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Background: Varicella is a highly infectious disease, particularly affecting children, that can lead to complications requiring antibiotics or hospitalization. Antibiotic use for varicella management is poorly documented. This study assessed antibiotic use for varicella and its complications in a pediatric population in England., Methods: Data were drawn from medical records in the Clinical Practice Research Datalink and Hospital Episode Statistics data sets. The study included patients <18 years old with varicella diagnosed during 2014-2018 and 3-month follow-up available. We determined varicella-related complications, medication use, healthcare resource utilization, and costs from diagnosis until 3 months after diagnosis., Results: We identified 114 578 children with a primary varicella diagnosis. Of these, 7.7% (n = 8814) had a varicella-related complication, the most common being ear, nose, and throat related (37.1% [n = 3271]). In all, 25.9% (n = 29 706 of 114 578) were prescribed antibiotics. A higher proportion of patients with complications than without complications were prescribed antibiotics (64.3% [n = 5668 of 8814] vs 22.7% [n = 24 038 of 105 764]). Mean annualized varicella-related costs were £2 231 481 for the study cohort. Overall, antibiotic prescriptions cost approximately £262 007., Conclusions: This study highlights high antibiotic use and healthcare resource utilization associated with varicella management, particularly in patients with complications. A national varicella vaccination program in England may reduce varicella burden and related complications, medication use, and costs., Competing Interests: Potential conflicts of interest. S. A. K. and M. P. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, who may own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. V. B. was an employee of Adelphi Real World at the time of study design and initiation and is currently employed by and owns stocks/shares in Bayer. C. S. C. was an employee of Adelphi Real World during study completion. S. B. D. has provided consultancy and/or investigator roles in relation to product development for Janssen, AstraZeneca, Pfizer, Moderna, Valneva, MSD, iLiAD, and Sanofi, with fees paid to St George's, University of London. S. B. D. is a member of the UK Department of Health and Social Care's (DHSC) Joint Committee on Vaccination and Immunisation (JCVI) RSV subcommittee and a member of the Medicines and Healthcare products Regulatory Agency's (MHRA’s) Paediatric Medicine Expert Advisory Group (PMEAG), but the reviews expressed herein do not necessarily represent those of DHSC, JCVI, MHRA, or PMEAG. A. P., O. M., and T. H. are employees of Adelphi Real World; the company received funding from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA to conduct the study. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Hemorrhagic varicella (HV) is a particular form of chicken pox.,with high mortality in adults. This form of the disease is rare, to date, approximately 4 cases have been reported. Occasional cases of HV have been documented in adults with hematologic disorders or other diseases. While there is one reported case of simultaneous reactivation of cytomegalovirus in an adult with chickenpox, there is a lack of information regarding changes in liver function indicators for such patients. This is unfortunate, as CMV reactivation can further exacerbate liver failure and increase mortality. In this report, we present a case of hemorrhagic varicella reactivation with cytomegalovirus and provide some relevant discussions., Case Presentation: We present the case of a 25-year-old male with HV, who had a history of nephrotic syndrome generally controlled with orally administered prednisone at a dosage of 50 mg per day for two months. The patient arrived at the emergency room with complaints of abdominal pain and the presence of hemorrhagic vesicles on his body for the past 3 days. Despite medical evaluation, a clear diagnosis was not immediately determined. Upon admission, the leukocyte count was recorded as 20.96 × 10 9 /L on the first day, leading to the initiation of broad-spectrum antibiotic treatment. Despite the general interpretation that a positive IgG and a negative IgM indicate a previous infection, the patient's extraordinarily elevated IgG levels, coupled with a markedly increased CMV DNA quantification, prompted us to suspect a reactivation of the CMV virus. In light of these findings, we opted for the intravenous administration of ganciclovir as part of the treatment strategy. Unfortunately,,the patient succumbed to rapidly worsening symptoms and passed away. Within one week of the patient's demise, chickenpox gradually developed in the medical staff who had been in contact with him. In such instances, we speculate that the patient's diagnosis should be classified as a rare case of hemorrhagic varicella., Conclusion: Swift identification and timely administration of suitable treatment for adult HV are imperative to enhance prognosis., (© 2024. The Author(s).)

Background: Varicella infects 90% of children before age 9. Though varicella is self-limiting, its complications may require antibiotics, though how antibiotics are utilized for varicella in France is not well known. This study assessed antibiotic use and costs associated with varicella and its complications in pediatric patients managed in the outpatient setting in France., Methods: A retrospective cohort study using the Cegedim Strategic Data-Longitudinal Patient Database, an electronic medical record database from general practitioners and office-based specialists in France, was conducted. Children <18 years old diagnosed with varicella between January 2014 and December 2018 with 3-month follow-up available were included. We used descriptive analysis to assess varicella-related complications, medication use, healthcare resource utilization and costs., Results: Overall, 48,027 patients were diagnosed with varicella; 15.3% (n = 7369) had ≥1 varicella-related complication. Antibiotics were prescribed in up to 25.1% (n = 12,045/48,027) of cases with greater use in patients with complications (68.1%, n = 5018/7369) compared with those without (17.3%, n = 7027/40,658). Mean medication and outpatient varicella-related costs were €32.82 per patient with medications costing a mean of €5.84 per patient; antibiotics contributed ~23% to total costs annually., Conclusion: This study showed high antibiotic use for the management of varicella and its complications. A universal varicella vaccination program could be considered to alleviate complications and associated costs in France., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Post-exposure prophylaxis (PEP) with varicella immunoglobulin is recommended to minimize risk of varicella complications for high-risk children. However, providers frequently use alternatives like acyclovir or intravenous immunoglobulin., Methods: A retrospective cohort study was conducted of PEP for varicella in children from January 2009 to December 2019. Data were provided by 47 children's hospitals who participate in the Pediatric Health Information Systems database. Patients with clinical encounters for varicella exposure were reviewed. Choice of varicella PEP regimens, including differences by underlying condition and institution, and incidence of varicella disease were determined., Results: A total of 1704 patients with first clinical encounters for varicella met inclusion criteria. Of these patients, 509 (29.9%) were prescribed PEP after varicella exposure, and 65 (3.8%) ultimately had a subsequent encounter for varicella disease. Of 509 patients who received PEP, acyclovir was most frequently prescribed (n = 195, 38.3%), followed by varicella immunoglobulin (n = 146, 28.7%), IVIG (n = 115, 22.6%), and combination therapy (n = 53, 10.4%). The highest proportion of varicella immunoglobulin use (10/20, 50%) was amongst children with diagnoses of rheumatological/gastrointestinal conditions. The highest proportion of acyclovir use (29/684, 4.2%) was amongst children with diagnoses of oncology/stem cell transplant conditions. The proportion of patients who subsequently had clinical encounters for varicella disease was highest for Acyclovir (30/195, 15.4%) followed by varicella immunoglobulin (5/146, 3.4%), combination therapy (2/53, 3.8%), and intravenous immunoglobulin alone (0/115) (P < .0001)., Conclusions: Varicella PEP in high-risk children was highly varied among children's hospitals. In our dataset, use of acyclovir was associated with a higher rate of subsequent encounters for Varicella disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Herpes zoster, commonly known as shingles, is a neurocutaneous disease caused by the reactivation of the virus that causes varicella (chickenpox). After resolution of the varicella episode, the virus can remain latent in the sensitive dorsal ganglia of the spine. Years later, with declining immunity, the varicella zoster virus (VZV) can reactivate and cause herpes zoster, an extremely painful condition that can last many weeks or months and significantly compromise the quality of life of the affected person. The natural process of ageing is associated with a reduction in cellular immunity, and this predisposes older adults to herpes zoster. Vaccination with an attenuated form of the VZV activates specific T-cell production avoiding viral reactivation. Two types of herpes zoster vaccines are currently available. One of them is the single-dose live attenuated zoster vaccine (LZV), which contains the same live attenuated virus used in the chickenpox vaccine, but it has over 14-fold more plaque-forming units of the attenuated virus per dose. The other is the recombinant zoster vaccine (RZV) which does not contain the live attenuated virus, but rather a small fraction of the virus that cannot replicate but can boost immunogenicity. The recommended schedule for the RZV is two doses two months apart. This is an update of a Cochrane Review first published in 2010, and updated in 2012, 2016, and 2019., Objectives: To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults., Search Methods: For this 2022 update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2022, Issue 10), MEDLINE (1948 to October 2022), Embase (2010 to October 2022), CINAHL (1981 to October 2022), LILACS (1982 to October 2022), and three trial registries., Selection Criteria: We included studies involving healthy older adults (mean age 60 years or older). We included randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine (any dose and potency) versus any other type of intervention (e.g. varicella vaccine, antiviral medication), placebo, or no intervention (no vaccine). Outcomes were cumulative incidence of herpes zoster, adverse events (death, serious adverse events, systemic reactions, or local reaction occurring at any time after vaccination), and dropouts., Data Collection and Analysis: We used the standard methodological procedures expected by Cochrane., Main Results: We included two new studies involving 1736 participants in this update. The review now includes a total of 26 studies involving 90,259 healthy older adults with a mean age of 63.7 years. Only three studies assessed the cumulative incidence of herpes zoster in groups that received vaccines versus placebo. Most studies were conducted in high-income countries in Europe and North America and included healthy Caucasians (understood to be white participants) aged 60 years or over with no immunosuppressive comorbidities. Two studies were conducted in Japan and one study was conducted in the Republic of Korea. Sixteen studies used LZV. Ten studies tested an RZV. The overall certainty of the evidence was moderate, which indicates that the intervention probably works. Most data for the primary outcome (cumulative incidence of herpes zoster) and secondary outcomes (adverse events and dropouts) came from studies that had a low risk of bias and included a large number of participants. The cumulative incidence of herpes zoster at up to three years of follow-up was lower in participants who received the LZV (one dose subcutaneously) than in those who received placebo (risk ratio (RR) 0.49, 95% confidence interval (CI) 0.43 to 0.56; risk difference (RD) 2%; number needed to treat for an additional beneficial outcome (NNTB) 50; moderate-certainty evidence) in the largest study, which included 38,546 participants. There were no differences between the vaccinated and placebo groups for serious adverse events (RR 1.08, 95% CI 0.95 to 1.21) or deaths (RR 1.01, 95% CI 0.92 to 1.11; moderate-certainty evidence). The vaccinated group had a higher cumulative incidence of one or more adverse events (RR 1.71, 95% CI 1.38 to 2.11; RD 23%; number needed to treat for an additional harmful outcome (NNTH) 4.3) and injection site adverse events (RR 3.73, 95% CI 1.93 to 7.21; RD 28%; NNTH 3.6; moderate-certainty evidence) of mild to moderate intensity. These data came from four studies with 6980 participants aged 60 years or older. Two studies (29,311 participants for safety evaluation and 22,022 participants for efficacy evaluation) compared RZV (two doses intramuscularly, two months apart) versus placebo. Participants who received the new vaccine had a lower cumulative incidence of herpes zoster at 3.2 years follow-up (RR 0.08, 95% CI 0.03 to 0.23; RD 3%; NNTB 33; moderate-certainty evidence), probably indicating a favourable profile of the intervention. There were no differences between the vaccinated and placebo groups in cumulative incidence of serious adverse events (RR 0.97, 95% CI 0.91 to 1.03) or deaths (RR 0.94, 95% CI 0.84 to 1.04; moderate-certainty evidence). The vaccinated group had a higher cumulative incidence of adverse events, any systemic symptom (RR 2.23, 95% CI 2.12 to 2.34; RD 33%; NNTH 3.0), and any local symptom (RR 6.89, 95% CI 6.37 to 7.45; RD 67%; NNTH 1.5). Although most participants reported that their symptoms were of mild to moderate intensity, the risk of dropouts (participants not returning for the second dose, two months after the first dose) was higher in the vaccine group than in the placebo group (RR 1.25, 95% CI 1.13 to 1.39; RD 1%; NNTH 100, moderate-certainty evidence). Only one study reported funding from a non-commercial source (a university research foundation). All other included studies received funding from pharmaceutical companies. We did not conduct subgroup and sensitivity analyses AUTHORS' CONCLUSIONS: LZV (single dose) and RZV (two doses) are probably effective in preventing shingles disease for at least three years. To date, there are no data to recommend revaccination after receiving the basic schedule for each type of vaccine. Both vaccines produce systemic and injection site adverse events of mild to moderate intensity. The conclusions did not change in relation to the previous version of the systematic review., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Purpose: To determine the epidemiological trends in pediatric varicella and herpes zoster incidence and changes in healthcare resource use from 2005 to 2022 using a nationally representative database in Japan., Materials and Methods: We conducted a retrospective observational study consisting of 3.5 million children with 177 million person-months during 2005-2022 using Japan Medical Data Center (JMDC) claims database in Japan. We investigated trends in incidence rates of varicella and herpes zoster and changes in healthcare resource use (e.g., antiviral use, office visits, and healthcare costs) over 18 years. Interrupted time-series analyses were used to investigate the impact of the routine varicella vaccination program in 2014 and infection prevention measures against COVID-19 on incidence rates of varicella and herpes zoster and related healthcare utilization., Results: After the introduction of the routine immunization program in 2014, we observed level changes in incidence rates (45.6 % reduction [95 %CI, 32.9-56.0] of varicella cases, antiviral use (40.9 % reduction [95 %CI, 25.1-53.3]), and relevant healthcare costs (48.7 % reduction [95 %CI, 38.2-57.3]). Furthermore, infection prevention measures against COVID-19 were associated with additional level changes in varicella rates (57.2 % reduction [95 %CI, 44.5-67.1]), antiviral use (65.7 % reduction [59.7-70.8]), and healthcare costs (49.1 % [95 %CI, 32.7-61.6]). In contrast, the changes in incidence and healthcare costs for herpes zoster were relatively small, which showed 9.4 % elevated level change with a decreasing trend and 8.7 % reduced level change with a decreasing trend after the vaccine program and the COVID-19 pandemic. The cumulative incidence of herpes zoster in children born after 2014 was lower than that before 2014., Conclusions: Varicella incidence and healthcare resource use were largely affected by the routine immunization program and infection prevention measures against COVID-19, while these impacts on herpes zoster were relatively small. Our study indicates that immunization and infection prevention measures largely changed pediatric infectious disease practices., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To describe the clinical characteristics of varicella patients seeking medical consultation and the use of antimicrobials for their management in Thailand in the absence of universal varicella vaccination (UVV)., Methods: A multicenter, retrospective chart review of 260 children and adults with a primary diagnosis of varicella was conducted at one private and three public hospitals in Bangkok, Thailand. Charts of varicella patients (inpatient or outpatient) were randomly selected over a 5-year period. Key outcomes included clinical complications and the use of antibiotics, antivirals, and other medications., Results: Charts of 200 children (mean age 5.7 years, range 0.3-16 years) and 60 adults (mean age 27.9 years, range 18-50 years) were reviewed. Fourteen patients (including 8 children) were hospitalized. Five percent of the children and none of the adults were immunocompromised. At least 1 varicella-related complication was reported by 7.3% (7% of children, 8.3% of adults, p  = .778) of all patients, including 57.1% (62.5% of children, 50% of adults) of inpatients ( p  < .001, compared with outpatients). Skin/soft tissue infection (47.7%) and dehydration (47.4%) were the most common complications. Antivirals (mainly oral acyclovir) were prescribed to 46.5% of patients (31.5% of children, 96.7% of adults, p  < .001). Antibiotics were prescribed to 20.8% of patients (19% of children, 26.7% of adults, p  = .199). Topical, oral, and intravenous antibiotics were prescribed to 12.3%, 8.5%, and 1.2% of patients, respectively. Antimicrobial prescriptions were higher among adults ( p  < .001) and immunocompromised patients ( p  = .025). Apart from antimicrobials, acetaminophen (62.3%) and oral antihistamines (51.5%) were the most prescribed., Conclusion: A considerable number of varicella patients, both children and adults, seeking medical consultation in Thai hospitals are prescribed antibiotics and antivirals, with one-fifth of patients being prescribed an antibiotic and almost half prescribed an antiviral. The study may be of interest to policymakers in Thailand and other Asia-Pacific countries considering UVV implementation.

Background: Varicella zoster reactivation is an increasingly recognised event following mRNA COVID-19 vaccination. In addition, various ocular inflammatory and infectious adverse events following COVID-19 vaccination have been described in the literature. This case report describes acute retinal necrosis (ARN) secondary to varicella zoster virus (VZV) reactivation following COVID-19 mRNA vaccination., Case Description: A 42-year-old immunocompetent man developed left ARN 12 days following first dose of Pfizer BioNTech mRNA COVID-19 vaccination. Aqueous and vitreous tap polymerase chain reaction testing was positive for VZV. Good visual outcome was achieved with combination therapy, including intravitreal foscarnet, oral valaciclovir and prednisolone, topical dexamethasone and atropine, and barrier retinal laser. Second dose of the vaccine is planned under cover of high-dose oral valaciclovir therapy., Conclusion: This case illustrates the possible association between COVID-19 vaccination and potentially blinding VZV reactivation. Therefore, prompt ophthalmic assessment is recommended in patients with visual disturbance following COVID-19 vaccination.

What Is This Summary About?: This is a summary of an article originally published in the Multiple Sclerosis Journal . Cladribine tablets (MAVENCLAD ® ) are an oral (taken by mouth) medication, approved for the treatment of people with relapsing forms of multiple sclerosis (MS, with episodes of new or worsening symptoms). They are administered for a maximum of 10 days per year, over a period of 2 years. Cladribine tablets work by temporarily reducing the number of lymphocytes, which are immune cells that help to fight off infections. Because of this, people with MS (also called PwMS) may have concerns about the effect of cladribine tablets on vaccines, as these work via immune cells to build protection against infection., What Happened in the Magnify-Ms Study?: A study called MAGNIFY-MS investigated how long it takes for cladribine tablets to begin to work in people with a type of MS called highly active relapsing MS. During the study, some participants received their usual vaccinations against flu (influenza) and against the chickenpox virus (also called varicella zoster virus) as part of their routine medical care. The MAGNIFY-MS study gave the researchers an opportunity to look at how cladribine tablets affect the way the flu and chickenpox virus vaccines work in the body., What Were the Results?: Cladribine tablets do not affect how well the body responds to flu and chickenpox vaccines., What Do the Results Mean?: PwMS taking cladribine tablets who are vaccinated against chickenpox, flu or both can be protected against these diseases.

Objective: The varicella vaccine is not included in the national childhood immunization schedules in China. Varicella epidemics and outbreaks are frequently reported, and the evidence for the effectiveness of the varicella vaccine remains unclear. The aim of this study was to investigate varicella vaccine effectiveness in Wuxi, China., Methods: Varicella surveillance data were extracted from the China Information System for Disease Control and Prevention, and vaccination data were obtained from the Vaccination Integrated Service Management Information System of Jiangsu Province, China. Time-series analysis approaches were used to estimate varicella vaccine effectiveness., Results: A total of 16,093 varicella cases among children aged 1-6 years between January 2016 and December 2020 were analysed. A total of 217,297 children completed a two-dose varicella vaccination series. Compared with districts with lower vaccination rates, districts in Wuxi with higher varicella vaccination rates had a lower proportion of cases ( p  < 0.001). In the time-series approach, 0.8% fewer varicella cases were associated with a 1% increase in the two-dose varicella vaccination rate ( p  < 0.001), and similar effects were found in both the male and female populations., Conclusions: Two-dose varicella vaccination was recommended as an effective health intervention to prevent varicella in Wuxi, China. Varicella vaccination is urgently needed in routine childhood immunisation programs.

Background: Varicella is considered a mild and self-limiting disease, but, in some cases, it may complicate and require hospitalization. Antibiotics are not the first line therapy but in some cases are prescribed either for the management of varicella-related complications or as a preventive strategy. Aim of this study is to analyze the rate and the patterns of antibiotics used in pediatric patients hospitalized for varicella as well as the relative costs in order to increase insights in antibiotic use in varicella., Methods: Patients less than 18 years hospitalized for varicella at the Bambino Gesù Children's IRCCS Hospital in Rome, Italy, from the 1 st of November 2005 to the 1 st of November 2021 entered the study. Retrospective data were collected from the hospital's database electronic medical records. The rate, the patterns and the costs of antibiotics used were considered., Results: According to the inclusion criteria, we enrolled 810 patients, with a median age of 2.4 years. Out of them, 345 patients (42.6%) underwent antibiotic therapy, of which 307 for a complication (90.0%) and the other 10.0%, antibiotic for the fear of developing complications. The cost for varicella hospitalizations was EUR 2,928,749 (median cost EUR 2689). As for antibiotic therapy, it represented the 5.9% of the total cost (EUR 174,527), with a median cost of EUR 198.8. The cost in patients who underwent antibiotic therapy was significantly higher than in those who did not (p-value < 0.0001), as well as the hospitalization length (p-value < 0.0001). The most commonly prescribed antibiotics were Amoxicillin-clavulanate and Ceftriaxone, which represented the 36.0% and 25.0% of all antibiotic prescription, respectively. Antibiotics may negatively affect the economic cost of hospitalization and the prescription is not always in accordance to guidelines, with potential important repercussions on the development of antimicrobial resistance. Actually, resistance to antibiotics is considered a major risk to the future health of the world population as it may lead to longer hospital stay, increased risk of mortality, health care costs and treatment failures., Conclusion: Strategies to reduce economical cost, hospitalization length and antimicrobial resistance include ensuring appropriate prescription and administration of empiric antibiotics as well as reducing the circulation of preventable infectious diseases through immunization., (© 2022. The Author(s).)

Human herpes viruses belong to the DNA viruses and are among the most common viral pathogens. Currently, eight human herpes viruses have been characterized. Primary infection is typically followed by virus latency. Viral reactivations are more often symptomatic than primary infections and lead more often to medical consultation. In daily practice, infections with herpes simplex virus (HSV) and varicella zoster virus (VZV) are the most common. If HSV primary infections become clinically manifest, they are often accompanied by systemic symptoms whereas manifest HSV reactivations are usually harmless, self-limiting and present as grouped vesicles on an erythematous base (herpetiform). Primary VZV infection leads to the clinical picture of varicella (chickenpox). VZV reactivation manifests clinically as shingles and can be accompanied by severe acute neuralgiform pain. In immunosuppression, complicated (necrotizing, ulcerative, hemorrhagic, generalized) manifestations may occur. The diagnosis is usually made clinically. Therapeutic options include topical agents and systemic antivirals. Adequate therapeutic management includes the recognition and treatment of complications such as the possible involvement of other organ systems and pain. Infection during pregnancy may result in transmission to the unborn child., (© 2022 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Varicella pneumonia is uncommon among adults and can present as potentially life-threatening complications of varicella. Here we report a case of a 43-year-old man with no known history of chronic disease and no allergic history who presented to our hospital emergency department with widespread skin eruptions over the entire body and hemoptysis. Varicella pneumonia was diagnosed based on the patient being in contact with his 6-year-old son who had contracted chickenpox 10 days back, typical cutaneous lesions, pulmonary symptoms and radiographic findings. The patient was treated with oral acyclovir and was admitted to the intensive care unit for monitoring. The patient recovered completely after 10 days of treatment., Keywords: chickenpox; pneumonia; skin eruptions.

Background: In 1995, the CDC recommended one-dose routine varicella immunization for children <12 years of age, expanding its recommendation to two doses in 2006. Today, with widespread varicella vaccination coverage, an estimated 3.5 million cases of varicella, 9,000 hospitalizations, and 100 deaths are prevented annually in the United States. Since varicella infections are now uncommon, health care providers (HCPs) may not recognize varicella infections and may prescribe inappropriate treatment., Methods: An online survey of HCPs was conducted to assess recognition and management of varicella infections. Responses to eight varicella vignettes describing patients with varying varicella symptoms were analyzed and descriptive analyses performed. Stratified analysis comparing responses of those licensed before and in/after 1996 was also performed., Results: 153 HCPs (50 nurse practitioners, 103 doctors) completed the survey. Mean age of respondents was 44 years. 62% were female, and 82% were licensed before 1996. Varicella infection was correctly diagnosed 79% of the time. HCPs correctly recognized uncomplicated varicella vignettes 85% of the time versus 61% of the time for complicated varicella vignettes. Antibiotics were recommended 17% of the time and antivirals 18% of the time, of which 25% and 69% (respectively) were not appropriate per guidelines. HCPs licensed before 1996 were better able to recognize varicella compared to those licensed later, but prescribed more antimicrobials medications to treat varicella., Conclusions: Although most HCPs recognized varicella infection, a sizable proportion could not recognize cases with complications, and some of the varicella cases were inappropriately treated with antibiotics and/or antivirals. Additional HCP training and high vaccination coverage are important strategies to avoid inaccurate diagnoses and minimize unnecessary exposure to antimicrobial/antiviral therapies., Competing Interests: This work was supported by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. M. Pawaskar, S. Samant, and S. Surati are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and stockholders of Merck & Co., Inc., Kenilworth, NJ, USA. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Our objective was to estimate the impact of universal varicella vaccination (UVV) on the use and costs of antibiotics and antivirals for the management of varicella among children in the United States (US)., Methods: A decision tree model of varicella vaccination, infections and treatment decisions was developed. Results were extrapolated to the 2017 population of 73.5 million US children. Model parameters were populated from published sources. Treatment decisions were derived from a survey of health care professionals' recommendations. The base case modelled current vaccination coverage rates in the US with additional scenarios analyses conducted for 0%, 20%, and 80% coverage and did not account for herd immunity benefits., Results: Our model estimated that 551,434 varicella cases occurred annually among children ≤ 18 years in 2017. Antivirals or antibiotics were prescribed in 23.9% of cases, with unvaccinated children receiving the majority for base case. The annual cost for varicella antiviral and antibiotic treatment was approximately $14 million ($26 per case), with cases with no complications accounting for $12 million. Compared with the no vaccination scenario, the current vaccination rates resulted in savings of $181 million (94.7%) for antivirals and $78 million (95.0%) for antibiotics annually. Scenario analyses showed that higher vaccination coverage (from 0% to 80%) resulted in reduced annual expenditures for antivirals (from $191 million to $41 million), and antibiotics ($82 million to $17 million)., Conclusions: UVV was associated with significant reductions in the use of antibiotics and antivirals and their associated costs in the US. Higher vaccination coverage was associated with lower use and costs of antibiotics and antivirals for varicella management., Competing Interests: M. Pawaskar and S. Samant, are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and own stocks in Merck & Co., Inc., Kenilworth, 257 NJ, USA. P. Veeranki, and C. Harley, are employees of PRECISIONheor, which received financial support from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA for the execution of this research. Though they received no payment for their work on this study, J. H. Conway reports grants and personal fees from Sanofi Pasteur, Pfizer, Merck, GSK, and Centers for Disease Control outside of the submitted work while J. Fergie reports personal fees from Merck Sharp & Dohme Corp, outside the submitted work.

We herein report the case of a 78-year-old woman who was diagnosed as having disseminated herpes zoster (DHZ) complicated with probable varicella-zoster pneumonia during maintenance therapy for microscopic polyangiitis. Because the patient had severe renal dysfunction, amenamevir administration was started to avoid any neurotoxicity of acyclovir, which is suggested to be optimal for treatment. It ameliorated her symptoms without any adverse events. This is the first report suggesting the efficacy of amenamevir in the treatment of severe herpes zoster infection with coexisting DHZ and probable varicella-zoster pneumonia. Amenamevir could thus be a treatment option for severe varicella zoster virus infections.

Objectives: Burden of comorbidities are largely unknown in JIA. From 2000, national and international patient registries were established to monitor biologic treatment, disease activity and adverse events in patients with JIA. The aim of this analysis was to investigate in parallel, for the first time, three of the largest JIA registries in Europe/internationally-UK JIA Biologic Registers (BCRD/BSPAR-ETN), German biologic registers (BiKeR/JuMBO), multinational Pharmachild-to quantify the occurrence of selected comorbidities in patients with JIA., Methods: Information on which data the registers collect were compared. Patient characteristics and levels of comorbidity were presented, focussing on four key conditions: uveitis, MAS, varicella, and history of tuberculosis. Incidence rates of these on MTX/biologic therapy were determined., Results: 8066 patients were registered into the three JIA registers with similar history of the four comorbidities across the studies; however, varicella vaccination coverage was higher in Germany (56%) vs UK/Pharmachild (16%/13%). At final follow-up, prevalence of varicella infection was lower in Germany (15%) vs UK/Pharmachild (37%/50%). Prevalence of TB (0.1-1.8%) and uveitis (15-19%) was similar across all registers. The proportion of systemic-JIA patients who ever had MAS was lower in Germany (6%) vs UK (15%) and Pharmachild (17%)., Conclusion: This analysis is the first and largest to investigate the occurrence of four important comorbidities in three JIA registries in Europe and the role of anti-rheumatic drugs. Combined, these three registries represent one of the biggest collection of cases of JIA worldwide and offer a unique setting for future JIA outcome studies., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Primary varicella infection has typical cutaneous lesions which aid in clinical diagnosis. Infants with transplacental transfer of varicella antibody can have varied cutaneous lesions. We report a 4-month-old infant with primary varicella meningoencephalitis without cutaneous lesions whose mother had no history of varicella during antenatal or post-natal period. Diagnosis was made possible by CSF DNA PCR. Infants with encephalitis pose diagnostic challenge to clinicians in resource limited settings. Varicella encephalitis is one such aetiology for which definitive therapy with Acyclovir is available. CSF PCR is the definitive and cost-effective test for the diagnosis varicella encephalitis. In children with meningoencephalitis it is prudent to add Acyclovir empirically pending CSF viral PCR results.

The review article provides information about the features of the Varicella-zoster virus (VZV), about the clinical manifestations of CNS damage in acute and chronic VZV infection in children and adults, about the mechanisms of interaction of the pathogen with the immune system during the development of the disease. The question of whether to consider neurological disorders in VZV infection as a complication or manifestation of the disease caused by a defective virus or the presence of subclinical immunodeficiency is discussed, which is confirmed by modern scientific studies. The critical mechanisms of immune defense against VZV, which are the main reason for the penetration of the virus into the CNS and the development of neurological disorders, as well as the relationship between VZV genotypes, the presence of mutations in the gE gene and the nature of the course, the identification of rare variants of the POLR3A, POLR3C, POLR3E and POLR3F genes associated with violation of IFNs induction, and the development of severe VZV infection, in which vasculopathy also occurs, which is the basis for the use of vascular drugs of complex action, such as Cytoflavin, the effectiveness of which has been proven by the authors. A special place is given to the analysis of intrathecal immunopathogenesis, which is likely to be associated with the presence and severity of neurological manifestations, their relapses. The issue of the causes of the development of a severe course of the disease in patients vaccinated against chickenpox, as well as the issue of resistance to specific antiviral drugs, probably associated with the presence of mutations responsible for the resistance of the virus to therapy, is discussed.

Although Varicella or chickenpox infection which is caused by the varicella-zoster virus (VZV) has significantly been managed through vaccination, it remains an infection that poses threats to the nearest future due to therapeutic drawbacks. The focus of this research was geared towards in silico screening for the identification of novel compounds in plants of ethnopharmacological relevance in the treatment of chicken pox in West Africa. The work evaluated 65 compounds reported to be present in Achillea millefolium, Psidium guajava and Vitex doniana sweet to identify potential inhibitors of thymidine kinase, the primary drug target of varicella zoster virus. Out of the 65 compounds docked, 42 of these compounds were observed to possess binding energies lower than -7.0 kcal/mol, however only 20 were observed to form hydrogen bond interactions with the protein. These interactions were elucidated using LigPlot + and MM-PBSA analysis with residue Ala134 predicted as critical for binding. Pharmacological profiling predicted three potential lead compounds comprising myricetin, apigenin- 4' -glucoside and Abyssinone V to possess good pharmacodynamics properties and negligibly toxic. The molecules were predicted as antivirals including anti-herpes and involved in mechanisms comprising inhibition of polymerase, ATPase and membrane integrity, which were corroborated previously in other viruses. These drug-like compounds are plausible biotherapeutic moieties for further biochemical and cell-based assaying to discover their potential for use against chickenpox. Communicated by Ramaswamy H. Sarma.

Varicella-Zoster virus (VZV) infection is well-known for its dermatological appearances, such as chickenpox and shingles. In addition to its dermal disease, we report a case of visceral dissemination of VZV in immunocompromised patients. A 38-year-old male Caucasian with a history of bone marrow transplantation due to diffuse large B-cell-lymphoma presented himself with severe abdominal pain. Immediate endoscopy revealed numerous gastric and duodenal ulcerations, while histological and molecular evaluation on tissue biopsies and blood samples confirmed VZV infection. Positive serological findings and history of chickenpox during childhood supported visceral VZV dissemination due to reactivation of VZV. The patient received Aciclovir treatment and fully recovered. This case illustrates that visceral dissemination of VZV may lead to acute abdominal pain due to severe mucosal ulcerations even in the absence of dermatological manifestations. Early endoscopic evaluation may therefore be crucial and the only means to immediately guide differential diagnosis, especially in immunocompromised patients. Characteristic histomorphological findings from mucosal ulcerations should lead to the immediate initiation of antiviral therapy and specific molecular evaluation in order to avoid detrimental spread of visceral VZV infection.

Background: To evaluate the effectiveness of varicella vaccine (VarV) as post-exposure prophylaxis (PEP) among children during varicella outbreaks., Material and Methods: A comprehensive literature search was performed in PubMed, Embase, Web of Science, SinoMed, Wanfang and CNKI. Relevant outcomes included the incidence of varicella. Pooled estimates were calculated using a fixed-effects or random-effects model according to the heterogeneity among studies., Results: A total of 15 studies with 7,474 children that received one or two dosages of VarV as PEP and 183,827 children who received no VarV were included in the meta-analysis. In total, one-dose and two-dose VarV as PEP had 43% (95% confidence interval (CI):27%, 55%) and 60% (95%CI: 35%, 75%) efficacy, respectively. When PEP was applied within 3 days, the pooled VarV as PEP for prevention of varicella was 80% (95%CI: 68%, 88%); when PEP was administered beyond 3 days, the pooled VarV as PEP for the prevention of varicella was 50% (95%CI: 11%, 72%). If the PEP was implemented with a coverage of more than 80%, the VarV could prevent 82% of varicella cases from occurring (95%CI: 15%, 96%); if the PEP covered a maximum of 80% of the susceptible cases, the VarV could prevent 65% of varicella cases from occurring (95%CI: 50%, 76%)., Conclusion: The two-dose VarV had better efficacy than one-dose VarV in the control of varicella outbreaks, especially if PEP was applied within 3 days of an outbreak and in conjunction with a high coverage rate ≥80%.

Background: Varicella is a highly contagious infection that typically occurs in childhood. While most cases have a generally benign outcome, infection results in a considerable healthcare burden and serious complications may occur., Objectives: The objective of this study was to characterize the burden of varicella in a real-world primary care setting in Belgium, including the rate of varicella-related complications, medication management and general practitioner (GP) visits., Methods: The study was a retrospective observational study using data from a longitudinal patient database in a primary care setting in Belgium. Patients with a GP visit and a varicella diagnosis between January 2016 and June 2019 were eligible and data one month prior and three months after the diagnosis were included. Outcomes included varicella-related complications, antibiotic use, antiviral use, and GP follow-up visits. Antibiotic use could be specified by class of antibiotic and linked to a diagnosis. Complications were identified based on concomitant diagnosis with varicella during the study period., Results: 3,847 patients with diagnosis of varicella were included, with a mean age of 8.4 years and a comparable distribution of gender. 12.6% of patients with varicella had a concomitant diagnosis of a varicella-related complication. During the follow-up period, 27.3% of patients with varicella were prescribed antibiotics, either systemic (19.8%) and/or topical (10.3%). The highest rate of antibiotic prescriptions was observed in patients with complications (63.5%) and in patients younger than 1 year (41.8%). Nevertheless, 5.3% of the patients were prescribed antibiotics without a concomitant diagnosis of another infection. The most commonly prescribed systemic antibiotics were amoxicillin alone or combined with beta-lactamase inhibitor, and thiamphenicol. Fusidic acid and tobramycin were the most prescribed topical antibiotics. Antivirals were prescribed for 2.7% of the study population. 4.7% of the patients needed a follow-up visit with their GP., Conclusions: This study reports a substantial burden of varicella in a primary care setting in Belgium, with high rates of complications and antibiotic use., (© 2021. The Author(s).)

A 2.5-year-old boy presented to his pediatrician with progressive pallor, asthenia, fever, splenomegaly, and hematomas. Leukemia was suspected, and a bone marrow aspirate confirmed acute lymphoblastic leukemia. Before chemotherapy induction, the child developed a vesicular rash and was diagnosed clinically with chickenpox. Acyclovir treatment was initiated immediately, whereas induction chemotherapy was postponed by 10 days. At the time of chickenpox resolution, a spontaneous partial recovery of his blood counts and a 50% decrease of blastic bone marrow infiltration were noted. After a brief nonsystematic review, we discuss the potential beneficial effect of acyclovir and chickenpox infection in children with leukemia., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Viral pneumonia caused by varicella-zoster virus (VZV) infection is a rare but important complication, especially regarding varicella infections. Although disseminated cutaneous herpes zoster (DCHZ) is often associated with visceral diseases, there have been few reports of DCHZ-related pneumonia. We herein report a rare case of a lethal disseminated VZV infection that caused severe pneumonia in a Japanese patient who had chronic interstitial pneumonia. Physicians should consider the possibility of VZV-related pneumonia, especially in patients with a medical history of hematopoietic stem cell transplantation and immunosuppressive therapy.

Chickenpox during pregnancy can cause serious complications for both mother and fetus. This includes varicella pneumonia in the mother, fetal varicella syndrome and varicella of newborn. Primary prevention includes vaccination against varicella infection and is part of standard childhood immunisation programme in many countries. Timely post-exposure prophylaxis of susceptible pregnant women with varicella zoster immunoglobulin is key to preventing chickenpox during pregnancy and its adverse fetomaternal sequelae. Antiviral therapy and appropriate supportive treatment improve maternal and neonatal outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Miller Fisher syndrome (MFS), an acute demyelinating neuropathy, is characterised by a triad of areflexia, ataxia and ophthalmoplegia. It is the most common variant of Guillain-Barre Syndrome (GBS). In about 5.6%-7.1% of MFS cases, patients also suffer from progressive motor weakness of the limbs. This condition is termed MFS/GBS overlap syndrome. Whether it is in MFS or GBS, bilateral vocal cord paralysis (BVCP) is a rare manifestation with limited cases reported in the literature. We report an extremely rare case where a 65-year-old man developed BVCP in an MFS/GBS overlap syndrome. We have also reviewed previous case reports in the literature for comparison., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Varicella zoster virus central nervous system infections can present as aseptic meningitis, encephalitis, myelitis, and vasculopathy. Diagnosis is based on identification of varicella zoster virus deoxyribonucleic acid (DNA) in the cerebrospinal fluid by polymerase chain reaction. Therapy for these infections is acyclovir or valacyclovir. However, acyclovir can have neurotoxic effects that can mimic the presentation of varicella zoster virus central nervous system disease. We present a rare presentation of a patient who had acyclovir-induced neurotoxicity who also had a false-positive cerebrospinal fluid varicella zoster virus polymerase chain reaction result, creating a management dilemma. We review the clinical characteristics of acyclovir-induced neurotoxicity. In addition, we present the diagnostic characteristics of the cerebrospinal fluid viral polymerase chain reaction and alternative methods to diagnose central nervous system varicella zoster virus disease., Case Presentation: A 68-year-old Hispanic man with end-stage renal disease was diagnosed with cutaneous zoster at an outside facility and was started on acyclovir 4 days prior to admission. His family noted worsening confusion, agitation, speech difficulty, and hallucinations, leading them to bring him to the emergency department. His cerebrospinal fluid varicella zoster virus polymerase chain reaction result was positive, indicating the presence of varicella zoster virus deoxyribonucleic acid in the cerebrospinal fluid; however, he did not have cerebrospinal fluid pleocytosis typical of varicella zoster virus meningoencephalitis. Pharmacy records from the outside hospital revealed supratherapeutic acyclovir dosing. This led to a diagnostic dilemma over whether this patient had varicella zoster virus encephalitis or acyclovir-induced neurotoxicity. Acyclovir was discontinued, and the patient underwent two sessions of hemodialysis to remove acyclovir, which led to a full neurologic recovery., Conclusions: Varicella zoster virus encephalitis and acyclovir-induced neurotoxicity can have similar presentations. Varicella zoster virus deoxyribonucleic acid can be present in the cerebrospinal fluid during active cutaneous zoster in the absence of central nervous system disease. If concern for central nervous system varicella zoster virus disease remains high, additional testing with cerebrospinal fluid serology can be performed. Compared with central nervous system varicella zoster virus disease, acyclovir-induced neurotoxicity has a more predictable clinical resolution once drug therapy is discontinued or the patient undergoes hemodialysis, which can aid in making the diagnosis. Clinicians should be aware of this rare and dangerous complication of acyclovir. In addition, clinicians should have an understanding of the diagnostic limitations of cerebrospinal fluid viral polymerase chain reaction and have alternative approaches available to diagnose central nervous system varicella zoster virus disease when it is suspected.

Toxic epidermal necrolysis is a rapidly progressive exfoliating dermatosis which simulates second degree burns. The authors describe a fatal case reported as due to burns. Around 95% of the deceased's total body surface area was affected, with epidermolysis over face, chest, abdomen, limbs and associated with mucosal involvement. Histopathological findings revealed epidermal necrolysis and confirmed the autopsy suspicion. Because of its sudden onset and rapid progression, toxic epidermal necrolysis often arises suspicion of burns by investigators. We emphasise the differentiating features between toxic epidermal necrolysis and burns and its implications.

Competing Interests: None

Aim: Recent studies focusing on morbidity and mortality rates of immunocompromised children with varicella-zoster virus (VZV) infections are scarce. We aimed to summarise our experience., Methods: The study was a retrospective analysis of the medical records of children, who were admitted to Hadassah-Hebrew University Medical Centre, Jerusalem, Israel, during the period of 2008-2016. Data regarding baseline characteristics, treatment and outcome were extracted from patient's medical files., Results: We enrolled 74 patients (43% males) with a mean age of 8 (1-19) years. Most patients (72%) had no reported complications. Clinical outcome was favourable with 73 (99%) patients who had completely recovered and none died. Multivariable analysis identified the presence of fever (P = .005 and 0.02; hazard ratio (HR) 7.72 and 17.61, for total and herpes zoster groups, respectively) and prolonged interval period from clinical presentation to treatment onset (P = .021 and 0.025; HR 1.68 and 2.26, respectively), as associated with higher rates of complications., Conclusion: Our results found low complication rate of VZV-associated infections in immunocompromised children admitted to a single centre. This should encourage conducting further large multicentre studies evaluating management of low-risk patients with oral acyclovir treatment., (© 2019 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Varicella zoster virus (VZV) causes varicella primarily in childhood, and some rare adults also report varicella. Herpes zoster mainly occurs in adults by endogenous reactivation of latent VZV. Until now, varicella and herpes zoster have seldom been reported simultaneously in one patient. Here, we report a rare case co-presenting with varicella and herpes zoster in a Chinese adult., Case Presentation: A 44-year-old Chinese man suffered papules and vesicles with pain on the left ear. Five days after onset, he was admitted to the Department of Dermatology of The Third Hospital of Xiamen. Physical examination revealed that small vesicles surrounded by erythema had developed on his trunk, back and neck, and unilateral papules and vesicles in ribbons had also developed on the left ear. This patient was excluded from human immunodeficiency virus and Treponema pallidum infections by ELISA antibody tests. Laboratory tests revealed that the ratio of eosinophils (0.1%) and eosinophil count (0.0 × 10 9 /L) were significantly downregulated. Treatment with valacyclovir, ebastine, mecobalamine, pregabalin and calamine lotion for 5 days was effective therapy for varicella and herpes zoster. Polymerase chain reaction for vesicular fluids from varicella and herpes zoster was positive for VZV, and further phylogenetic analysis and single nucleotide polymorphism variations confirmed that the VZV genotype was type J (clade 2)., Conclusions: This rare case highlights awareness of varicella and herpes zoster caused by VZV infection in adults. Our report provides novel insight into the rare clinical presentation of VZV genotype J.

Natural circulating antibodies (NAbs) to endogenous regulators have shown to be potential biomarkers in medicine. Due to the lack of reliable assays, only few of them have been well studied. To employ NAbs as biomarkers, an evaluation of changes over the course of a treatment is required. This paper describes our work to analyze the dynamics of NAbs titer to interferon-gamma (IFN-γ) among healthy children of different age and in patients with varicella infection receiving an antiviral drug Anaferon for children (AC, the API are highly diluted antibodies to IFN-γ) in comparison with placebo, and to correlate the findings with the treatment results. IFN-γ plays an essential role during varicella infection, and this fact causes the consequent increase of NAbs to IFN-γ level. The mean anti-IFN-γ NAbs level in the healthy volunteer group was 101 × 10 3 U/ml (age: 0-15 years), which was significantly lower than the mean pre-treatment value in patients with varicella infection 167 × 10 3 U/ml (age: 3-17 years). In the AC group, the NAbs level observed on days 5 and 10 decreased significantly to a level of 154 × 10 3 U/ml, whereas in the placebo group it continued to rise in a time-dependent manner reaching 229 × 10 3 U/ml on day 10. Our findings suggest that treatment with AC is characterized by "normalization" of the anti-IFN-γ NAbs levels in patients with varicella infection., Competing Interests: Declaration of Competing Interest The author(s) declared the potential conflicts of interest with respect to the the following: Elena Don, Mikhail Putilovskiy and Sergey Tarasov are employees of OOO “NPF “Materia Medica Holding” (fully or partly). The employees of OOO “NPF “Materia Medica Holding” performed statistical analysis, made a decision to publish the work, and covered the current article processing charges. Anaferon for Children is a commercial drug produced and marked by OOO “NPF “Materia Medica Holding”., (Copyright © 2019 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Although long-term antiviral prophylaxis is recommended to prevent varicella zoster virus (VZV) infection in seropositive recipients of allogeneic and autologous (auto-) hematopoietic cell transplantation (HCT), studies of VZV infections in pediatric auto-HCT recipients are rare. This study aimed to investigate the incidence and characteristics of VZV infection in pediatric auto-HCT recipients and explore the risk factors of VZV infection and its effect on survival outcomes. This study included all pediatric patients who underwent auto-HCT at Samsung Medical Center, Seoul, Korea, between January 1998 and December 2013. Before 2006, short-term acyclovir prophylaxis was provided until neutrophil engraftment; thereafter, routine prophylaxis was not provided. Patients who developed either herpes zoster or chickenpox within 2 years from transplantation were identified, and a chart review was performed. A total of 413 recipients and 698 auto-HCTs were included. Sixty-one episodes of VZV infections were identified in 54 patients. Fourteen cases of VZV infection (23%; 14 of 61) occurred within 30 days after auto-HCT. The cumulative incidence of the first episode of VZV infection at 2 years after transplantation was 14% (95% confidence interval [CI], 7.9% to 22.8%) in all recipients and 9% (95% CI, 1.0 to 26.6) in VZV-seronegative patients. Notably, the VZV infection rate increased with age and the VZV infection rate in patients age 15 to 19 years was almost three times higher than in patients age 0 to 4 years (28% versus 10%; P = .003). However, there was no difference in the VZV infection rate between recipients of single auto-HCT and recipients of tandem auto-HCT. Two patients died of disseminated VZV infection. VZV infection is a considerable risk in auto-HCT recipients with or without short-term prophylaxis. Universal antiviral prophylaxis might be considered, particularly in older children, regardless of VZV serologic results. To our knowledge, this is the largest study of VZV infection in pediatric auto-HCT recipients reported to date., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Varicella zoster virus (VZV) causes a life-threatening infection in immunocompromised hosts. The immune response to VZV of healthy subjects has been rigorously assessed, but little is known about that of immunocompromised individuals. This study aimed to clarify the primary response to VZV infection in immunocompromised children. This prospective study enrolled six immunocompromised children (median age, 33 months; range, 20-62) receiving steroids or immunosuppressants, and 10 immunocompetent children (median age, 32 months; range, 15-81) with varicella. The immunocompromised children were three patients with acute lymphoblastic leukemia, two recipients with liver transplantation and one patient with juvenile idiopathic arthritis. Interferon-γ-producing CD69 + T-cells produced by VZV stimulation (VZV-specific T-cells) were studied during the acute or convalescent phase. To further address the direct effect of immunosuppressants, we analyzed the number of VZV-specific T-cells after stimulating peripheral blood mononuclear cells obtained from healthy adults with live-attenuated VZV with or without prednisolone, cyclosporine-A, or tacrolimus. The circulating numbers of lymphocytes in the convalescent stage but not acute stage were lower in immunocompromised children compared with immunocompetent children. In the acute stage, immunocompromised patients showed lower VZV-specific CD8 + T-cell counts than immunocompetent subjects. In contrast, in the convalescent phase, immunocompromised patients had lower VZV-specific CD4 + T-cell counts than immunocompetent hosts. The in vitro culture of activated lymphocytes with prednisolone or immunosuppressants significantly decreased the proportion of VZV-specific CD4 + T-cells. In conclusion, the decreased numbers of VZV-specific CD8 + T-cells during the acute phase and VZV-specific CD4 + T-cells during the convalescent phase of disease may account for severe varicella in immunocompromised children.

Live vaccine-acquired infection should attest for the occurrence of inborn errors of immunity. Autosomal recessive immunodeficiency 31B, a result of a signal transducer and activator of transcription 1 genetic mutation, results in defected interferon pathways: interferon alpha/beta and interferon gamma. These interferons are crucial for the defence against viral and mycobacterial infections. Recognition is important for preventive and therapeutic approaches. Herein, we report the presentation of a newly diagnosed 13-month-old child with immunodeficiency 31B after presenting with disseminated measles and varicella infection after Measles, Mumps, Rubella and Varicella vaccination., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Varicella is normally a self-limited childhood disease caused by varicella-zoster virus infection. However, it sometimes causes severe diseases, especially in immunocompromised individuals. We report a case of severe varicella in a young woman., Case Presentation: A 19-year-old woman presented to the emergency department with abdominal pain and a rash after taking methylprednisolone for 2 weeks for systemic lupus erythematosis. The laboratory data showed leukocytosis, thrombocytopenia, an elevated level of the liver transaminases and disseminated intravascular coagulation. Computed tomography of the abdomen revealed multiple air-fluid levels in the intestines. Hemorrhagic varicella was considered and antiviral therapy as well as immunoglobin were applied. Her condition deteriorated and she eventually died due to multi-organ failure and refractory shock. Next-generation sequencing performed on fluid from an unroofed vesicle confirmed the diagnosis of varicella., Conclusion: In its severe form, VZV infection can be fatal, especially in immunocompromised patients. Hemorrhagic varicella can be misdiagnosed by clinicians because of unfamiliar with the disease, although it is associated with a high mortality rate. In patients with suspected hemorrhagic varicella infection, antiviral therapies along with supportive treatment need to be initiated as soon as possible in order to minimize the case fatality rate.

Objective: In-depth example of two new group sequential methods for postmarket safety monitoring of new medical products., Study Design and Setting: Existing trial-based group sequential approaches have been extended to adjust for confounders, accommodate rare events, and address privacy-related constraints on data sharing. Most adaptations have involved design-based confounder strategies, for example, self-controlled or exposure matching, while analysis-based approaches like regression and weighting have received less attention. We describe the methodology of two new group sequential approaches that use analysis-based confounder adjustment (GS GEE) and weighting (GS IPTW). Using data from the Food and Drug Administration's Sentinel network, we apply both methods in the context of a known positive association: the measles-mumps-rubella-varicella vaccine and seizure risk in infants., Results: Estimates from both new approaches were similar and comparable to prior studies using design-based methods to address confounding. The time to detection of a safety signal was considerably shorter for GS IPTW, which estimates a risk difference, compared to GS GEE, which provides relative estimates of excess risk., Conclusion: Future group sequential safety surveillance efforts should consider analysis-based confounder adjustment techniques that evaluate safety signals on the risk difference scale to achieve greater statistical power and more timely results., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Varicella is a highly contagious childhood disease. Generally benign, serious complications necessitating antibiotic use may occur. The objective of this study was to characterize the rate, appropriateness and patterns of real-world antibiotic prescribing for management of varicella-associated complications, prior to universal varicella vaccination (UVV) implementation., Methods: Pooled, post-hoc analysis of 5 international, multicenter, retrospective chart reviews studies (Argentina, Hungary, Mexico, Peru, Poland). Inpatient and outpatient primary pediatric (1-14 years) varicella cases, diagnosed between 2009 and 2016, were eligible. Outcomes, assessed descriptively, included varicella-associated complications and antibiotic use. Three antibiotic prescribing scenarios were defined based on complication profile in chart: evidence of microbiologically confirmed bacterial infection (Scenario A); insufficient evidence confirming microbiological confirmation (Scenario B); no evidence of microbiological confirmation (Scenario C). Stratification was performed by patient status (inpatient vs. outpatient) and country., Results: Four hundred one outpatients and 386 inpatients were included. Mean (SD) outpatient age was 3.6 (2.8) years; inpatient age was 3.1 (2.8) years. Male gender was predominant. Overall, 12.2% outpatients reported ≥1 infectious complication, 3.7% ≥1 bacterial infection, and 0.5% ≥1 microbiologically confirmed infection; inpatient complication rates were 78.8, 33.2 and 16.6%, respectively. Antibiotics were prescribed to 12.7% of outpatients and 68.9% of inpatients. Among users, β-lactamases (class), and clindamycin (agent), dominated prescriptions. Scenario A was assigned to 3.9% (outpatients) vs 13.2% (inpatients); Scenario B: 2.0% vs. 6.0%; Scenario C: 94.1% vs. 80.8%., Conclusions: High rates of infectious complications and antibiotic use are reported, with low rates of microbiological confirmation suggesting possible antibiotic misuse for management of varicella complications.

A 49-year-old kidney transplant recipient, presented with a skin rash, and interstitial infiltrates three weeks after receiving a live attenuated varicella-zoster vaccine. Varicella-zoster Oka-vaccine strain was detected in plasma by polymerase chain reaction and sequencing analysis targeting open reading frame 62 (ORF 62). She was treated successfully with intravenous acyclovir. Our case report supports the current contraindication of live attenuated varicella-zoster vaccine in the solid-organ transplant recipients. Recombinant subunit varicella-zoster vaccine may be the vaccine of choice in these patients; nevertheless, further information is required to establish its safety, efficacy, and optimal timing., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Context: Since 2007, 2 doses of varicella vaccine have been routinely recommended, with a catch-up second dose recommended for those who received only 1 prior dose., Objective: To examine varicella vaccination coverage with 2 or more doses and the proportions of adolescents with evidence of immunity to varicella (≥2 doses of vaccine or varicella history) during 2007-2014. To assess timing of second-dose receipt, factors associated with 2 or more vaccine doses, and missed second-dose opportunities during 2014., Design, Setting, and Participants: We used data from the 2007-2014 National Immunization Survey-Teen (NIS-Teen), which collects information on adolescents aged 13 to 17 years in the United States., Results: From 2007 to 2014, varicella vaccination coverage with 2 or more doses increased from 8.3% to 66.9% in 13- to 15-year-olds and from 3.6% to 56.7% in 16- to 17-year-olds. The proportions with evidence of immunity also increased from 68.0% to 84.1% (13- to 15-year-olds) and 78.6% to 83.4% (16- to 17-year-olds). In 2014, 13.4% of 13- to 15-year-olds and 3.2% of 16- to 17-year-olds had received their second dose at 4 to 6 years of age. Factors most significantly associated with lower coverage with 2 or more doses were not having an 11- to 12-year well-child visit, not receiving an adolescent vaccine, and residence in a state with no 2-dose immunization school entry requirement. Seventy-seven percent of 1-dose vaccinated adolescents had 1 or more missed opportunities to receive their second dose; if were they not missed, 2-dose coverage would have increased from 79.5% to 94.8%., Conclusions: Levels of varicella vaccination coverage with 2 or more doses and the proportion of adolescents with evidence of immunity increased from 2007 to 2014, though 16% lacked evidence of immunity in 2014. Although catch-up campaigns have succeeded, missed vaccination opportunities persist.