VZV-specific Cell-mediated Immunity Research Articles

Development of an IFN-γ ELISpot assay to assess varicella-zoster virus-specific cell-mediated immunity following umbilical cord blood transplantation.

Varicella zoster virus (VZV) is a significant cause of morbidity and mortality following umbilical cord blood transplantation (UCBT). For this reason, antiherpetic prophylaxis is administrated systematically to pediatric UCBT recipients to prevent complications associated with VZV infection, but there is no strong, evidence based consensus that defines its optimal duration. Because T cell mediated immunity is responsible for the control of VZV infection, assessing the reconstitution of VZV specific T cell responses following UCBT could provide indications as to whether prophylaxis should be maintained or can be discontinued. To this end, a VZV specific gamma interferon (IFN-γ) enzyme-linked immunospot (ELISpot) assay was developed to characterize IFN-γ production by T lymphocytes in response to in vitro stimulation with irradiated live attenuated VZV vaccine. This assay provides a rapid, reproducible and sensitive measurement of VZV specific cell mediated immunity suitable for monitoring the reconstitution of VZV specific immunity in a clinical setting and assessing immune responsiveness to VZV antigens.

Neurological complications of varicella zoster virus reactivation.

Varicella zoster virus (VZV) reactivation results in zoster, which may be complicated by postherpetic neuralgia, myelitis, meningoencephalitis, and VZV vasculopathy. This review highlights the clinical features, laboratory abnormalities, imaging changes, and optimal treatment of each of those conditions. Because all of these neurological disorders produced by VZV reactivation can occur in the absence of rash, the virological tests proving that VZV caused disease are discussed. After primary infection, VZV becomes latent in ganglionic neurons along the entire neuraxis. With a decline in VZV-specific cell-mediated immunity, VZV reactivates from ganglia and travels anterograde to the skin to cause zoster, which is often complicated by postherpetic neuralgia. VZV can also travel retrograde to produce meningoencephalitis, myelitis, and stroke. When these complications occur without rash, VZV-induced disease can be diagnosed by detection of VZV DNA or anti-VZV antibody in cerebrospinal fluid and treated with intravenous acyclovir. Awareness of the expanding spectrum of neurological complications caused by VZV reactivation with and without rash will improve diagnosis and treatment.

Update on varicella zoster virus vasculopathy.

Primary infection of humans with varicella zoster virus (VZV) causes varicella (chickenpox), after which the virus becomes latent in cranial nerve ganglia, dorsal root ganglia and autonomic ganglia along the entire neuraxis. As VZV-specific cell-mediated immunity declines in elderly and immunocompromised individuals, VZV reactivates from one or more ganglia and typically causes herpes zoster (shingles). Zoster may also be complicated by VZV vasculopathy due to productive virus infection of the cerebral arteries. In recent decades, the clinical spectrum of VZV vasculopathy has expanded to include not only transient ischemic attacks and ischemic and hemorrhagic stroke, but also multifocal VZV vasculopathy, with temporal artery infection mimicking giant cell arteritis, extracranial vasculopathy, aneurysm with and without subarachnoid hemorrhage, arterial dissection and dolichoectasia, ischemic cranial neuropathies, cerebral venous sinus thrombosis, spinal cord infarction and peripheral thrombotic disease.

Vaccination Against and Treatment of Acute Herpes Zoster for Prevention of Post-Herpetic Neuralgia

Zostavax (zoster vaccine) is a 1-dose, high-potency, live, attenuated varicella zoster virus (VZV) vaccine that boosts VZV-specific cell-mediated immunity (CMI), and this is its presumed mechanism of action. Other strategies focus on preventing the major complication of HZ, post-herpetic neuralgia (PHN). Evidence that the vaccine is effective in older patients comes from the pivotal Shingles Prevention Study. That study demonstrated that HZ vaccine significantly reduced morbidity due to HZ and PHN in older patients. However, the duration of efficacy beyond 5 years after vaccination remains unclear. The Long-Term Persistence Substudy, currently under analysis, may provide additional data on the duration of efficacy for zoster vaccine. This review discusses vaccination against HZ, and further reviews recent pharmacotherapy for prevention of PHN.

Varicella‐Zoster Virus‐Specific Cell‐Mediated Immunity in Facial Palsy: Comparison between Hunt Syndrome and Bell's Palsy

Objectives: 1) Compare Varicella-zoster virus (VZV)-specific cell-mediated immunity (CMI) in Hunt syndrome to Bell’s palsy using IFN enzyme-linked immunospot (ELISPOT). 2) Examine the role of VZV-specific CMI for VZV reactivation in the facial nerve in Hunt syndrome. Methods: This prospective study was conducted in our tertiary referral hospital between 2010 and 2012. Six Hunt syndrome and 28 Bell’s palsy patients were enrolled. Mononuclear cells were isolated from whole blood and incubated with VZV antigen in culture plates for 40 h. Anti IFN antibody was added and the ELISPOT system counted immunostained spots indicating VZV-specific CMI. Numbers of spots and the relationship between the spots and days from the onset of palsy were compared between Hunt syndrome and Bell’s palsy patients. Results: No difference in the number of spots was observed between Hunt syndrome and Bell’s palsy. However, Hunt syndrome showed a strong positive relationship between numbers of spots and days from the onset of palsy (r = 0.87). In the early days, spot numbers in Hunt syndrome were much lower, indicating low VZV-specific CMI. In contrast, Bell’s palsy showed no such relationship (r = -0.24). Conclusions: This study indicates that low CMI to VZV may play a role in VZV reactivation in the facial nerve. VZV vaccination may promote VZV-specific CMI, leading to prevention of Hunt syndrome.

Safety, humoral and cell-mediated immune responses to herpes zoster vaccine in subjects with diabetes mellitus

To evaluate varicella zoster virus-specific cell-mediated immunity and humoral immunogenicity against the herpes zoster vaccine, which is licensed as the Live Varicella Vaccine (Oka Strain) in Japan, in elderly people with or without diabetes mellitus. A pilot study was conducted between May 2010 and November 2010 at Kitano Hospital, a general hospital in the city of Osaka in Japan. A varicella skin test, interferon-gamma enzyme-linked immunospot assay and immunoadherence hemagglutination tests were performed 0, 3, and 6 months after vaccination. Vaccine safety was also assessed using questionnaires for 42 days and development of zoster during the one-year observational period. We enrolled 10 healthy volunteers and 10 patients with diabetes mellitus aged 60-70 years. The live herpes zoster vaccine boosted virus-specific, cell-mediated and humoral immunity between elderly people, with or without diabetes. Moreover, no systemic adverse reaction was found. None of the study participants developed herpes zoster. The live herpes zoster vaccine was used safely. It effectively enhanced specific immunity to varicella zoster virus in older people with or without diabetes mellitus.

Reconstitution of Protective Immune Responses against Cytomegalovirus and Varicella Zoster Virus Does Not Require Disease Development in Pediatric Recipients of Umbilical Cord Blood Transplantation

CMV and varicella zoster virus (VZV) are significant causes of morbidity and mortality following umbilical cord blood transplantation (UCBT). However, the kinetics of reconstitution and protective potential of antiviral cell-mediated immune responses following UCBT remain poorly characterized. In this study, the reconstitution of CMV- and VZV-specific T cell responses was assessed using IFN-γ ELISPOT in 28 children who underwent UCBT to treat hematological or inherited disorders. Barely detectable in the first 3 mo posttransplantation, CMV- and VZV-specific T cell responses were observed in 30.4% and 40.3% of study subjects after 36 mo of follow-up. Four of five CMV-seropositive subjects developed detectable levels of circulating CMV DNA (DNAemia), and 5 of 17 VZV-seropositive patients experienced herpes zoster during the posttransplant period. Four CMV-seronegative subjects developed IFN-γ responses against CMV, and four subjects developed a VZV-specific IFN-γ response without clinical signs of infection. No CMV- or VZV-related events were observed in study subjects following the development of CMV- or VZV-specific responses > 150 spot-forming units/10(6) PBMCs, consistent with T cell-mediated protection. Finally, famciclovir prophylaxis did not strictly prevent the reconstitution of the VZV-specific T cell repertoire, because the frequency of T cells producing IFN-γ in response to VZV Ags reached levels consistent with protection in two nonzoster subjects. Monitoring of CMV- and VZV-specific cell-mediated immunity could inform immunocompetence and guide the initiation and cessation of antiherpetic prophylaxis in UCBT recipients.

Varicella-Zoster Virus-Specific Enzyme-Linked Immunospot Assay Responses and Zoster-Associated Pain in Herpes Zoster Subjects

Varicella-zoster virus (VZV)-specific cell-mediated immunity (CMI) responses were compared over time following an episode of herpes zoster (HZ) with those of age-, race-, and gender-matched healthy controls (HC) without HZ, using a validated gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay. The zoster brief-pain inventory (ZBPI) was used to assess zoster-associated pain. HZ patients (n = 140) had significantly higher IFN-γ ELISPOT responses to VZV antigen than did HC (n = 140). ELISPOT geometric mean count (GMC) responses (with 95% confidence intervals [CI]) for subjects who presented within 72 h were as follows: for HZ patients ≥ 60 years of age, at day 0 the GMC was 110 and at week 2 the GMC was 235; for HZ patients 21 to 59 years of age, at day 0 the GMC was 111 and at week 2 the GMC was 198; for HC ≥ 60 years of age, at day 0 the GMC was 19 and at week 2 the GMC was 18; and for HC 21 to 59 years of age, at day 0 the GMC was 59 and at week 2 the GMC was 56. The mean pain score (95% CI) across age groups at 1 week postrash (n = 106) was 6.0 (5.5, 6.5) and at 2 weeks postrash (n = 119) was 3.5 (2.9, 4.0). The percentage of HZ patients with substantial pain (score ≥ 3) at 6 weeks postrash increased with age from 8% for patients 21 to 49 years of age to 16% for patients 50 to 59 years of age to 22% for patients ≥ 60 years of age. The VZV-specific CMI response was substantially boosted by an episode of HZ, as measured by ELISPOT results. Older adults had lower VZV-specific cellular immunity than younger subjects at baseline, but the boosting effect of HZ was substantial for all age groups. HZ patients experienced considerable zoster-associated acute (1 to 2 weeks after rash) pain across age groups, while chronic pain increased with age.

Varicella-zoster virus-specific cell-mediated immunity in subjects with herpes zoster

Though cell-mediated immunity (CMI) against varicella-zoster virus (VZV) is critical for prevention of the onset of herpes zoster (HZ), clinicians currently lack a simplified procedure to monitor CMI. We have recently developed an assay, called the IFN-γ release assay, and showed that it is a simple and reliable method to determine VZV-specific CMI. In the present study, we applied an IR assay to measure the VZV-specific CMI of patients with HZ. VZV-specific CMI levels were significantly high at the onset of the disease, but were decreased several weeks later. In contrast, CMI VZV-specific antibody titers increased in convalescent phase compared to those in acute phase. Thus, this technology is likely to be very useful in monitoring ongoing VZV-specific immune status.

Emerging drugs for varicella-zoster virus infections

Introduction: Varicella-zoster virus (VZV) is the etiological agent of two distinct diseases, varicella (chickenpox) and shingles (herpes zoster). Chickenpox occurs following primary infection, while herpes zoster (usually associated with ageing and immunosuppression) is the consequence of reactivation of the latent virus. Post-herpetic neuralgia is the major complication of shingles.Areas covered: This review will discuss vaccination strategies and the current status of antivirals against VZV. A live attenuated vaccine, Varivax, is available for pediatric varicella while Zostavax was developed to boost VZV-specific cell-mediated immunity in adults older than 60 years and, via this mechanism, to decrease the burden of herpes zoster and pain associated with post-herpetic neuralgia. Despite the availability of a vaccine, there is a need for new antiviral agents. Current drugs approved for the treatment of VZV infections include nucleoside analogs that target the viral DNA polymerase and depend on the viral thymidine kinase. Novel anti-VZV drugs have recently been evaluated in clinical trials, including the bicyclic nucleoside analog FV-100, the helicase–primase inhibitor ASP2151 and valomaciclovir (prodrug of the acyclic guanosine derivative H2G).Expert opinion: New anti-VZV drugs should be as safe as and more effective than acyclovir and its prodrug valacyclovir (current gold standard for the treatment of VZV).

Major depressive disorder and immunity to varicella-zoster virus in the elderly

Major depressive disorder has been associated with activation of inflammatory processes as well as with reductions in innate, adaptive and non-specific immune responses. The objective of this study was to evaluate the association between major depression and a disease-relevant immunologic response, namely varicella-zoster virus (VZV)-specific immunity, in elderly adults. A cross-sectional cohort study was conducted in 104 elderly community dwelling adults ⩾60years of age who were enrolled in the depression substudy of the shingles prevention study, a double blind, placebo-controlled vaccine efficacy trial. Fifty-two subjects had a current major depressive disorder, and 52 age- and sex-matched controls had no history of depression or any mental illness. VZV-specific cell-mediated immunity (VZV-CMI) was measured by VZV responder cell frequency (VZV-RCF) and interferon-γ enzyme-linked immunospot (ELISPOT) assays, and antibody to VZV was measured by an enzyme-linked immunosorbent assay against affinity-purified VZV glycoproteins (gpELISA). VZV-CMI, measured by VZV-RCF, was significantly lower in the depressed group than in the controls (p<0.001), and VZV-RCF was inversely correlated with the severity of depressive symptoms in the depressed patients. In addition, an age-related reduction in VZV-RCF was observed in the depressed patients, but not in the controls. Furthermore, there was a trend for depressive symptom severity to be associated with lower ELISPOT counts. Finally, VZV-RCF was higher in depressed patients treated with antidepressant medications as compared to untreated depressed patients. Since lower levels of VZV-RCF appear to explain the increased risk and severity of herpes zoster observed in older adults, these findings suggest that, in addition to increasing age, depression may increase the risk and severity of herpes zoster.

Zoster Vaccine: Current Status and Future Prospects

Live, attenuated Oka/Merck varicella-zoster virus (VZV) vaccine (zoster vaccine) protects immunocompetent adults from herpes zoster and its complications. Success of zoster vaccine in preventing the clinical manifestations of latent VZV reactivation contrasts with the failure to achieve similar results with vaccination to prevent recurrent herpes simplex. This reflects major differences in the pathophysiology of latency and reactivation of these 2 alphaherpesviruses. The Shingles Prevention Study and many others have demonstrated that VZV-specific cell-mediated immunity, but not VZV antibody, plays a critical role in limiting reactivation and replication of latent VZV and, thus, in preventing herpes zoster and its complications. Consequently, induction of VZV-specific cell-mediated immunity and not antibody should be used as a proxy for the clinical efficacy of new formulations and uses of zoster vaccine. Prospects for improved zoster vaccines and their use in immunocompromised patients are discussed, and questions related to zoster vaccine use are addressed.

Prevention strategies for herpes zoster and post-herpetic neuralgia

Impairment of varicella zoster virus (VZV)-specific cell-mediated immunity, including impairment due to immunosenescence, is associated with an increased risk of developing herpes zoster (HZ), whereas levels of anti-VZV antibodies do not correlate with HZ risk. This crucial role of VZV-specific cell-mediated immunity suggests that boosting these responses by vaccination will be an effective strategy for reducing the burden of HZ. Other strategies focus on preventing the major complication of HZ--post-herpetic neuralgia. These strategies include pre-emptive treatment with drugs such as tricyclic antidepressants, anticonvulsants and analgesics.

Does herpes zoster ophthalmicus increase the risk of stroke?

Varicella zoster virus (VZV), a ubiquitous human herpesvirus, causes chicken pox on primary infection and then establishes lifelong latency in all cranial nerve, dorsal root, and autonomic ganglia. When VZV-specific cell-mediated immunity declines, such as in elderly and immunocompromised individuals, virus reactivates in one or more ganglia and typically travels peripherally to cause herpes zoster in the corresponding dermatomes. Herpes zoster can be complicated by stroke and has been described clinically as VZV vasculopathy, granulomatous angiitis, post varicella arteriopathy, and herpes zoster ophthalmicus (HZO) with delayed contralateral hemiparesis. The likely mechanism for stroke caused by VZV is direct viral infection of cerebral arteries. This assertion is supported by animal studies identifying afferent fibers from trigeminal and dorsal root ganglia to both intracranial and extracranial blood vessels, providing an anatomic pathway for spread of the virus,1,2 and observations of viral particles, antigens, and DNA in affected arterial vessels in VZV vasculopathy cases.3,4 Several studies have examined varicella and the risk of stroke in children,5,6 but large studies in the adult population regarding the frequency and risk of …

Vaccination: a new option to reduce the burden of herpes zoster

There is a strong correlation between the incidence of herpes zoster (HZ) and increasing age, with a marked rise in incidence from approximately the age of 50–60 years. The lifetime risk is approximately 25% and the disease is associated with acute and sometimes persistent pain, which substantially reduces the day-to-day functioning and quality of life of affected individuals, particularly older adults. The disease most commonly occurs as a result of an age-related decline in cell-mediated immunity. A live attenuated zoster vaccine has been developed to boost the varicella–zoster virus-specific cell-mediated immunity of older adults and, via this mechanism, protect the individual against HZ and its complications. Evidence that the vaccine is effective in older patients comes from the pivotal Shingles Prevention Study. This was a randomized, double-blind, placebo-controlled trial involving approximately 40,000 adults aged 60 years or more. The HZ vaccinated group had a 51% lower incidence of HZ, a 67% reduction in postherpetic neuralgia (defined as pain rated at three or more on a scale ranging from zero [no pain] to ten [pain as bad as you can imagine], persisting or occurring 3 months or more after rash onset), and a 61% lower burden of illness (a composite measure of the incidence, severity and duration of pain and discomfort caused by HZ), indicating that the vaccine decreased both the incidence of HZ and the average severity of HZ in vaccinees who developed HZ. Moreover, there was a 73% reduction in the number of cases of HZ with severe and long-lasting pain. Overall, the vaccine was well-tolerated with the most common adverse events being mild injection site reactions and headache. A continuation trial from the Shingles Prevention Study involving over 14,000 patients ∼7000 in the HZ vaccine and placebo groups) confirmed that the efficacy of vaccination against HZ is durable through 7 years in terms of a significantly reduced incidence of HZ, a reduced incidence of postherpetic neuralgia and a markedly lower burden of illness. Although significant improvements have been made, available treatment options are only partially effective, and once postherpetic neuralgia is established, management is difficult. Therefore, the introduction of the zoster vaccine is a promising strategy to reduce morbidity associated with HZ, a particular concern in older adults.

Zoster Vaccine (Zostavax®)

Individuals who have been infected with varicella zoster virus (VZV) are at risk for developing herpes zoster and this risk appears to be related to a decline in VZV-specific cell-mediated immunity (CMI). Zostavax (zoster vaccine) is a one-dose, high-potency, live, attenuated VZV vaccine that boosts VZV-specific CMI and this is its presumed mechanism of action. Zoster vaccine is registered in the EU for use in adults aged >or=50 years for the prevention of herpes zoster and herpes zoster-related postherpetic neuralgia. In the Shingles Prevention Study, a placebo-controlled trial in adults aged >or=60 years (n = 38 546), zoster vaccine led to a sustained boost of VZV-specific CMI. Over a mean herpes zoster surveillance period of 3.1 years, zoster vaccine reduced the herpes zoster-related burden of illness by 61%, reduced the incidence of herpes zoster by 51% and reduced the incidence of postherpetic neuralgia by 67%. Zoster vaccine recipients who developed herpes zoster had a shorter illness duration and severity than placebo recipients who developed herpes zoster. Zoster vaccine had continuing efficacy in a Shingles Prevention Study subpopulation followed for 7 years post-vaccination. Zoster vaccine was generally well tolerated in older adults. While cost-effectiveness estimates in pharmacoeconomic analyses varied widely according to vaccine and herpes zoster parameter cost/benefit estimates, an analysis from a UK perspective found a zoster vaccine immunization programme in adults aged 65 years to be cost effective. In older adults, the zoster vaccine has the potential to significantly reduce the herpes zoster burden of illness by decreasing the incidence of herpes zoster or reducing its severity.

Comparison of Varicella‐Zoster Virus–Specific Immunity of Patients with Diabetes Mellitus and Healthy Individuals

Cell-mediated immunity (CMI) has been shown to be critical for the prevention and control of varicella-zoster virus (VZV)-related diseases. Because a large population-based study has revealed that diabetes mellitus is a risk factor for herpes zoster, we studied VZV-specific immune responses of patients with diabetes mellitus and compared them with those of healthy individuals. In this study, we found that patients with diabetes mellitus had significantly lower CMI to VZV than did healthy individuals. These results suggest that the increased risk for herpes zoster among patients with diabetes mellitus may be related to decreased VZV-specific CMI.

Interferon-γ release assay: A simple method for detection of varicella-zoster virus-specific cell-mediated immunity

Herpes zoster is closely related to decreased varicella-zoster virus (VZV)-specific cell-mediated immunity. We validated a new assay for measuring VZV-specific immunity. We cultured the whole blood of healthy subjects with live attenuated VZV vaccine. Cultured supernatants were harvested at 24-h intervals and assayed for interferon-gamma (IFN-γ) by an enzyme-linked immunosorbent assay (ELISA). The 48-h culture was suitable for estimating IFN-γ release. IFN-γ production was stable after standing for at least 4 h at room temperature. IFN-γ production was observed in whole blood from subjects with recent VZV infection, but not in blood from subjects naïve to the virus. Thus, the IFN-γ release assay may be useful as a new surrogate assay for measuring VZV-specific immunity.

A PHASE I–II STUDY OF LIVE ATTENUATED VARICELLA-ZOSTER VIRUS VACCINE TO BOOST IMMUNITY IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED CHILDREN WITH PREVIOUS VARICELLA

Herpes zoster, may be severe and recurrent in HIV-infected children. We determined the safety and immunogenicity of live attenuated varicella-zoster virus (VZV) vaccine in 46 HIV-infected children who had experienced varicella. There were no serious adverse events. Two years after vaccination 82% of subjects remained VZV-antibody positive and 60% had VZV-specific cell-mediated immunity. No child developed herpes zoster.

End-stage renal disease (ESRD) contributes to the increasing prevalence of herpes zoster

Sir, Varicella-zoster virus (VZV) causes two clinically distinct diseases: varicella (chickenpox) and herpes zoster (HZ; shingles). The lifetime cumulative incidence is ∼10–20% of the population [1]. The incidence rates progressively increase with age, presumably owing to decline in the VZV-specific cell-mediated immunity [2]. Age is the most important risk factor for the development of HZ; however, immunocompromised patients such as transplant recipients, patients receiving selective immunomodulatory therapy and HIV-infected patients have an increased risk of VZV reactivation [3,4]. Further, immunosuppressed individuals with HZ exhibit a significantly higher rate of complications (e.g. dissemination of the disease and ocular involvement) [5]. Patients who have end-stage renal disease (ESRD) with uraemia exhibit an impaired host immune response. The reported immunological abnormalities in ESRD patients include decreased phagocytic function of granulocytes and monocytes/macrophages, defective antigen presentation by monocytes/macrophages, reduced antibody production by B lymphocytes and impaired T-cell-mediated immunity [6]. Physicians working in dialysis facilities generally presume that ESRD contributes to the increase in the prevalence of HZ. Despite this presumption, the morbidity of HZ in ESRD has not been previously reported. This retrospective study includes information on all septuagenarian patients who visited the outpatient clinic of the nephrology division and dialysis centre affiliated to our university. A total of 220 patients were followed up for at least 3 years within the last 3.5 years. Of these 220 patients, 45 were excluded from this study because they exhibited one or more already identified risk factors for HZ (e.g. corticosteroid and/or immunomodulatory therapies, carcinomas and autoimmune disorders). Potential patients were identified by searching the diagnostic and billing codes of hospital records. If HZ was confirmed in a patient, the medical records were reviewed to verify that the case of HZ was indeed a new one. Our results revealed that the incidence of HZ increased with the progression in the stages of chronic kidney disease (CKD) (Table ​(Table1,1, Figure ​Figure1).1). In fact, the incidence rate of HZ was 84.8 per 1000 person-years in our outpatients undergoing haemodialysis or continuous ambulatory peritoneal dialysis. However, in patients with CKD stage 1, 2 or 3, the incidence rate (8.2 per 1000 person-years) was as low as that in septuagenarian HZ patients without kidney disease [5]. Diabetic nephropathy is the most important cause of ESRD that requires renal replacement therapy. Diabetes as well as CKD is a risk factor for some infectious diseases because these conditions result in a compromised immune system. However, the incidence of HZ and diabetes was not found to be significantly related as determined by the examinations performed in our hospital followed by analysis with the chi-square test. Table 1 The number of patients per group and their gender, classified according to their CKD stage Fig. 1 The graph shows the incidence (%) of HZ in patients classified by chronic kidney disease (CKD) stage. We concluded that ESRD, which requires renal replacement therapy, may contribute to the increased prevalence of HZ. Conflict of interest statement. None declared.