ABSTRACT
Herpes zoster (HZ) is characterized by a unilateral, painful rash, which in most cases requires medical attention and pharmacological treatment. Several complications, including postherpetic neuralgia (PHN), may increase the burden of illness and healthcare costs. The objective of this study was to evaluate healthcare resource utilization (HCRU), and direct and indirect costs incurred by patients with HZ from a private sector perspective in Mexico. We carried out a retrospective, medical chart review at five private clinics in Mexico (Mexico City, Monterrey, Aguascalientes, Durango City, León Guanajuato). Healthcare data from patients having an episode of HZ between 2018–2022 were extracted and HCRU and health outcomes were captured over a 6-month period following HZ diagnosis. Outcomes and costs were analyzed by PHN status, age category and comorbidity. Overall, 228 patients with HZ were identified; 59% of patients were women and 67% of patients had at least one comorbidity. Seventy-six (33%) patients developed PHN in the overall population, while among people with comorbidities, 39% developed PHN. Eight (4%) patients were hospitalized. Median direct costs per HZ episode were higher in patients with vs without PHN (United States dollars $836 vs $535) and tended to increase with increasing age. Our results show that HZ imposes a significant burden on patients and the private healthcare system, especially on people developing PHN. PHN and increasing age were the principal cost drivers in this study.
KEYWORDS: Burden of illness, direct costs, herpes zoster, indirect costs, medical chart review, Mexico, postherpetic neuralgia, private healthcare sector
Plain Language Summary
Herpes zoster (HZ), also known as shingles, is a rash that causes severe pain. Older people and people with chronic diseases are more likely to have shingles. Pain can continue for months after the rash has healed, a condition which is called postherpetic neuralgia (PHN). In Mexico, there is little information about the costs and health issues caused by shingles. The goal of this study was to analyze medical records of patients with shingles to describe its economic burden and health consequences. Looking at medical records between 2018 and 2022 at 5 private clinics in Mexico, we identified 228 patients with shingles. Most patients (75%) were 50 years or older and 67% had at least one chronic condition, such as high blood pressure or diabetes. Only a few people had private insurance and 83% of patients paid out-of-pocket. One in three patients (33%) developed PHN and this increased healthcare costs. The cost for shingles without PHN was $535 (MXN 8,993), and it was almost double as much for shingles with PHN ($836 [MXN 12,058]). In this study, all patients were treated with antivirals, but many patients needed additional medication to treat their pain, and eight patients were hospitalized. Our results show that in Mexico, shingles occurs, requires medical attention and drug treatment, and can have long-term consequences such as PHN; costs are high and often carried by the patient. People and healthcare professionals must be aware of these risks, so that they can decide whether to get vaccinated against shingles.
GRAPHICAL ABSTRACT
Introduction
Herpes zoster (HZ) disease is characterized by debilitating pain and a blistering rash.1 While the initial rash typically disappears within two to four weeks, several complications may develop.2,3 The most common complication is postherpetic neuralgia (PHN), generally defined as pain persisting after three months from the initial rash onset.4 Up to 30% of patients with HZ develop PHN, which can significantly affect a person’s quality of life long after the acute episode.5,6 Other complications include herpes zoster ophthalmicus, disseminated zoster, neurological complications, and visceral involvement.3
HZ incidence increases with increasing age, with an estimated lifetime risk of 25% to 30%.7 HZ incidence is estimated between 3 and 5/1,000 patient-years but may reach up to 13/1,000 patient-years in those aged ≥80 years.6–8 Incidence increases monotonically with increasing age; in a retrospective, United States (US) healthcare database analysis, HZ incidence was 6.7/1,000 patient-years in 50–59 years old, 9.3/1,000 in 60–69 years old, 12.0/1,000 patient-years in 70–79 years old and 12.8/1,000 in ≥80 years old.8 In addition, the risk of HZ and PHN is higher in people with underlying disease and chronic conditions that may debilitate the immune system.9 In a systematic literature review (SLR) and meta-analysis focusing on studies from Latin America, the HZ incidence rate ranged between 6.4 and 36.5 cases/1,000 patient-years in populations at higher risk.10 No data on HZ incidence in the general population could be identified in this study for the Latin American region.
Severe HZ cases and/or cases with complications may require hospitalization and in rare cases may lead to death. SLRs reported hospitalization rates for HZ between 2 and 25/100,000 person-years with rates increasing steeply with increasing age; among patients hospitalized for HZ, more than 90% of patients are aged ≥50 years.6,11 In an SLR including studies from Latin America only, the frequency of hospitalization ranged between 3% and 35.7% in at-risk patients.10
Unsurprisingly, healthcare resource utilization (HCRU) in patients with HZ is high, and affects all types of healthcare, e.g., outpatient, inpatient, emergency room visits.12 In a retrospective case-control study using US healthcare claims, patients with HZ and/or PHN demonstrated excess healthcare resource use compared with matched controls, leading to incremental annual healthcare costs of US dollars ($) 1,308 per patient overall, and $5,463 per patient in case of HZ with PHN.12 In a pooled analysis of three prospective cohort studies in Brazil, Argentina and Mexico, average costs from the public healthcare perspective amounted to $1,464.59 per HZ episode, including both direct and indirect costs.13 Average costs were markedly higher in HZ cases with PHN ($2,001.13) compared with HZ without PHN ($867.72).
In Mexico, the healthcare system is highly fragmented into public and private healthcare providers, which are accessible to patients based on social security insurance and employment status.14–16 Private healthcare insurance is in demand as it offers more modern facilities compared with public healthcare providers. Furthermore, public providers often lack the necessary resources to cover all healthcare claims, leading to important out-of-pocket payments with 35% of households reporting to pay privately for healthcare in Mexico.15,16 There is limited information regarding the clinical and economic burden of HZ in Mexico from a private payer’s perspective. The burden of disease and cost of illness are factors decision-makers consider before introducing a vaccine into the private healthcare system. The objective of this study was to improve knowledge about the economic burden of HZ and HCRU in Mexican private healthcare settings. In addition, the study aimed at characterizing HZ treatment pathways in the private healthcare setting in terms of disease presentation, management, and outcome.
Materials and methods
In this retrospective medical chart review, healthcare data from five private clinics in Mexico were analyzed between 2018 and 2022. The five private clinics were representative of urban centers (Mexico City, Monterrey, Aguascalientes, Durango City, León Guanajuato) in Mexico.
Participants with a diagnosis of HZ were included, and data related to the objectives of this study were extracted. Main outcomes included HCRU, pharmacological treatment, complications, and HZ sequelae.
Participants
Patients with a confirmed HZ diagnosis, based exclusively on clinical findings and coded according to the pre-determined coding of the International Classification of Diseases, Tenth Revision (ICD-10), between 2018 and 2022 and aged 18 years and older were identified via medical chart review (Supplementary information, Table S1). HCRU and costs were extracted over six months following the HZ diagnosis. In addition, HCRU and costs that were related to HZ disease but occurred prior to establishing HZ diagnosis at the private clinic, were also assessed; in practice, previous physician visits and referrals to the private clinic are usually recorded in the patient’s medical record based on specific questions asked by the physician during the first consultation at the clinic.
Participants were stratified into several age categories (i.e., 18–29, 30–39, 40–49, 50–59, 60–69, 70–79 and ≥80 years).
Data extraction
Data extraction was carried out by the principal investigator at each center using a study-specific data-extraction form with pre-specified categories and response options (Appendix A). The extraction tool was tested in a pilot study including ten patients across all centers. The extraction form was modified based on the outcome of the pilot study to ensure optimal completion rates and accuracy in data capturing.
Data from all participants were entered anonymously into the final Excel extraction form (Appendix A).
Baseline demographics included age, sex, health insurance type, and name of clinic. Relevant medical history included comorbidities, recurrent HZ (over the last 12 months), history of varicella, and HZ complications. The extraction form specified 11 comorbidities (e.g., diabetes, tumors, cardiovascular disease) and allowed for adding other comorbidities in free format (Appendix A). Similarly, common HZ complications (e.g., PHN, ophthalmic HZ) were pre-programmed, while additional complications could be added as free text (Appendix A). HCRU data included previous general physician and/or specialist visits due to the current condition (i.e., HZ and/or PHN), previous laboratory tests due to the current condition, laboratory tests after HZ diagnosis, prescribed medication and number of days of therapy, hospitalization and number of days hospitalized, and number of follow-up visits and type of follow-up treatments if recovered with and without sequelae (Appendix A). Only data recorded in the medical charts of the private clinic were considered. This could include other physician visits, which occurred outside of the clinic but were recorded in the patient’s medical chart; however, no other database was consulted to account for possible healthcare resource use outside of the private clinic’s network.
Outcomes
Outcomes included the number of HZ and PHN cases overall and by age category, HCRU, and direct and indirect costs. Patients could recover with or without sequelae. Sequelae were defined as symptoms persistent beyond the acute phase and no longer associated with active infection. Exploratory subgroup analyses were carried out by most common comorbidities, i.e., hypertension, type 2 diabetes mellitus, human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), and hypothyroidism.
Costs
Direct medical costs
Direct medical costs were calculated using private clinic tariffs for physician consultation, hospitalization, and anesthetic nerve block treatment averaged over the five private clinics (Supplementary information, Table S2). Similarly, the cost of antiviral therapy and other treatments (e.g., pain medication) represents average prices from local suppliers.
Prices for antiviral drugs were estimated based on pharmacy prices in the five selected locations, as well as the dose and duration of treatment according to the prescription.
Thus, direct costs represent average treatment costs based on local tariffs rather than individual patient costs.
Indirect costs
Indirect costs included days off work due to healthcare visits, exams, and/or hospitalization related to HZ and/or PHN for the HZ patients who had to take days off work (Supplementary information, Table S3). Mexican unemployment rates were included in the estimation of time off work.17 The average daily wage was set to 576.20 Mexican pesos (MXN), corresponding to the average Mexican wage as of February 2024.18
Costs were estimated in MXN and converted into 2024 $, using the OANDA currency converter accessed on 15 May 2024.19 The resulting average daily wage was $34.25. All costs are reported in $, and selected costs in MXN are shown in parentheses or included as supplementary information.
All patient information was anonymized in accordance with general data protection rules and the ethical principles of the Declaration of Helsinki. No approval by an ethics committee was required for this non-interventional, observational study, which respected national and international data protection regulations.20
Results
Participants
Overall, 228 patients with an HZ diagnosis were identified across five private clinics. Most participants (n = 126) were from Durango City, followed by Aguascalientes (n = 34), Mexico City (n = 33), León Guanajuato (n = 23) and Monterrey (n = 12).
There were more female patients (59%) than male patients (41%), and 75% of patients were aged ≥50 years (Table 1). Private insurance was uncommon, with the majority of participants (83%) paying out-of-pocket. Fifteen (7%) patients had recurrent HZ. For most patients (64%), it was unknown whether they had varicella in the past. In the case of 79 (35%) patients, past varicella could be confirmed based on medical charts. In 219 (96%) patients, PHN status (yes, no) could be inferred from medical charts; for nine (4%) patients, it was not known whether they had developed PHN or not.
Table 1.
Baseline characteristics and medical history.
| Total | Aguascalientes | Durango City | León Guanajuato | Mexico City | Monterrey | |
|---|---|---|---|---|---|---|
| (n) | 228 | 34 | 126 | 23 | 33 | 12 |
| Year, n (%) | ||||||
| 2018 | 37 (16) | 1 (3) | 26 (21) | 9 (39) | 0 (0) | 1 (8) |
| 2019 | 36 (16) | 0 (0) | 23 (18) | 7 (30) | 5 (15) | 1 (8) |
| 2020 | 35 (15) | 8 (24) | 22 (17) | 4 (17) | 0 (0) | 1 (8) |
| 2021 | 95 (42) | 25 (74) | 54 (43) | 3 (13) | 10 (30) | 3 (25) |
| 2022 | 25 (11) | 0 (0) | 1 (1) | 0 (0) | 18 (55) | 6 (50) |
| Sex, n (%) | ||||||
| Female | 134 (59) | 16 (47) | 85 (67) | 10 (43) | 15 (45) | 8 (67) |
| Male | 94 (41) | 18 (53) | 41 (33) | 13 (57) | 18 (55) | 4 (33) |
| Age Category, n (%) | ||||||
| 18–29 | 7 (3) | 2 (6) | 1 (1) | 1 (4) | 2 (6) | 1 (8) |
| 30–39 | 23 (10) | 5 (15) | 10 (8) | 3 (13) | 4 (12) | 1 (8) |
| 40–49 | 28 (12) | 6 (18) | 7 (6) | 1 (4) | 10 (30) | 4 (33) |
| 50–59 | 48 (21) | 10 (29) | 24 (19) | 8 (35) | 5 (15) | 1 (8) |
| 60–69 | 58 (25) | 5 (15) | 37 (29) | 6 (26) | 7 (21) | 3 (25) |
| 70–79 | 40 (18) | 4 (12) | 31 (25) | 2 (9) | 2 (6) | 1 (8) |
| 80+ | 24 (11) | 2 (6) | 16 (13) | 2 (9) | 3 (9) | 1 (8) |
| Insurance Type, n (%) | ||||||
| Social Security | 16 (7) | 0 (0) | 0 (0) | 0 (0) | 16 (48) | 0 (0) |
| Private health insurance | 12 (5) | 0 (0) | 0 (0) | 0 (0) | 7 (21) | 5 (42) |
| IMSS (Mandatory) | 11 (5) | 1 (3) | 0 (0) | 0 (0) | 7 (21) | 3 (25) |
| CENSIA | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Out-of-pocket | 189 (83) | 33 (97) | 126 (100) | 23 (100) | 3 (9) | 4 (33) |
| Recurrent HZ Case (past 12 months), n (%) | ||||||
| Yes | 15 (7) | 10 (29) | 4 (3) | 1 (4) | 0 (0) | 0 (0) |
| No | 213 (93) | 24 (71) | 122 (97) | 22 (96) | 33 (100) | 12 (100) |
| Previous Number of Days with Physician Visits, n (%) | ||||||
| None | 173 (76) | 22 (65) | 126 (100) | 11 (48) | 12 (36) | 2 (17) |
| 1–2 days | 53 (23) | 11 (32) | 0 (0) | 11 (48) | 21 (64) | 10 (83) |
| 3–4 days | 2 (1) | 1 (3) | 0 (0) | 1 (4) | 0 (0) | 0 (0) |
| Previous Lab Test, n (%) | ||||||
| None | 227 (100) | 34 (100) | 126 (100) | 23 (100) | 33 (100) | 11 (92) |
| 3 time | 1 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 1 (8) |
| Past History of Varicella, n (%) | ||||||
| Yes | 79 (35) | 19 (56) | 7 (6) | 14 (61) | 27 (82) | 12 (100) |
| No | 3 (1) | 1 (3) | 1 (1) | 0 (0) | 1 (3) | 0 (0) |
| Unknown | 146 (64) | 14 (41) | 118 (94) | 9 (39) | 5 (15) | 0 (0) |
| Past medical conditions/comorbidity | ||||||
| Yes | 153 (67) | 12 (35) | 86 (68) | 16 (70) | 29 (88) | 10 (83) |
| No | 75 (33) | 22 (65) | 40 (32) | 7 (30) | 4 (12%) | 2 (17) |
CENSIA, Centro Nacional para la Salud de la Infancia y Adolescencia (National Center for Infant and Adolescent Health); IMSS, Instituto Mexicano del Seguro Social (Mexican institute of social security); n, number of patients.
Comorbidities were common in these patients; 153/228 (67%) patients had at least one comorbidity (Supplementary information, Table S4). HZ patients with comorbidities tended to be younger than those without comorbidity (Supplementary information, Table S5). The most common comorbidities were hypertension (51 [33%] patients), type 2 diabetes mellitus (34 [22%] patients), HIV/AIDS (18 [12%] patients), and hypothyroidism (15 [10%] patients). Among patients with these four common comorbidities (n = 118), seven (6%) had recurrent HZ and 46 (39%) had PHN complications. Varicella status was unknown for 80% of patients with comorbidities, while 19% of patients had a documented history of varicella.
Health outcomes
The majority reported no HZ complications (n = 143, 63%). Seventy-six (33%) participants had PHN, and nine (4%) participants had other complications (HZ ophthalmic: n = 6; infection: n = 2, HZ with other complication n = 1) (Table 2). Among patients with known PHN status (n = 219), the proportion of patients aged ≥50 years was higher in patients with PHN (86%) compared to those without PHN (69%) (Table 3). A higher proportion of patients with PHN had at least one comorbidity (75% vs 63% of patients with and without PHN, respectively) (Table 3). In the overall patient population (n = 228), 148 (65%) recovered from HZ without sequelae, while 80 (35%) patients had sequelae related to HZ. Among patients with the four common comorbidities (n = 118), 39% developed PHN. Fifty-nine percent (59%) recovered from HZ without sequelae vs 41% recovering with sequelae (Supplementary information, Table S5).
Table 2.
Overview of HZ outcomes and HCRU.
| Total (N = 228) | Aguascalientes (n = 34) | Durango City (n = 126) | León Guanajuato (n = 23) | Mexico City (n = 33) | Monterrey (n = 12) | |
|---|---|---|---|---|---|---|
| Complications with HZ, n (%) | ||||||
| HZ with no complications | 143 (63) | 26 (76) | 81 (64) | 15 (65) | 17 (52) | 4 (33) |
| PHN | 76 (33) | 8 (24) | 43 (34) | 8 (35) | 11 (33) | 6 (50) |
| HZ Ophthalmic | 6 (3) | 0 (0) | 1 (1) | 0 (0) | 5 (15) | 0 (0) |
| Infections | 2 (1) | 0 (0) | 1 (1) | 0 (0) | 0 (0) | 1 (8) |
| HZ with other complications | 1 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 1 (8) |
| Hospitalization, n (%) | ||||||
| Yes | 8 (4) | 1 (3) | 0 (0) | 0 (0) | 2 (6) | 5 (42) |
| No | 220 (96) | 33 (97) | 126 (100) | 23 (100) | 31 (94) | 7 (58) |
| Number of Days of Hospitalization, n (%) | ||||||
| None | 220 (96) | 33 (97) | 126 (100) | 23 (100) | 31 (94) | 7 (58) |
| 1–5 days | 3 (1) | 1 (3) | 0 (0) | 0 (0) | 2 (6) | 0 (0) |
| 6–10 days | 5 (2) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 5 (42) |
| Laboratory Test for Patients with HZ, n (%) | ||||||
| None | 226 (99) | 34 (100) | 126 (100) | 23 (100) | 33 (100) | 10 (83) |
| PCR | 1 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 1 (8) |
| Tissue culture | 1 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 1 (8) |
| Medication Given, n (%) | ||||||
| Yes | 228 (100) | 34 (100) | 126 (100) | 23 (100) | 33 (100) | 12 (100) |
| No | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Number of Days of Therapy, n (%) | ||||||
| 1–10 days | 189 (83) | 24 (71) | 122 (97) | 23 (100) | 8 (24) | 12 (100) |
| 11–19 days | 35 (15) | 7 (21) | 3 (2) | 0 (0) | 25 (76) | 0 (0) |
| 20–30 days | 4 (2) | 3 (9) | 1 (1) | 0 (0) | 0 (0) | 0 (0) |
| HZ Health Outcome, n (%) | ||||||
| Recovered without sequelae/follow-up | 148 (65) | 24 (71) | 82 (65) | 15 (65) | 18 (55) | 9 (75) |
| Recovered with sequelae/follow-up | 80 (35) | 10 (29) | 44 (35) | 8 (35) | 15 (45) | 3 (25) |
| Death | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Number of Days of Follow-up Visits (if recovered with sequelae and followed up), n (%) | ||||||
| None | 159 (70) | 25 (74) | 99 (79) | 17 (74) | 8 (24) | 10 (83) |
| 1–3 days | 60 (26) | 9 (26) | 26 (21) | 5 (22) | 20 (61) | 0 (0) |
| 4–6 days | 1 (0) | 0 (0) | 1 (1) | 0 (0) | 0 (0) | 0 (0) |
Note: Sum of percentages may not equal 100 due to rounding. HCRU, healthcare resource utilization; HZ, herpes zoster; N, total number of patients; n, number of patients at specific clinical site; PCR, polymerase chain reaction; PHN, postherpetic neuralgia.
Table 3.
Patients’ demographics and disease characteristics by HZ PHN status.
| Patient Characteristics | PHN Status |
|
|---|---|---|
| No N = 143 |
Yes N = 76 |
|
| Age category, n (%) | ||
| 18–29 years | 7 (100) | 0 (0) |
| 30–39 years | 19 (83) | 4 (17) |
| 40–49 years | 19 (73) | 7 (27) |
| 50–59 years | 35 (74) | 12 (26) |
| 60–69 years | 32 (55) | 26 (45) |
| 70–79 years | 18 (47) | 20 (53) |
| 80+ years | 13 (65) | 7 (35) |
| Sex, n (%) | ||
| Female | 88 (67) | 43 (33) |
| Male | 55 (63) | 33 (38) |
| Number of days of therapy, n (%) | ||
| 1–10 days | 125 (68) | 60 (32) |
| 11–19 days | 15 (50) | 15 (50) |
| 20–30 days | 3 (75) | 1 (25) |
| Past medical conditions/comorbidity, n (%) | ||
| Yes | 90 (61) | 57 (39) |
| No | 53 (74) | 19 (26) |
| HZ health outcome, n (%) | ||
| Recovered without sequelae/follow-up | 141 (98) | 3 (2) |
| Recovered with sequelae/follow-up | 2 (3) | 73 (97) |
| Death | 0 (0) | 0 (0) |
HZ, herpes zoster; N, total number of patients; n, number of patients per category; PHN, postherpetic neuralgia.
Healthcare resource utilization and treatment pathway
Fifty-five (24%) patients had at least one physician visit for symptoms associated with HZ prior to visiting a private clinic.
After diagnosis of HZ, all patients received pharmacological treatment; the duration varied between 5 and 30 days. The most common treatments prescribed after the initial diagnosis were antivirals (acyclovir, valacyclovir) (Figure 1). Following the initial diagnosis, every patient, irrespective of their recovery status or any ensuing sequelae, had at least one follow-up appointment, during which they could receive additional prescriptions (Table 2, Figure 1). The most common type of medication prescribed during follow-up visits included medication to treat neuritic pain (pregabalin, gabapentin) and other pain medication (e.g., paracetamol, tramadol) (Figure 1).
Figure 1.
Number of prescriptions for pharmacological treatments after initial diagnosis and during follow-up visits.
Each patient could receive more than one medication; the number of prescriptions may be larger than the number of patients.
Laboratory exams were extremely rare, with only one patient being prescribed biological tests.
Only a few patients needed hospitalization (n = 8; 4%). Mean length of stay was six days (range: 1–10 days) (Table 2; Supplementary information, Table S6). Among patients with comorbidities, three patients with diabetes required hospitalization for infection, ophthalmic HZ and PHN, respectively.
Costs
Median direct unit cost per HZ episode was $535 (MXN 8,993) for patients without PHN and $836 (MXN 12,058) for patients with PHN.
PHN was the major cost driver, leading to higher median and mean unit costs in all age categories (Figure 2, Table 4). The largest differences in median cost per HZ episode depending on PHN status were observed in the 50–59 years age category: median unit cost per HZ episode was $2,035 (MXN 34,239) vs $248 (MXN 4,180) in patients with and without PHN respectively, and in the 60–69 years age category: median unit cost per HZ episode was $1,515 (MXN 25,496) vs $535 (MXN 8,993) in patients with and without PHN, respectively. A similar picture emerged in other age categories, though less pronounced (Figure 2).
Figure 2.
Average costs per HZ case by age category and PHN status.
HZ, herpes zoster; Max, maximum; Min, minimum; PHN, postherpetic neuralgia; Q, quartile; USD, United States dollars; y, years.
Table 4.
Costs per HZ episode (USD).
| Without PHN |
With PHN |
|||
|---|---|---|---|---|
| Age Category | Mean | Median (Q1; Q3) | Mean | Median (Q1; Q3) |
| Direct Unit Costs per HZ Case (USD) | ||||
| 18–29 years | 316 | 248 (179; 391) | – | – |
| 30–39 years | 418 | 461 (179; 568) | 694 | 745 (614; 825) |
| 40–49 years | 791 | 394 (217; 535) | 2,871 | 914 (669; 2,132) |
| 50–59 years | 747 | 248 (179; 535) | 6,868 | 2,035 (801; 12,989) |
| 60–69 years | 688 | 535 (321; 580) | 6,067 | 1,515 (537; 11,063) |
| 70–79 years | 495 | 535 (353; 535) | 5,359 | 836 (401; 4,430) |
| ≥80 years | 402 | 535 (209; 535) | 4,924 | 717 (564; 5,827) |
| All age categories | 612 | 535 (204; 535) | 4,706 | 836 (401; 2,231) |
| Indirect Unit Costs per HZ Case (USD) | ||||
| 18–29 years | 34 | 34 (34; 34) | – | – |
| 30–39 years | 36 | 34 (34; 34) | 94 | 86 (60; 120) |
| 40–49 years | 41 | 34 (34; 34) | 147 | 137 (86; 205) |
| 50–59 years | 40 | 34 (34; 34) | 88 | 86 (60; 103) |
| 60–69 years | 39 | 34 (34; 34) | 58 | 68 (34; 103) |
| 70–79 years | 34 | 34 (34; 34) | 68 | 68 (34; 103) |
| ≥80 years | 34 | 34 (34; 34) | 83 | 68 (51; 103) |
| All age categories | 38 | 34 (34; 34) | 79 | 68 (34; 103) |
HZ, herpes zoster; PHN, postherpetic neuralgia; Q, quartile; USD, United States dollars.
An additional cost driver in this population was the presence of comorbidities. Patients with at least one comorbidity had higher mean direct unit costs in some age categories, but not all (Figure 3; Supplementary information, Table S7). These results should be interpreted with caution due to the small sample size in the younger and older subgroups.
Figure 3.
Mean direct unit costs by PHN status in patients with and without comorbidities.
HZ, herpes zoster; n, number of patients; PHN: postherpetic neuralgia; USD, United States dollars; y, years.
Hospitalization could be an additional cost driver. In this study, only eight (4%) patients were hospitalized. Among patients hospitalized, costs per patient ranged between $664 (MXN 11,178) and $15,374 (MXN 258,644) with a median cost of $3,207 (MXN 53,961). The direct cost per HZ patient correlated with length of stay and was in general higher if patients also developed PHN.
Physician visits and exams carried out prior to HZ diagnosis led to additional direct costs of $6,742 (MXN 113,422), i.e., $837 (MXN 14,079) per HZ case (Supplementary information, Table S8).
Median indirect unit costs per HZ episode were $68 and $34 for patients with and without PHN, respectively (Table 4). Indirect costs were similar in all age categories, except in patients aged 40–49 years with PHN, whose median indirect unit costs were estimated at $137. Indirect costs accounted for approximately 7% and 6% of median costs per HZ episode with and without PHN, respectively.
Exploratory cost analysis for patients with comorbidities was carried out by PHN status and age category. Among patients with comorbidities, direct costs per HZ episode were consistently higher in patients who developed PHN compared to those without PHN, regardless of comorbidity (Supplementary information, Tables S7 and S9). In patients with hypertension and PHN, median unit cost was $782 compared to $535 in patients without PHN. In patients with type 2 diabetes mellitus, median unit cost in patients with PHN was $816 compared with $535 in patients without PHN.
Finally, in patients with comorbidities, median indirect unit costs varied between $34 and $137 per HZ episode depending on comorbidity and PHN status.
Discussion
In this study, the economic burden of HZ and its complications have been evaluated from a private payer’s perspective in Mexico. Overall, 228 patients were diagnosed with HZ at five representative private clinics between 2018 and 2022. Median direct unit costs per HZ episode were high, $535 without PHN and $836 with PHN. Indirect costs of $34 to $137 per HZ episode need to be added due to workdays lost by the patient. The major cost driver for both direct and indirect costs was the development of PHN.
Information regarding the burden of HZ on the healthcare system and people in Latin America is limited.21 Rampakakis et al. analyzed direct and indirect costs due to HZ and PHN in three Latin American countries, including Brazil (n = 145), Argentina (n = 96), and Mexico (n = 142).13 Average direct costs estimated through the pooled analysis were in the same order of magnitude as those obtained in our study ($421.5 and $1,227.7 for HZ cases without and with PHN). Studies from other countries, i.e., Canada, Spain and Italy, carried out from a public healthcare perspective, revealed a similar picture: average costs per HZ episode with PHN were 1.5 to 6-fold higher compared with HZ episodes without PHN.22–24 Even though direct costs reported in these studies cannot be compared directly to our results because of different timeframes, currencies and perspectives (public vs private), direct costs per HZ/PHN episode were in the same order of magnitude as those observed in our study. On the other hand, costs reported for the US, based on healthcare claims between 2008 and 2011, were higher than those obtained in our study; excess healthcare costs were estimated at $1,308 for HZ without complications and $5,463 for HZ with PHN.12
In the study by Rampakakis et al, indirect costs were substantial, namely $392 for any HZ episode regardless of PHN status ($427 and $252 for HZ with and without PHN, respectively), accounting for 36% of total costs. In our analysis, indirect costs represented approximately 6% of total median costs per HZ episode without PHN and approximately 7% of total median costs for HZ with PHN. The difference between the two studies stems from a more conservative approach adopted in our analysis, where days off work were estimated based on HCRU only, namely days off work due to physician visits, laboratory exams and days of hospitalizations. Any days off work because of disease-related incapacity were not accounted for in this analysis. In addition, the national average wage was used to calculate indirect costs, while the study population presenting to private clinics are likely to have higher wages. On the other hand, Rampakakis et al. assessed work effectiveness prospectively via patient-reported questionnaires; in this analysis, 62% of all patients had to take time off work, with an average of 41 days lost.13
PHN was the most common complication in our study (33% of patients), followed by ocular HZ (3%). This matches numbers reported in systematic reviews and observational studies.3,7,25 The proportion of patients developing PHN ranged between 5% to more than 30%, while ophthalmic HZ complications were reported in up to 6% of patients.3,6 Other potential HZ complications include secondary infections, neurological complications, visceral involvement, and disseminated zoster.3 In our study, two (1%) patients had infections subsequent to HZ, and one patient had another complication not further specified.
Several systematic literature reviews and meta-analyses have identified risk factors for HZ, PHN and severe HZ disease.9,26–28 Increasing age is among the primary risk factors for HZ due to a decrease in cell-mediated immunity against varicella zoster virus.29 People with immunocompromised conditions because of disease or immunosuppressive therapy, people with comorbidities such as diabetes or respiratory disease, and people with autoimmune disorders and psychiatric conditions are also at increased risk of developing HZ, even at a younger age.9,26 Data collected in this study confirmed that a) the majority of HZ cases (75%) occurred in people aged ≥50 years, b) the majority of PHN cases (86%) occurred in people ≥50 years, c) all but one complication occurred in patients ≥50 years and d) people with comorbidities accounted for 67% of the overall study population and were younger than the overall population.
Our results suggest that people with comorbidities are at increased risk of HZ at an earlier age compared with people without health issues. In a retrospective medical claims analysis, the odds ratio of HZ in people with vs without comorbidities was greater than one in all age groups but more so in the youngest age group (18–49 years).30 The presence of underlying conditions, such as chronic obstructive pulmonary disease, diabetes, rheumatoid arthritis and immunosuppressive diseases and/or therapy was also associated with an increased risk of HZ and PHN.31–33
In addition, our results suggest that PHN, older age and presence of comorbidities led to an increase in direct costs per HZ case, though there were some exceptions in this trend. Unit costs per HZ episode decreased again in older age groups (≥70 years). This could be due to the smaller sample size in older age groups, high variability in cost data or differences in healthcare seeking behavior in these age categories.
As many other countries worldwide, Mexico is facing a demographic shift toward an older population, which may lead to a rise in healthcare costs, including health issues caused by vaccine-preventable diseases such as HZ.22,34,35 To avert an increase in healthcare costs and to improve quality of life, several countries promote strategies for healthy aging, including investments in preventive healthcare. HZ vaccination effectively protects against HZ and PHN.36,37 HZ vaccination also lowers the risk of other HZ-related complications, e.g., ophthalmic zoster-related complications and ischemic stroke,38 further lending support for preventive HZ strategies. Evidence gathered in this study helps in assessing potential benefits of HZ vaccination in Mexico.
There are several limitations to this study. The patient sample is a convenience sample of patients seeking medical care at private clinics. The study population seeking private healthcare may not be representative of the overall Mexican population. However, in Mexico, the private healthcare sector plays a pivotal role, holding two thirds of hospitals and over half of outpatient clinics. Even if 65% of Mexico’s population has public health insurance, many seek private healthcare due to perceived higher quality, shorter waiting times, and better access to medication.39 Another caveat of this study is that HCRU and costs were evaluated based on the medical chart records at the clinic. Healthcare visits outside of the private clinic with other suppliers would not have been captured in this analysis, potentially leading to an underestimation of HZ-related HCRU and costs. In addition, HZ is not a notifiable disease, which may lead to underreporting both in the public as well as in the private sector.40 However, the comparison of HZ epidemiology, including the proportion of patients developing PHN and other complications, hospitalization rate and direct costs, is comparable with results reported in the public healthcare sector elsewhere.13 In this study, 64% of patients were unsure about their past varicella history. Varicella infection is a precondition to develop HZ later in life, as the responsible varicella zoster virus remains dormant in dorsal root ganglia after varicella disease, where it can reactivate and lead to HZ. Therefore, HZ epidemiology is tightly linked to varicella history. However, research in Mexico found that even without recalling a prior varicella history, seropositivity for HZ is high ( >85%) and increasing with increasing age.41 Previous HZ vaccination was not recorded in our study and therefore, no estimate of the real-world effectiveness of HZ vaccination in Mexico could be made. The observation window included the coronavirus disease 2019 pandemic. This could have impacted HZ incidence as well as healthcare seeking behavior of people.42 However, since HZ is associated with significant symptoms, most people will seek medical help even during a pandemic.
Conclusion
HZ and associated complications impose a significant burden on patients and the private healthcare sector in Mexico with a median direct cost of up to $535 and $836 for HZ without and with PHN, respectively. Age and comorbidities can exacerbate the risk of HZ and severe disease, leading to an increase in HCRU and costs. HZ vaccination protects older adults and at-risk people against HZ and may decrease the burden of illness.
Supplementary Material
Acknowledgments
The authors would like to thank Desirée A.M. van Oorschot, Bella Dragova-Maurin, and Ahmed Mohy (GSK) for their contribution to this manuscript. The authors also thank Enovalife Medical Communication Service Center for editorial assistance, manuscript coordination, and writing support, on behalf of GSK; and Katrin Spiegel for medical writing support, on behalf of GSK.
Biography
Dr. Nurilign Ahmed holds a doctoral degree in Health Economics and Public Health from the London School of Hygiene and Tropical Medicine, London, UK. Her thesis centered on decision analytics, cost and cost-effectiveness of HIV testing services in Zambia. During her doctoral work, she co-chaired the WHO’s cost-effectiveness of HIV testing services group. Post-PhD, she advised Rwanda’s and Zambia’s Health Ministries on essential medicine lists and worked with Africa CDC to establish a Health Economics Unit to support the African Union’s 54 member countries in evidence-based decision-making for healthcare priority setting. She has extensive experience across sub-Saharan Africa and led the CDC-US funded Couples HIV Testing program. Dr. Ahmed also has a Master of Public Health (MPH) in Global Health Infectious Disease from Emory University, Rollins School of Public Health, Atlanta, Georgia, USA and BSc in Molecular and Neurobiology from the University of Wisconsin Madison, Wisconsin, USA. Since 2022, she has been an Associate Director at GSK, leading Real World Evidence & health outcomes studies for vaccines.
Funding Statement
GSK funded this study [GSK study identifier: VEO-000519] and was involved in all stages of study/research conduct, including analysis of the data. GSK also took in charge all costs associated with the development and publication of this manuscript.
Disclosure statement
Nurilign Ahmed, Adriana Guzman-Holst and Gloria Huerta-Garcia are employed by GSK. Nurilign Ahmed and Adriana Guzman-Holst hold financial equities in GSK. Adrian Camacho-Ortiz declares consulting fees from AstraZeneca and payment for lectures from Pfizer and MSD. These authors declare no other financial and non-financial relationships and activities. Edgar Perez Barragan, Francisco Marquez-Díaz, Alejandro E. Macías, and Juan Carlos Tinoco declare no financial and non-financial relationships and activities and no conflicts of interest.
Data availability statement
The datasets used to derive results for this article are not readily available because of the private and proprietary nature of the data (medical charts).
Informed consent statement
Patient consent was waived due to the non-interventional, retrospective and anonymized nature of the study.
Institutional review board statement
Ethical review and approval were waived for this study due to its observational and retrospective design.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/21645515.2025.2563199
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets used to derive results for this article are not readily available because of the private and proprietary nature of the data (medical charts).