, age- and risk-concentrated burden in Chinese adults, with PHN being the principal driver of resource use and costs. These real-world estimates support prioritising zoster vaccination for adults ≥ 50 years and clinically vulnerable groups, and integrating HZ surveillance and management within chronic-disease programmes.
Supplementary Information
The online version contains supplementary material available at 10.1007/s40121-026-01308-5.
Keywords: Herpes zoster, Increased-risk conditions, Disease burden, Temporal trends
Key Summary Points
| Why carry out this study? |
| Herpes zoster (HZ) incidence is common in adults and can lead to substantial clinical and economic burden, particularly through complications such as postherpetic neuralgia (PHN); incidence appears to be increasing in many settings. |
| Evidence comparing incidence and burden between the general adult population and clinically increased-risk groups (including younger adults) is needed to inform vaccination prioritisation when resources are constrained. |
| We quantified HZ incidence and temporal trends (2015–2021) and assessed complications, healthcare resource utilisation and direct medical costs in the general adult population and among adults with increased-risk conditions. |
| What was learned from the study? |
| HZ incidence increased with age, was higher among adults with increased-risk conditions and showed an overall upward trend from 2015 to 2021. |
| Adults with increased-risk conditions and HZ-related complications had higher healthcare utilisation and greater direct medical costs, with PHN contributing disproportionately to burden. |
| These findings support risk-stratified prevention strategies and can help prioritise zoster vaccination towards groups most likely to benefit under budget constraints. |
Introduction
Herpes zoster (HZ) arises from reactivation of latent varicella zoster virus (VZV) in cranial or dorsal root ganglia [1, 2]. Risk increases with declining cell-mediated immunity due to ageing, immunocompromised status, autoimmune disease (AID) or immunosuppressive therapy; consequently, older adults and immunocompromised (IC) persons bear the highest burden [3–7]. The lifetime risk is roughly one in three [8]. Postherpetic neuralgia (PHN) – classically pain persisting ≥ 90 days after rash onset – is the most frequent complication and a major driver of long-term morbidity and costs [9, 10].
Globally, HZ incidence rises steeply with age and has increased over calendar time, with reported rates around 3–5 per 1000 person-years in North America/Europe and 3–10 per 1000 person-years in the Asia-Pacific region [3, 6, 11–16]. The economic burden is substantial, encompassing direct medical costs and productivity losses [17, 18].
In China, emerging data indicate a rising burden. Surveillance from Shandong Province, China, showed increasing incidence in the general population (2013–2017), while regional studies in eastern China reported higher incidence and costs among adults ≥ 50 years and markedly elevated risk among IC cohorts [6, 19]. Together, these findings underscore two challenges: increasing incidence and concentrated resource use in high-risk groups. Yet, in China, most real-world studies have focused on older or IC populations, offering limited inference for younger adults and few head-to-head comparisons between the general adult population and increased-risk subgroups that integrate incidence, complications (particularly PHN), healthcare utilisation, and costs – evidence needed to inform vaccination priorities under budget constraints [4, 6, 7].
To address these gaps, we conducted a population-based cohort study using the Yinzhou Health Database, which links outpatient, inpatient and mortality records. We quantified HZ incidence and temporal trends (2015–2021) and assessed complications (with emphasis on PHN), healthcare resource utilisation and direct medical costs in both the general adult population and adults with increased-risk conditions, to generate contemporary, policy-relevant estimates.
Methods
Study Design and Data Source
We conducted a population-based retrospective cohort study in eastern China using the Yinzhou Health Information Platform [Data Analysis Service (DaaS)], which included 98% of all permanent residents with a valid identifier in 2018. This integrated system links electronic outpatient and inpatient records with public health registries and administrative datasets for permanent residents of Yinzhou District, Ningbo city, enabling person-level, longitudinal follow-up with capture of diagnoses, encounters, dispensations and vital status [20, 21]. Yinzhou is an economically developed district in China’s eastern coastal region and is highly urbanised (82.23% urban residents in the 2020 national census).
Ethical Approval
The study protocol was reviewed and approved by the Ethics Committee of Zhejiang Chinese Medical University (approval no. AF-20220921-1). This study utilised de-identified data from existing databases and was conducted in accordance with the principles of the Declaration of Helsinki and its subsequent amendments. As this was a database-based study, the requirement for patient consent was waived by the institutional review board.
Study Population and Cohort Definition
Eligible participants were adults aged ≥ 18 years who were permanent residents recorded in the Yinzhou database and contributed follow-up between 1 January 2015 and 31 December 2021. To exclude prevalent HZ, we applied a 1-year washout (1 January 1 to 31 December 2014) requiring no HZ diagnosis during this period. The cohort was partitioned into:
Non-IC/AIDs (reference): adults without documented immunocompromising (IC) conditions or autoimmune diseases (AIDs) per diagnostic coding (Supplementary Material Table S1).
Increased-risk group: adults with ≥ 1 qualifying IC/AID diagnosis recorded 1 January 2015 to 30 June 2021. For this group, follow-up began at the first qualifying diagnosis; individuals with HZ prior to the first qualifying diagnosis were excluded from this subgroup.
Definitions of Increased-Risk Conditions
Increased-risk conditions were ascertained using International Classification of Diseases, Tenth Revision (ICD-10) codes and Traditional Chinese Medicine Diagnosis (TCD) codes (Supplementary Material Table S1) and included: hematopoietic stem cell transplant (HSCT), haematologic malignancies (HM), human immunodeficiency virus (HIV) disease, solid tumours (ST), solid organ transplant (SOT), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis, psoriatic arthritis, multiple sclerosis (MS) and inflammatory bowel disease [IBD: Crohn’s disease (CD) and ulcerative colitis (UC)].
Case Ascertainment and Complications
Herpes zoster (HZ) was identified from outpatient or inpatient records via ICD-10 code B02 (Supplementary Material Table S2). Incident HZ was defined as the first HZ diagnosis during follow-up after meeting washout criteria. Complications were classified by B02 subcodes, including postherpetic neuralgia (PHN; B02.2× and related terms), ocular disease (B02.3×), neurologic complications (e.g. zoster meningitis/encephalitis), disseminated zoster (B02.7) and other specified complications (B02.8) (Supplementary Material Table S2).
Outcomes
Primary outcomes were HZ incidence overall, by age, sex and health-status subgroup, and temporal trends (2015–2021). Secondary outcomes included the incidence/proportions of complications (with emphasis on PHN); HZ-related healthcare resource utilisation (HCRU) – outpatient visits, hospitalizations and length of stay; and direct medical costs (Chinese yuan, ¥; US dollars, $). For costing, outpatient encounters were those with HZ diagnosis codes; inpatient costs were evaluated for admissions with HZ as the primary diagnosis. Cost components (e.g. examination and medication expenditures) were summarised separately for outpatient episodes and inpatient admissions, consistent with the tabulated outputs.
Follow-Up and Person-Time
For the non-IC/AIDs group, person-time accrued from 1 January 2015 (or cohort registration thereafter) until the first HZ, death, or 31 December 2021, whichever occurred first. For the increased-risk group, person-time accrued from the date of first qualifying IC/AID diagnosis until the same endpoints. Only the first HZ episode per participant contributed to incidence analyses.
Standardization and Temporal Trend Analysis
We calculated age-specific and sex-specific incidence rates per 1000 person-years (PY) with exact Poisson 95% confidence intervals (CIs). Direct standardization was used to obtain age-standardised, sex-specific rates; and age- and sex-standardised overall rates, following the stratification scheme used in Supplementary Material Table S8. Temporal trends in incidence were assessed using joinpoint regression, fitting a sequence of log-linear segments, identifying statistically significant joinpoints and estimating annual percentage change (APC) with 95% CIs for each interval. Trends were classified as increasing if the APC and its lower CI bound were > 0 and decreasing if the APC and its upper CI bound were < 0, and otherwise not statistically significant.
Statistical Analysis
Baseline characteristics were summarised overall and by subgroup. Incidence was computed as incident HZ cases divided by accumulated person-years. Group comparisons included incidence rate ratios (IRRs) with 95% CIs (non-IC/AIDs as reference); exact Poisson limits were used for sparse strata. All analyses were conducted using SAS version 9.4 (SAS Institute, Cary, NC, USA). All figures were generated using R (version 4.3.2).
Results
Cohort Characteristics
During 2015–2021, 790,410 adults (≥ 18 years) contributed 5,417,263 person-years (PY) of follow-up; 25,980 (3.29%, 95% CI 3.25–3.33%) met criteria for increased-risk conditions. Mean age was 39.70 ± 14.90 years. Within the increased-risk subgroup, solid tumours were most common, and HSCT was least common (Table 1; Supplementary Material Table S3).
Table 1.
Incidence rate (IR/1000 PY) of herpes zoster by population group, age and sex
| Overall adults | Group with increased risks | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| N (%) | Cases | Person-years | IR (95% CI) | N (%) | Cases | Person-years | IR (95% CI) | ||
| Age groups | |||||||||
| 18–29 | 245,614 (31.07) | 3127 | 1,709,940.64 | 1.83 (1.77, 1.89) | 1242 (4.78) | 17 | 4365.89 | 3.89 (2.27, 6.23) | |
| 30–39 | 184,005 (23.28) | 3887 | 1,275,383.01 | 3.05 (2.95, 3.15) | 2746 (10.57) | 66 | 8580.62 | 7.69 (5.95, 9.79) | |
| 40–49 | 165,497 (20.94) | 5602 | 1,139,809.41 | 4.91 (4.79, 5.05) | 3983 (15.33) | 188 | 13,017.82 | 14.44 (12.45, 16.66) | |
| 50–59 | 103,604 (13.11) | 6088 | 702,687.18 | 8.66 (8.45, 8.88) | 5913 (22.76) | 316 | 17,641.55 | 17.91 (15.99, 20.00) | |
| 60–69 | 62,136 (7.86) | 5038 | 412,984.65 | 12.20 (11.86, 12.54) | 6772 (26.07) | 416 | 19,788.09 | 21.02 (19.05, 23.14) | |
| 70–79 | 20,800 (2.63) | 1691 | 132,771.62 | 12.74 (12.14, 13.36) | 3980 (15.32) | 181 | 10,001.43 | 18.10 (15.56, 20.93) | |
| 80– | 8754 (1.11) | 422 | 43,686.67 | 9.66 (8.76, 10.63) | 1344 (5.17) | 48 | 2967.43 | 16.18 (11.93, 21.45) | |
| Sex | |||||||||
| Male | 384,388 (48.63) | 12,254 | 2,633,532.87 | 4.65 (4.57, 4.74) | 13,431 (51.70) | 577 | 38,726.48 | 14.90 (13.71, 16.17) | |
| Female | 406,022 (51.37) | 13,601 | 2,783,730.28 | 4.89 (4.80, 4.97) | 12,549 (48.30) | 655 | 37,636.34 | 17.40 (16.10, 18.79) | |
| Overall | 790,410 (100.00) | 25,855 | 5,417,263.15 | 4.77 (4.71, 4.83) | 25,980 (3.29)a | 1232 | 76,362.82 | 16.13 (15.25, 17.06) | |
95% CIs were calculated using exact Poisson limits
N (%) are within column percentages
Person time for increased risk accrues from first qualifying diagnosis
CI confidence interval, IR incidence rate
aValues are reported as a percentage of the total population (n = 790410)
Incidence Overall and by Age/Sex
We identified 25,855 incident HZ cases. The overall adult IR was 4.77/1000 PY (95% CI 4.71–4.83). In the increased-risk subgroup, the IR was 16.13/1000 PY (95% CI 15.25–17.06) compared with 4.70/1000 PY (95% CI 4.64–4.76) in non-IC/AIDs, yielding an IRR = 3.44 (95% CI 3.20–3.70). Female individuals had higher IRs than male individuals in both strata (overall adults: 4.89 versus 4.65; increased-risk subgroup: 17.40 versus 14.90 per 1000 PY). IRs rose with age, peaking at 70–79 years in the overall adult population and at 60–69 years in the increased-risk subgroup. Among incident HZ, adults ≥ 50 years accounted for > 50% overall and ~75% in the increased-risk subgroup (Table 1; Figs. 1 and 2).
Fig. 1.
Incidence and distribution of herpes zoster by age. PY person-years
Fig. 2.
Incidence (per 1000 PY) of herpes zoster by health status in increased-risk group. *Non-IC/AIDs was taken as the reference. PY person-years, IC immunocompromising conditions, HM haematologic malignancies, ST solid tumours, SOT solid organ transplant, AID autoimmune diseases, RA rheumatoid arthritis, SLE systemic lupus erythematosus, IBD inflammatory bowel disease
Incidence by Increased-Risk Condition
Condition-specific IRs (versus non-IC/AIDs) were highest for haematologic malignancies (HM): 33.32/1000 PY (95% CI 26.90–40.82); IRR = 7.09 (95% CI 5.79–8.70). Elevated IRs were also observed for HSCT (29.97/1000 PY; 95% CI 0.75−166.00, very wide CI, IRR = 6.34, 95% CI 0.89–45.04) and MS (28.26/1000 PY; IRR = 6.02, 95% CI 1.50–24.06). ST, SOT and RA showed moderate increases (IRR ≈ 3–5). Estimates for rare strata (e.g. HSCT, MS) had wide CIs (Fig. 2; Supplementary Material Table S4).
Among all HZ cases, 2975 developed complications; among increased-risk HZ cases, 169 (13.72%) had complications. PHN was the most frequent complication: 8.96% of general-adult HZ (IR 0.43/1000 PY, 95% CI 0.41–0.45) and 10.88% of increased-risk HZ (IR 1.75/1000 PY, 95% CI 1.47–2.08). PHN incidence increased with age and was slightly higher in female individuals; HM, ST, RA and IBD were associated with higher PHN incidence than non-IC/AIDs (Table 2; Supplementary Material Tables S5 and S6).
Table 2.
Incidence rate (IR/1000 person-years) and proportions of herpes zoster cases with complications
| General adults | Group with increased- risks | |||
|---|---|---|---|---|
| N (%)a | IR (95% CI) | N (%)b | IR (95% CI) | |
| Complications | 2975 (11.51) | 0.55 (0.53, 0.57) | 169 (13.72) | 2.21 (1.89, 2.57) |
| PHNc | 2317 (8.96) | 0.43 (0.41, 0.45) | 134 (10.88) | 1.75 (1.47, 2.08) |
| Herpes zoster ophthalmicus | 403 (1.56) | 0.07 (0.07, 0.08) | 18 (1.46) | 0.24 (0.14, 0.37) |
| Zoster encephalitis | 153 (0.59) | 0.03 (0.02, 0.03) | 10 (0.81) | 0.13 (0.06, 0.24) |
| Disseminated zoster | 16 (0.06) | 0.00 (0.00, 0.00)d | 1 (0.08) | 0.01 (0.00, 0.07) |
| HZ with other complications | 187 (0.72) | 0.03 (0.03, 0.04) | 13 (1.06) | 0.17 (0.09, 0.29) |
aPercentages were based on the total number of herpes zoster cases (N = 25,855)
bPercentages were based on the total number of herpes zoster cases in increased-risk adults (N = 1232)
cPHN was defined by ICD-10 B02.2 × without a 90-day threshold. Identification was based on B02.2 × codes; duration criterion was not enforced
d0.30 (0.17, 0.48)/100,000 PY
95% CIs were calculated using exact Poisson limits
Multiple complications per individual were allowed
CI confidence interval, PHN postherpetic neuralgia, HZ herpes zoster
Temporal Trends (Joinpoint Analysis)
Crude adult HZ incidence increased from 3.27 to 5.74/1000 PY between 2015 and 2021. Age- and sex-standardised incidence rose from 4.67 to 7.51/1000 PY, with an overall APC = 7.94% (95% CI 6.78–9.12%). APCs were 8.06% (5.86–10.31%) in male individuals and 7.82% (6.49–9.16%) in female individuals. Most of the increase occurred during 2015–2019 (overall APC 12.47%, 95% CI 10.41–14.58), followed by stability in 2019–2021 (APC ≈ 0) (Fig. 3; Supplementary Material Tables S7 and S8).
Fig. 3.
Joinpoint regression of age‑ and sex‑standardised HZ incidence, 2015–2021. *APC and 95% CI from log‑linear segments. Directly standardised using the China 2020 population; overall rate standardised by age and sex; sex-specific rates by age only
Healthcare Resource Utilization (HCRU) and Costs
Of 25,855 incident cases, 25,760 (99.63%) had ≥ 1 outpatient visit, and 348 had HZ-related hospitalization (hospitalization rate 1.35%, 95% CI 1.21–1.49). Cost data were available for 25,589 outpatients and 171 inpatients (HZ as primary diagnosis). Total direct costs were ¥17.29 ($2.61) million (outpatient) and ¥1.63 ($0.25) million (inpatient). Mean (median) cost/episode was ¥625.52 (¥332.24)/$94.35 ($50.11) for outpatients and ¥8854.03 (¥5796.16)/$1335.45 ($874.23) for inpatients. Among increased-risk outpatients, mean (median) costs were higher [¥1205.47 (¥417.71)]/[$181.82 ($63.00)] than in general adults. Outpatient costs increased with age (from ¥372.54 to ¥837.53). Complications – especially PHN – were associated with more visits (mean 4.58 for PHN versus 2.79 without complications) and higher outpatient costs [mean ¥1456.79 (219.73) for PHN versus ¥566.67 ($85.47) without complications] (Table 3; Supplementary Material Tables S9 and S10).
Table 3.
Summary statistics of direct economic expenditures (¥) for outpatients and inpatients with herpes zoster
| Episodes in overall adults | P-value | Episodes in increased-risk groups | P-value | |||
|---|---|---|---|---|---|---|
| Outpatienta | Inpatientb | Outpatientc | Inpatientd | |||
| Cost per episode | < 0.001 | 0.058 | ||||
| Mean | 625.52 | 8854.03 | 1205.47 | 7928.21 | ||
| SD | 1397.37 | 10,516.89 | 4329.07 | 8229.51 | ||
| Median | 332.24 | 5796.16 | 417.71 | 5455.33 | ||
| Minimum | 0.00 | 0.02 | 1.35 | 216.77 | ||
| Maximum | 100,907.69 | 66,862.07 | 100,907.69 | 27,135.53 | ||
| Examination cost per episode | < 0.001 | 0.004 | ||||
| Mean | 141.45 | 5500.96 | 265.39 | 4663.81 | ||
| SD | 468.04 | 7881.65 | 917.28 | 5493.85 | ||
| Median | 47.00 | 3201.59 | 62.00 | 3117.57 | ||
| Minimum | 0.00 | 0.02 | 0.00 | 108.00 | ||
| Maximum | 25,544.04 | 57,915.23 | 15,896.56 | 21,012.65 | ||
| Medication cost per episode | < 0.001 | < 0.001 | ||||
| Mean | 460.40 | 3353.07 | 889.52 | 3264.40 | ||
| SD | 1144.54 | 4067.34 | 3818.09 | 3696.89 | ||
| Median | 239.18 | 2347.94 | 282.96 | 1866.68 | ||
| Minimum | 0.00 | 0.00 | 0.00 | 0.00 | ||
| Maximum | 98,553.78 | 36,583.78 | 98,553.78 | 14,887.39 | ||
| Other cost per episode | ||||||
| Mean | 23.68 | – | 29.44 | – | ||
| SD | 30.32 | – | 39.20 | – | ||
| Median | 16.53 | – | 17.00 | – | ||
| Minimum | 0.00 | – | 0.00 | – | ||
| Maximum | 472.68 | – | 314.27 | – | ||
| Frequency of visits per episode | < 0.001 | – | < 0.001 | |||
| Mean | 2.99 | 1.05 | 3.50 | 1.11 | ||
| SD | 3.36 | 0.25 | 3.84 | 0.42 | ||
| Median | 2.00 | 1.00 | 2.00 | 1.00 | ||
| Minimum | 1.00 | 1.00 | 1.00 | 1.00 | ||
| Maximum | 116.00 | 3.00 | 42.00 | 3.00 | ||
| Duration of hospital stay | ||||||
| Mean | – | 12.80 | – | 14.84 | ||
| SD | – | 11.18 | – | 9.38 | ||
| Median | – | 10.00 | – | 14.00 | ||
| Minimum | – | 1.00 | – | 3.00 | ||
| Maximum | – | 99.00 | – | 53.00 | ||
Costs are presented in Chinese Yuan (¥) and were converted to US dollars ($) using annual average exchange rates corresponding to each study year (2015–2021). Mean (median) values converted to US dollars are provided for reference:
aOverall adults, outpatient episodes: $94.35 ($50.11)
bOverall adults, inpatient episodes: $1335.35 ($874.23)
cEpisodes in increased-risk groups, outpatient episodes, $181.82 ($63.00)
dEpisodes in increased-risk groups, inpatient episodes: $1195.81 ($822.83)
SD standard deviation
Discussion
In this 7-year, population-based cohort using the integrated health system, we estimated age- and sex-standardised herpes zoster incidence and temporal trends with joinpoint regression, and compared complications, healthcare utilisation and direct medical costs between the general adult population and pre-specified increased-risk groups. We observed a rising, age-concentrated burden with consistently higher rates in increased-risk adults and post-herpetic neuralgia as the principal driver of care and costs; these real-world estimates support prioritising adult HZ vaccination in China – especially for older adults and those with increased-risk conditions – and integrating prevention within chronic-disease programmes.
Overall adult incidence was 4.77 per 1000 person-years, within published ranges from North America/Europe and the Asia-Pacific region [14, 15], whereas adults with increased-risk conditions experienced a markedly higher rate (16.13 per 1000 person-years; IRR 3.44 versus non-IC/AIDs). Condition-specific patterns showed the greatest excess in haematological malignancy, with high rates also seen after HSCT, and in HIV and solid organ transplant recipients, and more moderate – yet still elevated – rates in solid tumours and autoimmune diseases (e.g. rheumatoid arthritis, SLE or ulcerative colitis); estimates for rare strata carried wide confidence intervals, reflecting small numbers and heterogeneous case mix. These findings accord with international evidence and prior regional data, reinforcing the concentration of HZ risk in states of impaired cell-mediated immunity [7, 22–24].
HZ incidence rose steeply with age, peaking at 70–79 years in the overall cohort and 60–69 years among increased-risk adults; the apparent decline at ≥ 80 years likely reflects competing risks and lower care-seeking rather than reduced biological risk [25, 26]. Women consistently had higher rates than men across strata [7, 9, 27], a pattern seen elsewhere and plausibly related to immunobiological differences and diagnostic/health-seeking behaviours [28, 29]. Complications were frequent (≈ 11–14%), with PHN predominating; in our cohort, PHN occurred in 8.96% of general-adult HZ and 10.88% of increased-risk HZ, increased with age and was slightly more common in women.
From 2015 to 2021, age- and sex-standardised HZ incidence rose overall (APC 7.94%, 95% CI 6.78–9.12), driven by a marked increase in 2015–2019 (APC ≈ 12.5%) and stabilisation in 2019–2021 (APC ≈ 0), with similar patterns in men and women. These joinpoint results accord with global upward trends [12, 13, 16, 30], but the post-2019 plateau should be interpreted cautiously – potentially influenced by pandemic-related healthcare-seeking changes and early vaccine uptake – and warrants continued surveillance as services normalise.
Hospitalisation was uncommon but costly: Almost all incident HZ cases used outpatient care, while 1.35% (95% CI 1.21–1.49) were hospitalised. Mean (median) direct costs per inpatient admission were ¥8854 (¥5796) versus ¥626 (¥332) per outpatient episode; outpatient spending was medication-driven, whereas inpatient costs were dominated by diagnostic examinations. Adults with increased-risk conditions incurred higher outpatient costs than general adults (mean ¥1205; median ¥418), and outpatient expenditure rose with age (from ≈ ¥373 in 18–29-year-olds to ≈ ¥838 in 70–79-year-olds). Complications – particularly PHN – amplified utilisation and costs (e.g. 4.58 versus 2.79 outpatient visits; ¥1457 versus ¥567). This pattern accords with international evidence of greater healthcare utilisation in immunocompromised cohorts[7]; our hospitalisation rate lies above that for immunocompetent adults and below that for immunocompromised adults aged 18–49 years reported in England [18]. Collectively, increased-risk status and PHN emerge as the principal drivers of the economic burden.
In our cohort, adults with increased-risk conditions comprised 3.29% (95% CI 3.25–3.33). An illustrative national extrapolation applying this proportion and the observed increased-risk HZ and PHN rates and mean outpatient cost to China’s adult population yields ≈ 36.59 (95% CI 36.15–37.03) million increased-risk adults, ≈ 0.59 (95% CI 0.56–0.62) million HZ and ≈ 64,000 (95% CI 54,000–76,000) PHN cases per year, and ≈ ¥0.72 (median 0.25) billion in direct outpatient medical expenditure; these indicative figures warrant caution given regional heterogeneity and the absence of vaccination and indirect-cost data.
The scale of burden observed here argues for prevention. Recombinant zoster vaccination provides durable protection against HZ and its complications in older adults [31–33]; prioritising adults ≥ 50 years and those with increased risk conditions within China’s adult immunisation programme could avert hospitalisations, outpatient visits and downstream costs. Existing economic evaluations indicate favourable value for money at ≥ 50 years [33], and integrating vaccination and HZ surveillance into chronic disease, oncology and transplant pathways would facilitate timely identification and delivery for high-risk patients. These real-world estimates offer parameters for programme planning and cost-effectiveness models in the Chinese context.
Strengths
Strengths of this study include a large, population-based cohort with linkage of outpatient, inpatient and mortality records; a 1-year washout to define incident HZ; and standardised joinpoint analyses, enabling robust estimates of incidence, complications and direct medical costs [21].
Although some participants could theoretically have been vaccinated against zoster, this vaccine was only approved in China in June 2020. Studies indicate that vaccination coverage remained very low (~0.2–2.1%) between 2020 and 2024 [34, 35], suggesting that any potential impact on our study results is likely negligible. This finding supports the robustness of our results despite the recent introduction of the vaccine.
Limitations
Limitations of this study include use of coded diagnoses from a single, relatively developed and urbanised region (generalisation may be limited); capture of medically attended cases only (likely under-ascertainment of incidence and resource use); lack of vaccination, treatment and socioeconomic data; and identification of PHN by diagnostic codes without enforcing a ≥ 90-day pain threshold, which may misclassify prolonged acute pain as PHN. Because individual-level varicella vaccination histories and detailed data on household or occupational contact with children were unavailable, we could not directly evaluate whether changes in varicella vaccine coverage and related contact patterns influenced the HZ incidence observed in this population. Future multi-centre studies across diverse settings that capture vaccine exposure and richer sociodemographic and contact information are needed to refine burden estimates and inform equitable, evidence-based prevention policy.
Conclusion
These findings support prioritising zoster vaccination for Chinese adults ≥ 50 years and at-risk adults, embedding PHN-focused care within chronic-disease programmes, and strengthening routine surveillance in China.
Supplementary Information
Below is the link to the electronic supplementary material.
Author Contributions
Chuanxi Fu conceptualised the study; contributed to the overall design of the survey experiment, analysis and interpretation of the data; and is the guarantor for the study. Zhenwei Li performed the analyses, drew the figures, conducted literature searches, and wrote the first draft of the manuscript. Shenjia Gu, Jiajun Li, Guomin Zhang and Zheng Wu performed the analyses, drew the figures and conducted literature searches. Kan Chen and Zhexin Xu participated in in-depth discussions on the results and data interpretation, with Hongbo Lin providing substantial contributions to refining the interpretation and critically reviewing multiple revisions of the manuscript to ensure clarity and coherence. All authors reviewed and approved the final manuscript for submission.
Funding
This work was supported by the GlaxoSmithKline Biologicals SA (GSK study identifier: 14302). The funder provided the opportunity to review a preliminary version of this manuscript for factual accuracy, but the authors are solely responsible for final content and interpretation. The authors received no financial support or other forms of compensation related to the development of the manuscript. The journal’s Rapid Service Fee was funded by the authors.
Data Availability
Datasets related to this article are available from the corresponding author upon reasonable request after ethical approval.
Declarations
Conflict of Interest
The authors, including Zhenwei Li, Shenjia Gu, Jiajun Li, Guomin Zhang, Zheng Wu, Hongbo Lin, Kan Chen, Zhexin Xu and Chuanxi Fu, declare that they have no conflicts of interest.
Ethical Approval
The study protocol was reviewed and approved by the Ethics Committee of Zhejiang Chinese Medical University (approval no. AF-20220921-1). This study utilised de-identified data from existing databases and was conducted in accordance with the principles of the Declaration of Helsinki and its subsequent amendments. As this was a database-based study, the requirement for patient consent was waived by the institutional review board.
Footnotes
Prior Presentation: Part of the data included in this manuscript were previously presented as an abstract at the 24th China Biological Products Annual Conference, held in Suzhou, China, from 22 to 24 April 2025. The abstract was titled ‘Epidemiological characteristics and disease burden of herpes zoster in adults and increased-risk groups’.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Zhenwei Li, Shenjia Gu, Jiajun Li, Guomin Zhang and Zheng Wu contributed to the article equally.
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Data Availability Statement
Datasets related to this article are available from the corresponding author upon reasonable request after ethical approval.