A systematic literature review to assess the burden of herpes zoster disease in China

Figures & data

Figure 1. Article selection

Figure 2. Distribution of studies published in Chinese and English literature across provinces in China

Table 1. Incidence of Herpes zoster (HZ) in Taiwan and mainland China (English literature)

Author	Study design	Region population	Study period	Age (years)	Case ascertainment	Cases	Incidence
Wu CY, 2010 [13]	Retrospective observational study	Taiwan N = 702,932 (7744 health-care workers and 695,188 adults in the general population)	2000–2005	≥20	ICD-9-CM code 053	HZ cases: 24,527 –8241 cases were in ≥60 year-olds.	Annual incidence rate per 1000 persons: 2000: 4.94 2001: 5.10 2002: 5.70 2003: 5.84 2004: 6.83 2005: 7.00 ≥60 year-olds: 12.0
Jih JS, 2009 [14]	Retrospective observational study	Taiwan 1,000,000 randomly selected from NHIRD	2000–2006	All ages	ICD-9-CM code 053	HZ cases: 34,280 (16,332 men, 17,948 women) 11,421 were ≥60 years. PHN cases: 2944	Incidence per 1000 person-years: Overall incidence: 4.89 F: 5.09 M: 4.71 >80 years: 13.69
Lu WH, 2018 [15]	Population-based propensity score-matched cohort study	Taiwan	2004–2008	All ages	ICD-9-CM code 053	HZ cases: 601,090 newly diagnosed cases	Incidence per 1000 person-years: 2004: 5.04 (65–74 years 12.28; 75–84 12.58; 85 + 11.15) 2005: 5.30 (65–74 years 12.10; 75–84 12.57; 85 + 11.39) 2006: 5.29 (65–74 years 12.10; 75–84 13.01; 85 + 10.97) 2007: 5.38 (65–74 years 12.50; 75–84 13.05; 85 + 11.81) 2008: 5.65 (65–74 years 12.81; 75–84 13.52; 85 + 12.41) p < 0.01 for trend in all age groups
Wu PY, 2013 [12]	Ecological study	Taiwan	2000–2009	All ages	ICD-9-CM code 053	NA	4.04 to 6.24 per 1000 person-years
Ke CC, 2016 [18]	Population-based retrospective case-control study	Taiwan	2005–2011	≥18	ICD-9-CM code 053	HZ cases: 25,345. Controls: 101,380 (age and gender matched)	Incidence per 1000 person-years: <30 years: 1.53 >70 years: 9.53 Average incidence: 3.6
Chao DY, 2012 [16]	Epidemiological study	Taiwan	2000–2008	All ages	ICD-9-CM code 053	HZ cases per year 2000: 963 2001: 1002 2002: 1184 2003: 1212 2004: 1353 2005: 1481 2006: 1541 2007: 1547 2008: 1625	Incidence per 1000 person-years: 2000: 4.45 2001: 4.57 2002: 5.35 2003: 5.34 2004: 5.97 2005: 6.23 2006: 6.51 2007: 6.55 2008: 6.89 >60 years: 2000: 11.45 2001: 11.85 2002: 14.04 2003: 14.15 2004: 14.90 2005: 15.35 2006: 15.79 2007: 16.21 2008: 15.46
Lin YH, 2010 [17]	A population-based study	Taiwan	2000–2005	All ages	ICD-9-CM code 053	HZ cases: 672,782	Annual incidence per 1000 population: Women: 5.20 Men: 4.72 <40 years: 1.64–3.15 40–49 years: 5.18 50–59 years: 8.36 60–69 years: 11.09 ≥70 years: 11.77 Overall: 4.97
Zhu Q, 2015 [9]	Cross-sectional community survey	Guangdong, China −34 randomly sampled counties/districts	2011– Oct 2013	≥50	Self-reporting	Year-HZ cases 2011: 29 2012: 24 2013: 34	Incidence per 1000 person-years: 2011: 4.1 2012: 3.4 2013: 5.8
Lu L, 2018 [10]	Community-based retrospective survey	Beijing (Xicheng, Changping, Miyun), China	Dec 2012– Mar 2013	All ages	Self-reporting/doctor	HZ cases: 237 incident cases in 118,220 residents. 219 were diagnosed by healthcare workers, 18 were self-diagnosed. Of 217 cases interviewed, 193 were primary, 24 recurrent and 10 PHN.	Incidence per 1000 population: Crude: 2.0Adjusted: 1.9
Li Y, 2016 [11]	A community-based retrospective survey	4 rural townships (Jiangsu, Heilongjiang, Jiangxi, Hebei) 1 urban area (Shanghai), China	2010–2014	≥50	Self-reporting, health care records/hospital outpatient logs & inpatient records	HZ cases 1126 in 49,721 residents: 461 men, 665 women. 2010: 144 cases 2011: 159 cases 2012: 208 cases	Incidence per 1000 population: Average: 3.43 ≥50 years: 2010: 2.9 2011: 3.2 2012: 4.18 50- year-olds: 2.66 80- year-olds: 8.55 F: 3.95 M: 2.89 Urban: 7.65 Rural: 2.06

ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) format; F, Female; M, Male; NA, not mentioned in literature; NHIRD, National Health Insurance Research Database; PHN, postherpetic neuralgia.

Figure 3. Adjusted ratios comparing the incidence of HZ in persons with a range of underlying co-morbidities compared to a comparator population. Only studies from Taiwan are shown. Tabulated data including adjusted variables, references are provided in Table S4

Table 2. The percentage of patients with herpes zoster (HZ) who developed complications (English and Chinese literature)

Author	Study type	Study period	Age	Complication	Definition	No. of cases*	%*
Mainland China
Yan K (2014) [62]	Retrospective hospital-based study	2012–2013	10–90 (age: 36.5)	Ophthalmic	Not specified	4	0.76
				Pneumonia or encephalitis		7	1.34
				Motor nerve palsy		3	0.57
				Gastrointestinal and urinary tract		6	1.15
Zhang Y (2016) [63]	Retrospective hospital-based study	2014	7–89 (mean: 54)	Ophthalmic	Not specified	9	4.46
				Skin infection		13	6.44
				Ramsay Hunt syndrome		1	0.5
Chen D (2017) [64]	Retrospective hospital-based study	2009–2013	18–75 (mean: 35.0)	Pneumonia	Not specified	2	4.35
				Sepsis		2	4.35
				Cellulitis		1	2.17
Liu TH (2005) [32]	Retrospective hospital-based study	2000–2004	18–87 (mean: 49.68)	Ophthalmic	Not specified	6	2.78
				Otitis media		1	0.46
Qiu HX (2002) [39]	Retrospective hospital-based study	1998–2001	22–36 (mean: 26); 60–90 (mean: 68.15)	Ophthalmic	Not specified	10	12.82
				Urinary retention		3	3.85
				Ramsay Hunt syndrome		1	1.28
Xu G (2001) [65]	Retrospective hospital-based study	1995–2000	All ages	Ophthalmic	Not specified	6	1.67
				Meningoencephalitis		4	1.11
Zhong TT (2016) [66]	Retrospective hospital-based study	2013–2015	59–88 (mean: 73.90)	Post-herpetic stroke	Not specified	21	1.26
Zhao FQ (2006) [67]	Prospective hospital-based study	1993–2005	38–78 (mean: 61)	Ophthalmic	Not specified	14	26.42
Taiwan
Lin SY (2012) [21]	Retrospective cohort population-based study	1996–2008	≥20 (mean: 63)	Meningitis	ICD-9-CM code 053.0	2053	36.98
				- with other nervous system complications	ICD-9-CM code 053.1
				- with ophthalmic complications	ICD-9-CM code 053.2
				- with other specified complications	ICD-9-CM code 053.7
				- with unspecified complications	ICD-9-CM code 053.8
Chen JY (2015) [68]	Nationwide population-based cohort study	2001–2011	≥20 (mean: 55.66)	Ophthalmic	ICD-9-CM	51	3.79
				Neurologic		120	8.92
				Dermatological		175	12.86
				Others		34	2.53
Wang WY (2016) [69]	Retrospective population-based cohort study of patients with HZ	1996–2000	All ages (mean 54.9–57.6)	Ophthalmic/ocular	ICD-9-CM	894	3.6
				Cutaneous		893	3.64
				Neurologic		3355	13.7
				Primary trigeminal neuralgia		1300	5.3
Lin YH (2010) [17]	Retrospective population-based study	2000–2005	All ages	Ophthalmic	ICD-9-CM	2225	11.3
				Skin/soft tissue infection		1752	8.9
				Lower respiratory tract infection		925	4.7
Hong Kong
Ming WK (2019) [53]	Retrospective observational study of patients admitted to 2 hospitals with HZ	2011–2013	≥50 (mean: 71.2)	Ophthalmic	Physician diagnosis from medical charts	7	7.78
				Disseminated HZ		0	0
				Ramsay Hunt Syndrome		1	1.11
Chan DYW (2018) [70]	Longitudinal study using national reporting by public hospitals Inpatients	1999–2014	All ages	Any complication	ICD-9-CM	2989	23.2
				Ophthalmic		627	4.9
				Ramsay Hunt Syndrome		400	3.1
				Disseminated zoster		77	0.6
				Neurological		2047	15.9
	Accident & Emergency presentations			Any complication		426	1.8
				Ophthalmic		699	2.9
				Ramsay Hunt Syndrome		318	1.4
				Disseminated zoster		13	0.1
				Neurological		1920	8.2

* Number of cases of the specified complication in the cohort studied (or control group in studies of co-morbidities). % of the total number of patients with HZ. HZ, Herpes zoster; ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) format.

Table 3. Estimates of the cost of disease in patients with Herpes zoster (HZ) (English and Chinese literature)

Author	Study type	Region	Study period	Age	Study perspective	Costs	Standardized costs in 2019 values RMB (USD)
Xia YJ (2015) [41]	CEA	Yongren county, Yunnan province	Mar 2013- Feb 2015	17–70 (mean 36.6–37.7)	Health care payer	Cost by treatment group (RMB): Mean ± SE: Acyclovir: 782.9 ± 127.6 Valaciclovir: 866.7 ± 168.4 Ribavirin: 648.8 ± 97.2	865 (125) 957 (139) 717 (103)
Xu ZY (2004) [42]	CEA	Foshan city, Guangdong province	1999–2003	15–73	Health care payer	Cost by treatment group (RMB): Mean ± SE: Acyclovir: 1798.38 ± 319.73 Valaciclovir: 1185.05 ± 307.64 Ribavirin: 1170.72 ± 263.78	2732 (396) 1810 (262) 1787 (259)
Yang JY (2005) [43]	CEA	Xiamen city, Fujian province	Not reported	NA	Health care payer	Registration and examination fee (RMB): 6 Cost of treatment (RMB): Valaciclovir: 292 (280 drug cost, 12 inspection cost) Acyclovir: 29.5 (17.5 drug cost, 12 inspection cost).	Not able to calculated
Jie JJ (2009) [44]	CEA	Wuhan city, Hubei province	Not reported	30–65	Health care payer	Cost of treatment (RMB): Oxycodone: 106.14 (10 doses per pack, 2 packs) Ibuprofen sustained-release capsules: 15.40 (20 doses per pack, 1 pack)	Not able to calculate
Li LQ (2015) [45]	CEA	Beijing	Mar 2009-May 2014	16–72 (mean: 49.21)	Health care payer	Cost by treatment group (RMB): Mean ± SE: Acyclovir: 594.23 ± 96.75 Valaciclovir: 721.77 ± 101.32 Ribavirin: 518.46 ± 89.16 (significantly different).	667 (97) 810 (117) 582 (84)
Yang HN (2010) [46]	CoI	Guangzhou city, Guangdong province	Dec 2008-Jun 2009	6–90 (mean: 52.11)	Health care payer	Outpatient total cost (RMB): median 407.58, range 71.45 to 2183.34, mean 502.18 ± 347.49 Western medicine (RMB): 333.39 ± 209.51 Chinese traditional medicine (RMB): 112.40 ± 102.01, Treatment cost (RMB): 56.40 ± 124.01	median 530 (77) mean 654 (95) 435 (63) 146 (21) 73 (11)
Chen FC (2009) [47]	CEA	Shiyan city, Hubei province	Jan 2007-Oct 2008	18–65 (mean: 38.6–39.8)	Health care payer	Cost by treatment group (RMB): Ganciclovir: 529.0 Acyclovir: 421.2	700 (101) 558 (81)
Wei W (2004) [48]	CEA	Shanghai	Not reported	>50	Health care payer	Cost by treatment group (RMB): Prednisone: 470 Hydrocortisone: 690 Betamethasone: 500	Not able to calculated
Xu YN (2005) [50]	CEA	Xiangtan city, Hunan province	Not reported	Mean: Women: 52 Men: 50	Health care payer	Traditional Chinese medicine (RMB): 157.40 Western medicine (RMB): 594.50 (p < 0.05).	Not able to calculate
Gao SR (2017) [52]	BoD	Shalan town, Heilongjiang province	Study ended 31 December 2012	≥39	Health care payers	Total (RMB):14,873 (n = 52) The cost of hospital visits: 13,589 The cost of drug by self-purchased: 259 Transportation expenses: 960 Other expenses: 65 Average cost (RMB): 286.02 (14,873/52)	17,366 (2516) 15,867 (2298) 302 (44) 1121 (162) 76 (11) 334 (48)
Li Y (2016) [11]	BoD	4 rural areas (Jiangsu, Heilongjiang, Jiangxi, Hebei)1 urban area (Shanghai)	2010–2014	≥50	Health care payer	Outpatient expenses (RMB): 543.8 (range 0–13,312) Hospitalization expenses (RMB): 4502.4 (range 136.6–30,000) Other (RMB): 109.4 (range 0–4401) Total (RMB): mean = 840.6 (range 0–30,002) Total indirect cost (RMB): 109.4	619 (90) 5128 (743) 124 (18) mean = 957 (139) 124 (18)
Li XW (2012) [49]	CEA	9 hospitals in Chengdu, Guangzhou, Wuhan province	Not reported	18–70 (mean 43.76–46.51)	Health care payer	Western medicine (RMB): 371.68 Cotton-sheet moxibustion (RMB): 254.52 Surrounding acupuncture plus electric acupuncture (RMB): 238.68 Tapping/cupping (RMB): 223.56 Hot needle puncture (RMB): 221.76.	Not able to calculate
Wang HZ (2017) [51]	CoI	Beijing	Oct 2016–Jan 2017	30–65	Health care payer	Outpatient service charge (RMB): 11,091.54 Inpatient cost (RMB): 178.90 Total direct costs (RMB): 1270.44 Total indirect costs (RMB): 344.03 including transportation expenses (105.08 RMB), nutrition and other expenses (238.95 RMB).	11,779 (1709) 190 (28) 1.351 (196) 365 (54)/112 (16)/254 (37)
Jih JS (2009) [14]	BoD	Taiwan	2000–2006	All ages	Health insurance payer	Home care case: €53.30 Hospitalized case: €1224.70	€68 (RMB 520) (USD 75) €1567 (RMB 11,983) (USD 1735)
Lin YH (2010) [17]	BoD	Taiwan	2000–2005	All ages	Health insurance payer	Medical expenditures in 2000–2004 USD 7.7 million to USD 9.8 million. Costs ≥80 years: USD 204 per patient.	USD 10.91 million to 13.3 million. USD 278
Ming WK (2019) [53]	CoI	Hong Kong	2011–2013	≥20 (immuno- compromised: 64.3 Immuno-competent: 71.2)	Health care payer	105 cases with total hospitalization costs of USD 4883 ± 6271 Immunocompromised (n = 15) USD 9891 ± 9383 Immunocompetent (n = 90) USD 4049 ± 5212 Mean daily costs: Hospital stay: USD 689 ± 29 Medication: USD 8 ± 10 Laboratory: USD 6 ± 12	USD 4976 USD 10,079 USD 4126 USD 702 USD 8.15 USD 6.11
You JHS (2018) [54]	CEA	Hong Kong	2011–2013	≥50	Societal	Median (IQR) of hospitalization: Ophthalmicus: USD 3068 (1938–4932) Secondary skin and soft tissue infection: USD 1900 (1292–4386) Disseminated HZ: USD 6299 (5039–7558) Central nervous system infection: USD 26,269 (21,015–31,523) Ramsay Hunt Syndrome: USD 6597 (2532–10,662) No complication: USD 2887 (1930–4816) Uncomplicated outpatient case: USD 309 (144–813)	USD 3258 USD 2018 USD 6691 USD 27,902 USD 7007 USD 3066 USD 328

CEA, cost-effectiveness analysis; BoD, burden of disease study; CoI, cost of illness analysis; NA, Not mentioned in the literature; RMB, Renminbi; SE: Standard error; USD, United States dollar; IQR, inter-quartile range.

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