Varicella-zoster virus infection in the pediatric population with acute lymphoblastic leukemia in Poland

Varicella-zoster virus (VZV) infection in pediatric hemato-oncology patients can be a therapeutic problem when children are exposed to immunosuppression. The aim of this study is to evaluate the incidence of VZV infection, antiviral therapy and outcome in children with ALL treated in polish hemato-oncological centers between 2012 and 2019 years. This study included medical records of 1874 patients, aged 1 to 18 years, with newly diagnosed acute lymphoblastic leukemia. During chemotherapy, 406 children out of 1874 (21.6%) experienced viral infections. The incidence of VZV infection in the whole group children with ALL was 1.8%. Among them, 34 (8.4%) patients were diagnosed with VZV infection. Thirty-five episodes of viral infections were identified. The median time of VCV therapy was 12 days. Herpes zoster infection occurred in 24 (70.6%) children, and varicella in 10 (29.4%) ones. The average time from the start of chemotherapy to the appearance of herpes zoster was 7.26 ± 4.05 months. VZV infection occurred mainly during the maintenance therapy, the reinduction and induction phases. There was no correlation between steroid dosage or type and subsequent zoster. The total lymphocyte count of these patients on the first day of zoster was reduced. No serious complications were observed due to this infection. All patients survived. In conclusion, a low incidence of VZV infection was observed among pediatric patients with ALL in Poland. This analysis indicates that currently used therapeutic methods are effective in children with cancer and VZV infection. The main focus should be on the prevention of delayed chemotherapy.     

Recovery of Varicella-Zoster Virus–Specific T Cell Immunity after T Cell–Depleted Allogeneic Transplantation Requires Symptomatic Virus Reactivation

Reactivated varicella-zoster virus (VZV) infection causes herpes zoster and commonly occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because VZV-specific T cell immunity is essential to prevent virus reactivation, we developed an interferon-γ enzyme-linked immunosorbent spot (ELISPOT) assay for the sensitive detection of VZV-reactive T cells at the single-cell level ex vivo. We used this assay to monitor the frequency of VZV-reactive T cells in 17 seropositive patients during the first year after T cell–depleted allo-HSCT. The patients did not receive anti-herpesvirus prophylaxis after stem cell engraftment. Independent of the magnitude of transferred donor immunity, VZV-reactive T cell numbers decreased to low levels (median, 2/mL; range, 0 to 35/mL) in peripheral blood early after transplantation. Only patients with subsequent zoster (n = 5) exhibited a dramatic boost in VZV-reactive T cells (median, 366/mL; range, 158 to 756/mL), which was induced by the reactivation event. The postzoster VZV-reactive T cell levels were similar to those seen in healthy virus carriers. In contrast, antiviral T cell levels remained low in patients without VZV disease. Our results demonstrate that VZV-specific T cell immunity recovered efficiently during zoster in T cell–depleted allo-HSCT recipients. It did not reconstitute spontaneously in nonzoster patients, even in the absence of antiviral prophylaxis. Prospective studies should investigate whether VZV vaccination can substitute for natural resensitization by virus disease.     

Titration of IgG antibodies against varicella zoster virus before bone marrow transplantation is not predictive of future zoster

Serum antibodies to varicella zoster virus (VZV) were measured in 77 patients about to undergo allogeneic bone marrow transplantation, and in 65 of their donors. Ten patients developed zoster within the first 6 months following transplant. There was no significant difference in the mean pretransplant antibody titre between those patients who did or did not subsequently develop zoster. Likewise, the level of antibody to VZV amongst donors had no effect on the subsequent development of zoster. We conclude that the pretransplant level of antibody to VZV is not predictive of subsequent zoster infection, and would not be helpful in identifying patients for trials of antiviral prophylaxis. These results contrast with those previously found for another herpesvirus, herpes simplex (HSV), where antibody level pretransplant is predictive of future HSV recurrence.     

Severe Herpes Zoster Requiring Intravenous Antiviral Treatment in Allogeneic Hematopoietic Cell Transplantation Recipients on Standard Acyclovir Prophylaxis

Allogeneic hematopoietic cell transplantation (HCT) recipients are at increased risk for varicella zoster virus (VZV) reactivation and associated complications. The incidence, timing, and risk factors for severe herpes zoster (HZ) are not well described in the era of acyclovir (ACV) prophylaxis. We performed a retrospective cohort study of all patients who underwent first allogeneic HCT between October 2006 and December 2015 at our institution. Patients were followed until December 2017 for the development of severe HZ, defined as necessitating administration of i.v. antiviral medication. Out of 2163 patients who underwent allogeneic HCT, 22 (1.0%) developed severe HZ at a rate of 1 per 228 person-years, including dermatomal/multidermatomal disease (n = 5), disseminated skin disease (n = 5), HZ ophthalmicus (n = 4), meningitis/encephalitis (n = 4), pneumonia (n = 2), viremia (n = 1), and erythema multiforme (n = 1). Severe HZ infection occurred in a bimodal distribution during the early peri-HCT period and at 12 to 24 months post-HCT (median, 12.7 months). Twelve patients (54.5%) were compliant with ACV prophylaxis at the time of HZ diagnosis. Eleven patients (50%) died during the study period, only 2 of whom (9.1%) with active VZV infection. Mortality was higher in patients on immunosuppressive therapy (62.5% versus 16.7%; P = .045) and with concurrent graft-versus-host disease (75.0% versus 35.7%; P= .044). These data suggest that severe HZ remains an important consideration despite ACV prophylaxis.     

Relationship between preexisting anti-varicella-zoster virus (VZV) antibody and clinical VZV reactivation in hematopoietic stem cell transplantation recipients

Reactivation of latent varicella-zoster virus (VZV), presenting as localized zoster or as disseminated infection, is a common and potentially serious complication in hematopoietic stem cell transplantation (HSCT) recipients. We retrospectively studied anti-VZV immunoglobulin G titers by the immune adherence hemagglutination method after HSCT and also studied VZV DNA by real-time PCR during clinical VZV reactivation using cryopreserved serum samples. No significant difference was found between anti-VZV titers in 13 patients with VZV infection (localized zoster in 11 patients and disseminated zoster in 2 patients) and in 13 subjects without VZV infection at each time point after HSCT. Preexisting anti-VZV titers of disseminated zoster cases tended to be lower than those of localized zoster cases (P=0.10). Serum VZV DNA copy numbers at the onset of disseminated zoster cases tended to be higher than those of localized zoster cases (P=0.09). A strong inverse correlation was found between preexisting anti-VZV titer and serum VZV DNA at onset (r=-0.90, P=0.006). In HSCT recipients, preexisting antibody does not prevent the development of VZV reactivation but may contribute to decreased viral load at onset, resulting in a mild clinical course.     

Live Attenuated Varicella-Zoster Vaccine in Hematopoietic Stem Cell Transplantation Recipients

Hematopoietic stem cell transplantation (HSCT) recipients are at risk for varicella-zoster virus (VZV) reactivation. Vaccination may help restore VZV immunity; however, the available live attenuated VZV vaccine (Zostavax) is contraindicated in immunocompromised hosts. We report our experience with using a single dose of VZV vaccine in 110 adult autologous and allogeneic HSCT recipients who were about 2 years after transplantation, free of graft-versus-host disease, and not receiving immunosuppression. One hundred eight vaccine recipients (98.2%) had no clinically apparent adverse events with a median follow-up period of 9.5 months (interquartile range, 6 to 16; range, 2 to 28). Two vaccine recipients (1.8%) developed a skin rash (one zoster-like rash with associated pain, one varicella-like) within 42 days post-vaccination that resolved with antiviral therapy. We could not confirm if these rashes were due to vaccine (Oka) or wild-type VZV. No other possible cases of VZV reactivation have occurred with about 1178 months of follow-up. Live attenuated zoster vaccine appears generally safe in this population when vaccinated as noted; the overall vaccination risk needs to be weighed against the risk of wild-type VZV disease in this high-risk population.     

Varicella zoster virus infections following allogeneic bone marrow transplantation: frequency, risk factors, and clinical outcome.

Reactivation of varicella zoster virus (VZV) is a common event in patients undergoing allogeneic bone marrow transplantation (BMT) and may lead to life-threatening complications. We retrospectively analyzed the incidence, clinical outcome, and risk factors for VZV infections occurring within the first 5 years of transplantation in 100 consecutive adults undergoing allogeneic BMT between 1992 and 1997. Forty-one patients (41%) developed VZV reactivation a median of 227 days (range 45-346 days) post-transplantation. Twelve percent of VZV reactivation occurred in the first 100 days and 88% within the first 24 months. Among those who survived for 2 or more years after transplantation (n = 47), 59% developed VZV infection. Forty percent of patients with VZV reactivation required admission with a mean hospital stay of 7.2 days. Two patients developed encephalitis, and 1 died despite antiviral therapy. The most frequent complications were post-herpetic neuralgia and peripheral neuropathy (68%). Thoracic dermatomal zoster represented 41% of the infections; disseminated cutaneous involvement was observed in 17% of patients. No clinical or epidemiologic risk factors were associated with recurrence. Administration of ganciclovir for prevention of cytomegalovirus infection delayed the onset of VZV infection beyond 4 months (P = .06). In a further subset analysis, patients with a limited chronic graft-versus-host disease (GVHD) had a lower estimated incidence of VZV reactivation compared with those with extensive chronic GVHD (P = .11). We conclude that complications from reactivation of VZV infection are common and associated with considerable morbidity and mortality in patients undergoing allogeneic BMT.     

Genotypic analysis of varicella-zoster virus and its seroprevalence in Finland

We evaluated the seroprevalence of varicella-zoster virus (VZV) in the Finnish population among various age groups and genetically characterized VZV strains from documented cases of varicella and zoster. VZV-specific immunoglobulin G was measured in 2,842 serum samples that had been submitted for virological studies to the Department of Virology, University of Helsinki, from 1995 to 1996. Specimens for VZV genotyping were obtained from vesicular lesions from two pediatric patients and 26 adult patients. Seroprevalence to VZV varied markedly by age: 45% in children aged < or = 2 months, 12.5% in children aged 6 to 8 months, and > 90% in children near 10 years of age, plateauing thereafter into advanced age. The seroprevalence rates indicate that in Finland, as in other countries with temperate climates, primary VZV infection usually occurs during the first decade of life. Twenty-eight VZV DNA-positive specimens were analyzed to identify VZV vaccine and wild-type genotypes. All analyzed specimens were wild type and the European (E) genotype.     

Varicella-Zoster Virus Disease Is More Frequent after Cord Blood Than after Bone Marrow Transplantation

Immune reconstitution may differ following cord blood transplantation (CBT) and bone marrow transplantation (BMT), and this may lead to a difference in varicella zoster virus (VZV) disease rates. One hundred fourteen VZV seropositive children received a CBT (37 patients), or a T-replete BMT (77 patients) at our institution. Patients did not received specific VZV disease prophylaxis. VZV disease was diagnosed by immunofluorescence or culture in 41 (36%) patients. In multivariate analysis, VZV disease was more frequent in older children (relative risk [RR] 1.11 per year; 95% confidence interval [CI], 1.04-1.18; P = .002), and after CBT (RR 2.27; 95% CI, 1.18-4.34; P = .013). The cumulative incidence of VZV disease at 3 years posttransplant was 46% following CBT. VZV disease incidence was 71% in CBT patients over 10 years old at transplant. Visceral dissemination occurred in 7 patients (6 CBT and 1 BMT) (P = .005). VZV disease is thus more frequent and more severe after CBT than after BMT.     

Frequency and specificity of varicella zoster virus IgM response

A direct ELISA was developed for determination of IgM antibody to varicella zoster virus (VZV). With this sensitive method VZV IgM antibodies were detected in all patients with a varicella and in 84% with a herpes zoster infection. All but one of 28 renal allograft recipients had previously had varicella. A primary infection was seen in the last patient, and reactivated infections in 11 of the others. The VZV IgM response seems to be specific since patients with a herpes simplex virus (HSV) infection and a heterotypic VZV IgG titer rise did not have detectable VZV IgM. An indirect enzyme-linked immunosorbent assay (ELISA) for detection of IgG antibodies has been used for serodiagnosis of VZV infections and to determine the immune status. After injection of zoster immune globulin, it was possible to measure passively transferred antibodies.     

Rapid diagnosis of varicella-zoster virus infection with a monoclonal antibody based direct immunofluorescence technique

Diagnosis of varicella-zoster virus (VZV) infection in immunocompromised patients is difficult because of the frequent atypical appearance. Accurate and early diagnosis is important to allow rapid commencement of antiviral chemotherapy, with consequent improvement in antiviral efficacy. A monoclonal based direct immunofluorescence antibody technique (VZV IFA) was assessed in parallel with viral culture in 56 patients with suspected VZV infection. A subgroup of 17 patients from this group with classical dermatomal herpes zoster all had positive VZV IFA tests. Only 6 patients (35%) were positive on viral culture. None of the 15 patients with proven herpes simplex virus infection had a positive VZV IFA, nor did any patient with positive VZV viral culture have a negative VZV IFA. The VZV IFA test is a rapid and sensitive technique for detecting infection with VZV.     

Prevention of VZV infection in immunosuppressed patients using antiviral agents

Antiviral agents play a key role in the prevention and treatment of varicella zoster virus (VZV) disease in immunosuppressed patients. Randomized trials show that aciclovir is effective in preventing VZV reactivation disease; however, no consensus exists on dose, duration and patient population for its use. The recent shortage of VZV-specific immunoglobulin has generated renewed interest in the use of antiviral agents as post-exposure prophylaxis. The use of antiviral agents for post-exposure prophylaxis is not supported by randomized trials, but uncontrolled experience suggests that it might be a reasonable alternative if varicella-specific immunoglobulin is not available. Current evidence on the use of antiviral agents in the prevention of reactivation disease and management of exposure to VZV is discussed.     

Progress in VZV vaccination? Some concerns

Since 1995, many countries have been aiming to replace the natural immunity against varicella by a vaccine-induced immunity to protect against varicella and herpes zoster. While the frequency of varicella in childhood has been significantly reduced, in future, herpes zoster morbidity might increase in the elderly due to the weaker immunity post-vaccination and the absence of immunity boosting silent reinfections. In countries, where less than 90 % of children are covered by universal vaccination, varicella zoster virus (VZV) infection is not completely eradicated, but might move from childhood to the age of young adults who suffer from more serious complications. A special VZV vaccine against herpes zoster in adults aged >60 years has proven to be effective in many cases, but not all vaccinees. This might lead to problems regarding the acceptance of vaccination and delay rapid antiviral therapy to prevent the post-zosteric neuralgia. An efficacious-inactivated VZV vaccine to protect immunocompromised patients is still missing. VZV vaccines and vaccination strategies have to be optimised to avoid that the quality of life and cost savings from varicella reduction in childhood are offset by more VZV diseases in adults.     

Incidence of Adenovirus Infection in Hematopoietic Stem Cell Transplantation Recipients: Findings from the AdVance Study

Adenovirus (AdV) is an increasingly recognized threat to recipients of allogeneic hematopoietic stem cell transplantation (allo-HCT), particularly when infection is prolonged and unresolved. AdVance is the first multinational, multicenter study to evaluate the incidence of AdV infection in both pediatric and adult allo-HCT recipients across European transplantation centers. Medical records for patients undergoing first allo-HCT between January 2013 and September 2015 at 50 participating centers were reviewed. The cumulative incidence of AdV infection (in any sample using any assay) during the 6 months after allo-HCT was 32% (95% confidence interval [CI], 30.9% to 33.4%) among pediatric allo-HCT recipients (n?=?1736) and 6% (95% CI, 4.7% to 6.4%) among adult allo-HCT recipients (n?=?2540). The incidence of AdV viremia ≥1000copies/mL (a common threshold for initiation of preemptive treatment) was 14% (95% CI, 13.0% to 14.8%) in pediatric recipients and 1.5% (95% CI, 1.1% to 2.0%) in adult recipients. Baseline risk factors for developing AdV viremia ≥1000copies/mL included younger age, use of T cell depletion, and donor type other than matched related. Baseline demographic factors were broadly comparable across patients of all ages and identified by multivariate analyses. Notably, the incidence of AdV infection decreased stepwise with increasing age; younger adults (age 18 to 34 years) had a similar incidence as older pediatric patients (<18 years). This study provides a contemporary multicenter understanding of the incidence and risk factors for AdV infection following allo-HCT. Our findings may help optimize infection screening and intervention criteria, particularly for younger at-risk adults.     

Varicella Zoster Virus Reactivation in Adult Survivors of Hematopoietic Cell Transplantation: How Do We Best Protect Our Patients?

Reactivation of varicella zoster virus (VZV) remains a significant public health burden for long-term survivors of hematopoietic cell transplantation. Delayed immune reconstitution after transplantation due to immunosuppression, post-transplant therapies, poor engraftment, and graft-versus-host disease leave a large number of patients at risk for herpes zoster (shingles) and its highly morbid complications. Although prophylaxis with acyclovir or valacyclovir has reduced the incidence of VZV reactivation as long as prophylaxis is continued, the incidence of disease in the late post-transplant period or after stopping prophylaxis is greater in the hematopoietic cell transplantation population than the general public. Therefore, additional interventions beyond long-term use of prophylactic antivirals are required to suppress VZV. Vaccines to elicit VZV-specific immunity represent one method to enhance prevention of VZV reactivation, but care must be taken with live vaccines. Inactivated vaccines have been developed and require well-designed studies to determine their safety and efficacy in this high-risk population. Here, we report the available evidence for established and newly developed vaccines for VZV and discuss our view on their role in protecting our transplant survivors against VZV reactivation.     

Frequency of subclinical herpes zoster in pediatric hematology-oncology patients receiving chemotherapy: A retrospective cohort analysis

Varicella-zoster virus (VZV) reactivation from the enteric nervous system can cause ileus (Ogilvie's syndrome) in adult patients. Since no pediatric cases have been described, we sought to retrospectively analyze VZV reactivation in pediatric hematology-oncology patients to determine whether VZV infection including subclinical VZV reactivation can induce gastrointestinal complications such as Ogilvie's syndrome. Thirty-five patients who received chemotherapy at our institution between September 2013 and June 2018 were included. Serum samples were collected weekly during hospitalization and every 3 months during outpatient maintenance chemotherapy. A real-time polymerase chain reaction assay was used to measure VZV DNA load in serum. The clinical features of patients with VZV infection were retrospectively analyzed. Of 1165 serum samples, 7 (0.6%) were positive for VZV DNA. VZV DNA was detected in 3 of 35 patients. In patient A, VZV DNA was detected during two episodes. The first episode involved varicella-like eruptions caused by the Oka VZV vaccine strain. The second episode involved herpes zoster (HZ) caused by the same strain. Patients B and C had a clinical course that was typical for HZ caused by wild-type VZV. No gastrointestinal symptoms were observed at the time of VZV infection in these three patients. VZV DNA was not detected in any other samples. No pediatric cases with Ogilvie's syndrome caused by VZV reactivation were demonstrated in this cohort. Additionally, no subclinical VZV reactivation was found in this cohort. Further study is needed to elucidate the precise incidence of pediatric Ogilvie's syndrome caused by VZV reactivation.     

Serum immunoglobulin A antibody to varicella-zoster virus in subjects with primary varicella and herpes zoster infections and in immune subjects.

Immunoglobulin A (IgA) antibodies to varicella-zoster virus (VZV) were measured in sera from subjects with acute varicella and herpes zoster, VZV-immune subjects remote from infection, and recipients of a live attenuated varicella vaccine, using a solid-phase radioimmunoassay. Primary infection with VZV was associated with early production of IgA antibodies. Among 36 subjects with varicella tested 1 to 5 days after onset, 22 had detectable IgA, and all of the negative sera were obtained before day 3 of the varicella exanthem. VZV IgA was detected in one of three sera obtained more than 60 days after onset of the illness. Four of five sera obtained from subjects within 1 week of the onset of herpes zoster had measurable levels of IgA. Between 1 and 4 weeks after onset of zoster, all 10 subjects tested had detectable IgA to VZV. VZV IgA was detected as late as 63 days after the onset of herpes zoster. Of 10 vaccine recipients, 5 developed VZV IgA which was detected as early as 4 weeks and persisted for as long as 16 weeks after vaccination. VZV IgA was not detected in sera from 42 children who had no detectable IgG antibody to VZV. VZV IgA was found on only 3 of 23 sera from adults who had varicella more than 20 years before.     

Prospective long-term study on primary CMV infections in adult liver transplant (D+/R−) patients after valganciclovir prophylaxis

BackgroundCytomegalovirus (CMV) can cause severe infections in transplanted patients. To prevent CMV infection, most liver centers use prophylaxis for CMV-seronegative recipients receiving an organ from a seropositive donor (D+/R−). Valganciclovir is mostly given for 3–6 months after transplantation. However, the patients may develop primary CMV infection after the cessation of prophylaxis and late-onset CMV disease may occur.ObjectivesA prospective long-term follow-up of CMV (D+/R−) adult liver transplant recipients after 3 months valganciclovir prophylaxis was investigated.Study designOf 154 consecutive adult liver recipients transplanted from 2006 to 2009, 20 (13%) were CMV D+/R− and received antiviral prophylaxis up to 3 months after transplantation. After excluding the recipients with incomplete prophylaxis or monitoring, 13 (D+/R−) patients with follow-up of >4 years after the 3-month period of valganciclovir prophylaxis were included in the study.The patients were monitored for CMV by real-time quantitative plasma PCR.ResultsNo break-through CMV infections were recorded during the prophylaxis period. After cessation of valganciclovir prophylaxis 12/13 (90%) patients demonstrated CMV-DNAemia following a post transplantation mean interval of 165 days (range 95–320). Ten patients with high viral loads (peak viral load mean 81,510, range 1900–648950 cps/ml) were successfully treated, 6 with valganciclovir, and 4 with ganciclovir. Two patients with low level CMV-DNAemia (<1000 cps/ml) were asymptomatic and not treated. No intragraft infection was seen, but one patient developed gastrointestinal CMV infection verified from ileum biopsy. During long-term follow-up, 3 patients demonstrated low-level viral replication, but no symptomatic recurrences occurred. One patient died of bacterial sepsis, but no patient or graft was lost due to CMV.ConclusionsPrimary CMV infections after cessation of prophylaxis were common, but were successfully treated with valganciclovir or ganciclovir.     

Immune evasion as a pathogenic mechanism of varicella zoster virus

Varicella zoster virus (VZV) is a human herpesvirus that causes varicella (chickenpox) during primary infection, establishes latency in dorsal root ganglia and may reactivate years later, producing herpes zoster. VZV must evade antiviral immunity during three important stages of viral pathogenesis, including the cell-associated viremia characteristic of primary infection, persistence in dorsal root ganglia during latency and the initial period of VZV reactivation. Our observations about the immunomodulatory effects of VZV document its capacity to interfere with adaptive immunity mediated by CD4 as well as CD8 T cells, ensuring the survival of the virus in the human population from generation to generation.     

Herpes zoster guideline of the German Dermatology Society (DDG).

Varicella zoster virus (VZV) causes varicella (chickenpox), remains dormant in dorsal root and cranial nerve ganglia and can be reactivated as a consequence of declining VZV-specific cellular immunity leading to herpes zoster (shingles). Patients older than 50 years of age affected by herpes zoster may suffer a significant decrease of quality of life. These patients and immunocompromised individuals are at increased risks for severe complications, involving the eye, the peripheral and the central nervous system (prolonged pain, postherpetic neuralgia). Such complications occur with and without cutaneous symptoms. The German Dermatology Society (DDG) has released guidelines in order to guarantee updated management to anyone affected by herpes zoster. Diagnosis is primarily clinical. The gold standard of laboratory diagnosis comprises PCR and direct identification of VZV in cell cultures. Detection of IgM- and IgA-anti VZV antibodies may be helpful in immunocompromised patients. Therapy has become very effective in the last years. Systemic antiviral therapy is able to shorten the healing process of acute herpes zoster, to prevent or to alleviate pain and other acute and chronic complications, particularly, when given within 48 h to a maximum of 72 h after onset of the rash. Systemic antiviral therapy is urgently indicated in patients beyond the age of 50 years and in patients at any age with herpes zoster in the head and neck area, especially in patients with zoster ophthalmicus. Further urgent indications are severe herpes zoster on the trunk and on the extremities, herpes zoster in immunosuppressed patients and in patients with severe atopic dermatitis and severe ekzema. Only relative indications for antiviral therapy exist in patients younger than 50 years with zoster on the trunk and on the extremities. In Germany acyclovir, valacyclovir, famciclovir and brivudin are approved for the systemic antiviral treatment of herpes zoster. These compounds are all well tolerated by the patients and do not differ with regard to efficacy and safety. Brivudin has a markedly higher anti-VZV potency than oral acyclovir, valacyclovir and famciclovir and thus offers a simpler dosing regimen. It must be given only once daily during 7 days in comparison to three and five times dosing per day of valacyclovir, famciclovir and acyclovir, respectively. Brivudin is an antiviral agent with no nephrotoxic properties, which is an advantage when compared to acyclovir. The most important aim of therapy of herpes zoster is to achieve painlessness. Appropriately dosed analgesics in combination with a neuroactive agent (i.e. amitriptylin) are very helpful when given together with antiviral therapy. The additive therapy with corticosteroids may shorten the degree and duration of acute zoster pain, but has no essential effect on the development of postherpetic neuralgia, which is a very difficult condition to treat. Thus early presentation to a pain therapist is recommended in specific cases.