Population immunity to varicella in Canada: A Canadian Immunization Research Network (CIRN) study.

INTRODUCTION: The incidence of varicella in Canada has decreased by almost 99% since vaccination was introduced. However, variation in the timing and eligibility of vaccination programs across the country has resulted in some cohorts being under-vaccinated and therefore potentially susceptible to infection. METHODS: We used nationally representative specimens from the Biobank of Statistics Canada's Canadian Health Measures Survey (CHMS) as well as residual specimens from Ontario collected between 2009-2014 to estimate population immunity across age-groups and geography, and identify any groups at increased risk of varicella infection. RESULTS: The weighted proportion of specimens with antibody levels above the threshold of protection was 93.6% (95% CI: 92.4, 95.0). Protection was lowest among those aged 3-5 years (54.3%; 95% CI: 47.3, 61.4), but increased with age. Individuals born outside Canada had more than twice the odds of varicella susceptibility than those born in Canada (aOR: 2.7; 95% CI: 1.4, 5.0; p = 0.004). There were no differences by sex or geography within Canada, and there were no statistically significant differences when Ontario CHMS sera were compared to Ontario residual sera, apart from in participants aged 12-19 year age-group, for whom the CHMS estimate (91.2%; 95% CI: 86.7, 95.7) was significantly higher (p = 0.03) than that from residual specimens (85.9%, 95% CI: 81.1, 90.8). DISCUSSION: Varicella immunity in Canada is changing. Children appear to have low population immunity, placing them at greater risk of infection and at increased risk of severe disease as they age. Our results underscore the importance of performing periodic serosurveys to monitor further population immunity changes as the proportion of vaccine-eligible birth-cohorts increases, and to continually assess the risk of outbreaks.

Analysis of the implementation effect and evaluation of the vaccine protection effect of the live attenuated varicella vaccine program for school-age children in Bao'an district of Shenzhen,China.

The objective of the study is to analyze the implementation effect of the Live Attenuated Varicella Vaccine (VarV) Vaccination Program for eligible children in Bao'an District, Shenzhen, and evaluate the vaccine effectiveness. Children's vaccination data was obtained from the Shenzhen Immunization Planning Information Management System, while varicella case data came from the China Disease Prevention and Control Information System. The Joinpoint regression method examined vaccination rate trends, and a retrospective cohort study assessed vaccine effectiveness. After program implementation, VarV vaccination rates significantly increased, surpassing provincial and national averages. Overall incidence declined 54.6% across age groups, with the largest reductions among 7- and 6-year-olds. One year post-vaccination, single-dose vaccine effectiveness was 91.1% (95% CI: 79.2% to 96.2%). However, two doses remained 91.4% effective(95% CI: 89.1% to 93.2%) after 7 years. Overall, Shenzhen's VarV program achieved positive results. For children under six, routine immunization with two doses of VarV should be strengthened. Furthermore, we recommend that physicians conduct thorough inquiries to ascertain patients' vaccination history and previous varicella infections. This will enable doctors to provide tailored vaccination recommendations based on comprehensive, practical evaluations.

Varicella-Zoster Virus Pretransplant Vaccination and Posttransplant Infections Among Pediatric Solid Organ Recipients in the Two-Dose Varicella Era: A Single-Center, Multi-Organ Retrospective Study.

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.

Safety and Immunogenicity of the Live Attenuated Varicella Vaccine in Vietnamese Children Aged 12 Months to 12 Years: An Open-Label, Single-Arm Bridging Study.

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.

Effectiveness of the varicella vaccine in the real world, a matched case-control study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The epidemiologic and economic impact of varicella and herpes zoster vaccination in South Korea: A mathematical modelling study.

BACKGROUND: 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). METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Immunogenicity and safety of an ORF7-deficient skin-attenuated and neuro-attenuated live vaccine for varicella: a randomised, double-blind, controlled, phase 2a trial.

BACKGROUND: 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). METHODS: 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 log10 plaque forming units (PFU; low-dose v7D group), 3·9 log10 PFU (medium-dose v7D group), and 4·2 log10 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, the Fundamental Research Funds for the Central Universities, and Beijing Wantai. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Serious neurological adverse events in immunocompetent children and adolescents caused by viral reactivation in the years following varicella vaccination.

Serious adverse events following vaccination include medical complications that require hospitalisation. The live varicella vaccine that was approved by the Food and Drug Administration in the United States in 1995 has an excellent safety record. Since the vaccine is a live virus, adverse events are more common in immunocompromised children who are vaccinated inadvertently. This review includes only serious adverse events in children considered to be immunocompetent. The serious adverse event called varicella vaccine meningitis was first reported in a hospitalised immunocompetent child in 2008. When we carried out a literature search, we found 15 cases of immunocompetent children and adolescents with varicella vaccine meningitis; the median age was 11 years. Eight of the children had received two varicella vaccinations. Most of the children also had a concomitant herpes zoster rash, although three did not. The children lived in the United States, Greece, Germany, Switzerland, and Japan. During our literature search, we found five additional cases of serious neurological events in immunocompetent children; these included 4 cases of progressive herpes zoster and one case of acute retinitis. Pulses of enteral corticosteroids as well as a lack of herpes simplex virus antibody may be risk factors for reactivation in immunocompetent children. All 20 children with adverse events were treated with acyclovir and recovered; 19 were hospitalised and one child was managed as an outpatient. Even though the number of neurological adverse events remains exceedingly low following varicella vaccination, we recommend documentation of those caused by the vaccine virus.

Low vaccine coverage and varicella outbreaks in Brazil - 2019-2022.

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).

An economic evaluation and incremental analysis of the cost effectiveness of three universal childhood varicella vaccination strategies for Ireland.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Immunogenicity and safety of live attenuated and recombinant/inactivated varicella zoster vaccines in people living with HIV: A systematic review.

Few papers focus their attention on VZV vaccination effectiveness among people living with HIV (PLWH). Flanking the live attenuated vaccine (VZL) available, a newly recombinant vaccine (RZV) was recently introduced and approved for HZ prevention among adults. PLWH represents a population on which a particular attention should be applied, in order to guarantee the vaccine efficacy and safety. We performed a literature search in USNLM, PubMed, PubMed Central, PMC and Cochrane Library. From all the publications found eligible, data were extracted and processed per population, vaccine type, immunogenicity and ADRs. The review of the 13 included studies shows that both RZV and VZL are immunogenic and have an acceptable safety profile in adults and children living with HIV. However, given the lack of research available about vaccine efficacy in preventing VZV and HZ in PLWH, additional studies need to be performed, in order to achieve a full completeness of data.

Phase 3 Safety and Immunogenicity Study of a Three-dose Series of Twenty-valent Pneumococcal Conjugate Vaccine in Healthy Infants and Toddlers.

BACKGROUND: Global pediatric immunization programs with pneumococcal conjugate vaccines (PCVs) have reduced vaccine-type pneumococcal disease, but a substantial disease burden of non-PCV serotypes remains. METHODS: This phase 3, randomized (1:1), double-blind study evaluated safety and immunogenicity of 20-valent PCV (PCV20) relative to 13-valent PCV (PCV13) in healthy infants. Participants received 2 infant doses and a toddler dose of PCV20 or PCV13, with diphtheria-tetanus-acellular pertussis combination vaccine at all doses and measles, mumps, rubella and varicella vaccines at the toddler dose. Primary pneumococcal immunogenicity objectives were to demonstrate noninferiority (NI) of PCV20 to PCV13 for immunoglobulin G geometric mean concentrations after infant and toddler doses and percentages of participants with predefined serotype-specific immunoglobulin G concentrations after infant doses. Safety endpoints included local reactions, systemic events and adverse events. RESULTS: Overall, 1204 participants were vaccinated (PCV20, n = 601; PCV13, n = 603). One month after the toddler dose, 19/20 serotypes met NI for immunoglobulin G geometric mean concentrations; serotype 6B narrowly missed NI [PCV20/PCV13 geometric mean ratio: 0.57 (2-sided 95% confidence interval: 0.48-0.67); NI criterion: lower 2-sided 95% confidence interval >0.5]. Sixteen/twenty serotypes met NI for ≥1 primary objective after 2 infant doses. PCV20 induced robust opsonophagocytic activity, and boosting responses were observed for all vaccine serotypes, including those missing statistical NI. The safety/tolerability profile of PCV20 was like that of PCV13. CONCLUSIONS: PCV20 3-dose series in infants was safe and elicited robust immune responses. Based on these results and PCV13 experience, PCV20 3-dose series is expected to be protective for all 20 vaccine serotypes. NCT04546425.

Development of a skin- and neuro-attenuated live vaccine for varicella.

Varicella caused by the primary infection of varicella-zoster virus (VZV) exerts a considerable disease burden globally. Current varicella vaccines consisting of the live-attenuated vOka strain of VZV are generally safe and effective. However, vOka retains full neurovirulence and can establish latency and reactivate to cause herpes zoster in vaccine recipients, raising safety concerns. Here, we rationally design a live-attenuated varicella vaccine candidate, v7D. This virus replicates like wild-type virus in MRC-5 fibroblasts and human PBMCs, the carrier for VZV dissemination, but is severely impaired for infection of human skin and neuronal cells. Meanwhile, v7D shows immunogenicity comparable to vOka both in vitro and in multiple small animal species. Finally, v7D is proven well-tolerated and immunogenic in nonhuman primates. Our preclinical data suggest that v7D is a promising candidate as a safer live varicella vaccine with reduced risk of vaccine-related complications, and could inform the design of other herpes virus vaccines.

The Childhood Vaccination Schedule and the Lack of Association With Type 1 Diabetes.

OBJECTIVES: Safety studies assessing the association between the entire recommended childhood immunization schedule and autoimmune diseases, such as type 1 diabetes mellitus (T1DM), are lacking. To examine the association between the recommended immunization schedule and T1DM, we conducted a retrospective cohort study of children born between 2004 and 2014 in 8 US health care organizations that participate in the Vaccine Safety Datalink. METHODS: Three measures of the immunization schedule were assessed: average days undervaccinated (ADU), cumulative antigen exposure, and cumulative aluminum exposure. T1DM incidence was identified by International Classification of Disease codes. Cox proportional hazards models were used to analyze associations between the 3 exposure measures and T1DM incidence. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated. Models were adjusted for sex, race and ethnicity, birth year, mother's age, birth weight, gestational age, number of well-child visits, and study site. RESULTS: In a cohort of 584 171 children, the mean ADU was 38 days, the mean cumulative antigen exposure was 263 antigens (SD = 54), and the mean cumulative aluminum exposure was 4.11 mg (SD = 0.73). There were 1132 incident cases of T1DM. ADU (aHR = 1.01; 95% CI, 0.99-1.02) and cumulative antigen exposure (aHR = 0.98; 95% CI, 0.97-1.00) were not associated with T1DM. Cumulative aluminum exposure >3.00 mg was inversely associated with T1DM (aHR = 0.77; 95% CI, 0.60-0.99). CONCLUSIONS: The recommended schedule is not positively associated with the incidence of T1DM in children. These results support the safety of the recommended childhood immunization schedule.

Meningitis Caused by the Live Varicella Vaccine Virus: Metagenomic Next Generation Sequencing, Immunology Exome Sequencing and Cytokine Multiplex Profiling.

Varicella vaccine meningitis is an uncommon delayed adverse event of vaccination. Varicella vaccine meningitis has been diagnosed in 12 children, of whom 3 were immunocompromised. We now report two additional cases of vaccine meningitis in twice-immunized immunocompetent children and we perform further testing on a prior third case. We used three methods to diagnose or investigate cases of varicella vaccine meningitis, none of which have been used previously on this disease. These include metagenomic next-generation sequencing and cytokine multiplex profiling of cerebrospinal fluid and immunology exome analysis of white blood cells. In one new case, the diagnosis was confirmed by metagenomic next-generation sequencing of cerebrospinal fluid. Both varicella vaccine virus and human herpesvirus 7 DNA were detected. We performed cytokine multiplex profiling on the cerebrospinal fluid of two cases and found ten elevated biomarkers: interferon gamma, interleukins IL-1RA, IL-6, IL-8, IL-10, IL-17F, chemokines CXCL-9, CXCL-10, CCL-2, and G-CSF. In a second new case, we performed immunology exome sequencing on a panel of 356 genes, but no errors were found. After a review of all 14 cases, we concluded that (i) there is no common explanation for this adverse event, but (ii) ingestion of an oral corticosteroid burst 3-4 weeks before onset of vaccine meningitis may be a risk factor in some cases.

Parental acceptance and knowledge of varicella vaccination in relation to socioeconomics in Sweden: A cross-sectional study.

Varicella infection is a highly contagious disease which, whilst mild in most cases, can cause severe complications. Varicella vaccination is available privately in Sweden and is currently being reviewed for inclusion in the Swedish Public Health Agency's national immunisation program (NIP). A cross-sectional study of parents of Swedish children aged 1-8 years (n = 2212) was conducted to understand parental acceptance, beliefs and knowledge around varicella infection and vaccination. Respondents generally viewed varicella infection as a mild disease, with only a small proportion aware of potential severe complications. While 65% of respondents were aware of the vaccine, only 15% had started the course of vaccination as of February 2019. Further, 43% of parents did not intend to vaccinate, most commonly due to lack of inclusion in the NIP, but also due to perception of mild disease. Nevertheless, if offered within the NIP, 85% of parents would be highly likely to vaccinate their child. A number of statistically significant differences in awareness and behaviours were observed between sociodemographic subgroups. In general, women were more aware of vaccination (72%) compared to men (58%). Among unemployed or respondents with elementary school education, awareness was below 43%, and among respondents with high income the awareness was above 75%. Similarly, among unemployed or respondents with a low income the vaccination rate was as low as 30% compared with at least 57% among respondents with a high income. Respondents from metropolitan areas, those with university degrees and respondents with a higher income were more likely to be aware of the varicella vaccine and to have vaccinated their child. Whilst inclusion in the NIP is clearly the main driver for uptake, these identified knowledge gaps should inform educational efforts to ensure that all parents are informed of the availability and benefits of the varicella vaccine independent of socioeconomic status.

Waning Effectiveness of One-dose Universal Varicella Vaccination in Korea, 2011-2018: a Propensity Score Matched National Population Cohort.

BACKGROUND: Despite high coverage (~98%) of universal varicella vaccination (UVV) in the Republic of Korea since 2005, reduction in the incidence rate of varicella is not obvious. The study aimed to evaluate the vaccine effectiveness (VE) of one-dose UVV by timeline and severity of the disease. METHODS: All children born in Korea in 2011 were included for this retrospective cohort study that analyzed insurance claims data from 2011-2018 and the varicella vaccination records in the immunization registry. Adjusted hazard ratios by Cox proportional hazard models were used to estimate the VE through propensity score matching by the month of birth, sex, healthcare utilization rate, and region. RESULTS: Of the total 421,070 newborns in the 2011 birth cohort, 13,360 were matched for age, sex, healthcare utilization rate, and region by the propensity score matching method. A total of 55,940 (13.29%) children were diagnosed with varicella, with the incidence rate 24.2 per 1000 person-year; 13.4% of vaccinated children and 10.4% of unvaccinated children. The VE of one-dose UVV against any varicella was 86.1% (95% confidence interval [CI], 81.4-89.5) during the first year after vaccination and 49.9% (95% CI, 43.3-55.7) during the 6-year follow-up period since vaccination, resulting in a 7.2% annual decrease of VE. The overall VE for severe varicella was 66.3%. The VE of two-dose compared to one-dose was 73.4% (95% CI, 72.2-74.6). CONCLUSION: We found lower long-term VE in one-dose vaccination and waning of effectiveness over time. Longer follow ups of the vaccinated children as well as appropriately designed studies are needed to establish the optimal strategy in preventing varicella in Korea.

Impact of a two-dose varicella immunization program on the incidence of varicella: a multi-year observational study in Shanghai, China.

BACKGROUND: It remains hesitant to include a two-dose varicella vaccine (VarV) in a national routine immunization program in China. We aimed to quantify the impact of the two-dose VarV on varicella incidence in Shanghai. RESEARCH DESIGN AND METHODS: We directly extracted the data of varicella cases and VarV doses in 2013-2020 in Shanghai, and then estimated the effects of two-dose VarV using a Serfling model. RESULTS: A two-dose VarV immunization program has been extensively implemented since October 2017 and become free since August 2018 in Shanghai. Before and after this program, varicella cases significantly declined in children (P < 0.01), whereas did not in adults aged >18 years (P = 0.22). Compared to the predicted number of varicella cases, actual number was significantly lower by 8% in 2018 and 28% in 2019. Among children aged 4-6 years, the reduction in varicella cases was largest. Moreover, there was a significant reduction in varicella cases throughout 2020 (P < 0.001), in which the decrease due to social distancing for the COVID-19 was 54%. CONCLUSIONS: A two-dose VarV immunization program may further reduce approximately one-third of varicella cases in Shanghai. Children <4 years and adults benefit less in this program, which warrants enhancing the immunization.