Economic burden of herpes zoster in Latin America: A systematic review and meta-analysis

Figures & data

Figure 1. PRISMA flow diagram.

PRISMA, Preferred Reporting Items for Systematic Literature Reviews and Meta-Analyses.

Table 1. Use of resources and costs per patient, as reported in reviewed studies (N = 23). Costs in 2018 international dollars ($).

Study	Study design	Country	Perspective	PHN	Type of resources reported	Direct use of resources	Total direct cost per patient	Indirect use of resources	Total indirect cost per patient
Bollea-Garlatti 2017^Citation47	Case series	Argentina	NA	Yes	NR	Medication, laboratory tests	NR	NR	NR
Corti 2015^Citation48	Case series	Argentina	NA	NR	NR	Laboratory tests, medication	NR	NR	NR
Rampakakis 2017^Citation49	Pooled cost analysis	Argentina	Social	Total^a Yes No	Direct and indirect	Visits to doctor, transportation, hospitalizations, nursing, medication, physical rehabilitation	$1,124.98 $1,583.22 $1,189.53	Missed days at work for the patient, missed days at work for the relative, impaired labor capacity	$1,328.34 $1,489.67 $837.18
Rozenek 2017^Citation50	Case series	Argentina	NA	Yes	NR	Medication, emergency visits, visits to doctor	NR	NR	NR
Vujacich 2008^Citation51	Case series	Argentina	NA	Yes	NR	Medication	NR	NR	NR
Vujacich 2016^Citation52	Cohort	Argentina	Out-of-pocket expense	Yes	Direct and indirect	Visits to doctor, transportation, hospitalizations, nursing, medication, physical rehabilitation	NR	Missed days at work for the patient, missed days at work for the relative, impaired labor capacity, caretakers	NR
Álvarez 2007^Citation53	Case series	Brazil	NA	Yes	NR	Medication	NR	NR	NR
Andrade 2019^Citation54	Case series	Brazil	NA	NR	NR	Medication	NR	NR	NR
Antoniolli 2019^Citation55	Case series	Brazil	NA	Yes	NR	Emergency visits, hospitalizations, medication	NR	NR	NR
Borba 2010^Citation56	Cohort	Brazil	NA	Yes	NR	Medication	NR	NR	NR
Gormezano 2015^Citation57	Case series	Brazil	NA	Yes	NR	Medication	NR	NR	NR
Rampakakis 2017^Citation49	Pooled cost analysis	Brazil	Social	Total Yes No	Direct and indirect	Visits to doctor, transportation, hospitalizations, nursing, medication, physical rehabilitation	$2,528.06 $4,177.91 $1,417.37	Missed days at work for the patient, missed days at work for the relative, impaired labor capacity	$1,151.80 $1,956.82 $1,151.80
Toniolo-Neto 2018^Citation58	Cohort	Brazil	Out-of-pocket expense	Yes	Direct and indirect	Visits to doctor, transportation, hospitalizations, nursing, medication	NR	Missed days at work for the patient, missed days at work for the relative, caretakers	NR
Ordoñez Molina 2013b^Citation59	Budget impact analysis	Colombia	Social	Yes	Direct and indirect	Medication, visits to doctor, physical rehabilitation	NR	NR	NR
Ordoñez Molina 2013^Citation60	Cost-effectiveness evaluation	Colombia	Social	Yes	NR	Medication	NR	NR	NR
Rampakakis 2019^Citation61	Cohort	Colombia	NA	Yes	Direct	Visits to doctor, emergency visits, medication	NR	NR	NR
Rampakakis 2017b^Citation62	Cohort	Costa Rica	NA	Yes	Direct	Visits to doctor, transportation, hospitalizations, nursing, medication, physical rehabilitation	NR	NR	NR
Rampakakis 2017^Citation49	Pooled cost analysis	Latin America	Social	Total^a Yes No	Direct and indirect	Visits to doctor, transportation, hospitalizations, nursing, medication, physical rehabilitation	NC NC NC	Missed days at work for the patient, missed days at work for the relative, impaired labor capacity	NC NC NC
Ortiz-Covarrubias 2015^Citation63	Cohort	Mexico	NR	Yes	Direct	Visits to doctor	$99.99	No	No
Rampakakis 2017^Citation49	Pooled cost analysis	Mexico	Social	Total^a Yes No	Direct and indirect	Visits to doctor, transportation, hospitalizations, nursing, medication, physical rehabilitation	$1,435.51 $2,690.95 $1,247.82	Missed days at work for the patient, missed days at work for the relative, impaired labor capacity	$797.23 $869.08 $511.33
Acosta 2017^Citation64	Cost-effectiveness evaluation	Colombia	Third-party payer	NR	NR	Medication	NR	No	No
Piedade 2017^Citation65	Cost-effectiveness evaluation	Brazil	Public sector	NR	NR	Medication	NR	No	No
Gonzalez 2013^Citation66	Case series	Mexico	NA	Yes	NR	Medication	NR	NR	NR
Kawai 2015^Citation67	Cohort	LAC	NA	Yes	NR	Medication	NR	NR	NR
Vazquez 2017^Citation68	Case series	Mexico	NA	Yes	NR	Hospitalizations	NR	NR	NR
Mendoza Rodriguez 2007^Citation69	Case series	Nicaragua	NA	Yes	NR	Medication, visits to doctor	NR	NR	NR

NA, not applicable; NR, not reported; NC, not calculable; PHN, postherpetic neuralgia.

^aAverage for Argentina, Brazil and Mexico.

Table 2. Hospitalizations due to HZ and treatment options.

Author and year of publication	Hospitalizations (n)	Antivirals (n and specific type)	Steroids (n)	Pain management treatment (n and specific type)	Antibiotics (n)	Prophylaxis (n)	Other treatments (n and specific type)
Bollea-Garlatti 2017^Citation47	NR	41 Acyclovir PO (35) Acyclovir IV (41)	NR	NR	NR	NR	NR
Corti 2015^Citation48	11	11 Acyclovir IV (11)	NR	NR	NR	NR	NR
Rozenek 2017^Citation50	38	1.177	NR	133 NSAIDs (97) Pregabalin (86)	NR	NR	NR
Vujacich 2008^Citation51	NR	271 Acyclovir PO (159) Valacyclovir PO (78) Famciclovir PO (3) Acyclovir IV (1) Foscarnet IV (1)	39	205 NSAIDs (94) Amitriptyline/Carbamazepine (48) Opioids (30)	NR	NR	41 vitamin B (40) Topical acyclovir (24) Alternative therapies (5)
Vujacich 2016^Citation52	4	87 Acyclovir PO (49) Valacyclovir PO (32) Famciclovir PO (9)	3	127 NSAIDs (74) Anti-epileptic drugs (17) Opioids (15) Antidepressants (9) Topical medication (12)	5	NR	5 Ophthalmic drugs (3) Anxiolytics (2)
Antoniolli 2019^Citation55	NR	760 Acyclovir PO (320) Acyclovir IV (440)	NR	NR	NR	NR	NR
Álvarez 2007^Citation53	NR	NR	NR	Amitriptyline (9) Chlorpromazine (6) Gabapentin (4) Carbamazepine (3) Imipramine (2)	NR	NR	NR
Andrade 2019^Citation54	NR	19 Acyclovir PO (17) Valacyclovir PO (2)	NR	NR	NR	NR	NR
Borba 2010^Citation56	9	51 Acyclovir PO (46) Acyclovir IV (5)	NR	51 NSAIDs (51)	NR	NR	NR
Gormezano 2015^Citation57	25	19 Acyclovir IV (19)	NR	NR	NR	NR	NR
Toniolo-Neto 2018^Citation58	13	40 Acyclovir PO (33) Valacyclovir PO (8)	9	99 Analgesics (50) (Acetaminophen (23), AAS (1) Metamizole (19), Hyoscine (2), Others (16)) Anticonvulsants (13) Antidepressants (13) Opioids (12)	NR	NR	114 Topical treatments (31) Anti-inflammatory drugs (5) Benzodiazepines (3) Antihypertensive drugs (5) Vitamins (5) Others (65)
Rampakakis 2019^Citation61	NR	148	NR	139	NR	NR	NR
Rampakakis 2017b^Citation62	16	31 Acyclovir PO (27) Valacyclovir PO (4) Famciclovir PO (2)	9	46 NSAIDs (7) Acetaminophen (12) Anti-epileptic drugs (13) Opioids (11) Antidepressants (3)	NR	NR	16 Topical treatments (antivirals, antibiotics, and steroids) (16) Anxiolytics (3)
Kawai 2015^Citation67	NR	118 Acyclovir PO Valacyclovir PO Famciclovir PO	NR	NR	NR	NR	NR
González 2013^Citation66	NR	12 Acyclovir PO (12)	9	19	NR	NR	Ophthalmic drugs
Vázquez 2017^Citation68	7042	NR	NR	NR	NR	NR	NR
Mendoza Rodríguez 2007^Citation69	NR	261 Acyclovir (184) Valacyclovir PO (60) Brivudine PO (17) Isoprinosine (4)	2	102 Analgesics (71) Tricyclic antidepressants (31)	9		535 Topical drying agents (445) Topical analgesics (1) Topical antivirals (10) Topical antibiotics (4) 2 or more topical drugs (63) Neurotropic vitamins (12)

AAS, anabolic-androgenic steroids; HZ, herpes zoster; IV, intravenous injection; PO, prescribed orally; NSAID, nonsteroidal anti-inflammatory drugs; NR, not reported.

Figure 2. Meta-analysis of number of days of hospitalization due to HZ in immunocompetent patients ≥65 years of age.

HZ, herpes zoster. References: Vujacich 2016;⁵² Toniolo-Neto2018;⁵⁸ Rampakakis 2017.⁶²

Table 3. Quality evaluation for use of resources and cost studies (n = 8).

Publication	Ordoñez Molina 2013^Citation60	Ordoñez Molina 2013b^Citation59	Ortiz-Covarrubias 2015^Citation63	Acosta 2017^Citation64	Piedade 2017^Citation65	Rampakakis 2017^Citation49	Toniolo-Neto 2018^Citation58	Vujacich 2016^Citation52
Country	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Population for analyses	Yes	Yes	Yes	Yes	No	Yes	Yes	Yes
Timelines	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Perspective	Yes	Yes	No	Yes	Yes	Yes	Yes	Yes
Discount rate	Yes	No	No	No	No	No	No	No
Adjustment based on inflation	No	No	No	No	No	No	No	No
Compared interventions	Yes	Yes	No	Yes	Yes	No	No	No
Direct costs	NR	Yes	Yes	NR	NR	Yes	Yes	Yes
Indirect medical costs	NR	Yes	No	No	No	Yes	Yes	Yes
Indirect costs	NR	Yes	No	No	No	Yes	Yes	Yes
Effectiveness	NR	NA	NA	NR	NR	NA	NA	NA
Treatment compliance/adherence	NR	NR	NR	NR	NR	NR	NR	NR
Decision model used?	Yes	Yes	No	Yes	Yes	No	No	No
Does it show costs, economic and/or health results?	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Uncertainty	Yes	Yes	No	Yes	Yes	Yes	No	No
Conflicts of interest and financing source	NR	NR	NR	NR	NR	Yes	Yes	Yes
Software	NR	NR	NR	NR	NR	Yes	Yes	No
Costs standardization	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Cost breakdown	NR	NR	NR	NR	NR	Yes	Yes	Yes
Summary suitable for audience	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Are RCT based EE results and decision models split?	NA	NA	NA	NA	NA	NA	NA	NA
Are DSA and PSA reported separately?	Yes^a	Yes^a	No	Yes^a	Yes^a	Yes^a	No	No

NA, not applicable; NR, not reported; DSA, deterministic sensitivity analysis; PSA, probabilistic sensitivity analysis.

Yes^a: Reporting only deterministic sensitivity analysis.

Table 4. Brazil. Costs of hospitalizations caused by varicella and HZ in patients ≥65 years of age in the public health system (SUS). Values in International dollars ($)^a per year.

Year	Total cost	Hospital service cost	Professional service cost	Costs per hospitalization			Costs per day of hospitalization
				Total cost	Hospital service cost	Professional service cost	Total cost	Hospital service cost	Professional service cost
2010	$ 1,324,051	$ 1,152,290	$ 171,762	$ 671	$ 584	$ 87	$ 100	$ 87	$ 13
2011	$ 1,122,124	$ 974,882	$ 147,242	$ 639	$ 555	$ 84	$ 95	$ 83	$ 13
2012	$ 799,812	$ 695,392	$ 104,420	$ 553	$ 481	$ 72	$ 82	$ 72	$ 11
2013	$ 1,154,579	$ 1,006,882	$ 147,697	$ 674	$ 588	$ 86	$ 88	$ 76	$ 11
2014	$ 905,426	$ 789,582	$ 115,844	$ 656	$ 572	$ 84	$ 92	$ 81	$ 12
2015	$ 853,862	$ 748,061	$ 105,801	$ 535	$ 468	$ 66	$ 75	$ 66	$ 9
2016	$ 876,809	$ 769,092	$ 107,717	$ 557	$ 489	$ 68	$ 76	$ 67	$ 9
2017	$ 935,404	$ 823,142	$ 112,262	$ 551	$ 485	$ 66	$ 73	$ 65	$ 9
2018	$ 867,152	$ 762,686	$ 104,466	$ 499	$ 439	$ 60	$ 64	$ 56	$ 8
2019	$ 791,948	$ 697,410	$ 94,457	$ 455	$ 401	$ 54	$ 62	$ 55	$ 7

HZ, herpes zoster.

^aExchange rates per year from Brazilian real to international dollars ($): 1.388 (2010), 1.473 (2011), 1.606 (2012), 1.701 (2013), 1.813 (2014), 1.989 (2015), 2.133 (2016), 2.182 (2017), 2.201 (2018), and 2.253 (2019).⁴⁶

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