Effectiveness of two-dose vs. one-dose varicella vaccine in children in Shanghai, China: a prospective cohort study.

Objective: Varicella, a highly contagious viral disease caused by the varicella-zoster virus (VZV), affects millions globally, with a higher prevalence among children. After the initial infection, VZV lies dormant in sensory ganglia and has the potential to reactivate much later, causing herpes zoster (HZ). Vaccination is one of the most effective methods to prevent varicella, and the two-dose varicella vaccine (VarV) regimen is widely used around the world. In China, the VarV has been included in the national immunization programme with a recommended single-dose regimen. This study aimed to compare the effectiveness of the two-dose vs. one-dose VarV regimen in children in Shanghai, China. Materials and methods: A prospective cohort study was conducted in Shanghai, China, from September 2018 to December 2022. The study enrolled children aged 3-18 years who had received either the one-dose, two-dose, or 0-dose VarV regimen. Vaccination history, varicella infection status, and relevant variables, including demographic information (name, date of birth and sex) and medical history (clinical features of varicella and illness duration) were collected through medical record review and parental interviews. Results: A total of 3,838 children were included in the study, with 407 in the 0-dose regimen group, 2,107 in the one-dose regimen group and 1,324 in the two-dose regimen group. The corresponding incidence density in these groups was 0.13, 0.05 and 0.03 cases per 1,000 person-days, respectively. The adjusted vaccine effectiveness (VE) was 81.7% (95%CI: 59.3-91.8%) for the two-dose regimen and 60.3% (95%CI: 29.3-77.7%) for the one-dose regimen, compared to the 0-dose regimen. The two-dose VarV regimen showed a protective effectiveness of 47.6% (95%CI: 2.5-71.9%) compared to the one-dose VarV regimen. Conclusion: This study provides evidence supporting the greater effectiveness of the two-dose VarV regimen in preventing varicella infection compared to the one-dose regimen.

Assessment of the Level of Knowledge and Attitude Towards Herpes Zoster and Its Vaccination Among Individuals at Risk in Saudi Arabia.

Background Herpes zoster (HZ) is a viral infection resulting from the reactivation of the varicella-zoster virus. The vaccination was proven to prevent herpes zoster and its complications for individuals over the age of 50 since they are more susceptible to herpes zoster infection. Therefore, it is essential to understand and acknowledge the herpes zoster infection and vaccine. This study aims to assess the level of knowledge and attitude towards herpes zoster and its vaccination among individuals at risk in Saudi Arabia. Methods A cross-sectional study was conducted between February 2023 and June 2023 among the general population in Saudi Arabia, using a self-administered online questionnaire adapted from a previous study after translating it into Arabic. Results A total of 1883 participants were included in this study, almost equally distributed across the five regions of Saudi Arabia. Females represented 62.4% (n=1175), and 56% (n=1062) of participants reported a positive history of chickenpox, while 3.6% (n=67) reported a history of herpes zoster. Furthermore, 78.9% (n=1486) have heard of herpes zoster, while 68.8% (n=1296) have at least one of the herpes zoster risk factors. Only 7.8% (n=147) had high knowledge about HZ, and only 3.1% (n=58) had adequate knowledge regarding the HZ vaccine. Conclusion Our study findings show that the general population of Saudi Arabia has inadequate knowledge about herpes zoster and its vaccine. For that reason, awareness and education programs targeting individuals at high risk of herpes zoster are required to enhance awareness and knowledge about herpes zoster and to improve their attitudes toward the herpes zoster vaccination.

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.

[Varicella vaccination, pregnancy and breastfeeding: The current situation]. / Vaccination contre la varicelle, grossesse et allaitement : un état des lieux.

The varicella vaccine is recommended for women with no history of varicella who are planning to become pregnant, as well as for post-pregnancy women, to prevent the occurrence of this illness and its severe complications, especially an embryopathy, when it occurs in a pregnant woman (congenital varicella syndrome). This live attenuated vaccine should not be administered during pregnancy, nor in the month preceding it. However, when this occurs inadvertently, the data collected on the outcomes of exposed pregnancies, although few in women seronegative at the time of vaccination, allow to reassure the patients to date, as no congenital varicella syndrome has been reported to date following accidental vaccination in early pregnancy. On the other hand, during breastfeeding, a woman may be vaccinated if there is an expected short- or medium-term benefit (varicella exposure, planned pregnancy…).

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.

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.

Knowledge, perception, and practice of Libyan mothers towards varicella and its vaccination Tripoli, Libya

This study was conducted to ascertain the level of knowledge, perception and practice towards chickenpox infection and its vaccination and to find out the relationship of knowledge to some of related characteristics of the mothers and their children. A cross sectional study was conducted among Libyan mothers in Albadri polyclinic the east district of Tripoli. Data analysis was performed using the SPSS version 26. A total of 204 Libyan mothers attending Albadri polyclinic participated in the study their mean age was 32.06 (± 7.664) years. Most of the respondents (95.6%) had heard about chickenpox and (84%) stated correctly about its mode of transmission. Majority were well aware of the signs and symptoms of the infection, (51%) of the respondents knew about chickenpox vaccination, and only (43.1%) have been known that the vaccine was available in Libya. Concerning perception (81.4%) of respondents had negative perception about their child might get chickenpox. (80.9%) of the respondents were agree about their believing that chickenpox is serious disease and only 12.3% respondents believed that vaccine was effective, (77.9%) of respondents had negative perception about safety of vaccine. Concerning practice approximately (80%) of the respondents had vaccinated or had intension for vaccination their children against chickenpox. The current study indicated considerable knowledge levels and practice on varicella disease and its vaccination were observed among Libyan mothers. Addressing concerns regarding vaccine effectiveness, safety and importance through educational campaigns to ensure that all mothers are informed of the availability and benefits of the varicella vaccine

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.

Explore the optimal timing for administering the second dose of the varicella vaccine in China.

The prevalence of varicella in China has been increasing annually, with a relatively high incidence rate of breakthrough cases. Administering two doses of the varicella vaccine (Varv) proves to be the most effective measure. The objective of this study is to assess the immunogenicity of two doses of the Varv at varying intervals and explore the optimal timing for administering the second dose of the Varv. Utilizing a prospective cohort study design, the quantification of varicella immunoglobulin G (IgG) antibodies' geometric mean concentrations (GMC) is conducted through glycoprotein-based enzyme-linked immunosorbent assay (gpELISA). A total of 903 infants were included in the per-protocol population. After completing the first dose of the Varv, the GMC of antibody after 1 month (Group A) was 463.8 (447.6-480.1) mIU/mL. There was a statistically significant difference in GMC and seroconversion rates among the groups (B/C/D) that received the second dose of the Varv (p < 0.05). Multiple comparisons revealed that the group with a 3-year interval between the two vaccine doses had a higher GMC of 665.2 (622.6-707.8) mIU/mL compared to the group with a 1-year interval of 611.1 (577.1-645.3) mIU/mL and the group with a 5-year interval of 564.7 (540.1-589.4) mIU/mL. To effectively prevent and control the varicella epidemic in Jiangsu Province, two dose Varv vaccination is recommended, the optimal time point for the second dose Varv is 3 years after the first vaccination.

Combined measles-mumps-rubella-varicella vaccine and febrile convulsions: the risk considered in the broad context.

INTRODUCTION: Studies on quadrivalent measles, mumps, rubella, and varicella (MMRV) vaccines have indicated a twofold increased relative risk of febrile convulsion (FC) after the first dose compared to MMR and V administered at the same medical visit (MMR+V). AREAS COVERED: This narrative review contextualizes FC occurrence after the first MMRV vaccine dose from a clinical perspective and outlines approaches to attenuate FC occurrence post-vaccination. EXPERT OPINION: While the relative FC risk increases after the first dose of MMRV compared to MMR+V vaccine in measles-naïve infants, the attributable risk is low versus the overall FC risk in the pediatric population triggered by other causes, like natural exposure to pathogens or routine vaccination. No increased risk of FC has been reported after MMRV co-administration with other routine vaccines compared to MMRV alone. Based on our findings and considering the MMRV vaccination benefits (fewer injections, higher coverage, better vaccination compliance), the overall benefit-risk profile of MMRV vaccine is considered to remain positive. Potential occurrence of FC in predisposed children (e.g. with personal/family history of FC) may be attenuated if they receive MMR+V instead of MMRV as the first dose. It is also important to monitor vaccinees for fever during the first 2 weeks post-vaccination.

Children under 5 years of age can sometimes have convulsions when they get a fever during illness or after vaccination. These are called febrile convulsions, and, in most cases, they leave no lasting damage, and the child outgrows them. After a combined vaccine against four childhood illnesses (measles, mumps, rubella, and varicella) became available, concerns appeared that measles-naïve children who received a first dose of this vaccine had a higher risk of febrile convulsions than children vaccinated with two separate vaccines (one against measles, mumps, and rubella, and one against varicella) administered during the same medical visit. However, this risk is low: during the first or the second week after the first vaccine dose, 1 additional child out of approximately 2500 children who receive the combined vaccine will have a febrile convulsion compared to those receiving 2 separate vaccines. In comparison, febrile convulsions due to any cause will appear in 1 out of 25 children younger than 5 years, and in 1 out of 43 children with measles. The combined vaccine has certain advantages over separate vaccines: children receive fewer injections and are more likely to be fully vaccinated against all four diseases. Children who had febrile convulsions before, or with a close relative who had febrile convulsions could be at higher risk of febrile convulsions after the first dose of the combined vaccine. Provided the informed consent from their parents or legal guardians, these children must receive separate vaccines, while all other children may receive the combined vaccine.

Varicella vaccine meningoencephalitis in a child receiving autologous bone marrow transplantation.

BACKGROUND: Varicella vaccine, a live-attenuated Oka-strain of varicella zoster virus (VZV), is a recommended childhood vaccine by many countries. As with wild varicella strain, after primary infection, the live-attenuated virus can establish latency in sensory ganglia and reactivate causing vaccine-strain illnesses: herpes zoster (HZ), visceral or peripheral and central nervous system dissemination. We report a case of early reactivation of live-attenuated virus-HZ and meningoencephalitis-in an immunocompromised child. METHODS: This is a retrospective descriptive report of a case, in a tertiary pediatric hospital, CHU Sainte-Justine (Montréal, Canada). RESULTS: An 18 month-year old girl diagnosed with a primitive neuro-ectodermal tumor (PNET) received the day prior to diagnosis, a first varicella vaccine (MMRV). She received chemotherapy 20 days post MMRV vaccine and autologous bone marrow transplantation 3 months post vaccination. She was considered not eligible, to acyclovir prophylaxis prior transplantation (positive for VZV IgG and negative for herpes simplex virus IgG by ELISA). At day 1 post transplantation, she developed dermatomal HZ and meningoencephalitis. Oka-strain varicella was isolated, she was treated with acyclovir and foscarnet. Neurologic status improved in 5 days. Control of VZV viral load in cerebrospinal fluid showed a slow decrease to from 5.24 log 10 copies/mL to 2.14 log 10 copies/mL in 6 weeks. No relapse was observed. She recovered without neurological sequelae. CONCLUSIONS: Our experience highlights the importance of conducting a thorough medical history regarding vaccination and serological status of newly immunocompromised patients. Intensive chemotherapy succeeding live vaccine administration <4 weeks could have influenced early and severe viral reactivation. Early initiation of prophylactic antiviral treatment is questioned in such circumstances.

Impact of implementing a free varicella vaccination policy on incidence in Wuxi City, China: an interrupted time series analysis.

Varicella vaccination is optional and requires self-payment. On 1 December 2018, Wuxi City launched a free varicella vaccination program for children. This study aimed to evaluate the changes in varicella incidence before and after the implementation of the policy. The data were obtained from official information systems and statistical yearbooks. We divided the period into chargeable (January 2017 to November 2018) and free (December 2018 to December 2021) periods. Interrupt time series analysis was used to conduct a generalised least-squares regression analysis for the two periods. A total of 51,071 varicella cases were reported between January 2017 and December 2021. After the implementation of the policy, there was a statistically significant decrease in the incidence of varicella (ß2 = -0.140, P = 0.017), and the slope of the incidence also decreased by 0.012 (P = 0.015). Following policy implementation, the incidence decreased in all age groups, with the largest decline observed among children aged 8-14 years (ß2 = -1.109, P = 0.009), followed by children aged ≤7 years (ß2 = -0.894, P = 0.013). Our study found a significant reduction in the incidence of varicella in the total population after the introduction of free varicella vaccination in Wuxi City.

Measles and Varicella Vaccination Program in a Hospital: Implementation and Impact on Contact Tracing.

Healthcare workers are recommended to get vaccinated against measles and varicella. This study aims to describe the implementation process of a measles and varicella vaccination program and report on the reduction in the number of susceptible healthcare workers exposed to measles, varicella, and disseminated herpes zoster at a tertiary hospital. The Consolidated Framework for Implementation Research (CFIR) model was used to describe the vaccination program implemented from October 2015 to September 2018. The number of exposed, reviewed, and susceptible healthcare workers during contact tracing for exposure to (a) measles and (b) varicella and disseminated herpes zoster in 2016, 2017, and 2018 is reported. A total of 6770 (95%) out of 7083 healthcare workers completed their immunization review by 2018. In 2016, 20 (10%) out of 198 healthcare workers exposed to measles were considered susceptible. In 2018, no one was found susceptible out of the 51 staff members exposed to measles (p < 0.01). For exposure to varicella and disseminated herpes zoster, seven (5%) out of 154 exposed healthcare workers were susceptible in 2016. In comparison, only two (1%) out of 377 exposed healthcare workers in 2018 were susceptible (p < 0.01). The vaccination program effectively reduced number of healthcare workers susceptible to measles, varicella, and disseminated zoster.

Disseminated vaccine-induced varicella infection in a kidney transplant recipient.

A 33-year-old kidney transplant (KT) recipient presented with a disseminated pruritic, painful, vesicular rash and hepatitis 3 weeks after receiving a varicella vaccine (VAR). A skin lesion biopsy sent to the Centers for Disease Control and Prevention for genotyping confirmed vaccine-strain varicella-zoster virus (VZV) (Oka strain; vOka). The patient was successfully treated with intravenous acyclovir during a prolonged hospital stay. This case supports the contraindication of VAR in adult KT recipients and highlights the potential for severe illness when used in this population. Optimally, VZV-seronegative KT candidates should receive VAR before starting immunosuppressive medications. If this opportunity is missed, the recombinant varicella-zoster vaccine might be considered following transplantation as it is already recommended to prevent herpes zoster in VZV-seropositive immunocompromised adults. Further study is needed as data are limited on the safety and efficacy of recombinant varicella-zoster vaccine for primary varicella prevention in VZV-seronegative immunocompromised adults.

Seroprevalence rates in children aged 3-6 years after implementing a two-dose varicella vaccination: A observational study.

The study evaluates the outcomes of including varicella vaccines (VarV) in the local expanded programme on immunization (EPI) on the seropositivity rates and corresponding protective effects for children aged 3-6 years in Suzhou. The study is observational. Varicella prevalence in children was assessed based on data from the China Information System for Disease Control and Prevention (CISDCP) and the Jiangsu Province Vaccination Integrated Service Management Information System (JPVISMIS). Seropositivity was determined using the enzyme-linked immunosorbent assay (ELISA). A total of 2,873 children aged 3-6 years were enrolled in this study. The seropositivity rates were 95.31% and 86.89% for children with and without the strategy, respectively. The difference in seropositivity rate in children using the different strategies was statistically significant (Trend χ2 = 0.397, P = .255). It is therefore suggested that Suzhou had a high rate of occult infection before the inclusion of varicella vaccine in the EPI. The difference in seroprevalence rate between children with no history of varicella vaccination and those with a history of varicella vaccination was statistically different (χ2 = 51.362, P < .001). The positive rates of antibodies increased with increasing doses of vaccination (χ2 = 56.252, P < .001). For the protective effect of one-dose and two-dose, it was found that the protection rates of one-dose were 72.98% and 100.00%, respectively. The varicella vaccine is an effective method to prevent varicella disease, which can increase serum seroprevalence levels and block the transmission of varicella disease.

Meningitis without Rash after Reactivation of Varicella Vaccine Strain in a 12-Year-Old Immunocompetent Boy.

Acute neurologic complications from Varicella-Zoster-Virus reactivation occur in both immunocompromised and immunocompetent patients. In this report, we describe a case of a previously healthy immunocompetent boy who had received two doses of varicella vaccine at 1 and 4 years. At the age of 12 he developed acute aseptic meningitis caused by vaccine-type varicella-zoster-virus without concomitant skin eruptions. VZV-vaccine strain DNA was detected in the cerebrospinal fluid. The patient made a full recovery after receiving intravenous acyclovir therapy. This disease course documents another case of a VZV vaccine-associated meningitis without development of a rash, i.e., a form of VZV infection manifesting as "zoster sine herpete".

Safety of measles, mumps, and rubella vaccine in adolescents and adults in the vaccine safety Datalink.

Background: Measles, mumps, and rubella vaccine (MMR) is routinely administered to children; however, adolescents and adults may receive MMR for various reasons. Safety studies in adolescents and adults are limited. We report on safety of MMR in this age group in the Vaccine Safety Datalink. Methods: We included adolescents (aged 9-17 years) and adults (aged ≥ 18 years) who received ≥ 1 dose of MMR from January 1, 2010-December 31, 2018. Pre-specified outcomes were identified by diagnosis codes. Clinically serious outcomes included anaphylaxis, encephalitis/myelitis, Guillain-Barré syndrome, immune thrombocytopenia, meningitis, and seizure. Non-serious outcomes were allergic reaction, arthropathy, fever, injection site reaction, lymphadenopathy, non-specific reaction, parotitis, rash, and syncope. All serious outcomes underwent medical record review. Outcome-specific incidence was calculated in pre-defined post-vaccination windows. A self-controlled risk interval design was used to determine the relative risk of each outcome in a risk window after vaccination compared to a more distal control window. Results: During the study period, 276,327 MMR doses were administered to adolescents and adults. Mean age of vaccinees was 34.8 years; 65.8 % were female; 53.2 % of doses were administered simultaneously with ≥ 1 other vaccine. Serious outcomes were rare, with incidence ≤ 6 per 100,000 doses for each outcome assessed, and none had a significant elevation in incidence during the risk window compared to the control window. Incidence of non-serious outcomes per 100,000 doses ranged from 3.4 for parotitis to 263.0 for arthropathy. Other common outcomes included injection site reaction and rash (157.0 and 112.9 per 100,000 doses, respectively). Significantly more outcomes were observed during the risk window compared to the control window for all non-serious outcomes except parotitis. Some variability was observed by sex and age group. Conclusion: Serious outcomes after MMR are rare in adolescents and adults, but vaccinees should be counseled regarding anticipated local and systemic non-serious adverse events.

National and provincial burden of varicella disease and cost-effectiveness of childhood varicella vaccination in China from 2019 to 2049: a modelling analysis.

Background: In China, varicella is the third most frequently reported vaccine-preventable infectious disease after tuberculosis and influenza, and imposes a heavy burden on families and society. To inform future immunization policy, we investigated disease burden of varicella in China and explored cost-effectiveness of different varicella vaccination strategies at national and provincial levels. Methods: A dynamic transmission model was developed to assess disease burden of varicella and the impact of varicella vaccination in China. A cost-effectiveness analysis of three alternative vaccination strategies in China's National Immunization Program (NIP) compared with no vaccination was conducted. Scenario analyses and sensitivity analyses were performed to check the robustness of the results. Findings: It was estimated that 3.35 million new varicella cases occurred in 2019, more than three times of 982 thousand cases officially reported from National Notifiable Infectious Disease Surveillance System (NNIDSS). The under-reported rate was approximately 71%. The economic analysis revealed that from the societal perspective, the incremental cost-effectiveness ratio (ICER) for one dose of varicella vaccination in NIP was US$ 2357 per QALY at the national level and it was cost-effective in 22 of 31 provinces. The ICER for one dose varicella vaccination plus a mass catch-up for unvaccinated children aged 2-11 years old would be US$ -5260 per QALY, cost-saving at the national level. The one dose plus mass catch-up NIP strategy was also cost-saving in 24 of the 31 provinces. Interpretation: Varicella incident cases were substantially under-reported in China. Varicella vaccination in the NIP could significantly contribute to reducing the burden of varicella disease. From the societal perspective, including varicella vaccination into China's NIP was highly cost-effective at the national level and in most provinces. Funding: Bill & Melinda Gates Foundation.

Anti-varicella-zoster virus antibody titers and seroprotection status from before the first dose of varicella vaccination to before entering elementary school in one region in Japan.

OBJECTIVE: We aimed to examine changes in anti-varicella-zoster virus (VZV) antibody titers and seroprotection status from before the first dose of vaccination to before 7 years old entering elementary school in children who received the routine two-dose varicella vaccination. METHODS: Participants were 37 healthy children who received the routine two-dose varicella vaccination at our hospital. A total of five serum samples per child were collected immediately before and 4-6 weeks after each dose of the vaccination and in the year before entry to elementary school. We measured anti-VZV antibody titers by immune adherence hemagglutination (IAHA) method and glycoprotein-based enzyme-linked immunosorbent assay (gpELISA). A positive antibody titer and the seroprotection level were set as ≥2-fold and ≥16-fold, respectively, for IAHA antibody and as ≥50 units and ≥105 units, respectively, for gpELISA-IgG antibody. RESULTS: The rates of IAHA antibody positivity in the five samples (in order of collection) were 0%, 65%, 38%, 100%, and 59%, and the rates of seroprotection were 0%, 43%, 8%, 100%, and 43%. The rates of gpELISA-IgG antibody positivity were 8%, 81%, 89%, 100%, and 100%, and the rates of seroprotection were 5%, 54%, 70%, 100%, and 89%. The mean IAHA antibody titer and mean gpELISA-IgG antibody titer before entering elementary school were both lower than the respective titers obtained after the second vaccination (both p < 0.01). CONCLUSIONS: Routine two-dose varicella vaccination leads to good antibody production, but titers of acquired antibodies decrease before children enter elementary school.