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Purpose: The aim of this study was to analyze treatment outcomes and their predictors in children hospitalized due to varicella complicated by bacterial superinfections after pandemic of COVID-19. Methods: This retrospective study analyzed data collected in a multicenter, nationwide, observational database dedicated for children aged 0–17 years hospitalized due to bacterial complications of varicella in 9 Polish tertiary healthcare inpatient centers. The primary endpoint of this study was the treatment outcome established after the end of hospital management assessed at a 4-point scale. The secondary endpoint was defined as the necessity of surgical intervention. Results: There were 458 patients with a median age of 4 (IQR 2–6) years. After the completed treatment, 319 (69%) participants were found fully recovered; 132 (29%) had transient complications; 2 (0.5%) had persistent complications; and 1 child (0.5%) died. Multivariate analysis revealed that implementation of ibuprofen in pre-treatment management of a child with varicella was associated with a 4.07-fold (2.50–6.60) increase in risk of complications after the treatment and it was associated with 2.87 times (1.39–5.89) higher risk of surgical intervention necessity. For other pre-hospital interventions (implementation of acyclovir, antibiotics or antihistaminics) no significant impact was observed. GAS infection increased the necessity of surgical intervention by 7.51 (3.64–15.49) times. Conclusions: One-third of patients treated for bacterial complications of varicella have post-treatment complications, most of them transient. GAS infection increases the need for surgical intervention. The use of ibuprofen in the treatment of varicella significantly increases the risk of complications and the need for surgical intervention. [ABSTRACT FROM AUTHOR]

To estimate the economic burden of varicella among children in France from family and societal perspectives. We conducted an online cross-sectional survey of caregivers of 185 French children (≤ 17 years) diagnosed with varicella in the previous six weeks. Data collected included varicella-related healthcare resource use, out-of-pocket costs, missed school days, and workdays missed by either parents or other caregivers. Mean and median direct and indirect costs (2022 Euros) were calculated using survey data and published literature. The annual societal burden of pediatric varicella in France was estimated. Of the 185 children, 95.1% had ≥ 1 outpatient visit, 10.3% had ≥ 1 emergency room visit, and 2.2% were hospitalized. The median [interquartile range, IQR] number of outpatient visits/child was 1.0 [1.0 – 2.0]. The median length of hospital stay among those hospitalized (n = 4) was 5.0 [3.5 – 6.5] days. Caregivers of 185 children missed a median of 2.0 [0 – 5.0] workdays; 113 families (61.1%) had ≥ 1 parent miss work. A median of 5.0 [3.0 – 7.0] school days were missed by 170 children who attended preschool or school. The median direct out-of-pocket cost to the family was €30.0 [€17.0 – €60.0]. The median [IQR] societal costs per varicella case were €455.2 [€70.5 – €1013.5]; the median [IQR] direct and indirect costs per child were €60.8 [€39.0 – €102.7] and €364.7 [€0.0 – €911.7] respectively. The annual societal burden of varicella among children in France was estimated to be €450,427,578 (95% CI: €357,144,618 – €543,710,538), with indirect costs accounting for 85%. Conclusions: A substantial economic burden is associated with pediatric varicella in France, primarily due to the productivity loss among caregivers. What is Known: • Although varicella is considered a mild disease, it poses a significant burden on caregivers and society. Our study aimed to estimate the economic burden of varicella among children in France from family and societal perspectives to support policymakers in understanding the value of UVV in France. What is New: • We conducted an online survey of caregivers of 185 French children (≤17 years) diagnosed with varicella and collected data on varicella-related healthcare resource use, missed school days and workdays. Our study estimated annual societal burden of pediatric varicella in France. Out of 185 children with varicella, most (95.1%) had at least one outpatient visit, 10.3% had at least one emergency room visit, and 2.2% were hospitalized. 61.1% of parents with sick child, missed work and median productivity loss was 2.0 workdays. Additionally, 170 children who attended school or preschool missed a median of 5.0 school days. • The societal burden of pediatric varicella in France was estimated to be €450,427,578 (95% CI, €357,144,618 - €543,710,538), with indirect costs accounting for 85%. Pediatric varicella is associated with a substantial economic burden in France, primarily due to high productivity losses among parents and caregivers. [ABSTRACT FROM AUTHOR]

Objectives: Analyse alternative methods of intrathecal antibody detection by comparing chemiluminescent immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) techniques to determine if CLIA can replace ELISA in the diagnosis of CNS infections. Methods: A panel of 280 paired samples—cerebrospinal fluid (CSF) and serum—with known antibody reactivities (Varicella, n = 60; Measles, n = 120) and negative samples (n = 100) were used to evaluate the performance of six serological test kits (Enzygnost, VirClia®, and Serion ELISA (Measles and Variella). Results: For Measles virus IgG, the VirClia® IgG monotest revealed 97% and 94% positive and negative agreement to the Enzygnost as reference test, respectively. In contrast, Serion ELISA kits yielded values of 18% and 90%. For the Varicella Zoster virus (VZV) IgG, the VirClia® IgG monotest showed 97% and 90% positive and negative agreement compared to Enzygnost. The Serion ELISA kits showed values of 55% and 86%, respectively. ROC analysis revealed that the areas under the curve for Measles and VZV IgGs were 0.7 and 0.852, respectively, using the Serion kit, and 0.963 and 0.955, for Vircell S.L CLIA technique. VirClia® monotest values were calculated using an antibody index cut-off of 1.3. Conclusion: The findings indicate that CLIA testing can improve antibody detection in CSF samples, aiding the diagnosis of infectious neurological impairments. [ABSTRACT FROM AUTHOR]

Simian varicella virus (SVV) produces peripheral inflammatory responses during varicella (primary infection) and zoster (reactivation) in rhesus macaques (RM). However, it is unclear if peripheral measures are accurate proxies for central nervous system (CNS) responses. Thus, we analyzed cytokine and Aβ42/Aβ40 changes in paired serum and cerebrospinal fluid (CSF) during the course of infection. During varicella and zoster, every RM had variable changes in serum and CSF cytokine and Aβ42/Aβ40 levels compared to pre-inoculation levels. Overall, peripheral infection appears to affect CNS cytokine and Aβ42/Aβ40 levels independent of serum responses, suggesting that peripheral disease may contribute to CNS disease. [ABSTRACT FROM AUTHOR]

The objective of this study is to provide practical recommendations on the management of pediatric patients with immune-mediated rheumatic diseases receiving immunosuppressive therapies. The recommendations specifically address the cases of surgery, fever, and opportunistic infections (varicella, herpes-zoster, tuberculosis, invasive fungal disease). A qualitative approach was applied. A narrative literature review was performed via Medline. Primary searches were conducted using MeSH terms and free text to identify publications on infections and vaccinations in pediatric patients with immune-mediated rheumatic diseases receiving immunosuppressive therapies. The results were presented and discussed in a nominal group meeting, comprising a committee of 12 pediatric rheumatologists from the Infection Prevention and Treatment Working Group of the Spanish Society of Pediatric Rheumatology. Several recommendations were generated. A consensus procedure was implemented via a Delphi process; this was extended to members of the Spanish Society of Pediatric Rheumatology and Spanish Society of Pediatric Infectious Disease of the Spanish Association of Pediatrics. Participants produced a score ranging from 0 (totally disagree) to 10 (totally agree). Agreement was defined as a vote ≥ 7 by at least 70% of participants. The literature review included more than 400 articles. Overall, 63 recommendations (19 on surgery, fever, and opportunistic infections) were generated and voted by 59 pediatric rheumatologists and other pediatric specialists. Agreement was reached for all 63 recommendations. The recommendations on special situations cover management in cases of surgery, fever, and opportunistic infections (varicella, herpes-zoster, tuberculosis, and invasive fungal disease). Conclusions: Hereby, we provided consensus and updated of recommendations about the management of special situations such as surgery, fever, and opportunistic in children with immune-mediated rheumatic diseases receiving immunosuppressive therapies. Several of the recommendations depend largely on clinical judgement and specific balance between risk and benefit for each individual and situation. To assess this risk, the clinician should have knowledge of the drugs, the patient's previous situation as well as the current infectious disease, in addition to experience. What is Known: • Infectious diseases and related complications are a major cause of morbidity and mortality in patients with immune-mediated rheumatic diseases. • Information on how to manage the treatment in situations of fever, opportunistic infections, and surgery in children is limited, and guidelines for action are often extrapolated from adults. What is New: • In the absence of strong evidence, a literature review and a Delphi survey were conducted to establish a series of expert recommendations that could support the clinical practice, providing a practical and simple day-to-day approach to be used by pediatric rheumatologists. [ABSTRACT FROM AUTHOR]

Introduction: Varicella (chickenpox) is an infectious disease caused by the varicella zoster virus affecting children, adolescents, and adults. Varicella symptoms are usually self-limiting; however, different complications with widespread and systemic manifestations can occur. This systematic literature review aims to explore and quantify varicella-associated complication rates. Methods: Two databases (Embase and MEDLINE), congress abstracts, and reference lists of systematic reviews were screened to identify evidence on varicella complications. Complications were identified and grouped into 14 clinically relevant categories. Proportional meta-analyses were conducted using a random-effects model and tests for heterogeneity and publication bias were performed. Subgroup, sensitivity, and meta-regression analyses were also conducted. A total of 78 studies, spanning 30 countries, were included in the meta-analysis. Results: Pooled prevalence was highest in severe varicella (22.42%; 95% confidence interval [CI] 10.13–37.77), skin-related complications (20.12%; 95% CI 15.48–25.20), and infection-related complications (10.03%; 95% CI 7.47–12.90). Cardiovascular (0.55%; 95% CI 0.08–1.33), genitourinary (1.17%; 95% CI 0.55–1.99), and musculoskeletal (1.54%; 95% CI 1.06–2.11) complications had the lowest pooled prevalence. The remaining complication categories ranged between 1% and 10%. Subgroup analysis showed that complications were more prevalent in children versus adults and in hospitalized patients versus outpatients. Meta-regression analysis found that no ecological level covariates were accurate predictors for the overall prevalence of varicella-associated complications. There was substantial heterogeneity and publication bias across all meta-analyses. Conclusion: Results suggest that different types of varicella-associated complications could be frequent, impacting quality of life, and healthcare resource utilisation and budgets. These findings are crucial to raise awareness of the health and economic burden of varicella disease. Plain Language Summary: A graphical plain language summary is available with this article. [ABSTRACT FROM AUTHOR]

The use of live attenuated vaccines in patients with immunosuppressive agents is contraindicated in package inserts and guidelines in Japan and other countries. However, patients receiving immunosuppressants have a high risk of infectious disease becoming severe, and the necessity to prevent infectious disease is high. To date, 2,091 vaccinations have been reported in 25 reports of live attenuated vaccines in people receiving immunosuppressants. Twenty-three patients (1.1%) became infected with the virus strain used in the vaccine, which was varicella virus in 21 patients. No reports have described life-threatening complications. A prospective study at the National Center for Child Health and Development conducted under certain immunological conditions (CD4 cell count ≥ 500/mm3, stimulation index of lymphocyte blast transformation by phytohemagglutinin (PHA) ≥ 101.6, serum immunoglobulin G ≥ 300 mg/dL) confirmed the serological effectiveness and safety. The evidence suggests that live attenuated vaccines can be used even in combination with immunosuppressants. Further evidence must be gathered and immunological criteria investigated to determine the conditions for safe use. Depending on the results of these investigations, the wording in package inserts and guidelines may need to be revised. [ABSTRACT FROM AUTHOR]

This multicenter study aimed to investigate the relationship between varicella incidence and meteorological factors including mean temperature, relative humidity, sunshine duration, diurnal temperature difference, wind speed, and rainfall, as previous studies have produced varying results. Our study also sought to identify potential sources of heterogeneity. Data on reported daily varicella numbers and meteorological factors were collected for 14 cities in Yunnan Province from 2017 to 2021. A distribution-lagged nonlinear model was constructed to explore the relationship between meteorological conditions and varicella incidence in each included city. We then used multiple meta-regression to explore sources of heterogeneity using demographic economics indicators, air pollutants, and geographic location as potential modifiers. The cumulative hazard effect plot showed an inverted S-shape for the relationship between temperature and varicella, with the smallest RR (relative risk) (0.533, 95% CI: 0.401–0.708) at temperatures up to 27.2 °C. The maximum RR (1.171, 95% CI: 1.001–1.371) was obtained when the relative humidity was equal to 98.5%. The RR (1.164, 95% CI: 1.002–1.352) was greatest at a diurnal temperature range of 2 °C (1.164, 95% CI: 1.002–1.352) and least (0.913, 95% CI: 0.834–0.999) at a diurnal temperature range of 16.1 °C. The maximum RR (1.214, 95% CI: 1.089–1.354) was obtained at 0 h of sunshine, and the minimum RR (0.808, 95% CI: 0.675–0.968) was obtained at 12.4 h of sunshine. The RR (0.792, 95% CI: 0.633–0.992) was minimum at a wind velocity of 4.8 m/s. Residual heterogeneity ranged from 1 to 42.7%, with PM10 (particles with an aerodynamic diameter less than 10 μm), GDP (gross domestic product), and population density explaining some of this heterogeneity. The temperature has a dual effect on varicella incidence. Varicella cases are negatively correlated with diurnal temperature range, sunshine duration, and wind speed, and positively correlated with relative humidity. GDP and PM10 may have a significant role in altering the association between temperature and varicella, while PM10 and population density may alter the association between wind velocity and varicella. [ABSTRACT FROM AUTHOR]

This study aims to provide practical recommendations on prophylaxis for infection in pediatric patients with immune-mediated rheumatic diseases receiving/scheduled to receive immunosuppressive therapy. A qualitative approach was applied. A narrative literature review was performed via Medline. Primary searches were conducted using MeSH terms and free text to identify articles that analyzed data on infections and vaccinations in pediatric patients with immune-mediated rheumatic diseases receiving immunosuppressive therapy. The results were presented and discussed in a nominal group meeting comprising a committee of 12 pediatric rheumatologists from the Prevention and Treatment of Infections Working Group of the Spanish Society of Pediatric Rheumatology. Several recommendations were generated. A consensus procedure was implemented via a Delphi process that was extended to members of the Spanish Society of Pediatric Rheumatology and the Vaccine Advisory Committee of the Spanish Association of Pediatrics. Participants produced a score ranging from 0 (completely disagree) to 10 (completely agree). Agreement was considered to have been reached if at least 70% of participants voted ≥ 7. The literature review included more than 400 articles. Overall, 63 recommendations were generated (23 on infection prophylaxis) and voted by 59 pediatric rheumatologists and other pediatric specialists, all of whom achieved the pre-established level of agreement. The recommendations on prophylaxis of infection cover vaccination and prophylaxis against varicella zoster virus, tuberculosis, Pneumocystis jiroveccii, and invasive fungal infections in pediatric patients with immune-mediated rheumatic diseases receiving/scheduled to receive immunosuppressive therapy. Conclusion: Based on current evidence and a Delphi process, we provided consensus and updated recommendations on prophylaxis and treatment of infections to guide those caring for pediatric rheumatology patients. What is Known: •Data largely derived from adults find that infectious diseases and related complications are a major cause of morbidity and mortality in patients with immune-mediated rheumatic diseases. •It is crucial to be aware of the preventive measures that should be implemented to prevent these infections in children, although most guidelines are often extrapolated from adult cases. What is New: •In the absence of evidence, a literature review and a Delphi survey were conducted to establish a series of expert recommendations that could prove useful in clinical practice, providing a practical and simple day-to-day approach to be used by pediatric rheumatologists. •The recommendations focus on tuberculosis, herpes zoster virus, fungal infections, and Pneumocystis jirovecii. [ABSTRACT FROM AUTHOR]

Varicella (chickenpox) is a serious public health problem in China, with the most reported cases among childhood vaccine-preventable infectious diseases, and its reported incidence has increased over 20-fold since 2005. Few previous studies have explored the association of multiple meteorological factors with varicella and considered the potential confounding effects of air pollutants. It is the first study to investigate and analyze the effects of multiple meteorological factors on varicella incidence, controlling for the confounding effects of various air pollutants. Daily meteorological and air pollution data and varicella cases were collected from January 1, 2015, to December 31, 2020, in Lu'an, Eastern China. A combination of the quasi-Poisson generalized additive model (GAM) and distributed lag nonlinear model (DLNM) was used to evaluate the meteorological factor-lag-varicella relationship, and the risk of varicella in extreme meteorological conditions. The maximum single-day lag effects of varicella were 1.288 (95%CI, 1.201–1.381, lag 16 day), 1.475 (95%CI, 1.152–1.889, lag 0 day), 1.307 (95%CI, 1.196–1.427, lag 16 day), 1.271 (95%CI, 0.981–1.647, lag 4 day), and 1.266 (95%CI, 1.162–1.378, lag 21 day), when mean temperature, diurnal temperature range (DTR), mean air pressure, wind speed, and sunshine hours were −5.8°C, 13.5°C, 1035.5 hPa, 6 m/s, and 0 h, respectively. At the maximum lag period, the overall effects of mean temperature and pressure on varicella showed W-shaped curves, peaked at 17.5°C (RR=2.085, 95%CI: 1.480–2.937) and 1035.5 hPa (RR=5.481, 95%CI: 1.813–16.577), while DTR showed an M-shaped curve and peaked at 4.4°C (RR=6.131, 95%CI: 1.120–33.570). Sunshine hours were positively correlated with varicella cases at the lag of 0–8 days and 0–9 days when sunshine duration exceeded 10 h. Furthermore, the lag effects of extreme meteorological factors on varicella cases were statistically significant, except for the extremely high wind speed. We found that mean temperature, mean air pressure, DTR, and sunshine hours had significant nonlinear effects on varicella incidence, which may be important predictors of varicella early warning. [ABSTRACT FROM AUTHOR]

Varicella is a rising public health issue. Several studies have tried to quantify the relationships between meteorological factors and varicella incidence but with inconsistent results. We aim to investigate the impact of temperature and relative humidity on varicella, and to further explore the effect modification of these relationships. In this study, the data of varicella and meteorological factors from 2011 to 2019 in 21 cities of Guangdong Province, China were collected. Distributed lag nonlinear models (DLNM) were constructed to explore the relationship between meteorological factors (temperature and relative humidity) and varicella in each city, controlling in school terms, holidays, seasonality, long-term trends, and day of week. Multivariate meta-analysis was applied to pool the city-specific estimations. And the meta-regression was used to explore the effect modification for the spatial heterogeneity of city-specific meteorological factors and social factors (such as disposable income per capita, vaccination coverage, and so on) on varicella. The results indicated that the relationship between temperature and varicella in 21 cities appeared nonlinear with an inverted S-shaped. The relative risk peaked at 20.8 ℃ (RR = 1.42, 95% CI: 1.22, 1.65). The relative humidity-varicella relationship was approximately L-shaped, with a peaking risk at 69.5% relative humidity (RR = 1.25, 95% CI: 1.04, 1.50). The spatial heterogeneity of temperature-varicella relationships may be caused by income or varicella vaccination coverage. And varicella vaccination coverage may contribute to the spatial heterogeneity of the relative humidity-varicella relationship. The findings can help us deepen the understanding of the meteorological factors-varicella association and provide evidence for developing prevention strategy for varicella epidemic. [ABSTRACT FROM AUTHOR]

Introduction: The reactivation of varicella zoster virus (VZV) in previously infected individuals can cause herpes zoster (HZ), which is characterized by a localized, painful dermatomal rash. While there is a global trend of increasing HZ cases, there is a lack of research examining the epidemiology of HZ within the Gulf Cooperation Council (GCC) countries. Therefore, we aimed to critically appraise evidence on VZV and HZ epidemiology in the GCC countries and identify gaps in the current literature. Methods: A literature review was conducted via a comprehensive appraisal of the literature. PubMed and local-language journals were searched to identify articles related to HZ and VZV published up until 31 January 2022, with a sole focus on the GCC countries. Included studies reported on surveillance data, seroepidemiology, and patient outcomes for HZ and VZV, and comprised primary data reports, case series, case reports, narrative and systematic literature reviews, studies reporting HZ incidence or prevalence, and Ministry of Health reports. Results: Thirteen studies were found that reported on VZV seroprevalence in Saudi Arabia, the United Arab Emirates (UAE), and Qatar, ranging from 15.0% to 92.2%, while no data were identified for Bahrain, Kuwait, or Oman. There was very limited country-wide information on the incidence of HZ in GCC countries, and three identified studies reported HZ prevalence as seen in a single clinic, ranging from 0.62% to 2.3%. A single study from Saudi Arabia and government surveillance data reported on the impact of VZV vaccination on VZV infection, though there was no evidence on the impact of VZV vaccination on HZ. Conclusion: There is a clear gap in the literature regarding the incidence of HZ infection, and the impacts of HZ and VZV vaccinations in the GCC countries. Further research into the epidemiology of HZ is necessary to inform the implementation of vaccination programs in the GCC countries. [ABSTRACT FROM AUTHOR]

We report two patients who developed atypical, disseminated herpes zoster infections while on dimethyl fumarate (DMF) treatment, one with varicella zoster virus (VZV) encephalitis and another with herpes zoster oticus resulting in lasting motor and sensory deficits. We recommend vaccination against VZV prior to DMF initiation be incorporated as standard of care, as ensuring patients are protected against VZV before starting DMF can prevent such severe outcomes. [ABSTRACT FROM AUTHOR]

Aim: Combination vaccines decrease the number of needles required, addressing a common concern of parents. However, some parents are hesitant about combination vaccines and/or want to opt out of certain vaccine components. This study assessed whether introduction of the combination MMRV vaccine influenced coverage levels for measles- and varicella-containing vaccines. Study and methods: This was a population-based study of children born in Alberta, Canada between 2006 and 2012. We utilized administrative health data to evaluate coverage for the first dose of measles- and varicella-containing vaccines at the age of 24 months (i.e. between 2008 and 2014) before and after introduction of the combination MMRV vaccine in 2010. Among those who were vaccinated, we assessed whether any children continued to receive separate vaccines after the combination vaccine was introduced. Results: Of 308,212 children, 272,345 (88.36%) were vaccinated with measles- and/or varicella-containing vaccines at the age of 24 months. Although coverage for measles-containing vaccines did not change overall between 2008 and 2014, coverage for varicella vaccine increased in the years following the introduction of MMRV. After the combination vaccine introduction, 96.55% of vaccinated children (n = 121,131) received MMRV vaccine. Conclusion: Vaccine coverage for varicella increased after the introduction of the combination MMRV vaccine, and there was a narrowing in the gap between MMR and varicella coverage. Very few children received separate vaccines after the introduction of the combination MMRV vaccine. These findings suggest that combination vaccines are acceptable to most parents and increase coverage for varicella in our setting. [ABSTRACT FROM AUTHOR]

The description of every possible adverse effect or event related to vaccines is mandatory during the ongoing worldwide COVID-19 vaccination program. Although cases of cutaneous varicella zoster virus (VZV) reactivation after COVID-19 vaccination have been increasingly reported in literature and database sets, a description of VZV-induced neurological disease (VZV-ND) is still lacking. In the present study, we retrospectively evaluated patients admitted to our clinic and diagnosed with VZV-ND during the COVID-19 vaccination campaign (January–April 2021) and in the same months in the previous two years. We identified three patients with VZV-ND after COVID-19 vaccination and 19 unvaccinated VZV-ND cases as controls. In the case–control analysis, the two groups showed no difference in clinical features, results of diagnostic investigations, and outcome. Thus, VZV reactivation with neurological involvement might be a possible event triggered by COVID-19 vaccination, but the benefit following COVID-19 vaccination overcomes significantly the potential risk associated with a VZV reactivation. [ABSTRACT FROM AUTHOR]

The impact of universal varicella vaccination on herpes zoster (HZ) risk in unvaccinated and vaccinated children, and its long-term influence on HZ epidemiology, remains unknown. We conducted a retrospective cohort study using population-based administrative health data for children born between 1993 and 2018 (n = 924,124). We calculated age-specific cumulative HZ incidence rates by vaccination status for cohorts born before (1993–1999) and after (2000–2018) programme implementation; results were used to calculate relative risk of HZ by age group, vaccination status and vaccine availability period. Annual HZ incidence rates were calculated for 1993–2018. HZ risk was higher among unvaccinated children compared to vaccinated children across age groups; 64% higher before universal vaccination (RR: 0.36, 95% CI: 0.33, 0.39), and 32% higher after universal vaccination (RR: 0.68, 95% CI: 0.64, 0.73). Among unvaccinated children, HZ risk was 60% lower after vaccine programme implementation (RR: 0.40, 95% CI: 0.38, 0.43). Two-dose receipt corresponded with a 41% lower risk of HZ compared to one-dose receipt (RR: 0.59, 95% CI: 0.53, 0.65). Crude annual HZ incidence rates declined 64% after programme implementation, with decreases observed across age groups. Universal varicella vaccination programme implementation corresponds to decreased paediatric HZ incidence across age groups, in both vaccinated and unvaccinated individuals. Results from this study can be used to help inform varicella vaccination programme decision-making in other countries. [ABSTRACT FROM AUTHOR]

Live attenuated vaccines are contraindicated for patients on immunosuppressive agents or biological agent, except for live attenuated varicella vaccine, although previous reports showed their effectiveness and safety. This study is the nationwide cross-sectional research about the current utilization of live attenuated vaccines for patients on immunosuppressive agents or biological agents in Japan. We sent questionnaires to pediatric centers and examined whether each institution offered live attenuated vaccines to patients with immunosuppressive agents or biological agents (institutional research). We also examined adverse events associated with live attenuated vaccines between 2013 and 2017 (patient research). In the institutional research, 46 out of 334 institutions (13.8%) administered live attenuated vaccines to patients receiving immunosuppressive agents. In contrast, only six out of 270 institutions (2.2%) administered live attenuated vaccines to patients receiving biological agents. However, 66.3% of physicians answered that patients receiving immunosuppressive agents should be immunized with live attenuated vaccines, and only 7.0% disagreed with them. In the patient research, data for 781 patients were collected. Vaccine-associated infections were observed in only two patients (0.3%), both of whom had varicella, although they recovered promptly. No life-threatening adverse events were noted. Conclusion: In pediatric centers, the demand for live attenuated vaccines in patients receiving immunosuppressive agents was high and most physicians think they should be immunized. Immunization with live attenuated vaccines appeared safe in patients receiving immunosuppressive agents, although further studies are needed for patients receiving biological agents What is known: • Live attenuated vaccines (LAV) are generally contraindicated for patients on immunosuppressive agents (IS) or biological agents (BA), except for live attenuated varicella vaccine, as immunocompromised patients are at greater risk for serious viral infection from the vaccine strains. • Viral infections, such as measles and varicella, cause serious complications in children receiving IS. • Several previous reports showed that LAV is relatively effective and safe for patients receiving IS. What is new: • In Japan, the demand for LAV in patients receiving IS was high, and most physicians hoped they should be immunized. • Vaccine-associated infection is rarely observed in patients with IS after LAV administration. • Immunization with LAV appeared safe in patients receiving IS. Trial registration: University Hospital Medical Information Network (UMIN). Trial registration number: UMIN000029176. Date of registration: 2017/09/19. [ABSTRACT FROM AUTHOR]

Introduction: Distinct skin lesions associated with coronavirus disease 2019 (COVID-19) have been described, but data regarding their time of onset during the COVID-19 course are scant. Our objective was to systematically review the studies reporting the time of onset of selected skin lesions with respect to the reported onset of the COVID-19 core symptoms. Methods: A comprehensive search of studies published before 21 January 2021 was performed on MEDLINE via PubMed database using a predefined strategy to identify relevant articles. Results: Out of 354 references, 87 were selected, reporting a total of 895 patients with skin lesions associated with COVID-19. The most frequent pattern was exanthema (n = 430, 48%), followed by vascular (n = 299, 33%), urticarial (n = 105, 12%) and others (n = 66, 7%). Skin lesions occurred more frequently in the first 4 weeks from the COVID-19 onset (n = 831, 92%), whereas prodromal or late lesions were rarer (n = 69, 8%). The urticarial and exanthema patterns were more frequent in the first 2 weeks. About the vascular pattern some differences were noted among its subtypes. Livedoid lesions occurred mainly in the first 2 weeks, while chilblain-like lesions between weeks 2 and 4. Purpuric/petechial lesions were equally distributed during the first 4 weeks. Several skin manifestations did not fall into the pattern classification, including erythema multiforme, generalized pruritus, Kawasaki disease and others. Conclusion: The diversity in the time of onset of skin lesions as well as their polymorphic nature likely reflects the diversity of the pathogenetic underlying mechanisms. PROSPERO database registration number: CRD42021236331. [ABSTRACT FROM AUTHOR]

Objective: To analyse the incidence of dermatoses in neonates, stress the importance of simple noninvasive diagnostic procedures with perspective to actual need of active intervention.Methods: Forty four neonates with vesicobullous lesions in Departments of Dermatology and Pediatrics were evaluated with respect to diagnosis, required treatments and follow ups.Results: Of the total 44 neonates, 29 were boys and 15 girls. Low birth weight (weight at birth less than 2,500 g as per WHO criteria) was seen in 19 neonates. Of the infectious dermatoses, most common were pyodermas. Four cases (9%) were diagnosed to be of staphylococcal pyoderma and impetigo and two cases each of Group A Streptococcal impetigo and neonatal tinea faciei (4.5% each), one case each of neonatal candidiasis, neonatal varicella/chickenpox and scabies (2.3% each) were seen. Of the transient skin lesions, erythema toxicum neonatorum was commonest of all, being seen in 18 neonates (41%), followed by four cases (9%) of miliaria crystallina, three cases of neonatal acne (6.8%) and two cases of sucking blisters (4.5%) and one case each of transient neonatal pustular melanosis, epidermolysis bullosa simplex, incontinentia pigmentii, eosinophilic pustular folliculitis, pemphigus vulgaris and neonatal herpes simplex (2.3% each) were enrolled in this study (Fig. 1). Fig. 1 Piechart showing percentage and number of neonates with different diagnostic profiles in the study CONCLUSIONS: Certain specific considerations have to be born in mind while evaluating and managing neonatal dermatoses. Care has to be instituted to identify accurately infectious diseases and distinguish them from benign transient neonatal dermatoses. Some disorders first manifesting during the neonatal period may also represent harbingers of potential problems during adulthood. Finally, treatment modalities are instituted taking in account the actual diagnosis and judging if the treatment really is required or not. [ABSTRACT FROM AUTHOR]

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Varicella and zoster, produced by varicella-zoster virus (VZV), are associated with an increased risk of stroke that may be due to persistent inflammation and hypercoagulability. Because substance P is associated with inflammation, hypercoagulability, and atherosclerotic plaque rupture that may contribute to increased stroke risk after VZV infection, we measured serum substance P in simian varicella virus–infected rhesus macaques. We found significantly increased and persistent serum substance P concentrations during varicella and zoster compared with pre-inoculation, supporting the hypothesis that VZV-induced increases in serum substance P may contribute to increased stroke risk associated with VZV infection. [ABSTRACT FROM AUTHOR]

Varicella zoster virus (VZV) is a pathogenic human herpes virus which causes varicella as a primary infection, following which it becomes latent in peripheral autonomic, sensory, and cranial nerve ganglionic neurons from where it may reactivate after decades to cause herpes zoster. VZV reactivation may also cause a wide spectrum of neurological syndromes, in particular, acute encephalitis and vasculopathy. While there is potentially a large number of coding viral mutations that might predispose certain individuals to VZV infections, in practice, a variety of host factors are the main determinants of VZV infection, both disseminated and specifically affecting the nervous system. Host factors include increasing age with diminished cell-mediated immunity to VZV, several primary immunodeficiency syndromes, secondary immunodeficiency syndromes, and drug-induced immunosuppression. In some cases, the molecular immunological basis underlying the increased risk of VZV infections has been defined, in particular, the role of POL III mutations, but in other cases, the mechanisms have yet to be determined. The role of immunization in immunosuppressed individuals as well as its possible efficacy in preventing both generalized and CNS-specific infections will require further investigation to clarify in such patients. [ABSTRACT FROM AUTHOR]

Vaccines against varicella-zoster virus (VZV) are under introduction in Hungary into the routine vaccination schedule, hence it is important to understand the current transmission dynamics and to estimate the key parameters of the disease. Mathematical models can be greatly useful in advising public health policy decision making by comparing predictions for different scenarios. First we consider a simple compartmental model that includes key features of VZV such as latency and reactivation of the virus as zoster, and exogeneous boosting of immunity. After deriving the basic reproduction number R 0 , the model is analysed mathematically and the threshold dynamics is proven: if R 0 ≤ 1 then the virus will be eradicated, while if R 0 > 1 then an endemic equilibrium exists and the virus uniformly persists in the population. Then we extend the model to include seasonality, and fit it to monthly incidence data from Hungary. It is shown that besides the seasonality, the disease dynamics has intrinsic multi-annual periodicity. We also investigate the sensitivity of the model outputs to the system parameters and the underreporting ratio, and provide estimates for R 0 . [ABSTRACT FROM AUTHOR]

The article explores how rare neurological complication in an adolescent with kidney failure secondary to systemic lupus erythematosus. Topics include case study of a 15-year-old female with kidney failure on intermittent hemodialysis secondary to Class IV lupus nephritis presented to the emergency department with progressively worsening right lower extremity pain; and Neurosurgery did not recommend surgical intervention, and neurology recommended electromyography/nerve conduction study.

Background: Universal varicella vaccination (UVV) for children introduced in Germany in 2004 resulted in a significant overall decline of varicella-related hospitalizations (VRHs). We investigated the incidence of specific types of varicella-related complications (VRCs) in hospitalized children and the impact of UVV on VRCs during the first 7 years of UVV. Methods: Children < 17 years of age hospitalized with an ICD-10-based (International Classification of Diseases, 10th Revision) discharge diagnosis of varicella were identified as VRH in pediatric hospitals in Bavaria by annual standardized data queries of the hospital databases (2005–2011). For each VRH, the hospitals reported basic demographic data, duration of hospital stay, all diagnostic and procedural codes, and outcome. VRCs were reported overall, per year, and by immune status. Complication rates were calculated as mean number per complication category per hospital and per year; VRC trends over time were assessed by linear regression. Results: Between 78% (2005) and 61% (2011) of Bavarian hospitals participated and reported a total of 1263 VRHs. Specific VRCs were reported in 954 (76%) children. Complication rates per hospital and year decreased from 6.7 [95% confidence interval (CI): 5.1–8.3] in 2005 to 1.5 (95% CI: 0.8–2.3) in 2011, with the strongest reduction of 90% in children < 5 years of age from 5.3 (95% CI: 4.0–6.6) in 2005 to 0.5 (95% CI: 0.1–0.9) in 2011. Significant decreases were observed for children with upper respiratory tract (URT, by 97%), lower respiratory tract (LRT, by 90%), skin (by 81%), gastrointestinal (by 78%), and neurologic (by 65%) VRCs. Forty-eight children with VRCs were immunocompromised; their annual rate decreased by 87%. Discussion: Corresponding to increasing varicella vaccination coverage in the population, the incidence of VRC decreased by 77% from 2005 to 2011, with the most substantial decrease in the target group for UVV. Conclusion: Within 7 years, UVV in Germany led to a decrease of about 77% of all types of VRCs, with the highest reductions observed for VRCs of the respiratory tract. [ABSTRACT FROM AUTHOR]

The introduction of mass vaccination against Varicella-Zoster-Virus (VZV) is being delayed in many European countries mainly because of the "fear" of a subsequent boom in natural herpes zoster (HZ) incidence in the first decades after the initiation of vaccination, caused by the expected decline in the protective effect of natural immunity boosting due to reduced virus circulation. Optimal control theory has proven to be a successful tool in understanding ways to curtail the spread of infectious diseases by devising the optimal disease intervention strategies. In this paper, we describe how a reduced 'toy' model can extract the essentials of the dynamics of the VZV transmission and reactivation in case of the study of optimal paths of varicella immunization programs. Results obtained using different optimization approaches are compared with the ones of a more realistic age-structured model. The reduced model shows some unreliable predictions in regards of model time scales about herpes zoster dynamic; nevertheless, it is able to reproduce the main qualitative dynamic of the more realistic model to the different optimization problems, while requiring a minimal number of parameters to be identified. Graphical abstract ᅟ. [ABSTRACT FROM AUTHOR]

Purpose of review: Patients with inflammatory bowel disease (IBD) are at increased risk of infectious diseases independent of their immunosuppression status, and yet, studies suggest that this population is not receiving standard vaccinations at the same rate as the general population. This review seeks to understand why IBD patients may not be receiving recommended immunizations and to provide guidelines on vaccinating this vulnerable population.Recent findings: Inactive vaccines are recommended for patients with IBD regardless of immunosuppression status due to the increased risk for many vaccine-preventable illnesses. Certain live vaccines can be administered to the immunocompromised patient with IBD. Additionally, many patients with IBD will be immunosuppressed some time in their disease course, further increasing their risk for infection. Despite this understanding, patients with IBD have poor vaccination rates. Inadequate knowledge, limited time with patients, and lack of consensus as to who is responsible for identifying and administering vaccinations are some of the most important barriers to vaccinating the patient with IBD.Summary: In this review, we discuss guidelines for vaccinating both the immunocompetent and immunosuppressed patient with IBD as well as provide vaccine-specific recommendations. The evidence suggests that patients with IBD are not receiving recommended vaccinations because of misconceptions on the part of patients as well as a paucity of knowledge by their health care team. Educational programs can be successfully implemented to increase knowledge about appropriate vaccinations and can ultimately increase vaccine uptake among patients with IBD. In the end, gastroenterologists and primary care physicians must work together with their patients with IBD to ensure that recommended vaccinations are administered. [ABSTRACT FROM AUTHOR]

Data from 215 pregnant women exposed to varicella and 276 with varicella observed at the Tuscany Reference Center for Infectious Diseases in Pregnancy, Florence, Italy, in the period 1997-2016 were retrospectively collected. The risk of developing varicella was lower in exposed women who received varicella zoster immunoglobulin compared with those who did not receive it [42% (21 of 50) vs 72% (13 of 18); p = 0.0263]. Typical congenital varicella syndrome was observed in 1.56% of fetuses/neonates born from pregnant women with varicella. [ABSTRACT FROM AUTHOR]

Varicella zoster virus (VZV) infection has been implicated in multiple sclerosis (MS), but direct causal involvement has been disputed. Nevertheless, knowledge of VZV exposure is important, given the risk of serious complications of first exposure while undergoing immunosuppressive treatment, in particular with fingolimod. We distributed questionnaires to MS clinic patients, requesting information about history of chickenpox, sibling/household/occupational exposure, history of zoster (shingles), and disease-modifying treatment. A random, proportionally representative sample of 51 patients that included patients with positive, negative, and unknown chickenpox history were selected for determination of VZV IgG by ELISA. Of 1206 distributed questionnaires, 605 were returned (50% response rate). Of these, 86% reported history of chickenpox, 5.6% gave negative history, and 8.5% did not know. Of 594 who answered the zoster question, 78% gave a negative response, 4% did not know, and 104 (17%) answered yes. Of these, 83 reported 1 episode; 12 had 2; 5 had 3; and 1 each reported 5, 6, and 15 episodes. Of 51 patients tested for VZV IgG (44 'yes,' 4 'no,' and 3 'I don't know' answers to the question of whether they had chickenpox), 48 were seropositive; the 3 seronegative all had reported having had chickenpox. The high rate of MS patients reporting prior chickenpox infection is comparable with previous reports. A substantial proportion of MS patients, estimated to be higher than an age-matched general population, report single or multiple episodes of zoster. These data are useful for consideration of immunosuppressive treatments and/or VZV and zoster vaccination. [ABSTRACT FROM AUTHOR]

Introduction: The current extent of migration to the European continent is associated with exceptional humanitarian challenges. In 2015, Western Europe faced an enormous immigration of refugees with largely unknown protection status against communicable diseases. To adapt vaccination strategies, we aimed at assessing seroprevalences against three of the most relevant vaccine preventable diseases (VPD) in a large representative cohort. Methods: IgG seroprevalences for rubella, varicella ( n = 554) and measles ( n = 552) were analyzed in inhabitants of a Northern German refugee camp in the summer of 2015. Results: Of the refugees, 77.9% were male (mean age 27.4 years for male and 26.8 years for female migrants). Most refugees came from the Eastern Mediterranean region (83.4%), followed by immigrants from Eastern Europe (7.4%), Africa (4.6%), or other regions (4.5%). The vast majority of migrants were protected against the three VPD: overall IgG seropositivity was 88.5% for measles, 77.9% for rubella and 95.9% for varicella. However, seroprevalences showed age- and origin-dependent differences. Varicella immunity, for example, was lowest in the youngest age group of both genders (10.1% of male/4.5% of female seronegative refugees <18 years vs. 100% seropositivity in men and women >49 years of age), and Sudanese migrants displayed particularly low rates of protection against varicella. Conclusion: In accordance with previous studies, our analyses show an overall satisfactory seropositivity against measles, rubella, and varicella in refugees entering Europe during the current exodus. However, this rate is not sufficient for preventing transmission. For example, the rate of 12.9-17.9% female refugees at reproductive age unprotected against measles and the low protection levels against varicella in minors observed in our cohort emphasizes the need for stringent vaccination strategies in refugees coming to Europe during the current crisis. [ABSTRACT FROM AUTHOR]

A quadrivalent MMRV (measles-mumps-rubella-varicella) combination vaccine has recently been launched in India. This vaccine is highly immunogenic, with seroconversion rates against all antigens reaching 96.6-100% at 42 to 56 days after the second vaccine dose in unvaccinated children or in those previously vaccinated with MMR+/-V. Two doses efficacy, against all varicella is 94.1% and effectiveness reaches 91%. The most frequent solicited local adverse event after MMRV vaccine is redness, and fever is the most common solicited general symptom. Higher rates of fever and febrile convulsions compared to MMR+/-V have been reported when used as first dose but not when used as the second of a measles containing vaccine, irrespective of age of the second dose. [ABSTRACT FROM AUTHOR]

Several outbreaks of varicella have occurred among refugees. We aimed to estimate the prevalence of varicella susceptibility among refugees, and identify risk factors for varicella susceptibility. All refugees rostered at Crossroads Clinic in Toronto, Canada in 2011-2014 were included in our study. Varicella serology was assessed at the initial visit. Refugees' age, sex, education, time since arrival, and climate and population density of birth country were abstracted from the chart. Multivariate logistic regression was used to identify risk factors for varicella susceptibility. 1063 refugees were rostered at Crossroads Clinic during the study; 7.9 % (95 % CI 6.1, 9.7) were susceptible to varicella. Tropical climate (OR 3.20, 95 % CI 1.53, 6.69) and younger age (OR 0.92, 95 % CI 0.88-0.96) were associated with increased varicella susceptibility. These risk factors for varicella susceptibility should be taken into account to maximize the cost-effectiveness of varicella prevention strategies among refugees. [ABSTRACT FROM AUTHOR]

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Purpose: The current extent of migration poses emerging socio-economic and humanitarian challenges. Little is known on vaccination rates in migrants entering Europe, and the implementation of guidelines for serological testing and vaccination of refugees are pending. Methods: We conducted seroprevalence analyses for measles, mumps, rubella and varicella (MMRV) in 678 refugees coming to Germany during the current crisis. Results: The mean age of refugees was 28.8±11.4 years, and 76.1 % of subjects were male. Overall, IgG seronegativity was 7.4 % (95 % CI 5.5-9.6) for measles, 10.2 % (95 % CI 8.0-12.5) for mumps, 2.2 % (95 % CI 1.2-3.4) for rubella, and 3.3 % (95 % CI 1.9-4.9) for varicella. Seropositivity rates were age-dependent with considerably low values in children. For example, overall MMR immunity was 90.9 % (95 % CI 88.8-93.1), but only 73.1 % of minor aged refugees displayed complete seroprevalence against all three diseases, and only 68.9 % of children and adolescents were completely MMRV immune. Conclusion: Our initial data set suggests overall satisfactory MMRV immunity in adult migrants coming to Europe, but the observed low MMRV seroprevalences in refugee children support thorough and prompt vaccination of young migrants entering Europe. Taken together, our data set underlines the urgent need to implement and validate vaccination guidelines for refugee care in the current crisis. [ABSTRACT FROM AUTHOR]

Background: Varicella is a common infectious disease primarily of childhood that is usually benign and self-limited. It is, however, increasingly seen in adults who are at a higher risk of severe infection. Ocular complications of varicella are relatively uncommon and have been rarely described in adults. We describe herein five adults who developed ocular involvement in association with primary varicella-zoster virus infection. Findings: Ocular manifestations included acute anterior uveitis in four eyes, with associated stromal keratitis in one of them, epithelial ulcerative keratitis in the two eyes of one patient, and acute retinal necrosis in one eye. One patient with acute anterior uveitis was treated with topical steroids and cycloplegic agents. The four other patients received topical or systemic antiviral drugs, with subsequent resolution of acute ocular inflammatory disease. Conclusions: The spectrum of chickenpox-associated ocular complications in adults is wide. Early diagnosis and appropriate management are mandatory to improve visual outcome. [ABSTRACT FROM AUTHOR]

Background: Varicella-zoster virus infection is associated with significant morbidity and mortality in immune-compromised children, despite treatment with antiviral agents. Universal varicella vaccine programs have significantly decreased this risk in many highincome countries, but in most low-income and middleincome countries, the burden of varicella in children treated for malignancy is poorly defined. Methods: We retrospectively reviewed records of children at the National Unit of Pediatric Oncology (UNOP) in Guatemala diagnosed with varicella between January 2009 and March 2013 in order to calculate incidence of varicella and evaluate morbidity, mortality, treatment interruption, and cost. Results: Fifty-nine cases of varicella were identified. Incidence was 23.4 cases per 1000 person-years (p-y). 66.1% of cases occurred in children with leukemia (median age 5.2 years; interquantile range 3.4-7 years) and 41.0% of these occurred during maintenance therapy. Source of exposure was identified for 14/59 (23.7%) children. Most were hospitalized (71.2%) and given intravenous acyclovir (64.4%). Eight (13.6%) children required critical care, and two (3.4%) died from disseminated varicella with multiorgan failure. Chemotherapy was delayed or omitted due to varicella in 50%. No significant differences in outcomes based on nutritional and immunologic status were detected. The minimum average cost of treatment per episode was 598.75 USD. Conclusions: Varicella is a significant problem in children treated for cancer in Guatemala, where effective post-exposure prophylaxis is limited. In the absence of universal varicella vaccination, strategies to improve recognition of exposure and the future use of novel inactivated vaccines currently under investigation in clinical trials could mitigate this burden. [ABSTRACT FROM AUTHOR]

Vaccination should be timed to take into account the potential interference of maternal antibodies. The purpose of this study was to determine the persistence of maternally acquired antibodies to hepatitis A and varicella zoster in a group of healthy infants between 6 and 24 months of age. These infants were divided into four groups according to the age at the time of follow-up visits. The study group consisted of infants who were brought to the 6-month follow-up visit (group 1, n = 100), 12-month follow-up visit (group 2, n = 99), 18-month follow-up visit (group 3, n = 59), and 24-month follow-up visit (group 4, n = 59). Hepatitis A, varicella IgG, and IgM antibodies were analyzed qualitatively. Hepatitis A IgG seropositivity was determined as 71 % in group 1, 41.4 % in group 2, 0 % in group 3, and 8.5 % in group 4 ( p < 0.001). Varicella IgG seropositivity was found to be 5 % in group 1, 4 % in group 2, 4 % in group 3, and 1 % in group 4 ( p > 0.05). Conclusion: We found that maternal hepatitis A antibodies in children disappear between 12 and 18 months, whereas maternal varicella antibodies substantially diminish following the sixth month. Therefore, the vaccination timing should be based on factors such as the interference of maternal antibodies, disease susceptibility period, and immune maturation. [ABSTRACT FROM AUTHOR]

We examined EEG in 35 children suffering from different forms of varicella-induced encephalitis. In nearly all patients (except for one child) slow-wave EEG components were present in EEG independently of the term of the disease. In two-thirds of the patients, diffuse paroxysmal slow-wave activity appeared in the EEG within first five days from the beginning of manifestation of neurological symptoms; the index of the main EEG activity did not exceed 20%. In the examined group, three-phase waves were not observed; periodically arising sharp waves were found only in a small number of cases (in two patients). [ABSTRACT FROM AUTHOR]

Varicella can cause complications that are potentially serious and require hospitalization. Our current understanding of the causes and incidence of varicella-related hospitalization in Turkey is limited and sufficiently accurate epidemiological and economical information is lacking. The aim of this study was to estimate the annual incidence of varicella-related hospitalizations, describe the complications, and estimate the annual mortality and cost of varicella in children. VARICOMP is a multi-center study that was performed to provide epidemiological and economic data on hospitalization for varicella in children between 0 and 15 years of age from October 2008 to September 2010 in Turkey. According to medical records from 27 health care centers in 14 cities (representing 49.3% of the childhood population in Turkey), 824 children (73% previously healthy) were hospitalized for varicella over the 2-year period. Most cases occurred in the spring and early summer months. Most cases were in children under 5 years of age, and 29.5% were in children under 1 year of age. The estimated incidence of varicella-related hospitalization was 5.29-6.89 per 100,000 in all children between 0-15 years of age in Turkey, 21.7 to 28 per 100,000 children under 1 year of age, 9.8-13.8 per 100,000 children under 5 years of age, 3.96-6.52 per 100,000 children between 5 and 10 years of age and 0.42 to 0.71 per 100,000 children between 10 and 15 years of age. Among the 824 children, 212 (25.7%) were hospitalized because of primary varicella infection. The most common complications in children were secondary bacterial infection (23%), neurological (19.1%), and respiratory (17.5%) complications. Secondary bacterial infections ( p < 0.001) and neurological complications ( p < 0.001) were significantly more common in previously healthy children, whereas hematological complications ( p < 0.001) were more commonly observed in children with underlying conditions. The median length of the hospital stay was 6 days, and it was longer in children with underlying conditions (<0.001). The median cost of hospitalization per patient was $338 and was significantly higher in children with underlying conditions ( p < 0.001). The estimated direct annual cost (not including the loss of parental work time and school absence) of varicella-related hospitalization in children under the age of 15 years in Turkey was $856,190 to $1,407,006. According to our estimates, 882 to 1,450 children are hospitalized for varicella each year, reflecting a population-wide occurrence of 466-768 varicella cases per 100,000 children. In conclusion, this study confirms that varicella-related hospitalizations are not uncommon in children, and two thirds of these children are otherwise healthy. The annual cost of hospitalization for varicella reflects only a small part of the overall cost of this disease, as only a very few cases require hospital admission. The incidence of this disease was higher in children <1 year of age, and there are no prevention strategies for these children other than population-wide vaccination. Universal vaccination is therefore the only realistic option for the prevention of severe complications and deaths. The surveillance of varicella-associated complications is essential for monitoring of the impact of varicella immunization. [ABSTRACT FROM AUTHOR]

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Two doses of a varicella-containing vaccine in healthy children <12 years are suggested to induce better protection than a single dose. Persistence of immunity against measles, mumps, rubella, and varicella as well as varicella breakthrough cases were assessed 3 years after two-dose measles, mumps, rubella, and varicella (MMRV) vaccination or concomitant MMR (Priorix™) and varicella (Varilrix™) vaccination. Four hundred ninety-four healthy children, 12-18 months old at the time of the first dose, received either two doses of MMRV vaccine (GlaxoSmithKline Biologicals) 42-56 days apart (MMRV, N = 371) or one dose of MMR and varicella vaccines administered simultaneously at separate sites, followed by another MMR vaccination 42-56 days later (MMR + V, N = 123). Three hundred-four subjects participated in 3-year follow-up for persistence of immunity and occurrence of breakthrough varicella (MMRV, N = 225; MMR + V, N = 79). Antibodies were measured by ELISA (measles, mumps, rubella) and immunofluorescence (varicella). Contacts with individuals with varicella or zoster and cases of breakthrough varicella disease were recorded. Three years post-vaccination seropositivity rates in subjects seronegative before vaccination were: MMRV-measles, 98.5% (geometric mean titer [GMT] = 3,599.6); mumps, 97.4% (GMT = 1,754.5); rubella, 100% (GMT = 51.9); varicella, 99.4% (GMT = 225.5); MMR + V-measles, 97.0% (GMT = 1,818.8); mumps, 93.8% (GMT = 1,454.6); rubella, 100% (GMT = 53.8); and varicella, 96.8% (GMT = 105.8). Of the subjects, 15-20% reported contact with individuals with varicella/zoster each year. After 3 years, the cumulative varicella breakthrough disease rate was 0.7% (two cases) in the MMRV group and 5.4% (five cases) in the MMR + V group. Conclusion: Immunogenicity of the combined MMRV vaccine was sustained 3 years post-vaccination. (208136/041/NCT00406211). [ABSTRACT FROM AUTHOR]

Clear recommendations for the management of acute varicella-zoster virus (VZV) infections for cases of significant exposure and the use of prophylactic drugs after solid-organ transplantation are missing due to the lack of evidence by prospective studies. Heterogeneity in patient groups, patient numbers, age groups, immunosuppressive regimens, timing, and dosage of aciclovir and/or varicella-zoster immunoglobulin (VZIG), pre-transplant vaccination or VZV wild-type infection and inconsistency of data make comparability of different studies impossible. Although the benefit of aciclovir and/or VZIG is uncertain in immunosuppressed children, prospective controlled double-blind studies are not feasible for ethical considerations as fatal cases with disseminating varicella disease are well known in these patient groups despite the use of aciclovir and/or VZIG, whereas severe side-effects of these drugs are rare. However, a reporting bias is likely as mainly severe or fatal cases might have been predominantly published or cases of successfully used aciclovir and/or VZIG in mild cases or in cases of breakthrough infections after vaccination. As neither VZIG prophylaxis nor treatment with intravenous aciclovir offers complete protection against severe VZV infection to immunosuppressed pediatric solid-organ transplant recipients, high priority should be given to vaccination against VZV prior to transplantation, and, most importantly, in their close contact persons. Clinical observations suggest that only assessment of humoral immunity together with cellular immunity may allow predication about protection in exposed patients. [ABSTRACT FROM AUTHOR]

The global surveillance of varicella-zoster virus (VZV) clades is an important tool for investigation into viral evolution, host-virus interactions, role of immigration and travel for importation of viral strains as well as possible recombination events between wild- and vaccine-type VZV strains. In this prospective study, comprehensive data on the current distribution of VZV clades in Germany were collected. VZV strains from 213 patients with varicella and 109 with zoster were genotyped using the scattered single-nucleotide polymorphism method on the basis of sequencing open reading frames 1, 21, 22, 37, 50, 54 and 60. In varicella, clade 3 was detected in 45.5%, clade 1 in 30.0%, clade 5 in 21.1% and clade 2 in 0.9% of the cases. The analysis of zoster strains revealed clade 3 in 50.5%, clade 1 in 46.8%, clade 2 and clade 4 in 0.9% of the cases each. Five strains from varicella and one strain from zoster could not be attributed to any of the major and provisional VZV clades. Statistical analysis verified significantly lower frequency of clade 1 and significantly higher frequency of clade 5 in patients with varicella compared to zoster. In addition, varicella patients with clade 5 strains were significantly younger than the patients with clade 3. In conclusion, almost one half of VZV infections in Germany were caused currently by VZV clade 3. In primary VZV infection, nearly 20% of clade 1 has been replaced by clade 5 that might spread more effectively in the population than the European VZV clades. [ABSTRACT FROM AUTHOR]

Chickenpox is often considered more severe during the first year of life, but its course is usually mild during the first 3 months of life, presumably owing to the persistence of maternal antibodies. Hospitalization and intravenous acyclovir therapy are generally restricted to severe cases but also systematically recommended in newborns in France, irrespective of the clinical severity of the infection. This recommendation was launched in 1998 when Varicella zoster virus (VZV)-specific immunoglobulins were not available in the country and has remained unchanged since. The aim of this prospective observational study was to describe complications of varicella infection in a population of 745 children hospitalized for varicella before 1 year of age, with a specific focus on newborns. Complications occurred in 65% of cases. They were very rare before the age of 1 month (10%) but their incidence then increased progressively with age and probably the disappearance of maternal antibodies: 42% (1-2 months), 66% (3-5 months), 70% (6-8 months), and 79% (9-12 months). Conclusion Chickenpox is usually mild in newborns because most of them are protected by VZV maternal antibodies. Unless the absence of maternal VZV immunity is demonstrated, newborns with mild chickenpox should not require antiviral therapy. [ABSTRACT FROM AUTHOR]

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Safe and effective vaccines against varicella zoster virus (VZV), the aetiological agent of varicella and shingles, have been available in Europe for the last 5-10 years. The USA has had a universal childhood vaccination policy since 1995 and this has resulted in a dramatic decrease in the incidence, morbidity and mortality related to varicella. The economic and medical burden of VZV has led to discussions regarding both the desirability and feasibility of a similar routine immunisation policy for all European children. This article examines the epidemiology of varicella in Europe and how the data emerging from the USA can be used to achieve adequate prevention of the disease. It looks into the current evidence of the health economic evaluation of universal varicella vaccination and explores the concerns surrounding such a policy, including the postulated impact on the incidence of zoster. In conclusion, the Society of Independent European Vaccination Experts (SIEVE) recommends that the immunisation of susceptible adolescents needs to be urgently implemented, in addition to the current recommendations targeting high-risk patients, their close contacts with a negative history of varicella and seronegative health-care workers. A universal policy, optimally incorporating a two-dose schedule, will be needed to finally reduce the burden of disease of varicella from a societal point of view. The SIEVE recommends the implementation of such a policy as soon as financially and practically possible. [ABSTRACT FROM AUTHOR]