Varicella Vaccine Research Articles

Development of Streptococcus pyogenes pneumnonia and pleural empyema post-chickenpox infection in a 5-year-old child: A case report

Background: The introduction of the varicella vaccine has led to a significant decrease in pediatric varicella-induced invasive Streptococcus pyogenes (group A streptococcal [GAS]) infections. However, the development of a pleural empyema following a chickenpox infection is a rare complication in pediatric patients. Case presentation: In this report, we present a 5-year-old male patient who presented to the emergency department with a deteriorating course two days after a chickenpox infection. The patient complained of high-grade documented fever, a congested throat, abdominal pain, shortness of breath, and most importantly, decreased air entry on the right side of the chest, along with the presence of crepitations. Such a deteriorated clinical picture suggested the presence of an infectious cause. The patient’s physical examination and radiological imaging provided evidence for the presence of lower right-sided lobar pneumonia. On the second day of hospitalization, the patient showed worsening respiratory distress, prompting further investigations that confirmed the development of a right-sided pleural empyema through radiological imaging. Pediatric surgery consultation was requested, and 500 cc of pus was drained following the insertion of a chest tube, which was later sent for analysis. The patient’s clinical picture improved significantly following this intervention. Due to the severity of his condition, the patient was transferred to the pediatric intensive care unit (PICU) for close monitoring. After one night in the PICU, during which his condition stabilized and oxygen therapy was gradually weaned off, the patient continued to improve on the general ward. Daily assessments and laboratory tests showed decreasing inflammatory markers and resolution of symptoms. Following three days of admission and confirmation of no underlying immunologic deficiency, the patient was discharged home with appropriate antibiotic therapy and follow-up instructions. Discussion: Similar cases have been sporadically documented in pediatric literature, with notable examples involving older patients. The pathophysiology involves complex immune interactions and virulence factors of GAS, contributing to severe outcomes such as pleural effusion. Conclusion: In this case, the 5-year-old patient experienced a severe progression from chickenpox to pleural empyema but ultimately improved following prompt medical intervention and chest tube drainage. The patient was discharged after a successful recovery, highlighting the efficacy of early recognition and treatment in managing such complications.

Evaluating the Impact of Moderate and Severe Varicella Infections on Danish Children Under 18 Years Old: A Comprehensive Analysis From 2015 to 2023

Background: Varicella (chickenpox) caused by varicella-zoster virus (VZV) is a highly contagious pediatric disease. While it typically manifests as a mild disease, complications leading to hospitalization are not uncommon. Knowing the current disease burden, seasonality and risk groups is pivotal for evidence-based decisions on the introduction of a varicella vaccine. Methods: Using the Danish National Patient Register and medical helpline records from the Capital Region, we estimated the burden of VZV infections among children younger than 18 years in Denmark from 2015 to June 2023. Results: We identified 14,443 cases with annual incidence rates of 325/100,000 children for mild-to-moderate varicella cases (helpline calls), 35/100,000 for moderate-to-severe cases (outpatients) and 10/100,000 for severe cases (hospitalized). Mild cases were most prevalent in children aged 1–4 years, while moderate-to-severe cases were most prevalent among infants <1 year old. Among hospitalized cases, 23.2% had underlying diseases and 47.3% experienced complications. In April 2022, rapid surge in all types of VZV cases occurred, where admissions surpassed the prepandemic level. Conclusion: This study documents that varicella is highly prevalent among Danish young children. Mild-to-moderately severe cases strain healthcare, causing increased helpline calls and posing a persistent hospitalization risk, especially for infants and children with underlying conditions.

Coverage with Selected Vaccines and Exemption Rates Among Children in Kindergarten - United States, 2023-24 School Year.

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 state-required 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.

Analysis of antibody dynamics in Chinese children aged 1-3 years after single-dose varicella vaccination: A 42 months prospective study

ABSTRACT In China, children aged 12 months receive only a single dose of the varicella vaccine and the incidence of varicella remains high. This study aims to evaluate the changes in immunity among children aged 1–3 years following a single dose of the varicella vaccine, providing a scientific basis for determining the optimal age for a second vaccination. This prospective cohort study employed glycoprotein enzyme-linked immunosorbent assay (gpELISA) for antibody detection. The changes in IgG antibody levels over time post-vaccination were analyzed using a restricted cubic spline (RCS) fitted binary logistic regression model. Varicella surveillance data were collected from the National Notifiable Disease Reporting System (NNDRS). Following a peak in varicella incidence in 2019, the incidence shifted toward older age groups. The cohort study results revealed a seropositivity rate of 100% in children during the 18 months post-vaccination, which subsequently declined to 71.6% by the 42 months. The geometric mean concentration (GMC) decreased from 307.6mIU/mL to 115.2mIU/mL. Additionally, 14 children contracted varicella during the follow-up period, resulting in a breakthrough rate of 2.85%. RCS analysis indicated that antibody levels fell below the protective threshold 18.69 months post-vaccination, with a non-linear decline in the odds ratio(OR) of maintaining antibody concentrations ≥ 50mIU/mL(p < .001, Pnonlinear ≤ 0.001). This study demonstrates that the long-term protective efficacy of a single dose of the varicella vaccine diminishes over time in children, underscoring the necessity of implementing a two-dose vaccination strategy. The findings provide scientific evidence for determining the optimal timing for administering the second dose of the vaccine.

Antibody responses to re-immunization in recipients of allogeneic hematopoietic cell transplantation

Abstract Background Immunologic memory against vaccine-preventable diseases is often lost after an allogeneic hematopoietic cell transplant (allo-HCT), therefore recipients are required to be re-immunized after allo-HCT to regain immunity against these infections. But the response to vaccination after an allo-HCT can be highly variable and is not well understood. We performed a single center retrospective study to examine immunization practices and determine the rate of vaccine protection and seroconversion following vaccination after allo-HCT. Methods Electronic medical records (EMR) from patients ≤18 years of age who underwent allo-HCT at St. Jude Childrens’ Research Hospital between 2005 - 2021 were reviewed. Clinical information and serology results before and after completion of the immunizations series were extracted from the EMR. The vaccines included in this analysis were diphtheria, measles, mumps, rubella (MMR), varicella, and polio. Protection was evaluated only for infections with established immune correlates. Seroconversion was defined as 4-fold increase in titers for vaccines with quantitative antibody assays, or as a change from negative to positive IgG for vaccines with qualitative antibody tests. Results 760 patients were included in this cohort. Demographic and clinical data are summarized in Table 1. The mean age at allo-HCT was 10.4 years, most were male (56.8%) and white (74.6%). Acute leukemia accounted for 66.4% of allo-HCT recipients. Conditioning was myeloablative for 53.45%, and reduced intensity for 37.9%. Most received transplants from mismatched-related donors, (44.9%), followed by matched unrelated donors (35.4%) and matched related donors (19.5%). The number of patients who received the full vaccination series at our institution differed by vaccine and ranged from 41-150, and the respective subsets with available pre-vaccination and post-vaccination titers ranged from 24-93. The median time from transplant to initiation of immunizations was 12 months (range: 6-58) for non-live vaccines, 25 months (range: 23, 63) for MMR vaccine, and 28 months (range: 16, 117)) for varicella vaccine. Protection post immunization varied, with less patients demonstrating protections for mumps (79%) and measles (82%) (Figure 1). Seroconversion also varied among the different vaccine components and types of vaccines. Conclusion Current strategies to re-immunize patients after allo-HCT do not provide protection to all patients. Understanding the factors associated with suboptimal immune responses is critical for advancing our knowledge in this area. Whether time-based approaches combined with immune reconstitution data are required to further optimize protection remains unclear. Additionally, different vaccine schedules (i.e., higher doses) may be required in these patients. Figure 1. Protection and seroconversion rate by vaccine target.

Incomplete Immunity for Varicella and Measles in Pediatric Organ Transplant Candidates. Real World Experience From an Infectious Diseases Pre-Transplantation Clinic.

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. 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. 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. 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.

Preliminary investigation and analysis of nucleotide site variability of nine glycoproteins on varicella-zoster virus envelope, Jilin Province, China, 2010-March 2024

Varicella is endemic worldwide. In China, varicella has not yet been included in the list of legal infectious diseases, nor has a unified national surveillance program been established. And the live attenuated varicella vaccine has not been included in routine immunization. In this study, we analyzed for the first time the varicella epidemiology in Jilin Province in the past 20 years, and the nucleotide site, amino acid site and N-glycosylation site variation of glycoprotein in varicella-zoster virus (VZV) surface 9 in the past 15 years. The results showed that the reported incidence of varicella in Jilin Province in the last 20 years was fluctuating above and below 20/100,000, especially after the epidemic of the COVID-19, and fatal cases appeared in individual years. The genotypic branching of VZV was monitored as Clade 2 in the last 15 years. 9 glycogen nucleotide sites of VZV had different degrees of variability, and the variability had specificity. Therefore, it gives us the idea that in order to reduce the incidence of varicella and herpes zoster, a provincial or even national surveillance program should be introduced as early as possible, and the dynamic monitoring of the variability of the nucleotide sites of VZV should be strengthened at the same time as the vaccine immunization strategy is introduced.

The impact of the implementation of the two-dose varicella vaccine immunization strategy in Quzhou: A retrospective birth cohort study

ABSTRACT Varicella is a vaccine-preventable disease caused by the varicella zoster virus (VZV), but the varicella incidence among children has increased in recent years. This was a retrospective birth cohort study based on the Zhejiang Provincial Immune Information System (ZJIIS) and the China Information System for Disease Control and Prevention (CISDCP) in Quzhou. A total of 1,291 clinically diagnosed varicella cases born from 2009 to 2014 were collected during 2009–2023, which were analyzed the impact of changes in vaccination strategy on the incidence of varicella based on the Cox-proportional hazards model. It was observed that the onset age of varicella shifted to the older age group and later to 9–11 years. After the change to the two-dose varicella vaccination strategy, the population affected by varicella was concentrated among students and received more than one dose of live attenuated varicella vaccine (VarV). Based on the Coxproportional hazards model and adjusting for all covariates, the risk of varicella infection in children decreased after the introduction of the two-dose varicella vaccination strategy (HR = 0.04, 95% CI: 0.03–0.05). Meanwhile, the Kaplan–Meier curves also showed that the hazards were lower after the change in vaccination strategy. It is recommended that two doses of VarV should be included in the national immunization schedule and that full vaccination should be completed approximately four years after the first dose.

A population database analysis to estimate the varicella vaccine effectiveness in children < 14 years in a high vaccination coverage area from 2004 to 2022

IntroductionIn the Veneto Region of Italy, universal varicella vaccination (VV) started in 2007 with a two-dose schedule at 12–15 months and 5–6 years of age achieving 90 % coverage in 2019. The study aimed at evaluating the vaccine effectiveness (VE) in children using a primary-care database MethodsThis retrospective analysis used Pedianet, a comprehensive database of 73 family paediatricians in the Veneto Region. Incidence rates (IR) of varicella were evaluated in children aged <14 years enrolled since birth, between January 2004 to April 2022. Cases were classified as breakthrough if happening beyond 42 days post-VV. Complications and prescription were evaluated. Subject were followed up from 2004 or the enrollment date, until the end of assistance/study or the first or second VV dose. Kaplan-Meier curves and log-rank tests were used to compare the varicella incidence by vaccination status. Hazard ratios of varicella infection, adjusted (aHRs) for sex, vaccinal status, age group, prematurity and socioeconomic status were estimated with Cox's regression. VE for one and two VV doses was defined as 1-aHR*. Results36,498 children, followed for 233,508 person-years from 2004 to 2022 experienced 1006 cases of varicella (13 complicated and 35 breakthrough). Younger children had a higher risk of experiencing varicella compared to children aged >7 years, irrespective of their vaccination status. Indeed, the IR increased from 5.5 to 19.5 × 1000 person-years and from 1.1 to 5.4 × 1000 person-years in unvaccinated and vaccinated children aged <12 months versus those aged 5–6 years, respectively. Varicella VE was 83.4 % and 94.7 % in those vaccinated with one and two doses. After six years, the cumulative probability of experiencing varicella was 10.7 % for unvaccinated subjects, and 2.5 % and 0.4 % for those vaccinated with one and two-doses (log-rank test, p < 0.001). ConclusionsTwo-dose schedule VV is effective in drastically reduce varicella episodes. Breakthrough varicella episodes remain rare events.

An Investigation of a Community Chickenpox Outbreak with a Fatal Case, Songkhla Province, Thailand, October 2022

In October 2022, a suspected chickenpox death was notified. A field investigation was done to verify the diagnosis and cause of death, describe the epidemiological characteristics, identify risk factors, and control the outbreak. We conducted a descriptive study and a matched case-control study. A case was defined as a person with multiple stages of skin lesions on at least two body areas in Subdistrict from 1 Aug 2022 to 24 Oct 2022. We reviewed medical records and searched for cases house-to-house. For the matched case-control study, cases were chickenpox cases residing in Bo Tru Subdistrict, from 1 Aug 2022 to 14 Oct 2022. Controls were neighbors without symptoms or chickenpox history, matched by age. Samples were tested using the reverse transcription polymerase chain reaction technique. Environmental surveys were performed. We identified 30 cases including the deceased, who was 49 years old. The median (interquartile range) age of the cases was 11 (7–38) years. Seventeen were elementary-school students. None of the cases received chickenpox vaccination or had a history of chickenpox. The secondary attack rate among household contacts was 41.2% (14/34). Reverse transcriptase polymerase chain reaction tests from three cases were all positive. Being a close contact with a case and sharing personal utensils were risk factors. We strengthened the surveillance system for early detection and treatment and provided risk communication in the community. Chickenpox cases should be isolated from susceptible persons. Standard treatment guidelines for complicated cases should be distributed among healthcare services.

Surveillance of adverse events following varicella vaccine immunization in Jiangsu province, China from 2017 to 2023

To assess the safety of varicella vaccine (VarV) by conducting post-marketing surveillance on adverse events following immunization (AEFI) in Jiangsu Province, China.MethodsWe utilized the AEFI Information System of mainland China to monitor and categorize adverse reactions associated with VarV.ResultsThe 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.ConclusionVarV 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.

Seroprevalence Assessment of Anti-Varicella Antibodies among Adults in the Province of Florence (Italy).

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.

Glycoprotein E-Displaying Nanoparticles Induce Robust Neutralizing Antibodies and T-Cell Response against Varicella Zoster Virus.

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.

Pediatric Varicella-related Hospitalization in Turkey Between 2008 and 2018: Impact of Universal Single Dose Varicella Vaccine (VARICOMP Study).

A single-dose varicella vaccine at 12 months of age was introduced to the National Immunization Program in February 2013 in Turkey. This study aimed to evaluate varicella-related hospitalization in children and the impact of a single-dose live attenuated varicella vaccine over the first 5.5 years of introducing a universal varicella vaccination. We analyzed data collected from the medical records of children <18 years old who required hospitalization due to varicella in 17 cities representing 50% of the childhood population in Turkey between 2008 and 2018. We calculated the rate of hospitalization for varicella per 100,000 children during the study period. The main objective of this study was to determine the yearly rate of hospitalization due to varicella and to compare these rates in the pre-vaccine and post-vaccine periods. The secondary objective was to compare demographic features, varicella-related complications, and outcomes between the pre-vaccine and post-vaccine periods. A total of 4373 children (2458 boys and 1915 girls; 72.3% previously healthy) were hospitalized for varicella over a 10-year period, including 2139 children during the pre-vaccine period and 2234 children during the post-vaccine period. Overall, varicella hospitalization rates decreased significantly after the introduction of varicella vaccination [pre-vaccine vs. post-vaccine period; 3.79 vs. 2.87 per 100,000 per year; P < 0.001; odds ratio 0.75; 95% confidence interval 0.64-0.88]. The incidence of varicella-related hospitalization among children between 1 and 5 years of age was significantly lower in the post-vaccine era than in the pre-vaccine era, with a 60.2% decrease in hospitalizations (2.43 vs. 6.12 per 100,000 children; P < 0.001, odds ratio 0.39; 95% confidence interval 0.34-0.46). In both the <1-year and 6- to 10-year age groups, the incidence of varicella-related hospitalizations was similar in the pre-vaccine and post-vaccine periods. The incidence of varicella-related hospitalization was higher in the post-vaccine era among 11-15 years and >15-year-old groups (P < 0.01 and P < 0.05). The mean age was higher during the post-vaccine period than during the pre-vaccine period (P < 0.001). The absolute number of secondary bacterial infections (P < 0.01), respiratory complications (P < 0.01), and neurological complications (P < 0.001) was significantly lower during the post-vaccine period. The incidence of severe varicella was lower during the post-vaccine period than during the pre-vaccine period (P < 0.001). After 5.5 years of routine single-dose varicella vaccine use, we observed the impact of varicella vaccination on the incidence of varicella-related hospitalizations, especially in the target age group. However, we did not observe herd protection in the other age groups. The implementation of a second dose of the varicella vaccine in the National Immunization Program would help control disease activity.

Diurnal rhythms in varicella vaccine effectiveness.

BACKGROUNDImmune processes are influenced by circadian rhythms. We evaluate the association between varicella vaccine administration time of day and vaccine effectiveness.METHODSA national cohort, children younger than 6 years, were enrolled between January 2002 and December 2023. We compared children vaccinated during morning (7:00-10:59), late morning to afternoon (11:00-15:59), or evening hours (16:00-19:59). A Cox proportional hazards regression model was used to adjust for ethnicity, sex, and comorbidities. The first varicella infection occurring at least 14 days after vaccination and a second dose administration were treated as terminal events.RESULTSOf 251,141 vaccinated children, 4,501 (1.8%) experienced breakthrough infections. Infection rates differed based on vaccination time, with the lowest rates associated with late morning to afternoon (11:00-15:59), HR 0.88, 95% CI 0.82-0.95, P < 0.001, and the highest rates with evening vaccination (16:00-19:59), HR 1.41, 95% CI 1.32-1.52, P < 0.001. Vaccination timing remained significant after adjustment for ethnicity, sex, and comorbidities. The association between immunization time and infection risk followed a sinusoidal pattern, consistent with a diurnal rhythm in vaccine effectiveness.CONCLUSIONWe report a significant association between the time of varicella vaccination and its clinical effectiveness. Similar association was observed with the COVID-19 vaccine, providing proof of concept consistent with a diurnal rhythm in vaccine effectiveness.

Varicella Vaccination as a Potential Multiple Sclerosis Prevention Strategy

Varicella Vaccination as a Potential Multiple Sclerosis Prevention Strategy

Exploring Varicella Vaccine Coverage and Influencing Factors in Rural and Pastoral Children of Qinghai Province: A Cross-Sectional Catch-Up Vaccination Study

&amp;lt;i&amp;gt;Background: &amp;lt;/i&amp;gt;Varicella is a respiratory infectious disease caused by varicella-zoster virus (VZV) infection. Varicella vaccine has been shown to be highly effective in preventing varicella disease, however it is not included in Qinghai Province’s local immunization planning program and must be paid for by families. Its use in local areas is options instead of compulsory, so high coverage is difficult to guarantee. Starting in October 2021, one dose of live attenuated varicella vaccine was recommended at lest for 3-17-year-old children in Qinghai. In 2022, it was conducted that an investigation of varicella vaccine coverage and factors influencing coverage among children in rural rural and pastoral areas to determine the impact of this VarV catch-up policy. &amp;lt;i&amp;gt;Objective: &amp;lt;/i&amp;gt; To explore varicella vaccine coverage and factors influencing caverage among 3-17-year-old children in rural and pastoral areas of Qinghai province. &amp;lt;i&amp;gt;Methods:&amp;lt;/i&amp;gt; A stratified cluster sampling method was used to select children aged 3-17 years from kindergartens and primary /secondary schools in rural and pastoral areas of Qinghai province for a questionnaire-based survey of their guardians. Coverage levels of one and two doses of VarV (VarV&amp;lt;sub&amp;gt;1&amp;lt;/sub&amp;gt; and VarV&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt;) before and after a catch-up vaccination activity initiated in October 2021, and identified factors influenceing VarV&amp;lt;sub&amp;gt;1&amp;lt;/sub&amp;gt; coverage. &amp;lt;i&amp;gt;Results:&amp;lt;/i&amp;gt; VarV&amp;lt;sub&amp;gt;1&amp;lt;/sub&amp;gt; and VarV&amp;lt;sub&amp;gt;2 &amp;lt;/sub&amp;gt;coverage levels after the catch-up activity were 79.06% (676/855) and 43.79% (363/829), respectively, and increased by 34.38 and 24.13 percentage points compared with before the catch-up activity. Multivariate logistic regression showed that VarV&amp;lt;sub&amp;gt;1 &amp;lt;/sub&amp;gt;coverage was higher in rural areas than in pastoral areas (OR=4.63, 95%&amp;lt;I&amp;gt;CI&amp;lt;/I&amp;gt;: 2.91-7.39), and higher among children whose guardians scored 4-6 or 7-10 points on knowledge about varicella and VarV than among children whose guardians scored 0-3 points (OR=8.61, 95%&amp;lt;I&amp;gt;CI&amp;lt;/I&amp;gt;: 4.73-15.69, OR=2.86, 95%&amp;lt;I&amp;gt;CI&amp;lt;/I&amp;gt;: 1.69-4.84). the main reasons for non-vaccination were guardians’ lack of understanding of VarV (48.6%, 87 children), guardians’ unawarness of the need for VarV vaccination (43.6%, 78 children), and unavailability of VarV at vaccination centers (31.3%, 56 children). &amp;lt;i&amp;gt;Conclusions: &amp;lt;/i&amp;gt;The catch-up activity significantly increased VarV coverage among children in the surveyed areas. It should been strengthened that health education on knowledge about varicella and VarV among guardians of children in Qinghai, especially in pastoral areas, to promote VarV vaccination of age-eligible children.

Health and Economic Benefits of Routine Childhood Immunizations in the Era of the Vaccines for Children Program - United States, 1994-2023.

Since 1994, the U.S. Vaccines for Children (VFC) program has covered the cost of vaccines for children whose families might not otherwise be able to afford vaccines. This report assessed and quantified the health benefits and economic impact of routine U.S. childhood immunizations among both VFC-eligible and non-VFC-eligible children born during 1994-2023. Diphtheria and tetanus toxoids and acellular pertussis vaccine; Haemophilus influenzae type b conjugate vaccine; oral and inactivated poliovirus vaccines; measles, mumps, and rubella vaccine; hepatitis B vaccine; varicella vaccine; pneumococcal conjugate vaccine; hepatitis A vaccine; and rotavirus vaccine were included. Averted illnesses and deaths and associated costs over the lifetimes of 30 annual cohorts of children born during 1994-2023 were estimated using established economic models. Net savings were calculated from the payer and societal perspectives. Among approximately 117 million children born during 1994-2023, routine childhood vaccinations will have prevented approximately 508 million lifetime cases of illness, 32 million hospitalizations, and 1,129,000 deaths, at a net savings of $540 billion in direct costs and $2.7 trillion in societal costs. From both payer and societal perspectives, routine childhood vaccinations among children born during 1994-2023 resulted in substantial cost savings. Childhood immunizations continue to provide substantial health and economic benefits, while promoting health equity.

Cost-Effectiveness of Varicella Vaccination for 1–4-Year-Olds in Shanghai, China

IntroductionVaricella has not yet been included in the National Immunization Program (NIP) in China, and varicella vaccination strategies vary by region. To determine the optimal varicella vaccination strategy in Shanghai, China, the cost-effectiveness and five-year costs of five immunization scenarios were analyzed. MethodsA static decision tree-Markov model was developed in 2022 to assess the cost-effectiveness and five-year costs of voluntary and routine varicella vaccination programs in the 2019 birth cohort in Shanghai from a societal perspective. Parameters were collected in 2022 from the varicella surveillance system, a questionnaire survey of 414 guardians of patients with childhood varicella, and semi-structured interviews with 20 experts on varicella outbreaks from different institutions in Shanghai. The outcomes included varicella cases avoided, quality-adjusted life year (QALY) loss, and incremental costs per QALY (ICER). The five-year costs were compared with local medical expenditures. ResultsAmong the five scenarios, one dose of routine varicella vaccination was the most cost-saving (USD 70.2) and cost-effective (Dominant) with a five-year immunization expenditure of USD 9.9 million. Two doses of routine varicella vaccination had the highest QALY (29.9), and its ICER (USD 791.9/QALY) was below the willingness-to-pay threshold (USD 5,203-23,767/QALY). The five-year immunization expenditure was USD 19.8 million. The effectiveness and price of vaccines, vaccination coverage, and per capita income are the four main factors that affect ICERs. ConclusionsIn Shanghai, the two doses of routine varicella vaccination strategy for 1- and 4-year-olds with a 95% coverage rate was found to be the optimal varicella immunization strategy.

Heightened incidence of adverse events associated with a live attenuated varicella vaccine strain that lacks critical genetic polymorphisms in open reading frame 62

ObjectivesThis 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. MethodsFrom 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. ResultsA 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. DiscussionLack 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.