Varicella outbreak at nursery school under routine immunization in Japan in 2017 and 2018 and vaccine effectiveness.

BACKGROUND: In Japan, routine administration to one-year-old children of two-dose immunization for varicella was introduced in October 2014. Object The object of this study was to report outbreaks of varicella under routine immunization at a nursery school and in its surrounding area using data of surrounding areas from the (Nursery) School Absenteeism Surveillance System. Then, we measured the effectiveness of routine two-dose immunization for varicella to onset. We tentatively assessed its severity in a nursery school. METHOD: The study period extended from April 2017 through March 2018. The study area comprised Nursery school B and other nursery schools, and elementary and junior high schools in City A. Subjects in Nursery school B were 120 children. We analyzed vaccine effectiveness (VE) as an observational study and assessed severity using Fisher's exact test. We also assessed VE for severity using linear regression. Severity was defined as the length of nursery school absence attributable to varicella infection. RESULTS: During the one month preceding a period of two weeks before the initial case at Nursery school B, there were 16 cases of varicella infection in nursery schools, 45 cases in elementary schools, and one case in junior high schools in City A. For children who had received one vaccine dose or more, VE was 48.1% for all ages and 49.2% among children three years old and older. No significant VE against infection was found. Vaccination using one dose or more can reduce severity significantly. DISCUSSION AND CONCLUSION: Because many nursery school children who had received two doses of vaccine were infected, VE was estimated as low in the nursery school and not significant. Although VE for severity with more than one dose was confirmed, a second dose might not reduce severity compared to one dose.

UK healthcare professionals' attitudes towards the introduction of varicella vaccine into the routine childhood vaccination schedule and their preferences for administration.

BACKGROUND: 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. OBJECTIVES: 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. DESIGN: 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. PARTICIPANTS: 91 HCPs working in the UK (81 % nurses/health visitors, 9 % doctors, 10 % researcher/other, mean age 48.7 years). RESULTS: 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. CONCLUSIONS: 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.

Nanopore sequencing in distinguishing between wild-type and vaccine strains of Varicella-Zoster virus.

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

Live vaccinations in dermatology for immunosuppressed patients: a narrative review.

Given the higher susceptibility to infectious disease in patients receiving immunosuppressive therapies for inflammatory dermatologic conditions, immunization is important in this population. While live vaccines protect against life-threatening diseases, they can be harmful in immunosuppressed patients given the risk of replication of the attenuated pathogen and adverse reactions. The utilization of live vaccines in immunosuppressed patients depends on multiple factors such as the vaccine and therapy regimen. To provide an overview of evidence-based recommendations for the use of live vaccines in patients receiving immunosuppressive therapies for dermatological conditions. A literature search of the PubMed database was performed using keywords live vaccine, live-attenuated vaccine, dermatology, immunosuppressed, and immunocompromised, and specific immunosuppressive therapies: corticosteroids, glucocorticoids, methotrexate, azathioprine, cyclosporine, mycophenolate mofetil, biologics. Relevant articles written in English were included. Using these keywords, 125 articles were reviewed, of which 28 were ultimately selected. Recommendations for live vaccines can be determined on a case-by-case basis. Measles, mumps, rubella, varicella (MMRV) vaccines may be safely administered to patients on low-dose immunosuppressive agents while the yellow fever vaccine is typically contraindicated. It may be safe to administer live MMRV boosters to children on immunosuppressive therapies and the live herpes zoster vaccine to patients on biologics. Given poor adherence to immunization guidelines in immunosuppressed patients, dermatologists have a critical role in educating patients and general practitioners regarding live vaccines. By reviewing a patient's vaccination history and following immunization guidelines prior to initiating immunosuppressive therapies, physicians can mitigate morbidity and mortality from vaccine-preventable diseases.

Burden of chickenpox complications in Poland, 2006 to 2021: A comprehensive registry-based study.

BackgroundChickenpox, a vaccine-preventable disease caused by the varicella zoster virus, generally presents with mild symptoms but can cause complications necessitating hospitalisation. In Poland, since 2009, vaccination has been obligatory for children up to 12 years of age who are particularly vulnerable to infection and for children in their vicinity.AimTo examine the burden of chickenpox complications and the trends of hospitalisation arising from these complications over time in the Polish population.MethodsData spanning 2006-21 were sourced from the Polish Infectious Diseases Surveillance System, the Nationwide General Hospital Morbidity Study and the Statistics Poland death registry. Standardised and age-specific incidence rates, hospital discharge rates and number of deaths because of chickenpox were calculated. Moreover, the joinpoint regression model was used to analyse trends of annual hospital discharge rates.ResultsOver the analysed timeframe, 25,804 hospitalisations and 52 deaths attributable to chickenpox complications were documented, and 1.0% of chickenpox cases required hospitalisation because of chickenpox. Age-standardised hospitalisation rates varied between 2.3 and 9.6 per 100,000 population. The analysis revealed no statistically significant trend in overall hospital discharge rates from chickenpox complications. However, a notable increase in hospitalisation rates was observed in children aged 0-4 and among inhabitants of rural areas, with annual percentage changes of 4.9% and 3.4% respectively.ConclusionsOur findings suggest that the implementation of a universal chickenpox immunisation programme, supported by health education, should be considered to reduce the number of hospitalisations and nearly eliminate deaths because of chickenpox.

Expanded spectrum of varicella disease and the need for vaccination in India.

Varicella vaccine was first licensed in Japan and South Korea in 1989 for use in healthy children and was introduced in US in 1995. So far, 29 countries have adopted varicella vaccine in their universal immunization program (UIP). No Asian country, India included, has adopted the varicella vaccine as part of their UIP. The extra-cutaneous sites for VZV diseases are central nervous system and gastrointestinal tract, the expanded disease spectrum includes vasculopathy, myelitis, inflammatory bowel disease, perforated ulcers, and gastritis. The actual disease burden of varicella is not known as most of the infected individuals may not visit the physician. The amplifiable VZV DNA will not always be detectable in cerebrospinal fluid (CSF) samples in protracted illnesses such as vasculopathies, but demonstrable anti-VZV IgG in CSF has diagnostic value. The World Health Organization (WHO) position paper 2014 recommends two doses of varicella and zoster vaccines in targeted population. In India, varicella vaccine is not included in the UIP due to the cost and the belief that lifelong immunity occurs following primary infection. The expanded spectrum of VZV disease and the mounting body of evidence, however, suggest the need for both varicella and zoster vaccines in routine immunization schedule.

A case series of live attenuated vaccine administration in dupilumab-treated children with atopic dermatitis.

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.

Effectiveness of the combined MMRV Priorix-Tetra™ vaccine against varicella in a large Italian region: A case-control study.

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.

A retrospective cohort study evaluating the incidence of herpes zoster and postherpetic neuralgia after a live attenuated Oka-strain herpes zoster vaccine in a real-world setting in Japan.

BACKGROUND: In Japan, freeze-dried live attenuated Oka-strain varicella-zoster virus vaccine, VVL (BIKEN), is available for adults aged ≥50 years to prevent herpes zoster (HZ). Although an increase in the antibody titer and cellular immune response has been demonstrated following vaccination with VVL (BIKEN), to date, no clinical studies have shown that the vaccine decreases the incidence of HZ and postherpetic neuralgia (PHN). This study investigated the incidence of HZ and PHN among adults aged ≥50 years who received a single dose of VVL (BIKEN) to prevent HZ. METHODS: This retrospective cohort study investigated the incidence of HZ and PHN among adults aged ≥50 years who received a single dose of VVL (BIKEN) at a large hospital and affiliated clinics in Japan. A dispensing database and electronic medical records were used to identify vaccine recipients and cases of HZ and PHN. The end date of the follow-up period and the reason to end the follow-up were defined to avoid underestimating the incidence. The analysis was stratified according to age, sex, immunocompromising conditions, and use of immunosuppressant therapy. Vaccine effectiveness was estimated using published estimates of the incidence of HZ and PHN in the unvaccinated population in Japan. RESULTS: A total of 1175 patients were enrolled in the study. During a median follow-up period of 3.36 years, HZ was diagnosed in 27 participants (15 men [2.8%] and 12 women [1.9%]). The incidence of HZ among VVL (BIKEN) recipients was 7.67/1000 person-years. The incidence of PHN was 0.82/1000 person-years. The vaccine effectiveness was estimated as 27.8% [95% confidence interval (CI), -29.8 to 63.9%] and 73.8% [95% CI, 38.6-100%] against HZ and PHN, respectively. CONCLUSIONS: The VVL (BIKEN) had limited effectiveness at preventing HZ, but relatively good effectiveness at preventing PHN. VVL (BIKEN) might have a role as an affordable alternative.

Immunogenicity and safety of a live-attenuated varicella vaccine in a healthy population aged 13 years and older: A randomized, double-blind, controlled study.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Parental perceptions of chickenpox and the varicella vaccine: A qualitative systematic review.

BACKGROUND: 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. OBJECTIVE: To examine parental perceptions of chickenpox and varicella vaccination, which may be crucial to effective vaccination campaigns. DESIGN: Qualitative systematic review and thematic analysis. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. REGISTRATION: The review was registered on PROSPERO, registration ID CRD42021236120.

Progressive shingles in a toddler due to reactivation of Varicella Zoster vaccine virus four days after infection with SARS-CoV-2; a case report.

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.

Case report: Hospital-acquired chickenpox in a healthcare setting.

Chickenpox (varicella) is a rare occurrence in healthcare settings in the USA, but can be transmitted to healthcare workers (HCWs) from patients with herpes zoster who, in turn, can potentially transmit it further to unimmunized, immunosuppressed, at-risk, vulnerable patients. It is uncommon due to the inclusion of varicella vaccination in the recommended immunization schedule for children and screening for varicella immunity in HCWs during employment. We present a case report of hospital-acquired chickenpox in a patient who developed the infection during his prolonged hospital stay through a HCW who had contracted chickenpox after exposure to our patient's roommate with herpes zoster. There was no physical contact between the roommates, but both patients had a common HCW as caregiver. The herpes zoster patient was placed in airborne precautions immediately, but the HCW continued to work and have physical contact with our patient. The HCW initially developed chickenpox 18 days after exposure to the patient with herpes zoster, and our patient developed chickenpox 17 days after the HCW. The timeline and two incubation periods, prior to our patient developing chickenpox, indicate transmission of chickenpox in the HCW from exposure to the herpes zoster patient and subsequently to our patient. The case highlights the potential for nosocomial transmission of chickenpox (varicella) to unimmunized HCWs from exposure to patients with herpes zoster and further transmission to unimmunized patients. Verification of the immunization status of HCWs at the time of employment, mandating immunity, furloughing unimmunized staff after exposure to herpes zoster, and postexposure prophylaxis with vaccination or varicella zoster immunoglobulin (Varizig) will minimize the risk of transmission of communicable diseases like chickenpox in healthcare settings. Additionally, establishing patients' immunity, heightened vigilance and early identification of herpes zoster in hospitalized patients, and initiation of appropriate infection control immediately will further prevent such occurrences and improve patient safety.This is a case report of a varicella-unimmunized 31-year-old patient who developed chickenpox during his 80-day-long hospitalization. He had different roommates during his long hospital stay but had no physical contact with them and neither had visitors. On most days, the same HCW rendered care to him and his roommates. One of the patient's roommates was found to have herpes zoster and was immediately moved to a different room with appropriate infection prevention measures. The HCW is presumably unimmunized to varicella and sustained significant exposure to the patient with herpes zoster during routine patient care which involved significant physical contact. The HCW was not furloughed, assessed for immunity, or given postexposure prophylaxis (PEP). The HCW had continued contact with our patient as part of routine care. On day 18, after exposure to the patient with herpes zoster, the HCW developed chickenpox. 17 days thereafter, our patient developed chickenpox. The time interval of chickenpox infection in the HCW after one incubation period after exposure to the patient with herpes zoster followed by a similar infection of chickenpox in our patient after another incubation period suggests the spread of varicella zoster virus (VZV) from the herpes zoster patient to the HCW and further from the HCW to our patient. Assessing the immunity of HCWs to varicella at the time of employment, ensuring only HCWs with immunity take care of herpes zoster and varicella patients, furloughing unimmunized exposed HCWs, offering PEP, and documentation of patients' immunity to varicella at the time of hospital admission could help prevent VZV transmission in hospital settings. This is an attempt to publish this novel case due to its high educational value and relevant learning points.

Assessing the impact of chickenpox and shingles vaccination using intermittent enhanced surveillance in Queensland, Australia.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Maternal varicella antibodies in children aged less than one year: Assessment of antibody decay.

OBJECTIVES: To investigate maternal antibody levels to varicella in infants <12 months of age in Ontario, Canada. STUDY DESIGN: In this study, we included specimens from infants <12 months of age, born at ≥37 weeks gestational age, who had sera collected at The Hospital for Sick Children (Toronto, Canada) between 2014-2016. We tested sera using a glycoprotein-based enzyme-linked immunosorbent assay (gpELISA). We measured varicella susceptibility (antibody concentration <150mIU/mL) and mean varicella antibody concentration, and assessed the probability of susceptibility and concentration between one and 11 months of age using multivariable logistic regression and Poisson regression. RESULTS: We found that 32% of 196 included specimens represented infants susceptible to varicella at one month of age, increasing to nearly 80% at three months of age. At six months of age, all infants were susceptible to varicella and the predicted mean varicella antibody concentration declined to 62 mIU/mL (95% confidence interval 40, 84), well below the threshold of protection. CONCLUSIONS: We found that varicella maternal antibody levels wane rapidly in infants, leaving most infants susceptible by four months of age. Our findings have implications for the timing of first dose of varicella-containing vaccine, infection control measures, and infant post-exposure prophylaxis recommendations.

Adding new childhood vaccines to China's National Immunization Program: evidence, benefits, and priorities.

China's National Immunization Program has made remarkable achievements but does not include several important childhood vaccines that are readily available in the private market, such as pneumococcal conjugate vaccine (PCV), rotavirus vaccine, Haemophilus influenzae serotype b (Hib) vaccine, and varicella vaccine. We reviewed the literature to assess these four non-National Immunization Program vaccines in terms of their disease burdens, coverage, inequalities, and cost-effectiveness in China and aimed to recommend priorities for introducing them to the National Immunization Program. Based on our calculations using the available evidence, incorporating these vaccines into China's National Immunization Program in 2019 could have averted 11 761 deaths among children younger than 5 years, accounting for 10·29% of the total deaths in children younger than 5 years and reducing the mortality rate from 7·8 per 1000 to 7·0 per 1000. The review showed that 13-valent PCV (PCV13) had the lowest and most inequitable coverage but could prevent the highest number of deaths. In a budgetary analysis for the cohort of newborns in 2023, we estimated that the projected aggregate government costs were US$1954·92 million for PCV13, $1273·13 million for pentavalent rotavirus vaccine, $415·30 million for Hib vaccine, and $221·64 million for varicella vaccine. Our overall multicriteria decision analysis suggested the following priority order for introducing these four non-programme vaccines to the National Immunization Program to benefit the Chinese population: PCV13, rotavirus vaccine, Hib vaccine, and varicella vaccine.

The Epidemiology of Chickenpox in England, 2016-2022: An Observational Study Using General Practitioner Consultations.

Chickenpox is a common childhood disease caused by varicella-zoster virus (VZV). VZV vaccination is not part of the UK childhood immunisation programme, but its potential inclusion is regularly assessed. It is therefore important to understand the ongoing burden of VZV in the community to inform vaccine policy decisions. General practitioner (GP) chickenpox consultations were studied from 1 September 2016 to 9 December 2022. Over the study period, the mean weekly chickenpox consultation rate per 100,000 population in England was 3.4, with a regular peak occurring between weeks 13 and 15. Overall, rates decreased over time, from a mean weekly rate of 5.5 in 2017 to 4.2 in 2019. The highest mean weekly rates were among children aged 1-4 years. There was no typical epidemic peak during the COVID-19 pandemic, but in 2022, rates were proportionally higher among children aged < 1 year old compared to pre-pandemic years. Chickenpox GP consultation rates decreased in England, continuing a longer-term decline in the community. The COVID-19 pandemic impacted rates, likely caused by the introduction of non-pharmaceutical interventions to prevent SARS-CoV-2 transmission. The lasting impact of the interruption of typical disease transmission remains to be seen, but it is important to monitor the chickenpox burden to inform decisions on vaccine programmes.

Trends in age-specific varicella incidences following the introduction of the general recommendation for varicella immunization in Germany, 2006-2022.

BACKGROUND: In Germany, general childhood varicella vaccination has been recommended since 2004. A feared effect of low vaccination coverage is a possible shift in incidence from children to teenagers and young adults who are at higher risk of severe outcomes. If true, this shift would possibly necessitate changes to the national immunization strategy. We aimed to evaluate the effects of the general vaccination recommendation on age-specific varicella incidences in Germany in general and examine specifically whether a shift from children to teenagers (15 to 19 years) has occurred. METHODS: Trends in age-specific incidences were evaluated using triangulation with the following datasets: national mandatory notification data (N) (2014-2022), billing data of the statutory health insurance associations (I) (2009-2017) and data from a doctor's sentinel system (S) (2006-2017). Similar clinical case definitions were used in N and S, while I used ICD-10-codes. Age groups were stratified as available in all three systems. Incidences per year were calculated based on the total population (N), the number of statutory health insured (I), and extrapolated from S to the total population. RESULTS: During all years of observation, age-specific incidences have dropped significantly across all age-groups for S und I. The age groups (under 10 years) with initially highest incidences were the ones with the strongest reductions (under 1 year: -90%, 1-4 years: -95.5%, 5-9 years: -89.2% for S; -67.7%, -78%, -79.3% for I). A single 53.1% increase in the low incidence in S among 15-19-year olds observed in 2017 compared to 2016 could not be confirmed in N or I. Increases in incidences during the first two years of N are probably due to improved notification behaviour over these years. In 2019, all age-specific incidences increased (N), with 15 to 19-year olds showing the highest relative increase (28.2%). CONCLUSIONS: Since the introduction of the general vaccine recommendation against varicella, incidences across all age-groups have declined significantly. Available data indicate no evidence for a shift in disease incidence to older age groups. Every incidence increase beyond childhood age should however be followed up closely. So far, children and adolescents have both benefitted from the current vaccination strategy.

Safety and Immunogenicity of Live Viral Vaccines in a Multicenter Cohort of Pediatric Transplant Recipients.

Importance: Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions. Objective: To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients. Design, Setting, and Participants: This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody levels at enrollment between January 1, 2002, and February 28, 2023. Eligibility for live vaccine was determined by individual US pediatric solid organ transplant center protocols. Exposures: Exposure was defined as receipt of a posttransplant live vaccine. Transplant recipients received 1 to 3 doses of MMR vaccine and/or 1 to 3 doses of VZV vaccine. Main Outcome and Measure: Safety data were collected following each vaccination, and antibody levels were obtained at 0 to 3 months and 1 year following vaccination. Comparisons were performed using Mann-Whitney U test, and factors associated with development of postvaccination protective antibodies were explored using univariate analysis. Results: The cohort included 281 children (270 [96%] liver, 9 [3%] kidney, 2 [1%] liver-kidney recipients) from 18 centers. The median time from transplant to enrollment was 6.3 years (IQR, 3.4-11.1 years). The median age at first posttransplant vaccine was 8.9 years (IQR, 4.7-13.8 years). A total of 202 of 275 (73%) children were receiving low-level monotherapy immunosuppression at the time of vaccination. The majority of children developed protective antibodies following vaccination (107 of 149 [72%] varicella, 130 of 152 [86%] measles, 100 of 120 [83%] mumps, and 124 of 125 [99%] rubella). One year post vaccination, the majority of children who initially mounted protective antibodies maintained this protection (34 of 44 [77%] varicella, 45 of 49 [92%] measles, 35 of 42 [83%] mumps, 51 of 54 [94%] rubella). Five children developed clinical varicella, all of which resolved within 1 week. There were no cases of measles or rubella and no episodes of graft rejection within 1 month of vaccination. There was no association between antibody response and immunosuppression level at the time of vaccination. Conclusions and Relevance: The findings suggest that live vaccinations may be safe and immunogenic after solid organ transplant in select pediatric recipients and can offer protection against circulating measles, mumps, and varicella.