Herpes zoster (HZ), commonly known as shingles, is a viral disease caused by the reactivation of the varicella-zoster virus which primarily presents as a painful vesicular skin rash (1, 2). Although HZ is usually self-limiting, it may also result in complications such as chronic pain in the area of the initial rash (post-herpetic neuralgia, PHN) which occurs in 5–30% of patients with HZ (2, 3). Other complications of HZ include ocular involvement with visual impairment and disseminated HZ in immunocompromised individuals (2, 3). Both HZ and its complications are associated with reduced quality of life and increased healthcare costs (4, 5).

The global incidence of HZ is increasing, with a systematic literature review of HZ incidence in the general population aged ≥50 years reporting an incidence rate ranging from 5.2 to 10.9 cases per 1,000 person-years (6). Older adult populations are particularly at risk of HZ infection due to a reduction in cellular immunity, with annual reported incidences of HZ increasing with age after ≥50 years and peaking in those aged 70–79 years (7, 8). Therefore, as the global population ages, an increased HZ burden is likely. Additionally, reduced immune function and other underlying conditions such as diabetes, chronic obstructive pulmonary disease (COPD), chronic kidney disease, and rheumatic disease can also increase the risk of HZ infection (9–11). For example, a recent meta-analysis reported a relative risk of HZ of 1.4 in patients with COPD, with additional data indicating that inhaled corticosteroids, a common treatment for COPD, may be a separate risk factor for HZ in this population (10, 12). Additionally, a 2023 observational study of a medical insurance database in Taiwan found a greater incidence of HZ in patients with rheumatoid arthritis than those without (incidence rate ratio: 1.7), with treatments for rheumatoid arthritis also being associated with higher risk of HZ (13).

HZ vaccines, such as the recombinant zoster vaccine, have been shown to effectively prevent HZ and PHN, and can alleviate the overall burden and disease complications associated with HZ and PHN (5, 6, 14). For example, implementing HZ vaccination into national immunization programs has been associated with long-term, substantial reductions in incidence of HZ in multiple countries, including England and Australia (15, 16). Despite the availability of effective vaccines against HZ, global uptake is limited due to several factors, including lack of awareness of the burden of HZ, and vaccines not being included in national immunization programs in many developing countries (17).

In Saudi Arabia, despite HZ vaccination being available free of charge since 2022 for individuals aged ≥50 years and individuals aged ≥18 years with immunocompromising conditions (18), uptake is particularly low. This is in part due to low public awareness of HZ complications and its vaccination in Saudi Arabia, with a recent study reporting that only 29.6% of participants recognized the risk of HZ following chickenpox infection (19). Another reported that only 7.8% of participants had a high level of knowledge regarding HZ, with even fewer participants having adequate knowledge of HZ vaccination (3.1%) (20). For individuals aware of HZ vaccination, uptake remains low, with multiple cross-sectional studies of adults aged ≥50 years conducted in 2023 reporting that although 55.8–57.2% of participants had heard of an HZ vaccine, only 5.4–7.7% had received it (21, 22).

Furthermore, in many countries, including Saudi Arabia, epidemiological studies are scarce due to limited routine surveillance of this disease, with HZ only recently being included in the list of mandatory notifiable diseases (23). As a result, HZ is often under-reported and therefore the burden of HZ in Saudi Arabia remains unknown. A review of the literature reporting on the epidemiology of HZ in the Gulf Cooperation Council countries (which includes Saudi Arabia) identified a clear lack of evidence for the incidence of HZ infection, demonstrating that further research is needed to inform the development of HZ vaccination programs in these countries (24).

In this retrospective electronic medical chart review, we estimate the prevalence of HZ and examine the epidemiological and clinical characteristics of HZ cases in outpatient and inpatient settings in the Ministry of National Guard Health Affairs (MNGHA) hospitals and affiliated Primary Healthcare Centers (PHCs) in Saudi Arabia. We also describe HZ clinical management and the patient pathway, and estimate direct costs and resource utilization associated with HZ treatment, hospitalization, and medical visits. A graphical abstract summarizing the key conclusions from this manuscript is available in Figure 1.

This multi-center hospital-based retrospective electronic medical chart review was conducted at the MNGHA hospitals in Saudi Arabia, which form part of the government healthcare system managed by the Corporate Health Affairs. Data from five MNGHA hospitals from the Central, Western, and Eastern regions were reviewed: Riyadh (1,796 beds), Jeddah (746 beds), Alahsaa (305 beds), Almadinah (331 beds), and Dammam (161 beds). A total of 71 Family Medicine Centers and PHCs are affiliated with these five hospitals. These hospitals and PHCs provide medical services to the entire local population including children, adolescents, adults, and older adults (25). Although the hospitals provide secondary and tertiary care, family medicine services are provided primarily via the PHCs.

This multi-center, hospital-based, retrospective medical chart review of MNGHA hospitals provides updated insights into HZ epidemiology in Saudi Arabia. The study showed that the majority of patients with HZ were of an older age (mean: 52.8 years), consistent previous studies and likely due to declining HZ-specific cell-medicated immunity which progresses with age (27–31). The study also showed a high prevalence of several chronic diseases among the study population (e.g., hypertension, diabetes mellitus, dyslipidemia, chronic lung disease, chronic kidney disease, and cardiovascular illnesses), which is consistent with a previous retrospective study of HZ epidemiology in a primary care setting in Saudi Arabia (31).

The number of HZ cases generally increased annually over the study period, from 89 cases in 2017 to 279 cases in 2022. Potential explanations for this increase may be improved reporting and a greater awareness of HZ amongst physicians, and the coronavirus disease 2019 (COVID-19) pandemic, with there being several recent reports of HZ incidence in patients infected with COVID-19 (32).

Females also showed relatively higher frequency of HZ infection than males. Previous studies investigating the sex-based HZ burden have reported mixed findings, with some also identifying a higher incidence of HZ in females and others finding no such difference (28, 33–37). This finding may be attributable to the demographic and clinical profile of the studied population, or health-seeking behavior, rather than a biological contribution (27).

History of known HZ vaccinations was low among the study population (7.1%). This is consistent with previous studies of acceptability of HZ vaccination in Saudi Arabia, in which only 25–53% of study participants were willing to receive the vaccine (21, 38), and less than 10% reported receiving the vaccine (21). The low uptake of HZ vaccination may be explained by the lack of awareness of the impact of HZ and availability of HZ vaccination previously reported amongst the general public in Saudi Arabia (19–22). For example, a recent study of public perception toward HZ and its vaccination in Saudi Arabia reported that over half of respondents were not aware that HZ vaccination is provided by the Saudi Ministry of Health for certain populations (19). Additional previously-identified reasons for poor HZ vaccination uptake in Saudi Arabia include hesitation due to concerns of vaccination costs and possible side effects, a perception of being in good health, and a lack of knowledge of the impact of HZ vaccination (22, 39, 40). This demonstrates that there is unmet need for general HZ and HZ vaccination awareness in Saudi Arabia. Further studies on HZ vaccination knowledge, attitudes, and practices, along with vaccination impact studies in Saudi Arabia, may be one method for achieving this.

The most common HZ-related complication in this study was PHN (17.6%) which was within the range reported by previous studies (5–30%) (3, 41–43). When investigating the characteristics that were predictors of developing complicated HZ, age ≥60 years, autoimmune conditions, medically-diagnosed depression, and chronic lung diseases were identified as significant. Additionally, age ≥50 years, organ transplantation, and coronary artery disease were identified as significant predictors of developing PHN. This is in line with published data that have shown the association of severe or recurrent HZ with several health conditions and associated medications, including cancer, autoimmune diseases, rheumatoid arthritis, and inflammatory bowel disease (44–48). Identifying risk factors is vital to reduce the burden of HZ among target populations through vaccination programs and early intervention with antiviral medications (27).

In the context of healthcare resource utilization, the present study attempts to describe the general HZ patient pathway to better contextualize the resource utilization and cost endpoints of patients with HZ in Saudi Arabia. The burden of HZ on healthcare resources in this study was significant, with 12.5% of cases resulting in hospital admission with a mean length of stay of 10.1 days. A further 9.1% of cases required airborne isolation, which from clinical practice, is often required for patients with disseminated disease or until disseminated disease is ruled out for those who are immunocompromised (49). Although it might be expected that outpatient visits would have a larger associated cost than medications and hospitalizations (as this is the typical starting point of the patient pathway), this study reported medications to have a greater cost, illustrating that certain patients were prescribed medications through different channels (i.e., directly through emergency department visits or through Family Medicine). This raises the concern of potential underestimation of both prevalence of cases and costs, with previous reviews of HZ epidemiology acknowledging that underreporting is a limitation of using retrospective databases (3, 6). There is, therefore, a need for prospective surveillance studies to truly capture the burden of HZ in Saudi Arabia. Additionally, improving reporting mechanisms for HZ across healthcare sectors in Saudi Arabia may help to improve the accuracy of these future epidemiological studies. Although HZ is now included in the list of notifiable diseases in Saudi Arabia, there is still a need to effectively disseminate information regarding HZ among healthcare providers to enhance their ability to accurately identify and report HZ (23). This is also true of other countries, including Qatar and Bahrain, where HZ is a notifiable disease but there remains a lack of HZ surveillance due to various infrastructural and social factors (24, 50, 51).

This study also found that a relatively high proportion of patients with HZ were diagnosed through emergency department visits. This may reflect the increased inappropriate utilization of emergency department by conditions that can be managed in PHCs. Several reasons for patient self-referral to emergency departments in Saudi Arabia have been discussed in a previous cross-sectional study, and include a perception of urgency, easy access, and perceived limited resources at PHCs (52). This provides valuable insights into the HZ patient pathway in Saudi Arabia, demonstrating that patients may not enter this pathway through an outpatient setting due to ease of access, instead entering the pathway via an emergency department visit. These patients may be discharged with a medication prescription, meaning they do not incur the same utilization or costs as inpatients. Some patients may have follow-up appointments at private hospitals, where costs are covered by the patient or by their medical insurance.

This study also estimated the mean total cost per case of HZ without PHN to be slightly higher than that of HZ with PHN. In contrast, previous studies have estimated the mean cost of HZ with PHN cases as higher than that of HZ cases without complications (53, 54), with one study of the population-based burden of HZ finding HZ with PHN contributed to 38.5% of total costs of HZ (55). This may reflect the likely underestimation of PHN-related costs in the MNGHA hospitals and affiliated PHCs included in the present study, as the long-term impact (i.e., recurrences, sequalae, treatment of associated chronic conditions) subsequent to PHN was not captured. In addition, any long-term treatments outside of the MNGHA hospital system, such as out-of-pocket payments, were not captured in this study. However, median total cost per case of HZ without PHN was estimated to the slightly lower than that of HZ with PHN, which is more reflective of previous studies (53, 54).

While the current study provided an estimate of the direct cost associated with management of HZ disease, the study was limited in that the indirect cost related to increased burden on the healthcare system, loss of productivity, debilitating pain, and impact on quality of life was not assessed (56–59). Estimating indirect cost associated with illness and disease has several established caveats; these include methodological differences that cause wide variation in cost estimates between studies and evidence gaps that hinder comprehensive analyses of these costs (4, 60, 61). Additionally, the generally older age of the population included in this study may have meant that their employment status and economic contributions were lower than the general population, further complicating measuring indirect costs in this population. Because of these limitations, indirect cost of HZ disease was not considered in the analyses of this study and, therefore, actual total costs (including indirect costs) may be higher than estimated in this study. Moreover, costs associated with mild cases and long-term consequences were also not assessed, leading to potential underestimation of overall direct medical cost associated with HZ. It is also worth noting that the healthcare service for eligible populations in the MNGHA hospitals is free, and although the estimate provided in this study is based on actual cost, this is much lower when compared to the other health sectors in Saudi Arabia and its surrounding countries.

This study may also be limited because of missing data and because the extent of miscoding, non-coding, and non-reporting of mild cases is not known. However, the latter is anticipated to be minimal as the data were verified using two sources of information (i.e., electronic medical records and reported data to IPC Department). An additional inherent limitation of this study is that the available databases are intended for patient care, and the data are not systematically recorded for research purposes. Furthermore, cost estimates did not include the costs of any laboratory or radiological tests performed during patients’ acute illness or hospital stay, which may have resulted in an underestimation of the total costs. The retrospective nature of the study also meant that the availability of variables is limited to those recorded.

Furthermore, the use of hospital-based data may be more representative of patients with severe HZ disease rather than the broader HZ population, limiting assessment of the burden of HZ across healthcare settings. Additionally, the study population of patients at MNGHA hospitals and affiliated PHCs may also not be representative of the national population of Saudi Arabia, with potential regional variation in socio-demographic and economic factors. Nevertheless, as eligibility for care in MNGHA hospitals and affiliated PHCs may be extended to family members and other non-eligible patients, and eligibility for military personal continues following retirement, the current findings of this study still provide useful insights into HZ epidemiology in Saudi Arabia.

In this study, we described clinical-epidemiological characteristics of patients with diagnosis of HZ reported to tertiary care hospitals in Saudi Arabia. Patients with older age (≥50 years) or altered immune function were at a higher risk of developing complicated HZ and PHN. These findings may help inform efforts to improve community awareness and preventive interventions targeting those at higher risk.

Future studies should focus on estimating both direct and indirect cost of HZ-related conditions. Moreover, further investigation into factors associated with increased risk of complicated zoster including persistent pain, disseminated zoster, and related hospitalization should also be pursued, as these require enhanced healthcare. Finally, improved public awareness of HZ and HZ vaccination is needed to alleviate the burden of the disease in Saudi Arabia.