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Background: Vaccinating pediatric solid organ transplant candidates against measles and varicella is crucial due to the risk of severe disease in immunosuppressed recipients and general avoidance of live virus vaccines post‐transplantation. The world saw a resurgence of measles starting 2012 prompting the American Society of Transplantation in 2015 to release guidelines on recognition, prevention, and post‐exposure prophylaxis of this disease in solid transplant recipients. This study aims to assess the extent of incomplete immunity to these viruses in candidates and the approach to immunity optimization during a period of heightened awareness. Methods: A cross‐sectional study from 2012 to 2016 at Cleveland Clinic Children's included pediatric solid organ transplant candidates. Data on vaccination history, serology, and demographics were collected. Incomplete immunity was defined by incomplete vaccination or seronegativity. Results: Among 91 candidates, 54.9% had complete varicella vaccination. Serological varicella immunity among patients tested varied by age: < 7 years, 50.0% positive in patients with complete schedules, none in the incomplete; ≥ 7 years, 50.0% positive in patients with complete schedules, 65.5% in the incomplete. For measles, 69.2% had complete vaccination, with immunity varying by age among those tested: < 7 years, 84.6% positive in patients with complete schedules, 42.9% in the incomplete; ≥ 7 years, 81.0% with complete, 62.5% with incomplete. Only 31.1% of those who qualified for a varicella additional dose and 28% who qualified for an additional measles dose received it, respectively. Conclusions: Incomplete immunity to varicella and measles was prevalent in pediatric solid organ transplant candidates at our center during the study period. Despite an increase in global measles activity, our efforts to optimize immunity through additional vaccine doses were only partially successful. Future research should focus on addressing strategies and understanding barriers to ensure timely vaccination for this vulnerable population prior to transplant, especially during periods of increased viral activity. [ABSTRACT FROM AUTHOR]

This study aimed to identify the specific vaccine strain associated with herpes zoster (HZ) in children following a series of diagnosed cases and to explore whether differences in single nucleotide polymorphisms (SNPs) among various vaccine strains are linked to an increased incidence of herpes zoster after vaccination. From February 2021 to March 2024, children <12 years old suspected of vaccine-related varicella-like rash or HZ were included. Varicella zoster virus DNA isolated from the patients were sequenced to differentiate vaccine type versus wild-type. 3D protein structures of pORF62 were simulated using open reading frame 62 sequences extracted from whole genome sequencing of vOka, MAV/06, Oka/SK vaccines, and pOka reference. A total of 27 children with a median age of 2.1 (interquartile range, 1.5–3.4) years old presented with vaccine-related varicella-like rash (n = 4/27, 14.8%) or HZ (n = 23/27, 85.2%). One patient with varicella-like rash and 34.8% (n = 8/23) with HZ had disseminated skin involvement. All were immunized with the Oka/SK strain varicella vaccine. Genotyping showed 88.2% (n = 15/17) had SNPs specific to the Oka/SK strain, and two had SNPs considered pOka type contained within the Oka/SK vaccine. Despite accumulations of SNPs in ORF 62 of Oka/SK, the translated amino acid sequence and 3D protein structure were identical to wild-type pOka's pORF62. In vOKA and MAV/06, changes in amino acids occurred at two positions, S628G and R958G, within pORF62. The predicted 3D protein structure of vOka and MAV/06's pORF62 showed that the α helical structure within region I undergoes conformational change, potentially increasing difficulties in interactions with infection-related proteins and thereby decreasing virulence. pORF62 in pOka and Oka/SK exhibited more stable structure complex of the α helical structure. Lack of structural alternations in region I of pORF62 due to the absence of critical genetic polymorphisms in open reading frame 62 could be associated with the heightened incidence of adverse events. [ABSTRACT FROM AUTHOR]

In the United States, states and local jurisdictions set vaccination requirements for school attendance, conditions and procedures for exemptions from these requirements, grace periods for submitting documentation, and provisional enrollment for students who need more time to be vaccinated. States annually report data to CDC on the number of children in kindergarten who meet, are exempt from, or are in the process of meeting requirements. Data reported by 49 states and the District of Columbia (DC) for the 2023-24 school year were used for national- and state-level estimates of the following measures: complete vaccination with required doses of measles, mumps, and rubella vaccine (MMR), diphtheria, tetanus, and acellular pertussis vaccine (DTaP), poliovirus vaccine (polio), and varicella vaccine (VAR); exemptions from vaccination; and school attendance while meeting requirements. The 2023-24 kindergarten class became age-eligible to complete most staterequired vaccinations during the COVID-19 pandemic, after schools had returned to routine in-person learning. Compared with approximated national coverage levels across all reported vaccines for the 2019-20 (95%) and 2022-23 (93%) school years, coverage dropped below 93% for the 2023-24 school year, ranging from 92.3% for DTaP to 92.7% for MMR. Exemptions increased to 3.3%, compared with those during the 2022-23 (3.0%) and 2021-22 school years (2.6%). Coverage with MMR, DTaP, polio, and VAR decreased in 35, 32, 33, and 36 jurisdictions, respectively, compared with the 2022-23 school year. Exemptions increased in 41 jurisdictions, with 14 reporting that >5% of kindergartners had an exemption from one or more vaccine. Efforts by health departments, schools, and providers are needed to ensure that students begin school fully vaccinated. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions We evaluated whether a history of low‐dose rituximab treatment affected herpes zoster development after living kidney transplantation.We enrolled 103 living kidney transplant recipients. Patients were divided into two groups according to their history of rituximab treatment; rituximab was administered to 50 living kidney transplant recipients. We assessed the difference in herpes zoster events between the two groups and determined the risk factors for herpes zoster using multivariate regression analysis.The total dose of rituximab in each kidney transplant recipient who received rituximab therapy was 200–400 mg. The rate of herpes zoster events after transplantation in recipients who received rituximab therapy (4 of 50, 8%) was not higher than that in recipients who did not receive rituximab (9 of 53, 17%) (p = 0.238). Herpes zoster‐free survival did not significantly differ between the two groups (p = 0.409). In the multivariate regression analysis, the association between varicella zoster vaccination before transplantation and herpes zoster events after transplantation was confirmed, whereas rituximab therapy was not associated with herpes zoster events.Low‐dose rituximab therapy in kidney transplant recipients did not influence herpes zoster development after transplantation. Varicella zoster vaccination before transplantation may play an important role in preventing herpes zoster after transplantation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Few studies have evaluated pediatric vaccination coverage in the Military Health System, although some evidence suggests lower than ideal coverage. This study assessed vaccine completion and timeliness among military dependents through age 24 months. METHODS: Children born at military hospitals from 2010 through 2019 were identified using Department of Defense Birth and Infant Health Research program data. Vaccine completion and timeliness were assessed for diphtheria, tetanus, and pertussis; polio; measles, mumps, and rubella; hepatitis B; Haemophilus influenzae type b; varicella; and pneumococcal conjugate individually and as a combined 7-vaccine series; rotavirus was assessed separately. Modified Poisson regression models were used to calculate risk ratios (RRs) and 95% confidence intervals (CIs) for noncompletion and delays, adjusting for demographic characteristics. RESULTS: Of 275 967 children, 74.4% completed the combined 7-vaccine series, and 36.2% of those who completed the series had delays. Completion peaked at 78.7% among children born in 2016 and 2017. Among all vaccines, completion was lowest for rotavirus (77.5%), diphtheria, tetanus, and pertussis (83.1%), Haemophilus influenzae type b (86.6%), and pneumococcal conjugate (88.4%). Risk for noncompletion was higher among children born to younger pregnant parents (adjusted RR 5 1.33; 95% CI 5 1.27-1.40) and with a well-child care location change (adjusted RR 5 1.10; 95% CI5 1.09-1.12). Risk for delays paralleled that for noncompletion. CONCLUSIONS: Vaccine completion and timeliness generally improved among military children, but greater noncompletion of vaccine series with more versus fewer doses and disparities for younger and mobile service members suggest system barriers remain. [ABSTRACT FROM AUTHOR]

(1) Background: The effect of varicella emergency vaccination (EV) has not been fully evaluated. (2) Methods: This was a cohort study. Participants were categorized into five groups based on their immune status: unvaccinated group, first dose as EV group, one dose no EV group, second dose as EV group, and two doses no EV group. A Cox proportional hazards model was employed to examine the association between the EV measures and the varicella incidence rate in this outbreak. (3) Results: Demographic characteristics, vaccination details, and disease onset information were 100% (918/918) collected. The crude attack rate was 44% (11/25), 8% (3/36), 11% (24/215), 3% (6/176), and 2% (8/466) among the unvaccinated group, first dose as EV group, one dose no EV group, second dose as EV group and two doses no EV group, respectively. Compared to the unvaccinated group and the one dose no EV group, the first dose varicella vaccine as EV and the second dose as EV demonstrated an incremental effectiveness of 90% (95% CI 65–97%) and 79% (95% CI 47–92%), respectively. (4) Conclusions: Both the first dose and the second dose as EV contributed to reducing the incidence rates of varicella and offered incremental vaccine effectiveness in an outbreak setting. Our study underscores the importance and benefits of initiating emergency varicella vaccination early to reduce the disease incidence rate in an elementary school setting where there was no complete coverage of the two doses of varicella vaccine and an outbreak occurred. [ABSTRACT FROM AUTHOR]

Objective To analyze the epidemiological characteristics of varicella and effectiveness of varicella vaccine in Jinan. Methods We collected data of varicella surveillance in Jinan from 2006 to 2022 from the Chinese Information System for Disease Control and Prevention and vaccination data for children born during 2010-2021 form the Jinan Immunization Planning Information System. All reported varicella cases from 2006 to 2022 in Jinan were analyzed with descriptive epidemiological methods; Coverage and effectiveness of varicella vaccine for children born during 2010 to 2021 were conducted with the screening method. Results 61 145 cases of varicella were reported in Jinan during 2006-2022, yielding an annual average incidence of 51.82 per 100 000 population; the incidence ranged from 74.48 per 100 000 in 2008 to 28.47 per 100 000 in 2022. Peak varicella incidences occurred between April and June and between November and the following January. The highest incidence rate was 5-9 years old group from 2006-2016 and was 15-19 years old group from 2017 to 2022. Coverage levels for one doses was 77.32% in the 2010-2021 births; the overall effectiveness of varicella vaccine was 91.83% (95%CI: 91.43%-92.30%). Coverage levels for two doses was 45.86% in the 2010-2018 births; the overall effectiveness of varicella vaccine was 95.14%(95%CI: 94.56%-95.66%). Conclusion The high incidence age group shifted from 5-9 years old to 15-19 years old. It was suggested that the vaccine administration should be used to targeted age groups. Levels of vaccine effectiveness for 2 doses of varicella vaccine were greater than levels of Vaccine effectiveness for one-doses. We suggest to introduce 2 dose of varicella vaccine into the national immunization program for children. [ABSTRACT FROM AUTHOR]

The Varicella zoster virus (VZV), responsible for both varicella (chickenpox) and herpes zoster (shingles), presents significant global health challenges. While primary VZV infection primarily affects children, leading to chickenpox, reactivation in later life can result in herpes zoster and associated post-herpetic neuralgia, among other complications. Vaccination remains the most effective strategy for VZV prevention, with current vaccines largely based on the attenuated vOka strains. Although these vaccines are generally effective, they can induce varicella-like rashes and have sparked concerns regarding cell virulence. As a safer alternative, subunit vaccines circumvent these issues. In this study, we developed a nanoparticle-based vaccine displaying the glycoprotein E (gE) on ferritin particles using the SpyCatcher/SpyTag system, termed FR-gE. This FR-gE nanoparticle antigen elicited substantial gE-specific binding and VZV-neutralizing antibody responses in BALB/c and C57BL/6 mice—responses that were up to 3.2-fold greater than those elicited by the subunit gE while formulated with FH002C, aluminum hydroxide, or a liposome-based XUA01 adjuvant. Antibody subclass analysis revealed that FR-gE produced comparable levels of IgG1 and significantly higher levels of IgG2a compared to subunit gE, indicating a Th1-biased immune response. Notably, XUA01-adjuvanted FR-gE induced a significant increase in neutralizing antibody response compared to the live attenuated varicella vaccine and recombinant vaccine, Shingrix. Furthermore, ELISPOT assays demonstrated that immunization with FR-gE/XUA01 generated IFN-γ and IL-2 levels comparable to those induced by Shingrix. These findings underscore the potential of FR-gE as a promising immunogen for the development of varicella and herpes zoster vaccines. [ABSTRACT FROM AUTHOR]

To assess the safety of varicella vaccine (VarV) by conducting post-marketing surveillance on adverse events following immunization (AEFI) in Jiangsu Province, China. Methods: We utilized the AEFI Information System of mainland China to monitor and categorize adverse reactions associated with VarV. Results: The incidence rate of AEFI was significantly higher after the first dose (48.79/100,000 doses) compared to the second dose (45.18/100,000 doses) (χ2 = 4.63, P = 0.031). Regional variations in AEFI incidence were observed within Jiangsu Province. Common reactions comprised 90.96% of AEFIs, while rare reactions and coincidental events accounted for 6.59% and 0.51%, respectively. Notably, there were no adverse events linked to vaccine quality, program errors, psychogenic reactions, or fatalities. Over 96% of AEFIs occurred within three days of VarV administration, with redness at the injection site (2.6 cm to 5 cm in diameter) being the most frequently observed symptom. Conclusion: VarV demonstrates a commendable safety profile. Although there was a slight increase in AEFI incidence between 2022 and 2023, common vaccine reactions were predominantly observed, and the rates of rare reactions remained very low. [ABSTRACT FROM AUTHOR]

Background: Varicella infections follow a benign course in around 90% of cases, with more severe forms occurring in adults. To identify potential pockets of susceptibility and to improve targeted immunization strategies, this study aims to critically assess immunological status by evaluating varicella seroprevalence among adults (18–99 years) in the province of Florence (Italy), nearly a decade after Tuscany introduced the vaccination program. Methods: A convenience sample of 430 subjects aged 18 to 94 years (mean age 51.8 ± 18.8 years), stratified by age and sex (53.7% of subjects were female; N = 231), was collected between 2018 and 2019. Sero-analytical analyses were conducted utilizing EUROIMMUN Anti-VZV ELISA (IgG) kits. Results: Most of them were of Italian nationality (87.4%; N = 376). Among the 430 tested samples, 385 (89.5%) were positive and 39 (9.1%) were negative. The remaining six sera (1.4%), confirmed as equivocal, were excluded from further analysis. No significant differences were found based on sex (p-value = 0.706) or nationality (p-value = 0.112). The application of trend tests (Mantel–Haenszel; Kendall Tau-b) showed a significant trend (p < 0.024 and p < 0.032, respectively), with an increasing probability of finding a positive anti-varicella serological status passing from a lower age group (84.2%) to a higher one (93.0%). By considering the female population aged 18–49 years, the seroprevalence of anti-varicella antibodies was found to be 88.4%, with a susceptibility of 11.6%, highlighting the risk of acquiring infection during pregnancy. Conclusions: The introduction of varicella vaccination has had a significant impact on public health in Tuscany and in Italy more generally. However, further efforts should be made to reduce the number of individuals still susceptible in adulthood, with particular attention given to women of childbearing age and the promotion of vaccination through mass and social media and institutional websites. [ABSTRACT FROM AUTHOR]

Healthcare workers (HCWs) are occupationally exposed to varicella zoster virus (VZV), and their inappropriate vaccination status could contribute to an outbreak involving both professionals and the patients they care for, with a potential impact on the general population. Therefore, since 2007, the Advisory Committee on Immunization Practices (ACIP) recommends that all HCWs have evidence of immunity against varicella. The present meta-analysis was therefore designed to collect the available evidence on the seronegative status of VZV among HCWs. PubMed, Scopus, and Embase databases were searched without backward limit for articles reporting on the seroprevalence of VZV among HCWs, and all articles meeting the inclusion criteria were included in a random-effect meta-analysis model. From 1744 initial entries, a total of 58 articles were included in the quantitative analysis (publication range: 1988 to 2024), for a pooled sample of 71,720 HCWs. Moreover, the included studies reported on seroprevalence data on measles (N = 36,043 HCWs) and rubella (N = 22,086 HCWs). Eventually, the pooled seronegative status for VZV was estimated to be 5.72% (95% confidence interval [95% CI] 4.59 to 7.10) compared to 6.91% (95% CI 4.79 to 9.87) for measles and 7.21% (5.36 to 9.64) for rubella, with a greater risk among subjects younger than 30 years at the time of the survey (risk ratio [RR] 1.434, 95% CI 1.172 to 1.756). Interestingly, medical history of either VZV infection/vaccination had low diagnostic performances (sensitivity 76.00%; specificity 60.12%; PPV of 96.12% but PNV of 18.64%). In summary, the available data suggest that newly hired HCWs are increasingly affected by low immunization rates for VZV but also for measles and rubella, stressing the importance of systematically testing test newly hired workers for all components of the measles–pertussis–rubella–varicella vaccine. [ABSTRACT FROM AUTHOR]

The objective of this analysis was to evaluate and compare the effects of the COVID-19 pandemic on routine and annual influenza vaccination in Iowa, Minnesota, and North Dakota. Routine and annual influenza vaccination uptake and coverage between 2017 and 2021 was collected from each state's immunization information system (IIS) by age group and stratified by provider and vaccine type. Data from 2017 to 2019 were averaged to obtain a pre-pandemic baseline and compared to 2020 and 2021 data. Percent changes were calculated to evaluate differences in uptake and coverage. Changes in coverage and administration varied by state, but each state had some level of decreased administration across the different age groups and vaccine types. The most consistent decreases in vaccine administration occurred in the 15-year-old cohort with each state finding decreased administrations in 2020 and 2021. The 12-year-old age group had decreased administration of hepatitis B, measles, mumps, and rubella, and varicella vaccine while the 2-year-old age group had the most consistent decrease in coverage across all vaccines analyzed. Trends by provider type were also noted in all three states, with local public health (LPH) experiencing the largest and most consistent declines in vaccine administrations by age group. Adult influenza coverage improved to varying degrees in 2020 (+ 14.1% IA, + 2.1% MN, + 1.5% ND), but either decreased or approached the 2017-19 average in 2021. All three states saw some level of decreased vaccine administration across the age groups, vaccines, and provider types assessed. The COVID-19 pandemic affected how many children and adults received recommended immunizations, leaving communities vulnerable to vaccine-preventable diseases. [ABSTRACT FROM AUTHOR]

Background The nonclassical antigen presentation molecule CD1d presents lipid antigens to invariant natural killer T (iNKT) cells. Activation of these cells triggers a rapid cytokine response providing an interface between innate and adaptive immune responses. The importance of CD1d and iNKT cells in varicella zoster virus (VZV) infection has been emphasized by clinical reports of individuals with CD1d or iNKT cell deficiencies experiencing severe, disseminated varicella postvaccination. Methods Three strains of VZV (VZV-S, rOka, and VZV rOka-66S) were used to infect Jurkat cells. Flow cytometry of VZV- and mock-infected cells assessed the modulatory impact of VZV on CD1d protein. Infected cell supernatant and transwell co-culture experiments explored the role of soluble factors in VZV-mediated immunomodulation. CD1d transcripts were assessed by reverse-transcription polymerase chain reaction. Results Surface and intracellular flow cytometry demonstrated that CD1d was strikingly downregulated by VZV-S and rOka in both infected and VZV antigen-negative cells compared to mock. CD1d downregulation is cell-contact dependent and CD1d transcripts are targeted by VZV. Mechanistic investigations using rOka-66S (unable to express the viral kinase ORF66) implicate this protein in CD1d modulation in infected cells. Conclusions VZV implements multiple mechanisms targeting both CD1d transcript and protein. This provides evidence of VZV interaction with and manipulation of the CD1d–iNKT cell axis. [ABSTRACT FROM AUTHOR]

The Oka varicella vaccine strain remains neurovirulent and can establish lifelong latent infection, raising safety concerns about vaccine-related herpes zoster. In this study, we aimed to evaluate the immunogenicity and safety of a skin-attenuated and neuro-attenuated varicella vaccine candidate (v7D vaccine). We did this randomised, double-blind, controlled, phase 2a clinical trial in Jiangsu, China. Healthy children aged 3–12 years with no history of varicella infection or vaccination were enrolled and randomly assigned (1:1:1:1) to receive a single subcutaneous injection of the v7D vaccine at 3·3 log 10 plaque forming units (PFU; low-dose v7D group), 3·9 log 10 PFU (medium-dose v7D group), and 4·2 log 10 PFU (high-dose v7D group), or the positive control varicella vaccine (vOka vaccine group). All the participants, laboratory personnel, and investigators other than the vaccine preparation and management staff were masked to the vaccine allocation. The primary outcome was assessment of the geometric mean titres (GMTs) and seroconversion rates of anti-varicella zoster virus immunoglobulin G (IgG) induced by different dose groups of v7D vaccine at 0, 42, 60, and 90 days after vaccination in the per-protocol set for humoral immune response analysis. Safety was a secondary outcome, focusing on adverse events within 42 days post-vaccination, and serious adverse events within 6 months after vaccination. This study was registered on Chinese Clinical Trial Registry, ChiCTR2000034434. On Aug 18–21, 2020, 842 eligible volunteers were enrolled and randomly assigned treatment. After three participants withdrew, 839 received a low dose (n=211), middle dose (n=210), or high dose (n=210) of v7D vaccine, or the vOka vaccine (n=208). In the per-protocol set for humoral immune response analysis, the anti-varicella zoster virus IgG antibody response was highest at day 90. At day 90, the seroconversion rates of the low-dose, medium-dose, and high-dose groups of v7D vaccine and the positive control vOka vaccine group were 100·0% (95% CI 95·8–100·0; 87 of 87 participants), 98·9% (93·8–100·0; 87 of 88 participants), 97·8% (92·4–99·7; 91 of 93 participants), and 96·4% (89·8–99·2; 80 of 83 participants), respectively; the GMTs corresponded to values of 30·8 (95% CI 26·2–36·0), 31·3 (26·7–36·6), 28·2 (23·9–33·2), and 38·5 (31·7–46·7). The v7D vaccine, at low dose and medium dose, elicited a humoral immune response similar to that of the vOka vaccine. However, the high-dose v7D vaccine induced a marginally lower GMT compared with the vOka vaccine at day 90 (p=0·027). In the per-protocol set, the three dose groups of the v7D vaccine induced a similar humoral immune response at each timepoint, with no statistically significant differences. The incidence of adverse reactions in the low-dose, medium-dose, and high-dose groups of v7D vaccine was significantly lower than that in the vOka vaccine group (17% [35 of 211 participants], 20% [41 of 210 participants], and 13% [27 of 210 participants] vs 24% [50 of 208 participants], respectively; p=0·025), especially local adverse reactions (10% [22 of 211 participants], 14% [30 of 210 participants] and 9% [18 of 210 participants] vs 18% [38 of 208 participants], respectively; p=0·016). None of the serious adverse events were vaccine related. The three dose groups of the candidate v7D vaccine exhibit similar humoral immunogenicity to the vOka vaccine and are well tolerated. These findings encourage further investigations on two-dose vaccination schedules, efficacy, and the potential safety benefit of v7D vaccine in the future. The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, the Fundamental Research Funds for the Central Universities, and Beijing Wantai. For the Chinese translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Background: Administration of live vaccines following liver transplant (LT) has historically not been recommended due to concerns regarding risk of vaccine‐attenuated disease. However, there is evidence suggesting that in select transplant recipients live vaccinations can be administered safely. Studies in other regions have indicated that despite this evidence many clinicians remain hesitant to administer live vaccinations. Method: A REDCap survey was distributed to gastroenterologists, pediatricians, and infectious diseases physicians at pediatric centers across Australia and New Zealand via email between September and November 2023. The survey included a series of questions regarding live vaccine and varicella postexposure prophylaxis (PEP) practices in pediatric LT recipients and barriers to live vaccine administration in this cohort. Results: There was a total of 16 responses to the survey, from 10 different pediatric centers, including 10/11 pediatric gastroenterology centers and all four pediatric LT centers in the region. Only 31% (5/16) of respondents (from 3/10 different centers) offer live vaccines. The main barrier to live vaccine administration was clinician reluctance and the main reason for not offering live vaccines was insufficient safety data. Sixty‐nine percent (11/16) of respondents take vaccination status and/or serology into account when deciding whether to offer varicella PEP to this cohort. Respondents universally offer varicella zoster immunoglobulin as PEP, though 31% (5/16) also offer antiviral medication. Conclusions: Many clinicians in our region remain hesitant to provide live vaccines to pediatric LT recipients, with concerns regarding insufficient safety data. Updated local guidelines may help to address this. [ABSTRACT FROM AUTHOR]

Background: Varicella‐zoster virus (VZV) pretransplant immunization rates, exposures, and posttransplant disease are poorly characterized among pediatric solid organ transplant (SOT) recipients in the two‐dose varicella vaccine era. Methods: A retrospective analysis of the electronic health records among children <18 years old who received SOT from January 1, 2011 through December 31, 2021, was performed at a single center to assess for missed pretransplant varicella vaccination opportunities, characterize VZV exposures, and describe posttransplant disease. Results: Among 525 children, 444 were ≥6 months old (m.o.) at SOT with a documented VZV vaccine status. Eighty‐five (19%) did not receive VZV Dose One; 30 out of 85 (35%) could have been immunized. Infants 6–11 m.o. accounted for 14 out of 30 (47%) missed opportunities. Among children ≥12 m.o. with documented Dose Two status (n = 383), 72 had missed vaccination opportunities; 57 out of 72 (79%) were children 1–4 years old. Most children had unclassifiable pre‐SOT serostatus as varicella serology was either not obtained/documented (n = 171) or the possibility of passive antibodies was not excluded (n = 137). Of those with classified serology (n = 188), 69 were seroimmune. Forty‐seven of 525 (9%) children had recorded VZV exposures; two developed varicella—neither had documented pre‐SOT seroimmunity nor had received post‐exposure prophylaxis. Nine additional children had medically attended disease: four primary varicella and five zoster. Of the 11 cases, 10 had cutaneous lesions without invasive disease; one had multi‐dermatomal zoster with transaminitis. Seven (64%) received treatment exclusively outpatient. Conclusions: VZV exposure and disease still occur. Optimizing immunization among eligible candidates and ensuring patients have a defined VZV serostatus pretransplantation remain goals of care. [ABSTRACT FROM AUTHOR]

Background: Varicella‐zoster virus (VZV) reactivation is the most common infectious complication in the late posthematopoietic stem cell transplantation (HSCT) period and is reported as 16%–41%. Acyclovir prophylaxis is recommended for at least 1 year after HSCT to prevent VZV infections. However, studies on the most appropriate prophylaxis are ongoing in pediatric patients. Methods: Patients who underwent allogeneic HSCT between January 1, 1996 and January 1, 2020 were retrospectively analyzed to outline the characteristics of VZV reactivation after allogeneic HSCT in pediatric patients using 6 months acyclovir prophylaxis. Results: There were 260 patients and 273 HSCTs. Median age was 10.43 (0.47–18.38), and 56% was male. Median follow‐up was 2325 days (18–7579 days). VZV reactivation occurred in 21.2% (n = 58) at a median of 354 (55–3433) days post‐HSCT. The peak incidence was 6–12 months post‐HSCT (43.1%). Older age at HSCT, female gender, history of varicella infection, lack of varicella vaccination, low lymphocyte, CD4 count, and CD4/CD8 ratio at 9 and 12 months post‐HSCT was found as a significant risk for herpes zoster (HZ) in univariate analysis, whereas history of varicella infection and low CD4/CD8 ratio at 12 months post‐HSCT was an independent risk factor in multivariate analysis. Conclusions: Tailoring acyclovir prophylaxis according to pre‐HCT varicella history, posttransplant CD4 T lymphocyte counts and functions, and ongoing immunosuppression may help to reduce HZ‐related morbidity and mortality. [ABSTRACT FROM AUTHOR]

Management of the exposure of pediatric oncology patients to varicella zoster virus (VZV) is controversial. We report the exposure of 56 patients to a single child with chicken pox at a pediatric cancer housing facility and describe our strategic approach for their management. We reviewed the immune and clinical status of 56 children with cancer receiving ongoing treatment at Memorial Sloan Kettering Cancer Center (MSK) who, while living at a pediatric cancer housing facility, were exposed to the index patient. The management of patients exposed included: (1) determination of immune status, (2) availability of vaccination history or VZV disease prophylaxis, (3) exposure status and subsequent isolation during the period of incubation, and (4) VZV disease prophylaxis. In addition to the 56 patients exposed to the index case, eight children with cancer treated at other facilities and 11 healthy siblings living in the facility were exposed. Of the 56 MSK patients, 21 were classified as immunosuppressed and received varicella zoster immune globulin (human), intravenous standard immune globulin, or acyclovir based on serostatus and immune function. The cohort was followed for 4 weeks after the exposure and no secondary infections were diagnosed. We performed a risk assessment and created a management plan to control and prevent further exposure and development of disease. No secondary cases developed. This strategic approach could serve as a model for the management of VZV exposure for other pediatric oncology centers. [ABSTRACT FROM AUTHOR]

In South Korea, the National Immunization Program has included one-dose varicella vaccination for 1-year-olds since 2005. This study examines the potential impact of introducing a two-dose varicella vaccination for children, along with zoster vaccination for adults, using either the zoster vaccine live (ZVL) or recombinant zoster vaccine (RZV). The investigation considered four strategies in a base case scenario. The first involved introducing zoster vaccination for 60-year-olds, with a 60 % coverage. The second strategy combined zoster vaccination with a second-dose varicella vaccination for 4-year-olds, with a 90 % coverage. An age-structured model spanning 50 years was employed, assuming a zoster vaccine catch-up campaign over the initial 5 years. Cost-effectiveness analyses were conducted, assessing incremental cost-effectiveness ratios (ICERs), incremental net monetary benefits (INMBs), and net loss under different ages at zoster vaccination (50, 60, 65, and 70 years) and varying willingness-to-pay (WTP) levels from ₩40 million ($34,998) to ₩84 million ($74,000). All strategies were cost-effective and significantly reduced herpes zoster (HZ) incidence, preventing approximately 3,077,000 to 7,609,000 cases, depending on the chosen strategy. The combined strategy prevented around 4,950,000 varicella and 653,000 HZ cases additionally. RZV outperformed ZVL by preventing twice as many HZ cases and offering greater QALY gains. However, ZVL was more cost-effective due to its lower cost. Probabilistic sensitivity analyses revealed that RZV became more cost-effective at higher WTP thresholds, exceeding ₩60.9 million ($53,193) in terms of ICER and ₩62.5 million ($54,591) for INMBs and net loss. The optimal age for zoster vaccination was 60 years concerning ICER but 50 years regarding INMB. Combining RZV with a two-dose varicella vaccination strategy reduced the disease burden and improved QALY more effectively, though ZVL remained more cost-effective at lower WTP levels. Decisions regarding vaccination policies should be balanced between the public health needs and WTP levels. [ABSTRACT FROM AUTHOR]

• The time since the last vaccination should be adjusted when comparing VE among subgroups. • Varicella vaccine was more effective when given at the early stage of the second year of life. • Matched case-control study design based on surveillance platforms could effectively reduce bias. • Logistic regression model with interaction term can be used to evaluate the interaction between factors. Universal varicella vaccination has been introduced in many countries, but there are a number of important differences in their vaccination strategies. It is essential to establish a vaccination program that can maximize the benefits of varicella vaccine, but there is a lack of comprehensive research on the effectiveness of varicella vaccine in different vaccination status. Using data from population-based surveillance platforms we conducted a 1:2 matched case-control study. The cases were clinically diagnosed varicella with onset from 2017 to 2021, 1–14 years old in Chaoyang District, Beijing. The controls were matched according to date of birth (±1 month), sex and residence. The vaccination data of the subjects were obtained from the Childhood Immunization Information Management System in Beijing. Using conditional logistic regression models with or without interaction terms, we evaluated the effectiveness of varicella vaccine in different vaccination status. A total of 2528 cases and 5056 controls were enrolled. This study found that whether the time since last vaccination was adjusted had a substantial effect on the comparing vaccine effectiveness (VE) between subgroups. After adjustment for the time since last vaccination, 1) the incremental VE of 2-dose was 49.6 % (95 % Confidence Interval [CI], 38.8–58.6) compared with 1-dose (93.9 % vs. 88.0 %); 2) Among children who received one dose, the risk of chickenpox in children vaccinated at 18–23 months was 1.382 (95 %CI, 1.084–1.762) times that in children vaccinated at 12–17 months. 3) the VE with less than one, two, and three year intervals is higher than that with six-year-intervals (P < 0.05), respectively. When comparing VE between subgroups of different vaccination status, the time since last vaccination should be adjusted. The first dose of varicella vaccine should be given as early as the second year of life, and the second dose can improve vaccine effectiveness. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We describe a case with natural killer cell deficiency of late-onset Oka vaccine varicella zoster virus (VZV) strain and Herpes simplex virus-1 (HSV-1) dual infection resulting in fatal clinical course. An 18-month-old boy presented with a papulovesicular rash, mucocutaneous candidiasis, encephalopathy, and severe respiratory distress 6 months after receiving varicella vaccine. VZV and HSV-1 were analysed by real-time reverse-transcriptase polymerase chain reaction (RT-qPCR) and Oka vaccine strain of VZV by gene sequencing. HSV-1 and VZV dual infection was detected in the blood and skin samples by RT-qPCR. Gene sequencing of VZV isolated from vesicular lesions was compatible with the Oka vaccine strain. Flow cytometry revealed a natural killer deficiency, but whole exome analysis failed to identify an associated genetic defect. Vesicular rashes in immunocompromised patients who were inadvertently vaccinated should be taken seriously, and antiviral therapy should be prompt and aggressive. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the safety and immunogenicity of the SKYVaricella vaccine in healthy Vietnamese children aged 12 months to 12 years. Methods: This open-label, single-arm study involved 201 children divided into two groups: 60 children aged 12 months to 5 years and 141 children aged 6 to 12 years. Safety was assessed through immediate reactions, solicited adverse events within 7 days, and unsolicited events up to Day 42. Immunogenicity was evaluated by seroconversion rates (SCR) and geometric mean titer (GMT) increments using fluorescent antibody-to-membrane antigen (FAMA) on the day of vaccination (D0) and 42 days after vaccination (D42). Results: All participants completed the follow-up. Immediate adverse events included pain (8.0%), redness (8.0%), and swelling (20.9%) at the injection site. Within 7 days, pain (17.9%) and swelling (12.4%) were mild and self-resolving. Unsolicited adverse events were infrequent and mild. Both age groups achieved 100% SCR. GMT of varicella-zoster virus antibodies increased from 1.37 (SD 1.97) at D0 to 18.02 (SD 2.22) at D42, a 13.12-fold rise. No Grade 3 adverse events were observed. Conclusion: The SKYVaricella vaccine shows a robust immunogenic response and favorable safety profile in Vietnamese children aged 12 months to 12 years. These findings endorse its potential inclusion in pediatric vaccination programs as a reliable preventive option against varicella. [ABSTRACT FROM AUTHOR]

In this study, we aimed to characterize a cohort of children hospitalized due to varicella before and after the outbreak of the COVID-19 pandemic. Medical charts of all children hospitalized in the Regional Hospital of Infectious Diseases in Warsaw due to varicella in the years 2019 and 2022 were retrospectively analyzed and compared. In total, 221 children were included in the analysis; 59 of them were hospitalized in 2019, whereas 162 were hospitalized in 2022. Children hospitalized in 2022 were older than those reported in 2019 (median 4.0 vs. 3.0 years, p = 0.02). None of the hospitalized children received complete varicella vaccination. The most common complication in both years was bacterial superinfection of skin lesions, found in 156/221 (70.6%) of patients. This complication rate was higher in 2022 (50.8% in 2019 vs. 77.8% in 2022, p = 0.0001), OR = 3.38, 95% CI: 1.80–6.35. Moreover, skin infections in 2022 more often manifested with cellulitis (in 2022 13.6% vs. 3.4% in 2019, p = 0.03), OR = 4.40, 95% CI: 1.00–19.33. Sepsis as a complication of varicella was almost five-fold more prevalent in 2022 than in 2019 (p = 0.009), OR = 5.70, 95% CI: 1.31–24.77. Antibiotic use increased between 2019 and 2022 (71.2% vs. 85.2%, p = 0.01). Furthermore, patients were treated more frequently with the combination of two different antibiotics simultaneously (only 3.4% of patients in 2019 compared to 15.4% in 2022, p = 0.01). Primary infections with varicella zoster virus in 2022 led to a more severe course of the disease. [ABSTRACT FROM AUTHOR]

The persistence of varicella outbreaks in Brazil has underscored the high concern with the low vaccine coverage in the last 4 years. Using publicly available data from the Brazilian Health System (SUS), this study analyzed varicella vaccine coverage and incidence trends from 2019 to 2022 in Brazilian States. Vaccine coverage decreased nationally in 2020, possibly influenced by the COVID-19 pandemic's initial phase. In Bahia State, we have the persistence of varicella with an incidence rate of 3.0 cases per 100,000 inhabitants (higher incidence compared to other States) in 2023. Under 15 months children and young children (4–6 Years old) faced the highest risk, urging the importance of vaccination. Despite a monovalent varicella vaccine being available through Brazil's National Immunization Program (NIP), Bahia fell short of achieving the ≥95 % disease control target for coverage. The study highlight the importance of vaccines to prevent some infectious diseases, as varicella, in poor tropical regions. Addressing vaccine hesitancy and misinformation, and augmenting awareness campaigns, are important to achieve and sustain high vaccine coverage over 80% as WHO guidelines to obtain a safe rate of protection for Brazilian population (Brazil's national immunization program has a target of 95% coverage). [ABSTRACT FROM AUTHOR]

Italy implemented two-dose universal varicella vaccination (UVV) regionally from 2003 to 2013 and nationally from 2017 onwards. Our objective was to analyze regional disparities in varicella outcomes resulting from disparities in vaccine coverage rates (VCRs) projected over a 50-year time-horizon (2020–2070). A previously published dynamic transmission model was updated to quantify the potential public health impact of the UVV program in Italy at the national and regional levels. Four 2-dose vaccine strategies utilizing monovalent (V) and quadrivalent (MMRV) vaccines were evaluated for each region: (A) MMRV-MSD/MMRV-MSD, (B) MMRV-GSK/MMRV-GSK, (C) V-MSD/MMRV-MSD, and (D) V-GSK/MMRV-GSK. Costs were reported in 2022 Euros. Costs and quality-adjusted life-years (QALYs) were discounted 3% annually. Under strategy A, the three regions with the lowest first-dose VCR reported increased varicella cases (+ 34.3%), hospitalizations (+ 20.0%), QALYs lost (+ 5.9%), payer costs (+ 22.2%), and societal costs (+ 14.6%) over the 50-year time-horizon compared to the three regions with highest first-dose VCR. Regions with low first-dose VCR were more sensitive to changes in VCR than high first-dose VCR regions. Results with respect to second-dose VCR were qualitatively similar, although smaller in magnitude. Results were similar across all vaccine strategies. [ABSTRACT FROM AUTHOR]

The cost effectiveness of childhood varicella vaccination is uncertain, as evidenced by variation in national health policies. Within the European Economic Area (EEA), only 10 of 30 countries offer universally funded childhood varicella vaccination. This study estimates the cost effectiveness of universal childhood varicella vaccination for one EEA country (Ireland), highlighting the difference in cost effectiveness between alternative vaccination strategies. An age-structured dynamic transmission model, simulating varicella zoster virus transmission, was developed to analyse the impact of three vaccination strategies; one-dose at 12 months old, two-dose at 12 and 15 months old (short-interval), and two-dose at 12 months and five years old (long-interval). The analysis adopted an 80-year time horizon and considered payer and societal perspectives. Clinical effectiveness was based on cases of varicella and subsequently herpes zoster and post-herpetic neuralgia avoided, and outcomes were expressed in quality-adjusted life-years (QALYs). Costs were presented in 2022 Irish Euro and cost effectiveness was interpreted with reference to a willingness-to-pay threshold of €20,000 per QALY gained. From the payer perspective, the incremental cost-effectiveness ratio (ICER) for a one-dose strategy, compared with no vaccination, was estimated at €8,712 per QALY gained. The ICER for the next least expensive strategy, two-dose long-interval, compared with one-dose, was estimated at €45,090 per QALY gained. From a societal perspective, all three strategies were cost-saving compared with no vaccination; the two-dose short-interval strategy dominated, yielding the largest cost savings and health benefits. Results were stable across a range of sensitivity and scenario analyses. A one-dose strategy was highly cost effective from the payer perspective, driven by a reduction in hospitalisations. Two-dose strategies were cost saving from the societal perspective. These results should be considered alongside other factors such as acceptability of a new vaccine within the overall childhood immunisation schedule, programme objectives and budget impact. [ABSTRACT FROM AUTHOR]

The introduction of varicella vaccines into routine pediatric immunization programs has led to a considerable reduction in varicella incidence. However, there have been reports of varicella, herpes zoster, and meningitis caused by the vaccine strain of varicella-zoster virus (VZV), raising concerns. Establishing the relationship between the wild-type and vaccine strains in VZV infections among previously vaccinated individuals is crucial. Differences in the single nucleotide polymorphisms (SNPs) among vaccine strains can be utilized to identify the strain. In this study, we employed nanopore sequencing to identify VZV strains and analyzed clinical samples. We retrospectively examined vesicle and cerebrospinal fluid samples from patients with VZV infections. One sample each of the wild-type and vaccine strains, previously identified using allelic discrimination real-time PCR and direct sequencing, served as controls. Ten samples with undetermined VZV strains were included. After DNA extraction, a long PCR targeting the VZV ORF62 region was executed. Nanopore sequencing identified SNPs, allowing discrimination between the vaccine and wild-type strains. Nanopore sequencing confirmed SNPs at previously reported sites (105,705, 106,262, 107,136, and 107,252), aiding in distinguishing between wild-type and vaccine strains. Among the ten unknown samples, nine were characterized as wild strains and one as a vaccine strain. Even in samples with low VZV DNA levels, nanopore sequencing was effective in strain identification. This study validates that nanopore sequencing is a reliable method for differentiating between the wild-type and vaccine strains of VZV. Its ability to produce long-read sequences is remarkable, allowing simultaneous confirmation of known SNPs and the detection of new mutations. Nanopore sequencing can serve as a valuable tool for the swift and precise identification of wild-type and vaccine strains and has potential applications in future VZV surveillance. [ABSTRACT FROM AUTHOR]

Background We describe clinicoepidemiologic characteristics of mpox-chickenpox coinfection in Nigeria. Methods A retrospective cohort analysis was performed of confirmed mpox cases in Nigeria from January 2022 to March 2023. Mpox and chickenpox were confirmed by real-time polymerase chain reaction (RT-PCR). Results Of 94 (60.0%) suspected cases, 56 had confirmed mpox, of whom 16 (28.6%) had chickenpox coinfection. The median age of confirmed mpox cases was 29 years (interquartile range, 20–37 years), 24 were men (60.7%), 6 (10.7%) were bisexual, and 5 (8.9%) died. Mpox-chickenpox–coinfected patients had more complications than mpox-monoinfected cases (56.3% vs 22.5%, P =.015). Conclusions The high frequency of mpox-chickenpox coinfection argues for accelerated access to mpox and chickenpox vaccines in Africa. [ABSTRACT FROM AUTHOR]

Varicella (chickenpox) is a highly contagious disease caused by the varicella-zoster virus. Although typically mild, varicella can cause complications leading to severe illness and even death. Safe and effective varicella vaccines are available. The Joint Committee on Vaccination and Immunisation has reviewed the evidence and recommended the introduction of varicella vaccine into the UK's routine childhood immunisation schedule. To explore UK healthcare professionals' (HCPs) knowledge and attitudes towards varicella vaccination, its introduction to the UK routine childhood immunisation schedule, and their preferences for how it should be delivered. We conducted an online cross-sectional survey exploring HCPs' attitudes towards varicella, varicella vaccine, and their preferences for delivery of the vaccine between August and September 2022 prior to the recommendation that varicella vaccine should be introduced. 91 HCPs working in the UK (81 % nurses/health visitors, 9 % doctors, 10 % researcher/other, mean age 48.7 years). All respondents agreed or strongly agreed that vaccines are important for a child's health. However, only 58% agreed or strongly agreed that chicken pox was a disease serious enough to warrant vaccination. Gaps in knowledge about varicella were revealed: 21.0% of respondents disagreed or were unsure that chickenpox can cause serious complications, while 41.8% were unsure or did not believe chickenpox was serious enough to vaccinate against. After receiving some basic information about chickenpox and the vaccine, almost half of the HCPs (47.3%) in our survey would prefer to administer the varicella vaccine combined with MMR. Given the positive influence of HCPs on parents' decisions to vaccinate their children, it is important to understand HCPs' views regarding the introduction of varicella vaccine into the routine schedule. Our findings highlighted areas for training and HCPs' preferences which will have implications for policy and practice when the vaccine is introduced. [ABSTRACT FROM AUTHOR]

This article presents a systematic review and meta-analysis of studies on the effectiveness of a two-dose varicella vaccination strategy in preventing varicella (chickenpox) infection. The analysis included 25 studies with a total of 49,265 participants. The results showed that the two-dose strategy was highly effective in reducing the risk of varicella infection compared to no vaccination or a one-dose strategy. The study suggests that a two-dose varicella vaccination is recommended for public health, but acknowledges limitations in the study design. [Extracted from the article]

Background: To analyze the epidemiological characteristics of varicella epidemics in Chongqing Municipality from 2014 to 2021, and to provide a scientific basis for the formulation of varicella prevention and control measures. Methods: Data on the incidence of varicella outbreaks and vaccination data in Chongqing from 2014 to 2021 were collected through the China Disease Control and Prevention Information System and statistically analyzed using descriptive epidemiological methods. Results: From 2014 to 2021, 213,715 cases of varicella were reported in Chongqing Municipality, with an average annual incidence rate of 86.26/100,000, with a statistically significant difference (χ2 = 24,972.069, P < 0.001); varicella incidence is seasonal, with peaks in May/June and October/December each year, presenting a "double-peak distribution". The average annual incidence rate of varicella in municipal districts was 90.74/100,000, which was higher than that of counties 69.62/100,000 and autonomous counties 84.04/100,000; the average annual incidence rate of varicella in males was 89.37/100,000, and in females, 82.22/100,000, with the difference not being statistically significant; the age of onset of the disease was mainly in the group of people under 15 years of age, with a total of 190,021 cases reported (88.9%), with 5-9 years old (35.7%) as the high incidence age group. The incidence occupation was dominated by students in 133,733 cases (62.6%). Conclusion: The overall varicella epidemic in Chongqing is on the rise, and has obvious seasonal, regional and population distribution characteristics. The prevention and control of varicella epidemic should be strengthened, the publicity of varicella vaccine should be increased, and it is recommended that varicella vaccine should be included in the national immunization program. [ABSTRACT FROM AUTHOR]

Measles, mumps, rubella (MMR), and varicella incidence rates have increased due to the delayed vaccination schedules of children secondary to the COVID-19 pandemic. Decreased herd immunity creates a risk for immunocompetent children and immunocompromised individuals in the community. Historically, live-attenuated vaccines (MMR and varicella) were recommended before solid organ transplants. The amount of time before transplant when this is appropriate is often debated, as is the utility of vaccine titers. MMR and varicella vaccines previously were not recommended in immunocompromised patients post-solid organ transplant due to the undue risk of transmission and posed infection risk. The new literature on live-attenuated vaccines in post-transplant pediatric patients provides more insight into the vaccines' safety and efficacy. The present article aims to provide guidance on live-attenuated vaccines (MMR and varicella) in the pre-transplant and post-operative solid organ transplant phases of care in pediatric patients. [ABSTRACT FROM AUTHOR]

• Real-world evidence of MMRV clinical protection against varicella is essential. • Data showed effectiveness of two doses MMRV against varicella of any severity of 93%. • Two-dose schedule should be recommended to optimise immunisation programmes worldwide. Priorix-Tetra ™ (MMRV GlaxoSmithKline Biologicals' vaccine) was developed based on the existing measles-mumps-rubella and varicella vaccines. In this study, we aimed to estimate the effectiveness of the combined measles-mumps-rubella-varicella Priorix-Tetra™ vaccine against varicella in real-world conditions. We conducted a post-marketing retrospective case-control study in the Apulia region of Italy in children aged 1–9 years born between January 1, 2008 and December 31, 2016. We assessed the effectiveness against varicella of all grades of severity (including hospitalisation) and against hospitalisation for varicella of a single and two doses of Priorix-Tetra™. Moreover, we also assessed effectiveness of monovalent varicella (monovalent-V) vaccine and any varicella vaccines. Vaccine effectiveness was calculated as (1–OR) x 100. We introduced demographic variables in the model to adjust Vaccine effectiveness (aVE) by potential confounders (sex and year of birth). We recorded 625 varicella cases and matched them with 1,875 controls. Among 625 cases, 198 had received a single MMRV dose, 10 two MMRV doses, 46 a single monovalent-V dose, none two monovalent-V doses; four a monovalent-V as first dose and MMRV as second dose, and one a MMRV as first dose and monovalent-V as second dose; 366 cases were not vaccinated. The aVE against varicella of all grades of severity was 77.0% and 93.0% after a single dose and after two doses of MMRV, respectively. The aVE against varicella of all grades was 72.0% after a single dose of monovalent-V vaccine. The aVE against varicella of all grades of severity was 76.0% after a single dose and 94.0% after two doses of any varicella vaccine. The aVE against varicella hospitalisation was 96% after a single dose of any varicella vaccine. Priorix-Tetra™ showed to be an effective vaccine and the two-dose schedule should be recommended to optimise immunisation programmes. A single dose was able to provide protection against varicella hospitalisation. [ABSTRACT FROM AUTHOR]

Background and Objective: Current regulatory labeling recommends avoiding live vaccine use in dupilumab‐treated patients. Clinical data are not available to support more specific guidance for live or live attenuated vaccines administration in dupilumab‐treated patients. Methods: Children (6 months–5 years old) with moderate‐to‐severe atopic dermatitis (AD) enrolled in a phase 2/3 clinical trial of dupilumab (LIBERTY AD PRESCHOOL Part A/B; NCT03346434) and subsequently participated in the LIBERTY AD PED‐OLE (NCT02612454). During these studies, protocol deviations occurred in nine children who received measles, mumps, rubella (MMR) vaccine with or without varicella vaccine; five with a ≤12‐week gap between dupilumab administration and vaccination and four with a >12‐week gap after discontinuing dupilumab. Results: Nine children (1 female; 8 male) had severe AD at baseline (8–56 months old). Of the nine children, five had a ≤12‐week gap ranged 1–7 weeks between dupilumab administration and vaccination who received MMR vaccine (n = 2) or MMR and varicella vaccines (n = 3); among these, one resumed dupilumab treatment as early as 2 days and four resumed treatment 18–43 days after vaccination. No treatment‐emergent adverse events, including serious adverse events and infections, were reported within the 4‐week post‐vaccination period in any children. Conclusions: In this case series of dupilumab‐treated children with severe AD who received MMR vaccine with or without varicella vaccine, no adverse effects (including vaccine‐related infection) were reported within 4 weeks after vaccination. Further studies are warranted to evaluate the safety, tolerability, and immune response to live attenuated vaccines in dupilumab‐treated patients. [ABSTRACT FROM AUTHOR]

We report a chickenpox outbreak among international students in Ontario, Canada. This paper highlights the complex challenges of clinical and public health response to outbreak situations. While the incidence of varicella infection has decreased due to widespread vaccination programs in Canada, specific groups, such as international students from areas with lower vaccination rates, remain at risk. The outbreak involved primarily unvaccinated international students residing in a college residence building. Coordinated and prompt contact tracing and administration of post-exposure vaccination were core strategies to control the outbreak. The incident highlighted several challenges that can arise in varicella outbreak management, from determining when and how to order and interpret serological tests, to adjusting isolation measures based on the community's low vaccination rate. Ethical considerations surrounding vaccination policies, particularly for international students came to the forefront. The disparity in access to preventive care highlights broader public health implications and prompts a discussion on equitable vaccination strategies. [ABSTRACT FROM AUTHOR]

Varicella-zoster virus (VZV) poses lifelong risks, causing varicella and herpes zoster (HZ, shingles). Currently, varicella and HZ vaccines are predominantly live attenuated vaccines or adjuvanted subunit vaccines utilizing VZV glycoprotein E (gE). Here, we propose our vaccine candidates involving a comparative analysis between recombinant baculoviral vector vaccines (AcHERV) and a live attenuated vaccine strain, vOka. AcHERV vaccine candidates were categorized into groups encoding gE only, VZV glycoprotein B (gB) only, or both gE and gB (gE-gB) as AcHERV-gE, AcHERV-gB, and AcHERV-gE-gB, respectively. Humoral immune responses were evaluated by analyzing total IgG, IgG1, IgG2a, and neutralizing antibodies. Cell-mediated immunity (CMI) responses were evaluated by enzyme-linked immunospot (ELISPOT) assay and Th1/Th2/Th17 cytokine profiling. In the mouse model, AcHERV-gE-gB elicited similar or higher total IgG, IgG2a, and neutralizing antibody levels than vOka and showed robust VZV-specific CMI responses. From the perspective of antigens encoded in vaccines and their relationship with CMI response, both AcHERV-gB and AcHERV-gE-gB demonstrated results equal to or superior to AcHERV-gE, encoding only gE. Taken together, these results suggest that AcHERV-gE-gB can be a novel candidate for alleviating risks of live attenuated vaccine-induced latency and effectively preventing varicella during early stages of life while providing strong CMI for effective resistance against HZ and therapeutic potential in later stages of life. [ABSTRACT FROM AUTHOR]

We aim to understand the varicella-zoster virus (VZV) antibody levels in children after vaccination and to construct VZV-IgG centile curves and reference values for children aged 1–7 years. From September to October 2023, a total of 806 children were recruited according to the time intervals of 1 month, 6 months, 1 year, 2 years, and 3 years after vaccination, as well as age groups. A generalized additive model for location, shape, and scale (GAMLSS) was applied to estimate P3, P10, P25, P50, P75, P90, and P97 centile reference values of VZV-IgG, and 95% reference intervals were calculated. A total of 785 children were included in the analysis, with an overall positivity rate of 70.3%, a median antibody concentration of 192.05 (82.89–571.14) mIU/mL, and a positivity rate of 57.7% for one dose of vaccine and 84.2% for two doses. Antibody positivity rates at 1 month, 6 months, 1 year, 2 years, and 3 years after vaccination were 65.1%, 74.4%, 80.4%, 67.7%, and 63.0%, respectively. The GAMLSS results showed that VZV-IgG had a tendency to increase and then decrease after vaccination, and the second dose of vaccination could significantly increase VZV-IgG. Two doses of varicella vaccine should be administered to children in a timely manner and included in the routine vaccination programs. [ABSTRACT FROM AUTHOR]

[Display omitted] • Chickenpox is a common childhood illness with a safe effective vaccine. • First qualitative systematic review of parental perceptions of varicella vaccination. • The varicella vaccine has been recommended for inclusion in the UK vaccine schedule. • Many parents exhibit complacency towards chickenpox and varicella vaccine hesitancy. • Public health messaging should consider these findings to ensure high vaccine uptake. In countries where varicella vaccination is not on the routine childhood immunisation schedule, such as those in the United Kingdom (UK), chickenpox is an almost universal disease of childhood. Chickenpox can cause serious complications, particularly in infants, pregnant women, and the immunocompromised. In November 2023 the varicella vaccine was recommended for inclusion in the UK routine childhood immunisation schedule. Successful rollout of the vaccine may be hindered by parental concerns about vaccine safety and efficacy, and perceptions of chickenpox as a mild illness. To examine parental perceptions of chickenpox and varicella vaccination, which may be crucial to effective vaccination campaigns. Qualitative systematic review and thematic analysis. Six electronic databases were systematically searched for studies published between 2016 and 2023: CINAHL, EMBASE, MEDLINE, PsycInfo, PubMed, and Web of Science. The included studies were appraised against the Critical Appraisal Skills Program checklist for qualitative studies. Thematic analysis was used to analyse qualitative data, through the development of themes. 22 articles were included in this review, and five themes identified: perceptions that chickenpox is a mild illness, that parents have concerns about varicella vaccine efficacy and safety, a notion of natural immunity as superior, social determinants of health influence vaccine decision making, and vaccination is overwhelming perceived as a parental decision. Whilst some parents displayed an acceptance and willingness to vaccinate against chickenpox, many expressed concerns, and perceived chickenpox as a routine unworrying childhood illness. Analysis demonstrated a knowledge gap in understanding UK parental opinions regarding chickenpox and varicella vaccination, highlighting the need for research in this area, particularly given ongoing reconsideration for inclusion in the UK vaccination schedule. The review was registered on PROSPERO, registration ID CRD42021236120. [ABSTRACT FROM AUTHOR]

• VarV reached non-inferior criteria of immunogenicity in population ≥ 13 years. • VarV offered a more flexible immunization schedule, with an interval of 4–10 weeks between the two doses. • VarV could induce good immune response in both adolescents and adults. • Vaccination with VarV did not increase additional safety risk. Vaccines for prevention against varicella are important for adolescents and adults, who have an increased risk of severe varicella. This study aimed to evaluate the immunogenicity and safety of a two-dose immunization schedule of a live-attenuated varicella vaccine (VarV) manufactured by Sinovac (Dalian) in healthy adolescents and adults. A randomized, double-blind, controlled clinical trial was conducted in healthy population aged ≥ 13 years old in China. Participants in block 1 were randomly assigned (1:1) to receive two doses of either the test vaccine or an active control vaccine, administered 4, 6 or 8 weeks apart. Participants in block 2 were randomly assigned (2:1) to receive two doses of test vaccine or placebo, administered 10 weeks apart. The primary immunogenicity endpoint was the seroconversion rates and GMTs of varicella zoster virus (VZV) antibodies measured by fluorescent-antibody-to-membrane-antigen (FAMA) 4 weeks post-immunization. The primary safety endpoint was the incidence of adverse reactions within 4 weeks after each dose. A total of 2398 participants were enrolled. The seroconversion rates of VZV antibodies were 79.55 % in the test group and 76.41 % in the active control group respectively 4 weeks after two doses of pooled schedule, with the difference of 3.14 % (95 %CI: −0.69 %, 6.97 %). The GMTs were 1:162.07 and 1:160.04 respectively, with the ratio of 1.013 (95 %CI: 0.910, 1.127). Both the seroconversion rates and GMTs reached the prespecified non-inferiority criteria. Two-dose schedule with an interval of 10 weeks could also induce high immune responses, with a seroconversion rate of 83.22 % and a GMT of 1:160.38 in the test group. Safety profiles were similar among the test group, active control group and placebo group. VarV, manufactured by Sinovac (Dalian), demonstrated higher immune response and better flexibility in the immunization schedule among heathy population aged 13 years and older, without increased safety risk. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to investigate the vaccination coverage and the factors associated with non-vaccination for vaccine-preventable diseases among patients with rheumatoid arthritis. Methods: This single-centre, cross-sectional study was conducted in a 715-bed regional tertiary-care teaching hospital in Japan from 1 September to 30 November 2020. Vaccination status and the factors and reasons for not receiving the influenza vaccine, 23-valent pneumococcal polysaccharide vaccine (PPSV23), 13-valent pneumococcal conjugate vaccine (PCV13), and varicella vaccine live (VVL) were investigated. Results: Among 991 patients, the vaccination coverage for the influenza vaccine, PPSV23, PCV13, and VVL was 62%, 46%, 14%, and 3%, respectively. The most common reasons for vaccine hesitancy were efficacy concerns for the influenza vaccine, safety concerns for the PPSV23 and PCV13, and both efficacy and safety concerns for the VVL. Younger age, no use of biologics or other hospital visits, and public assistance were factors significantly associated with non-vaccination for the influenza vaccine; younger age, short disease duration, and no visits to other hospitals for PPSV23; younger age, no hospitalisation, more experienced doctor, and no medical immunodeficiency for PCV13. Conclusions: We found that the factors associated with non-vaccination varied by vaccine type; therefore, vaccinations should be promoted with individualised strategies. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. The introduction of two-dose varicella vaccination was an effective intervention to prevent varicella in Wuxi, China. Varicella vaccination is urgently needed in routine childhood immunization programmes. [ABSTRACT FROM AUTHOR]

The Varicella Zoster Virus (VZV) presents a global health challenge due to its dual manifestations of chickenpox and shingles. Despite vaccination efforts, incomplete coverage, and waning immunity lead to recurrent infections, especially in aging and immunocompromised individuals. Existing vaccines prevent chickenpox but can trigger the reactivation of shingles. To address these limitations, we propose a polyvalent multiepitope subunit vaccine targeting key envelope glycoproteins of VZV. Through bioinformatics approaches, we selected six glycoproteins that are crucial for viral infection. Epitope mapping led to the identification of cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B cell linear (LBL) epitopes. Incorporating strong immunostimulants, we designed two vaccine constructs, demonstrating high antigenicity, solubility, stability, and compatibility with Tolllike receptors (TLRs). Molecular docking and dynamics simulations underscored the stability and affinity of the vaccine constructs with TLRs. These findings lay the foundation for a comprehensive solution to VZV infections, addressing the challenges of incomplete immunity and shingles reactivation. By employing advanced immunoinformatics and dynamics strategies, we have developed a promising polyvalent multiepitope subunit vaccine candidate, poised to enhance protection against VZV and its associated diseases. Further validation through in vivo studies is crucial to confirm the effectiveness and potential of the vaccine to curb the spread of VZV. This innovative approach not only contributes to VZV control but also offers insights into tailored vaccine design strategies against complex viral pathogens. [ABSTRACT FROM AUTHOR]

• Reports of varicella-zoster virus infections in Queensland have increased in the last 12 years. • The increase in varicella-zoster virus notifications is due to shingles in older age-groups. • Notification rates have declined among age-specific cohorts eligible for childhood chickenpox and adult shingles vaccines. • Routine age-group specific and targeted, intermittent enhanced surveillance is useful to understand vaccine impact. Chickenpox and shingles are vaccine preventable diseases caused by varicella-zoster virus (VZV). Chickenpox is more common in children before adolescence and shingles among ≥50 years of age. With this study we aimed to determine changes in VZV epidemiology following chickenpox and shingles vaccine introduction in Queensland. This case series study used notified cases of VZV infection in Queensland from January 2010 to December 2021. In Queensland, VZV notifications are received as mostly clinically unspecified cases from pathology laboratories. Intermittent enhanced surveillance was conducted using clinician follow up to determine chickenpox and shingles clinical presentation, and we then analysed these by age-group, time period, and within vaccine eligible cohorts. Of the 87,759 VZV notifications received, 70 % (n = 61,298) were notified as unspecified, followed by 23 % shingles (n = 19,927), and 7 % chickenpox (n = 6,534). Over the study period, the percent change in total notifications adjusted by age and sex was estimated to be an increase of 5.7 % (95 % CI 4.9–6.4) each year. The chickenpox notifications fell sharply at 18 months of age (eligible for chickenpox vaccine) with the rate being 57 % and 36 % lower among those aged 18–23 months compared to <12 and 12–17 months of age, respectively. Assuming all cases aged 60 years and older were shingles, notification rates of shingles decreased by 12–22 % among 70–79 years old (eligible for shingles vaccination) over the years 2017–2021 after vaccine introduction in 2016. The VZV notification rate has increased over time in Queensland. Impact of chickenpox and shingles vaccines funded under National Immunisation Program is seen with a decline in notification rates among age-specific cohorts eligible to receive the vaccines under the program. Introduction of a second childhood dose chickenpox vaccine and more effective recombinant shingles vaccine may further improve the impact of the vaccination program. [ABSTRACT FROM AUTHOR]

Background: Herpes zoster (HZ) is the clinical syndrome associated with reactivation of latent varicella-zoster virus (VZV). Several factors have been implicated to promote VZV reactivation; these include immunosuppression, older age, mechanical trauma, physiologic stress, lymphopenia, and more recently, infection with severe acute respiratory syndrome coronavirus-2 (SARS- CoV-2). Recent reports suggest an increase in the number of HZ cases in the general population during the global COVID-19 pandemic. However, it is unknown what proportion of HZ during the pandemic is due to reactivation of wild-type or vaccine-strain VZV. Case: Here we report the first known case of HZ concomitant with SARS-CoV2 infection in a 20-month-old female who was treated with a single dose of dexamethasone, due to reactivation of the vaccine-type strain of VZV after presenting with a worsening vesicular rash. Conclusion: In this case, we were able to show vaccine-strain VZV reactivation in the context of a mild acute symptomatic COVID-19 infection in a toddler. Being able to recognize HZ quickly and effectively in a pediatric patient can help stave off the significant morbidity and mortality associated with disease process. [ABSTRACT FROM AUTHOR]

Background There is little information on cell-mediated immunity (CMI) to COVID-19 mRNA vaccines in children. We studied adaptive and innate CMI in vaccinated children aged 6 to 60 months. Methods Blood obtained from participants in a randomized placebo-controlled trial of an mRNA vaccine before and 1 month after the first dose was used for antibody measurements and CMI (flow cytometry). Results We enrolled 29 children with a mean age of 28.5 months (SD, 15.7). Antibody studies revealed that 10 participants were infected with SARS-CoV-2 prevaccination. Ex vivo stimulation of peripheral blood mononuclear cells with SARS-CoV-2 spike peptides showed significant increases pre- to postimmunization of activated conventional CD4+ and γδ T cells, natural killer cells, monocytes, and conventional dendritic cells but not mucosa-associated innate T cells. Conventional T-cell, monocyte, and conventional dendritic cell responses in children were higher immediately after vaccination than after SARS-CoV-2 infection. The fold increase in CMI pre- to postvaccination did not differ between children previously infected with SARS-CoV-2 and those uninfected. Conclusions Children aged 6 to 60 months who were vaccinated with a COVID-19 mRNA vaccine developed robust CMI responses, including adaptive and innate immunity. [ABSTRACT FROM AUTHOR]