Management of herpesvirus reactivations in patients with solid tumours and hematologic malignancies: update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) on herpes simplex virus type 1, herpes simplex virus type 2, and varicella zoster virus.

Clinical reactivations of herpes simplex virus or varicella zoster virus occur frequently among patients with malignancies and manifest particularly as herpes simplex stomatitis in patients with acute leukaemia treated with intensive chemotherapy and as herpes zoster in patients with lymphoma or multiple myeloma. In recent years, knowledge on reactivation rates and clinical manifestations has increased for conventional chemotherapeutics as well as for many new antineoplastic agents. This guideline summarizes current evidence on herpesvirus reactivation in patients with solid tumours and hematological malignancies not undergoing allogeneic or autologous hematopoietic stem cell transplantation or other cellular therapy including diagnostic, prophylactic, and therapeutic aspects. Particularly, strategies of risk adapted pharmacological prophylaxis and vaccination are outlined for different patient groups. This guideline updates the guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) from 2015 "Antiviral prophylaxis in patients with solid tumours and haematological malignancies" focusing on herpes simplex virus and varicella zoster virus.

Evaluation of Recombinant Herpes Zoster Vaccine for Primary Immunization of Varicella-seronegative Transplant Recipients.

BACKGROUND: Immunization of varicella-zoster virus (VZV)-seronegative solid organ transplant (SOT) patients using the live-attenuated varicella vaccine is generally contraindicated, leaving no widely applicable immunization option. The recombinant subunit herpes zoster vaccine (RZV) is indicated for VZV-seropositive persons to prevent shingles but could potentially also protect VZV-seronegative persons against varicella. We performed a safety and immunogenicity evaluation of RZV in VZV-seronegative SOT recipients as an option for protection. METHODS: VZV-seronegative adult SOT patients with no history of varicella/shingles vaccine or disease were given 2 doses of RZV vaccine 2-6 mo apart. Blood was drawn prevaccination (V1), before the second dose (V2), and 4 wk after the second dose (V3). Humoral immunity (anti-glycoprotein E) and cell-mediated immunity were evaluated, with polyfunctional cells defined as cells producing ≥2 cytokines. RESULTS: Among 31 eligible VZV-seronegative SOT patients screened, 23 were enrolled. Median age was 38 y and median time since transplant procedure was 3.8 y. The most frequent transplant types were liver (35%) and lung (30%). Median anti-glycoprotein E levels significantly increased from V1 to V3 (P = 0.001) and V2 to V3 (P < 0.001), even though only 55% had a positive seroresponse. Median polyfunctional CD4 T-cell counts increased from V1 to V2 (54/106 versus 104/106 cells; P = 0.041) and from V2 to V3 (380/106; P = 0.002). Most adverse events were mild with no rejection episodes. CONCLUSIONS: RZV was safe and elicited significant humoral and cellular responses in VZV-seronegative SOT patients and has the potential to be considered as a preventive strategy against primary varicella.

Varicella-zoster virus: molecular controls of cell fusion-dependent pathogenesis.

Varicella-zoster virus (VZV) is the causative agent of chicken pox (varicella) and shingles (zoster). Although considered benign diseases, both varicella and zoster can cause complications. Zoster is painful and can lead to post herpetic neuralgia. VZV has also been linked to stroke, related to giant cell arteritis in some cases. Vaccines are available but the attenuated vaccine is not recommended in immunocompromised individuals and the efficacy of the glycoprotein E (gE) based subunit vaccine has not been evaluated for the prevention of varicella. A hallmark of VZV pathology is the formation of multinucleated cells termed polykaryocytes in skin lesions. This cell-cell fusion (abbreviated as cell fusion) is mediated by the VZV glycoproteins gB, gH and gL, which constitute the fusion complex of VZV, also needed for virion entry. Expression of gB, gH and gL during VZV infection and trafficking to the cell surface enables cell fusion. Recent evidence supports the concept that cellular processes are required for regulating cell fusion induced by gB/gH-gL. Mutations within the carboxyl domains of either gB or gH have profound effects on fusion regulation and dramatically restrict the ability of VZV to replicate in human skin. This loss of regulation modifies the transcriptome of VZV infected cells. Furthermore, cellular proteins have significant effects on the regulation of gB/gH-gL-mediated cell fusion and the replication of VZV, exemplified by the cellular phosphatase, calcineurin. This review provides the current state-of-the-art knowledge about the molecular controls of cell fusion-dependent pathogenesis caused by VZV.

Características epidemiológicas de pacientes notificados com Varicela Zoster em um hospital de referência de Goiânia-GO, Brasil / Epidemiological characteristics of patients notified with Varicella Zoster in a reference hospital in Goiânia-GO, Brazil

Este boletim trata-se de um estudo descritivo, de caráter quantitativo, realizados a partir dos casos notificados de varicela atendidos em um Hospital de Infectologia do Estado de Goiás no período de 01 de janeiro de 2010 a 31 de dezembro de 2019

This bulletin is a descriptive, quantitative study, carried out from the notified cases of chickenpox treated at an Infectology Hospital in the State of Goiás from January 1, 2010 to December 31, 2019

The situation of vaccines for the prevention of infections in adults: An opinion paper on the situation in Spain.

The childhood immunization schedule is well known and generally well implemented in developed countries. For various reasons, the same is not true of vaccines aimed at preventing infections in adults, in which vaccination coverage is incomplete and generally very deficient. In order to assess the situation of adult vaccination in Spain, the Fundación de Ciencias de la Salud has brought together a series of experts in different fields, including doctors, nurses, representatives of patient associations, health managers and economists, health authorities and journalists to deal with this issue. The format was that of a round table in which a series of questions previously formulated by the coordinators were to be answered and debated. The document presented is not an exhaustive review of the topic, nor is it intended to make recommendations, but only to give a multidisciplinary opinion on topics that could be particularly debatable or controversial. The paper reviews the main vaccine-preventable adult diseases, their clinical and economic impact, the possibilities of reducing them with vaccination programmes and the difficulties in carrying them out. The role of nursing, pharmacy services, patient associations and the health administration itself in changing the current situation was discussed. Prospects for new vaccines were discussed and we speculated on the future in this field. Finally, particularly relevant ethical aspects in decision-making regarding vaccination were discussed, which must be faced by both individuals and states. We have tried to summarize, at the end of the presentation of each question, the environment of opinion that was agreed with all the members of the table.

Live attenuated varicella-zoster virus vaccine does not induce HIV target cell activation.

BACKGROUND: Varicella-zoster virus (VZV) is under consideration as a promising recombinant viral vector to deliver foreign antigens including HIV. However, new vectors have come under increased scrutiny, since trials with adenovirus serotype 5-vectored (Ad5-vectored) HIV vaccine demonstrated increased HIV risk in individuals with pre-immunity to the vector that was thought to be associated with mucosal immune activation (IA). Therefore, given the prospect of developing an HIV/VZV chimeric vaccine, it is particularly important to define the impact of VZV vaccination on IA. METHODS: Healthy VZV-seropositive Kenyan women (n = 44) were immunized with high-dose live attenuated VZV vaccine, and we assessed the expression on CD4+ T cells isolated from blood, cervix, and rectum of IA markers including CD38 and HLA-DR and of markers of cell migration and tissue retention, as well as the concentration of genital and intestinal cytokines. A delayed-start group (n = 22) was used to control for natural variations in these parameters. RESULTS: Although immunogenic, VZV vaccination did not result in significant difference in the frequency of cervical activated (HLA-DR+CD38+) CD4+ T cells (median 1.61%, IQR 0.93%-2.76%) at 12 weeks after vaccination when compared with baseline (median 1.58%, IQR 0.75%-3.04%), the primary outcome for this study. VZV vaccination also had no measurable effect on any of the IA parameters at 4, 8, and 12 weeks after vaccination. CONCLUSION: This study provides the first evidence to our knowledge about the effects of VZV vaccination on human mucosal IA status and supports further evaluation of VZV as a potential vector for an HIV vaccine. TRIAL REGISTRATION: ClinicalTrials.gov NCT02514018. FUNDING: Primary support from the Canadian Institutes for Health Research (CIHR). For other sources, see Acknowledgments.

Efficacy of brincidofovir as prophylaxis against HSV and VZV in hematopoietic cell transplant recipients.

Allogeneic hematopoietic cell transplant (HCT) recipients are at risk for herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. Routine prophylaxis with acyclovir is recommended during periods of immunosuppression. Brincidofovir (BCV, CMX001), a lipid conjugate of cidofovir, has shown in vitro activity against HSV/VZV, but has not been formally studied for HSV/VZV prophylaxis. We report our clinical experience of BCV for HSV/VZV prophylaxis in HCT recipients. This was a retrospective review of 30 hematopoietic cell transplant (HCT) recipients between 8/2010 and 8/2015 who received BCV doses not exceeding 200 mg/week for adults/adolescents and 4 mg/kg/week for pediatric (<12 years) patients, for ≥14 days BCV without concomitant acyclovir under clinical trials or single patient use. HSV/VZV cases during BCV treatment were confirmed by viral culture or PCR and clinical symptoms. Of 30 patients who met the inclusion criteria, 27 (90%) patients were adults and 22 (73%) patients received T-cell depleted HCT. The most common indications for BCV were cytomegalovirus in 12 patients (40%) and adenovirus in 11 patients (37%). One patient was treated for acyclovir-resistant HSV and one for disseminated VZV. There were two breakthrough cases of HSV infection during 2170 patient-days. There were no cases of breakthrough VZV infection. The overall rate of breakthrough HSV infection was 1.0 per 1000 patient-days, without any breakthrough VZV infections. Our study provides the only available-albeit limited-evidence on the potential efficacy of BCV for HSV/VZV prophylaxis in HCT patients. Additional studies are needed to further assess the efficacy and safety of BCV in the setting.

Characterization of an anti-varicella-zoster virus compound that targets the portal protein encoded by ORF54.

An anti-varicella-zoster virus compound, a 5-chlorobenzo[b]thiophen derivative (45B5), was characterized. Its 50% effective concentration against the cell-free vaccine Oka strain and 50% cytotoxic concentration in human fibroblasts were 16.9 µM and more than 100 µM, respectively. Treatment with 45B5 decreased viral DNA synthesis and IE62 expression weakly but significantly. All 45B5-resistant viral clones isolated were found to have at least one mutation in ORF54 that encodes the portal protein. There were no effects on interaction between the portal and scaffold proteins. Thus, 45B5 may inhibit nuclear delivery of viral DNA.