Serologic evaluation of vaccine preventable infections and vaccination rates in kidney transplant candidates.

INTRODUCTION: Assessing vaccine serologic status presents opportunities to provide live vaccinations to kidney transplant candidates (KTC). This is especially important given the increased risk of infection while taking lifelong immunosuppression following transplant and the inability to routinely provide live vaccines to patients on immunosuppressive medications. In March 2019, the American Society of Transplantation Infectious Disease Community of Practice (AST-IDCOP) released updated guidelines for vaccination of KTC, which emphasize pretransplant viral serology screening and live vaccine administration prior to transplant. PRIMARY ENDPOINT: The primary endpoint of this study was to determine adherence to AST-IDCOP guidelines for live measles, mumps, and rubella (MMR) and VZV vaccination prior to transplant in KTC non-immune by serology. METHODS: This retrospective, descriptive study examined serologic status and rates of live vaccination in 672 patients listed for kidney transplant at our center between July 2014 and July 2019. Secondary endpoints included subgroup analysis of adherence to full AST-IDCOP vaccination recommendations and validation of CDC presumed immunity definitions for measles and VZV. RESULTS: Seventeen patients (2.7%) were nonimmune by serology for VZV, while 182 (27.1%) were nonimmune by serology to MMR. In a subgroup analysis of the seronegative KTC, none received VZV vaccination, and 6% received MMR vaccination prior to transplant or last follow-up. CONCLUSIONS: Overall, a large portion of KTC had immunity gaps that were not resolved before transplantation. These findings are limited due to the retrospective, single-center nature of this study and should be confirmed with larger, prospective assessments of serologic status and vaccine administration.

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.

Integrating Alternative Social Value Judgments Into Cost-Effectiveness Analysis of Vaccines: An Application to Varicella-Zoster Virus Vaccination.

OBJECTIVES: Cost-effectiveness analyses (CEA) are based on the value judgment that health outcomes (eg, quantified in quality-adjusted life-years; QALYs) are all equally valuable irrespective of their context. Whereas most published CEAs perform extensive sensitivity analysis on various parameters and assumptions, only rarely is the influence of the QALY-equivalence assumption on cost-effectiveness results investigated. We illustrate how the integration of alternative social value judgments in CEA can be a useful form of sensitivity analysis. METHODS: Because varicella-zoster virus (VZV) vaccination affects 2 distinct diseases (varicella zoster and herpes zoster) and likely redistributes infections across different age groups, the program has an important equity dimension. We used a cost-effectiveness model and disentangled the share of direct protection and herd immunity within the total projected QALYs resulting from a 50-year childhood VZV program in the UK. We use the UK population's preferences for QALYs in the vaccine context to revalue QALYs accordingly. RESULTS: Revaluing different types of QALYs for different age groups in line with public preferences leads to a 98% change in the projected net impact of the program. The QALYs gained among children through direct varicella protection become more important, whereas the QALYs lost indirectly through zoster in adults diminish in value. Weighting of vaccine-related side effects made a large difference. CONCLUSIONS: Our study shows that a sensitivity analysis in which alternative social value judgments about the value of health outcomes are integrated into CEA of vaccines is relatively straightforward and provides important additional information for decision makers to interpret cost-effectiveness results.

ACUTE RETINAL NECROSIS AND CONTRALATERAL CUTANEOUS ERUPTION AFTER THE SHINGLES VACCINE.

PURPOSE: To the best of our knowledge, we present a rare case report describing an occurrence of acute retinal necrosis in an otherwise healthy individual who received the shingles vaccine. METHODS: Observational case report. PATIENT: A 63-year-old healthy and immunocompetent white man presented with change of vision in the left eye after blunt trauma. A diagnosis of corneal abrasion was made. During follow-up, a detailed history discovered a progressive deterioration in vision over the past few weeks. Three months before presentation, he had received the shingles vaccine (Zostavax); 1 month before presentation, he reported an episode of varicella skin eruption on the face. RESULTS: On examination, the patient was found to have acute retinal necrosis with white satellite lesions in the fundus of the left eye. An anterior chamber paracentesis and polymerase chain reaction confirmed the diagnosis of varicella-zoster virus. CONCLUSION: Varicella-zoster virus reactivation after shingles vaccination may predispose both immunocompetent and immunocompromised individuals to herpes-zoster ophthalmicus, leading to acute retinal necrosis.

Investigation of varicella outbreak among residents and healthcare workers in psychiatric hospital- Saudi Arabia.

BACKGROUND: Outbreak is an infection control challenge in health care setting especially when it occurs in a special setting as psychiatric hospitals. Objectives: Investigate and control an outbreak of varicella among patients and healthcare workers (HCWs) in a psychiatric hospital of Saudi Arabia. Methods: A multidisciplinary team of different specialties assigned to assess the situation, confirm the diagnosis, identify the causes and put an action plan to deal with such a situation. Results: The team investigated the varicella outbreak as per the Ministry of Health's (MOH) outbreak guidelines. Multiple risk factors contributed to this outbreak as the location of the outbreak in a psychiatric hospital, breaches in the hospital infection control program. Conclusion: Investigation of this outbreak was conducted as per MOH and CDC definitions and guidelines. Outbreak control plan was instituted and successfully implemented including enforcement of infection control program, the establishment of an employee health program, basic infection control orientation programs.

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.

Measuring Infection Transmission in a Stochastic SIV Model with Infection Reintroduction and Imperfect Vaccine.

An additional compartment of vaccinated individuals is considered in a SIS stochastic epidemic model with infection reintroduction. The quantification of the spread of the disease is modeled by a continuous time Markov chain. A well-known measure of the initial transmission potential is the basic reproduction number [Formula: see text], which determines the herd immunity threshold or the critical proportion of immune individuals required to stop the spread of a disease when a vaccine offers a complete protection. Due to repeated contacts between the typical infective and previously infected individuals, [Formula: see text] overestimates the average number of secondary infections and leads to, perhaps unnecessary, high immunization coverage. Assuming that the vaccine is imperfect, alternative measures to [Formula: see text] are defined in order to study the influence of the initial coverage and vaccine efficacy on the transmission of the epidemic.

Insufficient awareness and vaccination practices for inflammatory bowel disease patients in China: A multi-center survey of Chinese gastroenterologists.

OBJECTIVE: The prevalence of inflammatory bowel disease (IBD) has been increasing worldwide, and the risk of infection has increased due to the use of immunosuppressive and biologic medications. Some of these infections can be prevented with vaccinations. The aim of this study was to evaluate the vaccination practices of Chinese gastroenterologists for patients with IBD. METHODS: Questionnaires based on quick response codes were sent using email and the WeChat platform to gastroenterologists at 20 hospitals in China. The vaccination practices of the gastroenterologists, including vaccinating for hepatitis B, hepatitis A, and varicella, were assessed. RESULTS: Of the 468 gastroenterologists who received the questionnaire, 307 (65.6%) completed it. Of the gastroenterologists who were most concerned about hepatitis B; 83.4% always or frequently asked about an infection history, 53.7% took an immunization history, and 73.6% tested patients for hepatitis B infection. However, few gastroenterologists did so for hepatitis A or varicella. The proportion of patients who were asked about an infection and immunization history and tested for varicella infection was 16.0%, 15.0%, and 9.4%, respectively. Only a few gastroenterologists recommended vaccination for patients without an infection before IBD medical treatment (26.7% for hepatitis A, 45.6% for hepatitis B, and 28% for varicella vaccination). CONCLUSION: Vaccination practices for patients with IBD used by Chinese gastroenterologists vary greatly, suggesting that education about immunization is needed.

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

Myths and Misconceptions: Varicella-Zoster Virus Exposure, Infection Risks, Complications, and Treatments.

Varicella zoster and herpes zoster are infections caused by the highly contagious varicella-zoster virus (VZV). Despite widespread availability of vaccines against VZV, as well as varicella vaccination rates >95%, VZV remains a public health concern because of several common myths and misconceptions. Because of the success of routine varicella vaccination programs, some people mistakenly believe that varicella and herpes zoster are now no longer a threat to public health. Another common misconception is that shingles is less infectious than varicella; however, clinical evidence indicates otherwise. Several knowledge gaps exist around VZV transmission and the availability and use of varicella zoster immune globulin (human) for postexposure prophylaxis against VZV. To help reduce the incidence of severe disease in high-risk individuals (eg, elderly people, pregnant women, unvaccinated persons, infants, and immunocompromised children and adults), this article addresses misbeliefs and broadens awareness of VZV exposure, infection risks, complications, and treatments.

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.

An ODE-based mixed modelling approach for B- and T-cell dynamics induced by Varicella-Zoster Virus vaccines in adults shows higher T-cell proliferation with Shingrix than with Varilrix.

Clinical trials covering the immunogenicity of a vaccine aim to study the longitudinal dynamics of certain immune cells after vaccination. The corresponding immunogenicity datasets are mainly analyzed by the use of statistical (mixed effects) models. This paper proposes the use of mathematical ordinary differential equation (ODE) models, combined with a mixed effects approach. ODE models are capable of translating underlying immunological post vaccination processes into mathematical formulas thereby enabling a testable data analysis. Mixed models include both population-averaged parameters (fixed effects) and individual-specific parameters (random effects) for dealing with inter- and intra-individual variability, respectively. This paper models B-cell and T-cell datasets of a phase I/II, open-label, randomized, parallel-group study (NCT00492648) in which the immunogenicity of a new Herpes Zoster vaccine (Shingrix) is compared with the original Varicella Zoster Virus vaccine (Varilrix). Since few significant correlations were found between the B-cell and T-cell datasets, each dataset was modeled separately. By following a general approach to both the formulation of several different models and the procedure of selecting the most suitable model, we were able to propose a mathematical ODE mixed-effects model for each dataset. As such, the use of ODE-based mixed effects models offers a suitable framework for handling longitudinal vaccine immunogenicity data. Moreover, this approach allows testing for differences in immunological processes between vaccines or schedules. We found that the Shingrix vaccination schedule led to a more pronounced proliferation of T-cells, without a difference in T-cell decay rate compared to the Varilrix vaccination schedule.

A double-blind, randomized, controlled, multi-center safety and immunogenicity study of a refrigerator-stable formulation of VARIVAX®.

OBJECTIVE: VARIVAX® (varicella virus vaccine, live Oka/Merck, Merck & Co., Inc., Kenilworth, NJ, USA) was originally licensed as a frozen formulation. A refrigerator-stable formulation of VARIVAX was subsequently developed to allow for increased availability of the product around the world. The objective of this study (V210-051) was to demonstrate that the safety, tolerability and immunogenicity profile of the refrigerator-stable formulation of VARIVAX was similar to the frozen formulation. METHODS: In this double-blind, randomized, multicenter study, healthy 12- to 23-month-old children with negative vaccination and clinical histories for measles, mumps, rubella, varicella, and zoster were vaccinated with either a refrigerator-stable formulation of VARIVAX (at two dosage levels; 8000 PFU [N = 320] or 25,000 PFU [N = 315]) or the frozen formulation of VARIVAX (10,000 PFU, N = 323) given concomitantly with M-M-RII® (measles, mumps, and rubella virus vaccine live, Merck & Co., Inc., Kenilworth, NJ, USA). Children were followed for 42 days after vaccination for adverse experiences. Immunogenicity was evaluated 6 weeks after vaccination. RESULTS: The refrigerator-stable formulation of VARIVAX was generally well tolerated. The incidence of adverse experiences was similar between all three groups. No vaccine-related serious adverse experiences were reported with any of the vaccine formulations. The immune response (percentage of subjects with varicella antibody titers ≥5 gpELISA units) for both refrigerator-stable formulations of VARIVAX at 6 weeks postvaccination was similar to that of the frozen formulation. Administration of either refrigerator-stable formulation of VARIVAX with M-M-RII yielded seroconversion rates and GMTs for measles, mumps and rubella that were comparable to those achieved after administration of the frozen formulation of VARIVAX with M-M-RII. CONCLUSION: The safety, tolerability, and immunogenicity profile of the refrigerator-stable varicella vaccine was similar to that of the frozen formulation.

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.

Vaccine Development for Varicella-Zoster Virus.

Varicella-zoster virus (VZV) is the first and only human herpesvirus for which a licensed live attenuated vaccine, vOka, has been developed. vOka has highly safe and effective profiles; however, worldwide herd immunity against VZV has not yet been established and it is far from eradication. Despite the successful reduction in the burden of VZV-related illness by the introduction of the vaccine, some concerns about vOka critically prevent worldwide acceptance and establishment of herd immunity, and difficulties in addressing these criticisms often relate to its ill-defined mechanism of attenuation. Advances in scientific technologies have been applied in the VZV research field and have contributed toward uncovering the mechanism of vOka attenuation as well as VZV biology at the molecular level. A subunit vaccine targeting single VZV glycoprotein, rationally designed based on the virological and immunological research, has great potential to improve the strategy for eradication of VZV infection in combination with vOka.