Detection of viral RNA and DNA and immune response following administration of live attenuated measles and varicella vaccines in children with chronic liver disease.

Infections preventable by live virus vaccines are surging in the setting of decreased herd immunity. Many children with chronic liver diseases (CLDs) are unimmunized and at increased risk for infection due to guidelines recommending against live vaccines within 4 weeks pretransplant. This prospective study of 21 children with CLD and 13 healthy controls defined the timing of measles virus and varicella-zoster virus (VZV) RNA- and DNA-emia following vaccination and compared immune responses to measles and varicella vaccines in both groups. Measles virus RNA and VZV DNA real-time PCR were measured weekly following vaccination; measles virus RNA was undetectable in all by 14 days postvaccination, but VZV DNA, which can be managed with antivirals, was detected in 1 child in the CLD group at 21 days and 1 control at 28 days postvaccination. Humoral or cell-mediated vaccine response was 100% to measles virus and 94% to VZV in the CLD group postvaccination, whereas it was 100% to both vaccines in controls. Our pilot study suggests that both live vaccines can be safely and effectively administered up to 14 days prior to transplantation in children with CLD. We anticipate this will improve vaccination rates and thus decrease rates of vaccine-preventable infections in vulnerable children with CLD.

Common Features Between Stroke Following Varicella in Children and Stroke Following Herpes Zoster in Adults : Varicella-Zoster Virus in Trigeminal Ganglion.

The cerebral arteries are innervated by afferent fibers from the trigeminal ganglia. Varicella-zoster virus (VZV) frequently resides in the trigeminal ganglion. Reports of arterial ischemic stroke due to VZV cerebral vasculopathy in adults after herpes zoster have been described for decades. Reports of arterial ischemic stroke due to post-varicella cerebral arteriopathy in children have also been described for decades. One rationale for this review has been post-licensure studies that have shown an apparent protective effect from stroke in both adults who have received live zoster vaccine and children who have received live varicella vaccine. In this review, we define common features between stroke following varicella in children and stroke following herpes zoster in adults. The trigeminal ganglion and to a lesser extent the superior cervical ganglion are central to the stroke pathogenesis pathway because afferent fibers from these two ganglia provide the circuitry by which the virus can travel to the anterior and posterior circulations of the brain. Based on studies in pseudorabies virus (PRV) models, it is likely that VZV is carried to the cerebral arteries on a kinesin motor via gE, gI and the homolog of PRV US9. The gE product is an essential VZV protein.

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

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

Varicella vaccine effectiveness evaluation in Wuxi, China: A retrospective cohort study.

Varicella is a vaccine-preventable infectious disease. Since 1 December 2018, the varicella vaccine has been included in the local Expanded Programme on Immunization (EPI) in Wuxi, China, and children born after 1 December 2014 are eligible for free vaccination. To evaluate the effect of varicella vaccination in Wuxi city, we selected 382 397 children born from 2012 to 2016 as subjects. Their disease data were obtained from the Chinese Disease Prevention and Control Information System, and their vaccination data were obtained from the Jiangsu Province Vaccination Integrated Service Management Information System. The incidence of breakthrough varicella cases increased in the first 4 years and reached the peak in the fifth year. With the increase of vaccination rate, the incidence of varicella decreased significantly. The vaccine effectiveness (VE) was found to be 88.17%-95.78% for one dose and 98.65%-99.93% for two doses. Although the VE per dose decreased from 99.57% in the first year to 93.04% in the eighth year, it remained high. These findings confirmed the effectiveness of varicella vaccination in children, supported the use of a two-dose varicella vaccination strategy to achieve better protection, and provided important insights into the optimal vaccination strategy for varicella prevention in children.

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.

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.

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.

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.

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.

No Consistent Evidence of Decreased Exposure to Varicella-Zoster Virus Among Older Adults in Countries with Universal Varicella Vaccination.

BACKGROUND: Universal varicella vaccination might reduce opportunities for varicella-zoster virus (VZV) exposure and protective immunological boosting, thus increasing herpes zoster incidence in latently infected adults. We assessed humoral and cell-mediated immunity (CMI), as markers of VZV exposure, in adults aged ≥50 years. METHODS: We repurposed data from placebo recipients in a large multinational clinical trial (ZOE-50). Countries were clustered based on their varicella vaccination program characteristics, as having high, moderate, or low VZV circulation. Anti-VZV antibody geometric mean concentrations, median frequencies of VZV-specific CD4 T cells, and percentages of individuals with increases in VZV-specific CD4 T-cell frequencies were compared across countries and clusters. Sensitivity analyses using a variable number of time points and different thresholds were performed for CMI data. RESULTS: VZV-specific humoral immunity from 17 countries (12 high, 2 moderate, 3 low circulation) varied significantly between countries (P < .0001) but not by VZV circulation. No significant differences were identified in VZV-specific CMI between participants from 2 high versus 1 low circulation country. In 3/5 sensitivity analyses, increases in CMI were more frequent in high VZV circulation countries (.03 ≤ P < .05). CONCLUSIONS: We found no consistent evidence of reduced VZV exposure among older adults in countries with universal varicella vaccination. CLINICAL TRIALS REGISTRATION: NCT01165177.

The Effectiveness of Varicella Vaccine: 25 Years of Postlicensure Experience in the United States.

We summarize studies of varicella vaccine's effectiveness for prevention of varicella and lessons learned during the first 25 years of the varicella vaccination program in the United States. One dose of varicella vaccine provided moderate protection (82%-85%) against varicella of any severity and high protection (100%) against severe varicella, with some waning of protection over time. The 1-dose program (1995-2006) had a substantial impact on the incidence both of varicella and of severe outcomes (71%-90% decrease) although it did not prevent low-level community transmission and some outbreaks continued to occur in highly vaccinated populations. Two doses of varicella vaccine improved the vaccine's effectiveness by at least 10% against varicella of any severity, with further declines in the incidence both of varicella and of severe outcomes as well as in both number and size of outbreaks. There is no evidence for waning of the effectiveness of 2 doses of the vaccine.

Safety Surveillance of Varicella Vaccines in the Vaccine Adverse Event Reporting System, United States, 2006-2020.

BACKGROUND: . The Vaccine Adverse Event Reporting System (VAERS) is the United States national passive vaccine safety surveillance system. We updated the data on the safety of single-antigen varicella vaccine (VAR) and assessed the safety of combination measles, mumps, rubella, and varicella vaccine (MMRV) licensed in the United States using VAERS data. METHODS: US VAERS reports received after administration of VAR and MMRV during 2006-2020 were identified. Reports were analyzed by vaccine type, age, seriousness, most common adverse events (AEs), and concomitant vaccines. We reviewed medical records of selected reports of AEs of special interest and conducted empirical Bayesian data mining to identify disproportionally reported AEs. RESULTS: During 2006-2020, approximately 132.8 million VAR doses were distributed; 40 684 reports were received in VAERS (30.6/100 000 doses distributed), with 4.1% classified as serious (1.3/100 000 doses distributed). Approximately 35.5 million MMRV doses were distributed; 13 325 reports were received (37.6/100 000 doses distributed) with 3.3% classified as serious (1.3/100 000 doses distributed). The most common adverse health events after both VAR and MMRV were injection site reactions (31% and 27%), rash (28% and 20%), and fever (12% and 14%), respectively. Vaccination errors accounted for 23% of reports after VAR administration and 41% after MMRV administration, but ≥95% of them did not describe an adverse health event. AEs associated with evidence of vaccine strain varicella-zoster virus (vVZV) infection included meningitis, encephalitis, herpes zoster, and 6 deaths (all in immunocompromised persons with contraindications for vaccination). No new or unexpected AE was disproportionally reported. CONCLUSIONS: No new or unexpected safety findings were detected for VAR and MMRV given as recommended, reinforcing the favorable safety profiles of these vaccines. Providers should obtain specimens for viral testing and strain-typing for serious AEs if they consider vVZV as the possible causative agent.

Health and Economic Impact of the United States Varicella Vaccination Program, 1996-2020.

BACKGROUND: The aim of this study was to evaluate the health and economic impact of the varicella vaccination program on varicella disease in the United States (US), 1996-2020. METHODS: Analysis was conducted using the Centers for Disease Control and Prevention or published annual population-based varicella incidence, and varicella-associated hospitalization, outpatient visit, and mortality rates in the US population aged 0-49 years during 1996-2020 (range, 199.5-214.2 million persons) compared to before vaccination (1990-1994). Disease costs were estimated using the societal perspective. Vaccination program costs included costs of vaccine, administration, postvaccination adverse events, and travel and work time lost to obtain vaccination. All costs were adjusted to 2020 US dollars using a 3% annual discount rate. The main outcome measures were the number of varicella-associated cases, hospitalizations, hospitalization days, and premature deaths prevented; life-years saved; and net societal savings from the US varicella vaccination program. RESULTS: Among US persons aged 0-49 years, during 1996-2020, it is estimated that more than 91 million varicella cases, 238 000 hospitalizations, 1.1 million hospitalization days, and almost 2000 deaths were prevented and 118 000 life-years were saved by the varicella vaccination program, at net societal savings of $23.4 billion. CONCLUSIONS: Varicella vaccination has resulted in substantial disease prevention and societal savings for the US over 25 years of program implementation.

Insights From Studies of the Genetics, Pathogenesis, and Immunogenicity of the Varicella Vaccine.

While the varicella vaccine was created with approaches established for other live attenuated viral vaccines, novel methods to probe virus-host interactions have been used to explore the genetics, pathogenesis, and immunogenicity of the vaccine compared to wild-type varicella-zoster virus (VZV). As summarized here, a mechanism-based understanding of the safety and efficacy of the varicella vaccine has been achieved through these investigations.

Clinical Manifestations of Varicella: Disease Is Largely Forgotten, but It's Not Gone.

After 25 years of varicella vaccination in the United States, classic varicella and its complications have become an uncommon occurrence. The clinical manifestation of varicella among vaccinated persons is usually modified, with fewer skin lesions, mostly maculopapular, and milder presentation. However, the potential for severe manifestations from varicella still exists among both vaccinated and unvaccinated persons, and thus healthcare providers should keep varicella in the differential diagnosis of a maculopapular or vesicular rash. The prompt recognition and diagnosis of varicella is important because when confirmed, clinical and public health measures need to be taken swiftly.

Randomised controlled trial showed long-term efficacy, immunogenicity and safety of varicella vaccines in Norwegian and Swedish children.

AIM: Several countries, such as Norway and Sweden, have not implemented universal varicella vaccination. We present data for Norway and Sweden that were generated by a paediatric multi-country Phase III study over a 10-year period. This assessed the efficacy, antibody persistence and safety of two varicella vaccines containing the same Oka strain. METHODS: This was an observer-blind, controlled trial conducted in 10 European countries. Children aged 12-22 months (n = 5803) were randomised 3:3:1 and vaccinated between 1 September 2005 and 10 May 2006. The two-dose group received two tetravalent measles-mumps-rubella-varicella vaccine doses. The one-dose group received one monovalent varicella vaccine dose after a measles-mumps-rubella vaccine dose. Control group participants received two measles-mumps-rubella vaccine doses. Main study outcomes were vaccine efficacy against confirmed varicella cases and incidence of adverse events. RESULTS: Vaccine efficacy in the two-dose group was ≥92.1% in both Norwegian and Swedish children compared to 72.3% in Norway and 58.0% in Sweden in the one-dose group. Incidences of adverse events and serious adverse events were similar in the Norwegian and Swedish study populations. CONCLUSION: Consistent with overall study results, high efficacy against varicella and acceptable safety profiles of the two varicella vaccines were observed in Norwegian and Swedish populations. These findings highlight the benefits of varicella vaccines, particularly when administered as a two-dose schedule.

Two-dose varicella vaccine effectiveness in China: a meta-analysis and evidence quality assessment.

BACKGROUND: The objectives of this review were to evaluate the vaccine effectiveness (VE) of the two-dose varicella vaccine for healthy children in China and explore the application of the approach of Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) in observational studies on VE. METHODS: We searched for observational studies on two-dose varicella VE for children in China aged 1-12 years that were published from 1997 to 2019, and assessed the quality of each study using the Newcastle Ottawa Scale (NOS). We used meta-analysis models to obtain the pooled two-dose VE, and the studies were divided into subgroups and analysed according to whether or not it was an outbreak investigation and its NOS score. The quality of evidence of VEs were rated by approach of the GRADE system. RESULTS: A total of 12 studies and 87,196 individuals were included. The pooled two-dose VE was 90% (95% confidence interval [CI]: 69-97%). The VE of outbreak studies (87% [95% CI: 76-93%]) was lower than non-outbreak studies (99% [95% CI: 98-99%]). There was no significant difference in VEs by different NOS quality. The quality of the evidence assessment of pooled two-dose VE was "low", which was rated down by one category in limitations and publication bias respectively and rated up by two category in large effect. The quality of evidence assessment in subgroup of NOS score ≥ 7 was "moderate". CONCLUSIONS: The VE of two-dose varicella vaccine is relatively high in preventing varicella, and is recommended for countries which need further control for varicella. However, higher quality evidence is needed as a supplement for stronger recommendations. The approach of GRADE could be applied for rating the quality of evidence in observational study.

Lack of persisting antibody in a post-transplant patient after vaccine-strain varicella.

BACKGROUND: LAVV have historically been avoided in children after solid organ transplantation. However, it has been reported that post-transplant, children without severe immunosuppression can generate anti-varicella antibody after immunization but the duration of the response is not clear. Furthermore, the origin of the varicella virus in immunosuppressed patients who develop varicella after vaccination is often unclear. CLINICAL PROGRESS: A female child received LAVV 30 months after a living donor liver transplant at the age of 2 months. Varicella rash appeared on the trunk 16 days after vaccination and gradually spread over the body. The patient was treated with intravenous acyclovir followed by oral therapy and recovered fully. The virus detected in blisters was derived from the vaccine-type strain. Paired sera before and after the onset of varicella showed an increase in antibody titer. However, 2 years after onset, the antibody titer decreased to undetectable again. CONCLUSIONS: This was an informative case of varicella due to vaccine strain attenuated virus. Antibody levels were not maintained over many years. Although varicella was caused by the vaccine-type strain, repeated vaccinations may be necessary for post-transplant patients who develop varicella.

Annual pattern and clinical characteristics of herpes zoster in immunocompetent children in a rural area.

This study aims to investigate the clinical signs, symptoms, complications and seasonal distribution of herpes zoster for otherwise healthy children and to demonstrate the outcome of varicella vaccinations on the herpes zoster incidence in a pediatric population. A retrospective study was conducted by using the data of the pediatric patients who were referred to two rural cities of Turkey, clinically diagnosed as Herpes Zoster (HZ). All participants were evaluated for clinical-epidemiological factors, signs, symptoms, complications and varicella vaccination status for HZ. This study was comprised of 69 pediatric patients (29 [42%] female and 40 [58%] male) who were diagnosed with HZ. The mean age was 10.57 (6 months-17) years old. The rash of HZ mostly appeared on the thoracic dermatome as seen in 29 patients. The findings revealed that among 56 unvaccinated patients of all, 25 (44.6%) had a painful rash, in comparison among vaccinated patients none reported pain as the characterization of shingles (P = .001). Annual distribution of cases showed two peaks (March and September), whereas in August no cases were detected. Of all participants, one patient had postherpetic neuralgia, who also had ophthalmic dermatomal involvement, and this was the only complication observed in this study cohort. In immunocompetent children, the most common involvement site was the thoracic dermatome. Our findings show that varicella vaccination has a protective role in the herpes zoster clinic, both by decreasing the prevalence and by making the infection course less severe.

Characteristics of within-household varicella transmission events associated with school outbreaks in Shanghai, China, 2009-2018.

Transmission of varicella occurs frequently in schools and households. We investigated the characteristics of varicella cases derived from within-household transmission and the modes of varicella transmission between school and household settings in Shanghai, China, from 2009 to 2018. Within-household transmission occurred in 278 households, of which 134 transmission events were between children. Sixty-one household varicella transmission events may be attributed to isolation procedures for infected students during school outbreaks, and 7.6% of school outbreaks were caused by schoolchildren cases derived from within-household transmission. The frequency of 'school-household-school' transmission adds an additional layer of complexity to the control of school varicella outbreaks. Administration of varicella vaccine as post-exposure prophylaxis after exposure is considered to be an effective measure to control varicella spread within households and schools.