Evaluation of the economic burden of Herpes Zoster (HZ) infection

Figures & data

Figure 1. Flowchart of the studies selected in accordance with the 2009 PRISMA guidelines.⁶⁷

Table 1. Main characteristics of studies included in the current systematic review

Country	Reference	Study years	Year evaluation costs	Study design	Concerned population/Cohort	Age	Case definition	Type of costs	Cost sources
Australia	28	1998–2006 (1998–2005 for hospitalizations and ED admissions; 2000–2006 for medical consultations; 2002–2006 for pharmaceuticals)	2007 for medical consultations and pharmaceuticals; 2004–2005 for hospitalizations	R	Patients of about 1,000 GPs; hospitalized patients	≥ 50 y	GP's clinical diagnosis, ICD-10-AM/AR-DRG	D	AD, HD, ID, PCD, PP
Belgium	29	2000–2009	2010	R	Patients of 150 sentinel GPs (about 1.5% of the Belgian population); a sample of 900 hospitalized patients	All ages	GP's clinical diagnosis and ICD-9-CM	D, I	AD, HD, ID, ad hoc questionnaires
Canada	30	1992–1996	1992–1996	R	British Columbia population	All ages	ICD-9	D	AD, HD
France	31	2005	2006	R	Immunocompetent patients of 231 GPs, 41 dermatologists, 15 neurologists and 5 specialists in pain medicine out of an initial list of attendants of 567 GPs, 75 dermatologists and 30 neurologists	≥ 50 y	GP's clinical diagnosis	D	HD, PCD, PP
Germany	32	2004–2009	2010	R	A sample of the Hesse insured population (about 240,000 individuals)	All ages	ICD-10	D, I	AD, HD, ID, PCD, PP
Italy	33	1997	1996 for the GP management and specialist referrals and consultations, 1997 for the hospitalizations and the pharmaceutical	P	61 subjects out of an initial cohort of 396 patients	All ages	Specialist's clinical diagnosis	D, I	AD, PCD
	22	2004	2003 for the consultations, GP management and for the hospitalizations, 2004–2005 for the pharmaceutical	P	26,394 patients of 24 GPs	≥ 14 y	GP's clinical diagnosis, ICD-9-CM	D	AD, HD, PCD, PP
	27	2003–2005	2005	R	About 450,000 patients of 342 GPs	≥ 50 y for direct costs, 50–64 y for indirect costs	ICD9-CM	D, I	AD, HD, PP, expert panel and focus group
Korea	34	2003–2007	2006–2007 for the direct costs, 2006–2008 for the indirect costs	R	Korean insured population (about 48–49 million individuals)	All ages	ICD-10	D, I	AD, ID
	35	2007–2010	2010	P	582 subjects out of an initial cohort of 12,635 individuals hospitalized in Seoul and in Gyeonggi-do	All ages	Clinical diagnosis	D	HD
Spain	36	2006–2007	2007	P	118 subjects out of an initial cohort of 146 individuals attending 25 GPs in Valencia	> 14 y	GP's clinical diagnosis	D, I	AD, PCD, PP
	37	1998–2004	2004	R	Hospitalized patients	≥ 30 y	ICD9-CM	D	AD, HD
	38	2007–2010	2009	P	1,506 patients attending 6 primary care centres and resident in Badalona	> 30 y	GP's clinical diagnosis, CIAP-2	D, I	AD, HD, PCD, PP
Taiwan	39	2000–2006	Average exchange rate in the period 2000–2006	R	1,000,000 persons (about 5% of Taiwan’s population), a sample of the National Health Insurance database which comprises more than 21 million and half individuals	All ages	ICD-9-CM	D	AD
	40	2000–2005	2000–2005	R	Insured population resident in Taiwan (approximately 22.9 million individuals)	All ages	ICD-9-CM	D	AD, ID
Thailand	41	2007–2008	2008	P	180 subjects (138 immunocompetent, 34 HIV positive, 7 suffering from cancer, 1 transplanted)	≥ 50 y and healthy, ≥ 20 y and immune- depressed	GP's clinical diagnosis	D, I	HD, PP, questionnaires (ZBPI, IZIQ, ADL and EQ-5D)
UK	42	1987–1991	1991–1992	P	168 attendants of a clinic for HZ-pain (Centre for Pain Relief, Walton Hospital, Liverpool)	All ages	GP's clinical diagnosis	D, I	AD, HD, PCD, ad hoc questionnaires (such as VAS), literature review
	43	2000–2006	2005–2006	R	Immunocompetent patients of 603 GPs, hospitalized patients	≥ 50 y	ICD-10	D	AD, HD, PCD, PP
	44	2003	2003	P	158,716 patients of 18 GPs from an initial list of attendants of 45 GPs in Tower Hamlets and Hackney	All ages	GP's clinical diagnosis, confirmed when necessary with PCR	D, I	AD, PCD, PP, estimations from EQ-5D and ad hoc surveys
USA	45	2001–2003	2004	R	Medicare and Medicaid insured population (approximately 28 million individuals)	All ages	ICD-10	D	ID
	46	2001–2003	2004	R	Medicare and Medicaid insured population (approximately 28 million individuals)	All ages	ICD-10	D	ID
	47	2005–2006	2006	R	Medicare and Medicaid insured population (approximately 28 million individuals)	All ages	ICD-9	D	ID
	48	2000–2001	2005	R	American privately insured population (> 4 million individuals)	All ages	ICD-9	D	ID, PP, panel of experts and review of literature
	49	2008–2009	2010	R	A convenience sample of 2.3 million subjects generalizable to approximately 31% of the American insured Medicare population (about 15.3 million retirees)	≥ 65 y	ICD-9-CM	D	AD, HD, ID, PCD, PP
	50	1997–2007	2007	R	Medicaid insured population resident in Florida, Iowa, Missouri and New Jersey (approximately 10 million individuals)	All ages	ICD-9-CM	D	ID, PP
	51	1997–2007	2007	R	Medicaid insured population resident in Florida, Iowa, Missouri and New Jersey (approximately 10 million individuals)	All ages	ICD-9-CM	D	ID, PP
	52	1986–1995	1986–1995	R	Connecticut residents hospitalized in Connecticut, New York, Massachusetts and Rhode Island hospitals	All ages	ICD-9-CM	D	HD
	53	2002–2007	2007	R	404 SNF residents from an initial list of 426 eligible patients	All ages	ICD-9	D	AD
	54	1999–2007 (1999–2006 for Medicaid patients, 1999–2007 for commercially insured and Medicare patients)	2007	R	Commercially insured, Medicare and Medicaid SOT recipients	All ages	ICD-9-CM	D	AD, ID
	55	1993–2004	2007	R	American hospitalized patients from 17 states in 1993 and from 37 states in 2004	All ages	ICD-9-CM	D	AD, HD, ID
	56	2005	2010	P	A sample target of 150 American insured population from an initial list of 3,859 eligible subjects	50–64 y	ICD-9-CM	I	AD, ID, telephone survey (ad hoc ADL and clinical questionnaires)
	57	1998–2003	2008	R	American insured subjects (approximately 14 million individuals)	All ages	ICD-9	D, I	ID
	58	1996–2001	2006	R	Olmsted county insured population	≥ 22 y	ICD-9-CM	D	ID

Abbreviations: AD: Administrative Database, ADL: Activities of Daily Living, CIAP-2: Clasificación Internacional de la Atención Primaria second revision, D: Direct, ED: Emergency Department, EQ5D: EuroQol five-dimension questionnaire, GP: General Practitioner, HD: Hospital Database, HIV: Human Immunodeficiency Virus, HZ: Herpes Zoster, I: Indirect, ICD-9: International Classification of Diseases Ninth revision, ICD-9-CM: International Classification of Diseases Ninth revision Clinical Modification, ICD-10: International Classification of Diseases Tenth revision, ID: Insurance Database, IZIQ: Initial Zoster Impact Questionnaire, P: Prospective study, PCD: Primary Care Database, PCR: Polymerase Chain Reaction, PP: Pharmaceutical Prescriptions, R: Retrospective study, SNF: Skilled Nursing Facility, SOT: Solid Organ Transplant, VAS: Visual Analogue Scale, ZBPI: Zoster Brief Pain Inventory.

Table

A. Direct costs of a HZ case

Ref.

Inpatient cost

Outpatient and consultations cost

Treatment cost and diagnostic procedures

Mean inpatient/outpatient cost

Values

Values 2013

Values

Values 2013

Values

Values 2013

Values

Values 2013

33

L.1,076,000^a

€774.66^a

L. 27,000^a-27,200^a

€19.95^a-20.10^a

L. 336,100^a-337,000^a

€241.97^a-242.62^a

L. 1,439,100^a

€1,036.07^a

41

$90.41^a ± 148.00^c

€68.05 ^a ± 111.40 ^c

No data

No data

No data

No data

No data

No data

29

€5,438^a (range €725–28,808)

€5,856.73^a (range €780.83–31,026.22)

€247^a (range €0–2,148)

€266.02^a (range €0–2,313.40)

No data

No data

No data

No data

36

No data

No data

€122.96^a ± 70.31^c at 1 mo €151.36^a ± 103.60 ^c at 3 mo

€140.17 ^a ± 80.15 ^c at mo €172.55 ^a ± 118.10 ^c at 3 mo

€71.48^a ± 56.44^c at 1 mo €81.61^a ± 59.38^c at 3 mo

€81.49 ^a ± 64.34 ^c at 1 mo €93.04 ^a ± 67.69 ^c at 3 mo

€194.44^a ± 90.16^c at 1 mo €232.97^a ± 119.41^c at 3 mo

€221.66 ^a ± 102.78 ^c at 1 mo €265.59 ^a ± 136.13 ^c at 3 mo

35

$1,312.7^a (range $330.9–2,602.1) ^, $317.4^a (range $150.4–1,165.6) ^, $319.1^a (range $158.0–946.0) *

€981.38^a (range €247.39–1,945.34) ^, €237.28^a (range €112.44–871.41) ^, €238.56^a (range €118.13–707.23) *

No data

No data

No data

No data

No data

No data

22

€3,857.73^a (average hospital admission), €2,898.68^a (day-hospital), €4,082.59^a (ordinary admission), €2,499.67^a with HZ as the principal diagnosis (€2,288.49^a without complications, €2,684.95^a with complications)

€4,725.72^a (average hospital admission), €3,550.88^a (day-hospital), €5,001.17^a (ordinary admission), €3,062.10 with HZ as the principal diagnosis, €2,803.40^a without complications, €3,289.06^a with complications

€136.06^a-360.69^a

€136.13 ^a -441.85 ^a

€102.76^a-214.39^a

€121.46 ^a -253.41^a

€3,503.28^a as computed from the study sample, €412.37^a estimated

€4,291.52^a as computed from the study sample, €505.16^a estimated

45

No data

No data

No data

No data

No data

No data

$757^a-1,313^a (excess cost)

€719.84 ^a-1,248.55 ^a (excess cost)

46

No data

No data

No data

No data

No data

No data

$4,331^a -7,229^a

€4,118.40 ^a -6,874.13 ^a

47

No data

No data

No data

No data

No data

No data

$6,220^a -12,062^a §§, $6,100.32^a -11,829.90^a §§

€6,100.32 ^a -11,829.90 ^a §§, €5,982.94 ^a -11,602.27 ^a

43

£27^a (additional cost)

€45.59^a (additional cost)

£75.63^a for the management (range 60.15–124.89 according to pain severity) £35.11^a ± 45.24 ^c for consultations (range £23.01–71.49 according to pain severity)

€127.69^a for the management (range 101.55–210.85 according to pain severity), €59.27 ^a ± 76.37^c for consultations (range €38.85–120.70 according to pain severity)

£40.52 ^a (range £37.14–53.40 according to pain severity)

€68.38^a (range €62.71–90.15

£103^a

€173.90

27

€2,592^a ± 1,313^c *

€3,063.74 ^a ± 1,551.97 ^c *

€122.68^a ± 97.51^c *

€145.01 ^a ± 115.26 ^c*

No data

No data

€166^a

€196.21^a

37

€3,200^a-3,719.53^a

€3,843.20^a -4,467.16^a

No data

No data

No data

No data

No data

No data

48

$79 ^a ± 12.3^b (incremental cost)

€68.56 ^a ± 10.67 ^b (incremental cost)

$170 ^a ± 8.3 ^b (incremental cost)

€147.53 ^a ± 9.81 ^b (incremental cost)

$137 ^a ± 3.3 ^b (incremental cost)

€118.89^a ± 2.86 ^b

$431 ± 17.6 (incremental cost), $373 ± 15.2 (incremental cost *), $674 ± 69.1 (incremental cost ^)

€374.01 ± 15.27 (incremental cost) €323.68 ± 13.19 (incremental cost *), €584.88 ± 59.96 (incremental cost ^)

39

€1,224.70^a

€1,416.98^a

€53.30^a

€61.67^a

No data

No data

No data

No data

52

$12,834^a (range $7,159- 15,583), $16,587^a in patients with comorbidities, $11,115^a in patients without comorbidities

€16,208.52^a (range €9,041.36–19,680.32), $20,948.31^a in patients with comorbidities, $14,037.52^a in patients without comorbidities

No data

No data

No data

No data

No data

No data

40

No data

No data

No data

No data

No data

No data

Up to $204

Up to €177.03

53

$18,813^a for the stay in the SNF, incremental cost of $1,079–1,673 (incremental cost of $466^a for the stay on the SNF, incremental cost of $613–1,207 for the hospitalization)

€16,284.60^a for the stay in the SNF, incremental cost of €933.99-€1,448.15 (incremental cost of €403.37^a for the stay on the SNF, incremental cost of €530.61–1,044.79 for the hospitalization)

No data

No data

No data

No data

No data

No data

31

No data

No data

€182.92^a

€211.64

No data

No data

No data

No data

54

$6,524^a ± 34,784^c in the commercially insured and Medicare SOT patients, $7,427^a ± 24,641^c in the Medicaid patients

€5,647.20^a ± 30,109.16^c in the commercially insured and Medicare SOT patients, €6,428.84^a ± 21,329.34^c in the Medicaid patients

$957^a ± 3,067^c in the commercially insured and Medicare SOT patients, $647^a ± 1,810^c in the Medicaid patients

€621.51^a ± 2,654.81^c in the commercially insured and Medicare SOT patients, 899.36^a ± 1,566.75^c in the Medicaid patients

$523^a ± 488^c in the commercially insured and Medicare SOT patients, $537^a ± 810^c in the Medicaid patients

€452.71^a ± 422.42^c in the commercially insured and Medicare SOT patients, €464.82^a ± 701.13^c in the Medicaid patients

$8,086^a ± 35,150^c in the commercially insured and Medicare SOT patients, $8,682^a ± 24,694^c in the Medicaid patients

€6,999.27^a ± 30,425.97^c 150^c in the commercially insured and Medicare SOT patients, €7,515.18^a ± 18,750.19^c 694^c in the Medicaid patients

55

$22,790^a in 1993, $26,825^a in 2004

€19,727.11^a in 1993, €23,219.82^a in 2004

No data

No data

No data

No data

No data

No data

44

No data

No data

£198.2^a (range £20–3,257)

€373.25^a (€37.67–6,133.48)

£70^a

€131.82^a

No data

No data

38

No data

No data

No data

No data

No data

No data

€395.1^a (€338.6^a for the GP management, €56.5^a for the specialist referrals and consultation, including also drug costs)

€431.45^a (€369.75^a for the GP management, €61.70^a for the specialist referrals and consultation, including also drug costs)

28

$4,527^a-4,764^a

€3,064.84^a-3,225.30^a

$298.2^a for non-ED admitted case, $36.13^a-46.14^a per GP consultation, $75.60^a for specialists consultations and referrals

€203.67^a for non-ED a dmitted case, €24.68^a-31.51^a per GP consultation, €51.63^a for specialists consultations and referrals

$175^a

€119.53^a

$537^a-561^a

€366.77^a-383.17^a

32

€2,984.22^a §

€3,214.00^a

€82.13^a

€88.45^a

€110.17^a (51.82^a for drug prescription, 58.35^a for procedures)

€118,65^a (€55.81^a for drug prescription, €62.84^a for procedures)

€210^a (range €190^a-230^a)

€226,17^a (range €204.63^a-247.71^a)

57

No data

No data

No data

No data

No data

No data

$583^a ± 27^b at 3 mo, $986^a ± 58^b at 1 y ($1,745^a ± 470^b ^, $983^a ± 57^b*) (incremental costs)

€438.80^a ± 20.32^b at 3 mo, €742.13^a ± 43.66^b at 1 y (€1,313.40^a ± 353.75^b ^, 739.87^a ± 42.90^b*) (incremental costs)

58

$240^a ± 52^b *, $253^a ± 153^b ^

€230.86^a ± 51.00^b*,, €248.13^a ± 150.05^b ^

$325^a ± 9^b *, $363^a ± 38^b ^

€318.74^a ± 8.83^b* €356.02^a ± 37.27^b^

$390^a ± 12^b *, $403^a ± 28^b ^

€382.49^a ± 11.77^b* €395.24^a ± 27.46^b^

$715^a ± 35^b §, $720a ± 35^b §§, $1,059^a ± 67^b *, $1,133^a ± 178^b ^

€701.25^a ± 34.33^b §, €706.14^a ± 34.33^b §§, €1,038.63^a ± 65.71^b* €1,111.19 ± 174.58^b^

B. direct costs of a PHN case

Ref.

Inpatient cost

Outpatient and Consultations cost

Treatment cost and diagnostic procedures

Mean inpatient/outpatient Cost

Values

Values 2013

Values

Values 2013

Values

Values 2013

Values

Values 2013

33

No data

No data

L. 57,000^a

€41.04^a

No data

No data

No data

No data

29

No data

No data

€456^a (range €0–4,765)

€491.11^a (range €0–5,131.91)

No data

No data

No data

No data

36

No data

No data

1 mo, €247.54^a ± 174.24^c; 3 mo, €361.45^a ± 222.59^c

1 mo, €282.20^a ± 198.63^c; 3 mo, €412.05^a ± 253.75^c

1 mo, €151.08^a ± 178.68^c; 3 mo, €273.82^a ± 283.54^c

1 mo, €172.23^a ± 203.70; 3 mo, €312.15^a ± 323.24^c

1 mo, €398.62^a ± 249.57^c; 3 mo, €635.27^a ± 360.48^c

1 mo, €454.43^a ± 284.51^c; 3 mo, €724.21^a ± 410.95^c

42

No data

No data

£273^a (£98 for the GP management, £175 for specialist consultations)

€516.22^a (€185.31 for the GP management, €330.91 for specialist consultations)

£325^a

€614.96^a

£770^a (£30–12,000), adjusted £600–990

€1,456.01^a (€56.72- 22,691.10), adjusted €1,134.55–1,872.02

45

No data

No data

No data

No data

No data

No data

$2,159^a-5,387^a for confirmed PHN;$2,292^a-5,742^a for possible PHN (excess cost)

€2,053.01^a -5122.55^a for confirmed PHN; €2,179.49^a -5,460.13^a for possible PH (excess cost)

46

$249^a-315^a (incremental cost)

€236.78^a-299.5^a (incremental cost)

$214^a-561^a (incremental cost)

€203.5^a-533.5^a (incremental cost)

$483^a-767^a (incremental cost)

€459.3^a-729.4^a (incremental cost)

$8,986^a-10,054^a

€8,544.89^a-9,560.45^a

47

No data

No data

No data

No data

No data

No data

$10,206^a -14,535^a

€10,009.61^a -14,255.32^a

43

£57 (mean additional cost)

€96.24 (mean additional cost)

1 mo: £284.38^a (range £166.62-£519.62, according to the pain severity) 3 mo: £340.04^a (range £199.47–615.55, according to the pain severity)

1 mo: €480.12^a (€281.30-€758.24 according to the pain severity) 3 mo: €574.09^a (€336.77–1,039.24 according to the pain severity)

1 mo: £13.59 (range £10.02–23.06 according to pain severity) (mean additional cost) 3 mo: £14.67 (range £10.97–24.68) (mean additional cost)

1 mo: €22.94 (range €16.91–38.93 according to pain severity) (mean additional cost) 3 mo: €24.77 (range €18.52–41.67) (mean additional cost)

1 mo: £341^a 3 mo: £397^a

1 mo: €575.7 ^a 3 mo: €670.26^a

27

€2,806^a ± 2,641^c

€3,316.69^a ± 3,121.66^c

1 mo: €446.10^a ± 442.97^c 3 mo: €416.65^a ± 406.30^c

1 mo: €527.29^a ± 523.59^c 3 mo: €492.48^a ± 618.88^c

No data

No data

€560^a

€661.92^a

49

$4,687^a ± 14,946^c

€3,504.03^a ± 11,173.70^c

$1,403^a ± 2,725^c

€1,048.89^a ± 2,037.22^c

$794^a ± 1,577^c

€593.60^a ± 1,178.97^c

$16,579^a ± $24,417^c

€12,394.55^a ± 18,254.28^a

50

$2,995^a-3,617^a

€2,592.49^a -3,130.88^c

$6,418^a-6,982^a

€5,555.45^a -6,043.64^a

$6,198^a-7,658^a

€5,365.01^a -6,628.79^a

$19,124^a-20,175^a

€16,553.80^a -17,463.56^a

51

$1,777^a-2,076^a

€1,538.17^a -1,796.99^c

$3,223^a-3,249^a

€2,789.84^a -2,812.35^a

$3,404^a-3,761^a

€2,946.51^a -3,255.53^a

$9,446^a-9,448^a

€8,176.49^a -8,178.22^a

31

No data

No data

€339.84^a

€393.19^a

No data

No data

No data

No data

38

No data

No data

No data

No data

No data

No data

€1,135^a (€884.1^a for the GP management, €250.8^a for the specialist referrals and consultation, including also drug costs)

€1,239.42^a (€965.44^a for the GP management, €273.87^a for the specialist referrals and consultation, including also drug costs)

32

€3,738.21^a (annualized)

€4,026.05^a (annualized)

€185.79^a

€200.10^a

€258.82^a (€210.46 for drug prescription, €48.36 for procedures)

€278.75^a (€226.67 for drug prescription, €52.08 for procedures)

€1,123^a (range €831–1,525)

€1.209.47^a (range €894.99–1,642.43)

57

No data

No data

No data

No data

No data

No data

PHN: 3 mo: $1,440^a ± 210^b, 1 y: $3,815^a ± 464^b (incremental costs)

PHN: 3 mo: €1,083.83^a ± 158.06^b, 1 y: €2,871.43^a ± 349.24^b (incremental costs)

58

$4,345^a ± $1,891^b^

€4,261.39^a ± €1,854.61^b ^

$910^a ± 84^b ^

892.49^a ± 82.38^b ^

$1,802^a ± 181^b for drug prescriptions, $269^a ± 31^b ^

1,767.32^a ± 177.52^b for drug prescriptions, 263.82^a ± 30.40^b ^

3 mo: $2,894^a ± 317^b, 1y: $4,388^a ± 745^b, $7,569^a ± 2,103^b ^

3 mo: €2,838.32^a ± 310.90^b, 1 y: €4,303.57^a ± 730.67^b, 7,423.35^a ± 2,062.53^b ^

(A) ^a = mean cost, ^b = standard error, ^c = standard deviation, * = for an immuncompetent subject, ^ = for an immunocompromised subject. § = up to 90 d from the diagnosis, §§ = up to 1 y from the diagnosis, SNF = Skilled Nursing Facility, SOT = solid organ transplant. (B) ^a = mean cost, ^b = standard error, ^c = standard deviation, ^ = for an immunocompromised subject

Table 3. Indirect costs for HZ and PHN

Ref	Economic values	Economic values (2013)
33	HZ: 590,000 Lire (global indirect cost)	HZ: €424.77 (global indirect cost)
41	$43.98–2,361.29 (use of hospital chaperone or caregiver)	€ 33.11–1,777.27 (use of hospital chaperone or caregiver)
29	Ambulatory-treated HZ: €234^a for absence from work) (range €0- 4,452), €81^a for hire of caregivers (€14°, maximum €415). Hospitalized HZ: €231° for hire of caregivers (range €1-€2,576); €47^a for lost work of caregivers, (maximum €1,781), €600^a for lost work of HZ patient (maximum €22,790)	Ambulatory-treated HZ: €252.02 for absence from work (range €0–4,794.80), €87.24^a for hire of caregivers (€15.08°, maximum €446.96). Hospitalized HZ: €248.79° for hire of caregivers (range €1.08-€2,774.35); €50.62^a for lost work of caregivers (maximum €1,918.14), €646.20^a for lost work of HZ patient (maximum €24,544.83)
36	HZ: €2.87 ± 9.94 at 1 mo (for absence from work), 41.25 ± 273.64 at 3 mo (€40.60 ± 273.55 for absence from work, €0.65 ± 6.91 for hire of caregiver) PHN1: €112.66 ± 461.56 (€111.44 ± 461.46 for absence from work, €1.22 ± 9.44 for hire of caregivers) PHN3: 130.03 ± 515.71 (for absence from work) **	HZ: €3.27 ± 11.33 at 1 mo (for absence from work), 47.03 ± 311.95 at 3 mo (€46.28 ± 311.85 for absence from work, €0.74 ± 7.88 for hire of caregiver) PHN1: €128.43 ± 526.18 (€127.04 ± 526.06 for absence from work, €1.39 ± 10.76 for hire of caregivers) PHN3: 148.23 ± 587.91(for absence from work) **
42	PHN: £80^a for home help service	PHN: €151.27 ^a for home help service
27	HZ: €556^a (global indirect cost) PHN: €795^a (global indirect cost)	HZ: €657.19 ^a (global indirect cost) PHN: €939.69 ^a (global indirect cost)
31	HZ: €163.86^a for absence from work PHN: €215.72^a for absence from work	HZ: €189.59^a for absence from work PHN: €249.59^a for absence from work
44	HZ: £325.9^a for absence from work	HZ: €613.73^a for absence from work
38	HZ: €62.4^a for loss of productivity PHN: €692.2^a for loss of productivity	HZ: €68.14^a for loss of productivity PHN: €755.88^a for loss of productivity
56	HZ: $2,350^a for work loss (absenteeism, presenteeism)	HZ: €1,756.87 ^a for work loss (absenteeism, presenteeism)
32	HZ: €1,759.71 (€380.48 sick-pay, €1,367.11 sick-leave, €12.12 co-payment) annualized cost PHN: 12,020.08 (€5,453.67 sick-pay, €6,529.99 sick-leave, €36.42 co-payment) annualized cost	HZ: €1,895,21 (€409.78 sick-pay, €1,472.38 sick-leave, €13.05 co-payment) annualized cost PHN: €12,945.63 (€5,873.60 sick-pay, €7,032.80 sick-leave, €39.22 co-payment) annualized cost
57	HZ: $471^a for short-term disability, $538^a for absence from work	€354.50 for short-term disability, €404.93 for absence from work

^a = mean cost, ° = median cost; **the values are referred to base-case on a convenience sample including working and not working subjects.

Table 4. Global costs for HZ-related infection broken down by country

Ref	Country	Hz incidence	Hospitalization rate	Annual total cost	Adjusted figure in € (1st januari 2013)
36	Spain	4.1/1000 population per year	No data	€59.6 million	€67.94 million
34	Korea	No data	0.22–0.32/1000 population per year	$75.9 million in 2003 ($65.5 million for direct costs, $10.4 million for indirect costs) - $143.8 million in 2007 ($123.8 million for direct costs, $20.0 million for indirect costs)	€57.13 million in 2003 (€49.3 Million for direct costs, €7.83 Million for indirect costs) – €108.23 million in 2007 (€93.18 Million for direct costs, €50.62 Million for indirect costs)
42	Uk	4.0/1000 Population per year	No data	£4.8–17.9 million (total cost due to phn) £1.5–5.8 million (best scenario) £10–37.6 million (worst scenario)	€9.07–33.85 million (total cost due to phn) €2.8–11.0 million (best scenario) €18.9–71.1 million (worst scenario)
22	Italy	1.59/1,000 population per year	0.12/1000 population per year	€2,427,209.82 (piedmont region)	€2,868,962.01 (piedmont region)
27	Italy	4.31/1000 population per year	0.10/1000 population per year	€41.2 million global cost (€28.2 million direct cost, €13 million indirect cost)	€48.7 million global cost (€33.3 million direct cost, €15.4 Million indirect cost)
37	Spain	No data	0.13/1000 population per year	€12,731,954	€15.291.076,75
52	Usa	No data	0.16/1000 population per year	$8,182,235 (connecticut state)	€10,333,634.07 (connecticut state)
40	Taiwan	4.97/1000 population per year	0.15/1000 population per year	$7.7 million in 2000 - $9.8 million in 2004	€10.16 million in 2000 – €9.32 Million in 2004
31	France	8.99/1000 population per year	No data	€170 million (€61 million for the insurance)	€196.69 million (€70.58 million for the insurance)
30	Canada	No data	No data	$5.33 million ($0.46 million dollars for medical honoraries, $4.87 million dollars for hospitalized hz cases)	€4.47 million (€0.39 million dollars for medical honoraries, €4.08 million dollars for hospitalized hz cases)
55	Usa	No data	0.25/1,000 population per year	$1.2 billion in 1993 - $1.9 billion in 2004	€1.04 billion in 1993 - €1.64 billion in 2004
28	Australia	9.67-10.10/1000 population per year	0.28–0.39/1000 Population per year	$32.8 million ($8.0 million for principal diagnosis hz cases, $10.8 million for non principal diagnosis hz cases, $8.2 million for drug prescriptions, $4.2 for hz management, $181,000 for specialist referrals, $562,000 for non-admitted ed hz cases, $710,000 for other encounters with gps for drug prescriptions)	€22.40 million (€5.5 million for Principal diagnosis hz cases, €7.4 million for non principal diagnosis hz cases, €5.6 million for drug prescriptions, €2.9 for hz management, €123,609.76 for specialist referrals, €383,804.9 for non-admitted ed hz cases, €484,878.1 for other encounters with gps for drug prescriptions)
32	Germany	5.79/1000 population per year	No data	€105.06 million from the payer perspective (€84.67 million for hz, €20.39 million for phn), €181.74 € million from the societal perspective (€151.87 million for hz, €29.87 million for phn)	€113.09 million from the payer perspective (€91.55 million for Hz, €21.54 million for phn), €196.01 million from the societal perspective (€163.80 millionfor hz, €32.21million for phn)
58	Usa	No data	No data	$1.1 billion	€1.08 billion
57	Usa	No data	No data	$1 billion and more	€0.75 billion and more

Table 5. Range of costs of HZ and PHN broken down by geographical areas

Geographical area	Inpatient cost	Outpatient and consultations cost		Treatment cost and diagnostic procedures
	Herpes Zoster
Asia	€118.13–707.23 (all ages, *) €112.44–1,945.34 (all ages, ^)	€61.67^a (all ages)	No data (all ages)
Europe	€4,725.72 (average hospital admission), €3,550.88 (day-hospital), €5,001.17 (ordinary admission), €3,062.10 with HZ as the principal diagnosis, €2,803.40 without complications, €3,289.06 with complications (> 14 y)	€136.13 ^a-441.85 ^a (> 14 y)	€81.49^a-253.41^a (> 14 y)
	€3,843.20^a-4,467.16^a (> 30 y)	No data (> 30 y)	No data (> 30 y)
	€3,063.74^a ± 1551.97^a (> 50 y)	€145.01^a-211.64^a (> 50 y)	No data (> 50 y)
	€774.66^a-31,026.22^a (all ages)	€0–6,133.48 (all ages)	€118.65^a-242.62^a (all ages)
Oceania	€3064.84^a-3225.30^a (> 50 y)	€203.67^a for non-ED admitted cases, €24.68^a-€31.^51a per GP consultation, €51.63^a for specialists consultations and referrals (> 50 y)	€119.53^a (> 50 y)
US	€230.86^a ± 51.00^b*, €248.13^a ± 150.05^b ^ (> 22 y)	€318.74^a ± 8.83^b* €356.02^a ± 37.27^b^ (> 22 y)	€382.49^a ± 11.77^b* €395.24^a ± 27.46^b^ (> 22 y)
	€9,041.36^a-23,219.82^a; €16,284.60^a for the stay in the SNF (all ages)	No data (all ages)	No data (all ages)
	€5,647.20^a ± 30,109.16^c in the commercially insured and Medicare SOT patients, €6,428.84^a ± 21,329.34^c in the Medicaid patients (all ages)	€621.51^a ± 2,654.81^c in the commercially insured and Medicare SOT patients, 899.36^a ± 1,566.75^c in the Medicaid patients (all ages)	€452.71^a ± 422.42^c in the commercially insured and Medicare SOT patients, €464.82^a ± 701.13^c in the Medicaid patients (all ages)
	$20,948.31^a (all ages, in patients with comorbidities)	No data	No data
	Post-herpetic neuralgia
Asia	No data	No data	No data
Europe	No data (> 14 y)	1 mo, €282.20^a ± 198.63^c; 3 mo, €412.05^a ± 253.75^c(> 14 y)	1 mo:, €172.23a ± 203.70; 3 mo, €312.15^a ± 323.24^c (> 14 y)
	No data (> 30 y)	No data (> 30 y)	No data (> 30 y)
	€3,316.69^a±3,121.66^c (> 50 y)	1 mo, €281.30^a-758.24^c; 3 mo, €574.09^a (€336.77^a-1,039.24^a) (> 50 y)	No data (> 50 y)
	€4,026.05^a (all ages)	range €0–5,131.91^a (all ages)	€278.75^a-614.96^a (all ages)
Oceania	No data	No data	No data
US	€4261.39^a ± 1854.61^b ^ (> 22 y)	892.49^a ± 82.38^b ^ (> 22 y)	1767.32^a ± 177.52^b for drug prescriptions, 263.82^a ± 30.40^b for procedures ^ (> 22 y)
	€3,504.03^a ± 11,173.70^c (> 65 y)	€1,048.89^a ± 2,037.22^c (> 65 y)	€593.60^a ± 1,178.97^c (> 65 y)
	€1,538.17^a-3,130.88^a (all ages)	€2,789.84^a-6,043.64^a (all ages)	€2,946.51^a-6,628.79^a (all ages)

Legend: ^: immunocompromised subjects; *: immunocompetent subjects; ED: Emergency Department; GP: General Practitioner; SNF: Skilled Nursing Facility; SOT: Solid Organ Transplant; ^amean; ^bstandard error; ^cstandard deviation.

Table 6. Search strategies used in the current systematic review

Group	Search items
1. used keywords	- PubMed/MEDLINE (“herpes zoster”[MeSH] OR “herpes zoster”[title/abstract] OR zona OR shingles[MeSH] OR shingles[title/abstract] OR varicella reactivation [title/abstract]) AND (cost [title/abstract] OR cost of illness [MeSH] OR cost of illness [title/abstract] OR drug cost [MeSH] OR drug cost [title/abstract] OR pharmaceutical fee [MeSH] OR prescription fee [MeSH] OR nursing cost [title/abstract] OR physician cost [title/abstract] OR employer health cost [MeSH] OR healthcare cost [MeSH] OR healthcare cost [title/abstract] OR hospital cost [MeSH] OR hospital cost [title/abstract] OR hospital charge [MeSH] OR cost analysis [title/abstract] OR costs and cost analysis [MeSH] OR economic burden [title/abstract] OR economic impact OR economic model [MeSH] OR economic model [title/abstract] OR econometric model [MeSH] OR econometric model [title/abstract] OR hospital economics [MeSH] OR hospital economics [title/abstract] OR nursing economics [mesh] OR nursing economics [title/abstract] OR economics [MeSH] OR economics [title/abstract] OR direct service cost [MeSH] OR health expenditure [MeSH] OR societal cost [title/abstract] OR direct cost [title/abstract] OR indirect cost [title/abstract] OR presenteeism [title/abstract] OR absenteeism [title/abstract] OR productivity loss [title/abstract]) - Scopus (“herpes zoster” OR “shingles”) AND (“cost of illness” OR cost OR “economic burden” OR “economic impact” OR “health expenditure” OR “societal cost” OR “direct cost” OR “indirect cost” OR presenteeism OR absenteeism OR “productivity loss”) using the “Article Title, Abstract, Keywords” option -ISI Web of Science (“herpes zoster” OR “shingles”) AND (“cost of illness” OR cost OR “economic burden” OR “economic impact” OR “health expenditure” OR “societal cost” OR “direct cost” OR “indirect cost” OR presenteeism OR absenteeism OR “productivity loss”) using the “Topic” option - ProQuest (“herpes zoster” OR shingles OR “varicella reactivation”) AND (“cost of illness” OR “drug cost” OR “pharmaceutical fee” OR “prescription fee” OR “nursing cost”OR “physician cost” OR “employer health cost” OR “healthcare cost” OR “hospital cost” OR “hospital charge” OR “cost analysis” OR “economic burden” OR “economic model” OR “econometric model” OR “direct service cost” OR “health expenditure” OR “societal cost” OR “direct cost” OR “indirect cost” OR presenteeism OR absenteeism OR “productivity loss”) using the “Peer-reviewed” and “Scholarly Journals” options - The Cochrane Library (“herpes zoster” OR “shingles”) AND (“cost of illness” OR cost OR “economic burden” OR “economic impact” OR “health expenditure” OR “societal cost” OR “direct cost” OR “indirect cost” OR presenteeism OR absenteeism OR “productivity loss”) using the “Title, Abstract, Keywords” option - EconLit (“herpes zoster” OR “shingles”) AND (“cost of illness” OR cost OR “economic burden” OR “economic impact” OR “health expenditure” OR “societal cost” OR “direct cost” OR “indirect cost” OR presenteeism OR absenteeism OR “productivity loss”)
2. targeted journals	Advances in health economics and health services research/Research in Health economics, BMC health services research, European Journal of Health economics, Evidence and policy, Expert review of pharmacoeconomics and outcomes research, Giornale Italiano di Farmacoeconomia e Farmacoutilizzazion, Healthcare management science, Health economics, Health Economics Review, Health policy, Health services and Outcomes research methodology, Journal of clinicoeconomics and outcomes research, Journal of evaluation in clinical practice, Journal of Health Economics, Journal of health organisation and management, Journal of health politics, policy and law, Journal of Health Services Research and Policy, Journal of Medical Economics, Medical decision making, Pharmacoeconomics

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