PMID: 

Vaccine. 2015 Jul 17 ;33(31):3636-49. Epub 2015 Jun 11. PMID: 26073015

Abstract Title: 

Risk of febrile seizure after measles-mumps-rubella-varicella vaccine: A systematic review and meta-analysis.

Abstract: 

BACKGROUND: Considering the febrile seizure rate, there is no longer a clear preference for use of measles-mumps-rubella-varicella (MMRV) vaccine over separate measles-mumps-rubella (MMR) and varicella (V) vaccine. This work was undertaken to assess the risk of febrile seizure after MMRV vaccine in children.METHODS: We searched PubMed, Embase, BIOSIS Previews, Scopus, Web of Science, Cochrane Library and other databases through 12 December 2014. Meta-analysis was conducted using R version 3.1.2 and Stata version 12.0.RESULTS: A total of thirty-nine studies were included. Thirty-one published or unpublished clinical trials involving about 40,000 subjects did not show significant differences in incidence of febrile seizure or vaccine related febrile seizure between MMRV and MMR with or without varicella vaccine after any doses, in the risk windows of 0-28, 0-42 or 0-56 days and 7-10 days. In addition, these studies showed that the receipt of concomitant use of MMRV and other pediatric vaccines was not a significant predictor of febrile seizure. Eight post-marketing observations involving more than 3,200,000 subjects were included. No evidence suggested elevated risk of febrile seizure associated with MMRV vaccine among children aged 4-6 years old during 7-10 days or 0-42 days after vaccination. However, an approximately 2-fold increase in risk of seizure or febrile seizure during 7-10 days or 5-12 days after MMRV vaccination was found among children aged 10-24 months, although the highest incidence of seizure was still lower than 2.95‰.CONCLUSIONS: First MMRV vaccine dose in children aged 10-24 months was associated with an elevated risk of seizure or febrile seizure. Further post-marketing restudies based on more rigorous study design are needed to confirm the findings.

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PMID: 

Elife. 2015 Jul 11 ;4. Epub 2015 Jul 11. PMID: 26259874

Abstract Title: 

Integrating between-host transmission and within-host immunity to analyze the impact of varicella vaccination on zoster.

Abstract: 

Varicella-zoster virus (VZV) causes chickenpox and reactivation of latent VZV causes herpes zoster (HZ). VZV reactivation is subject to the opposing mechanisms of declining and boosted VZV-specific cellular mediated immunity (CMI). A reduction in exogenous re-exposure 'opportunities' through universal chickenpox vaccination could therefore lead to an increase in HZ incidence. We present the first individual-based model that integrates within-host data on VZV-CMI and between-host transmission data to simulate HZ incidence. This model allows estimating currently unknown pivotal biomedical parameters, including the duration of exogenous boosting at 2 years, with a peak threefold to fourfold increase of VZV-CMI; the VZV weekly reactivation probability at 5% and VZV subclinical reactivation having no effect on VZV-CMI. A 100% effective chickenpox vaccine given to 1 year olds would cause a 1.75 times peak increase in HZ 31 years after implementation. This increase is predicted to occur mainly in younger age groups than is currently assumed.

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PMID: 

BMC Pediatr. 2016 Jan 13 ;16:7. Epub 2016 Jan 13. PMID: 26762528

Abstract Title: 

Varicella vaccine without human serum albumin versus licensed varicella vaccine in children during the second year of life: a randomized, double-blind, non-inferiority trial.

Abstract: 

BACKGROUND: GSK's varicella vaccine contains human serum albumin (HSA) which is used to stabilize the virus and prevent immunogens from adhering to the injection vial walls. However, because HSA is derived from human blood, there is a theoretical risk that it might contain infectious agents which could be unsafe for humans. Given this concern, a study was undertaken to compare the immunogenicity and safety of a new formulation without HSA with the currently licensed varicella vaccine in the Czech Republic and Hungary.METHODS: Healthy children aged 11-21 months received two doses of the varicella vaccine either with or without HSA. Antibody titres against varicella-zoster virus (anti-VZV) were measured 42 days after each dose, using an immunofluorescence assay (IFA, cut-off = 4dilution(-1)) and enzyme linked immunosorbent assay (ELISA, cut-off = 25 mIU/ml). Solicited local symptoms were recorded during a 4-day post-vaccination follow-up period; solicited general and unsolicited symptoms were recorded during a 43-day post-vaccination follow-up period and serious adverse event (SAEs) were recorded throughout the study.RESULTS: Of 244 children (mean age = 15.2 months [SD = 3.2]) vaccinated in the study, 233 (vaccine without HSA N = 117; vaccine containing HSA N = 116) formed the according-to-protocol immunogenicity cohort. Observed seroconversion/seroresponse rates were>98 and 100 %, 42 days after doses 1 and 2, respectively. The rates were within the same range in both groups, irrespective of the testing assay. The varicella vaccine without HSA was non-inferior to the licensed vaccine in terms of anti-VZV antibody Geometric Mean Titre/Concentration ratio (1.12 [95 % CI:0.86-1.46] by IFA; 1.12 [95 % CI:0.93-1.33] by ELISA) approximately six weeks after the first dose of the 2-dose vaccination course. The incidence of solicited and unsolicited symptoms was similar after both vaccines; low-grade fever was numerically higher after the first dose of the varicella vaccine without HSA. Seven SAEs were reported, none of which were fatal or considered to be vaccine-related.CONCLUSIONS: The first dose of a new varicella vaccine without HSA was immunologically non-inferior to the licensed varicella vaccine. After two doses, both vaccines had acceptable safety profiles in children aged 11-21 months in the Czech Republic and Hungary.TRIAL REGISTRATION: NCT00568334 , registered on 5 December 2007 ( http://www.clinicaltrials.gov ).

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PMID: 

Pediatr Infect Dis J. 2016 May ;35(5):595-6. PMID: 27071018

Abstract Title: 

Breakthrough Varicella Zoster Virus Infection in an Immunized Child with Cystic Fibrosis.

Abstract: 

[n/a]

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PMID: 

Sci Rep. 2019 Jun 19 ;9(1):8818. Epub 2019 Jun 19. PMID: 31217483

Abstract Title: 

The mediating effect of immune markers on the association between ambient air pollution and adult-onset asthma.

Abstract: 

We aim to investigate to what extent a set of immune markers mediate the association between air pollution and adult-onset asthma. We considered long-term exposure to multiple air pollution markers and a panel of 13 immune markers in peripheral blood samples collected from 140 adult cases and 199 controls using a nested-case control design. We tested associations between air pollutants and immune markers and adult-onset asthma using mixed-effects (logistic) regression models, adjusted for confounding variables. In order to evaluate a possible mediating effect of the full set of immune markers, we modelled the relationship between asthma and air pollution with a partial least square path model. We observed a strong positive association of IL-1RA [OR 1.37; 95% CI (1.09, 1.73)] with adult-onset asthma. Univariate models did not yield any association between air pollution and immune markers. However, mediation analyses indicated that 15% of the effect of air pollution on risk of adult-onset asthma was mediated through the immune system when considering all immune markers as a latent variable (path coefficient (β) = 0.09; 95% CI: (-0.02, 0.20)). This effect appeared to be stronger for allergic asthma (22%; β = 0.12; 95% CI: (-0.03, 0.27)) and overweight subjects (27%; β = 0.19; 95% CI: (-0.004, 0.38)). Our results provides supportive evidence for a mediating effect of the immune system in the association between air pollution and adult-onset asthma.

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PMID: 

J Am Osteopath Assoc. 2016 Jun 1 ;116(6):402-5. PMID: 27214778

Abstract Title: 

Disseminated Varicella-Zoster Virus After Vaccination in an Immunocompetent Patient.

Abstract: 

Severe adverse events associated with varicella-zoster virus (VZV) vaccination are rare. The authors describe a 53-year-old woman with no known immunodeficiency who presented with diffuse pruritic rash 17 days after receiving the varicella virus vaccine live. She had a low level of white blood cells and received a diagnosis of thrombocytopenia with elevated aminotransferase levels. Punch biopsy demonstrated positive VZV immunostaining and viral culture positive for VZV. After treatment with acyclovir, her rash improved and her white blood cell and platelet counts returned to normal. Mild reactions to vaccines including localized rash are well recognized. Disseminated infections have been reported in patients with congenital and acquired immunodeficiency, but systemic postvaccination infections are rare in immunocompetent adults. This case highlights the importance of recognizing adverse events associated with vaccination.

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PMID: 

Curr Opin Infect Dis. 2016 06 ;29(3):275-9. PMID: 26871403

Abstract Title: 

Varicella zoster virus and giant cell arteritis.

Abstract: 

PURPOSE OF REVIEW: Giant cell arteritis (GCA) is a serious disease and the most common cause of vasculitis in the elderly. Here, studies describing the recent discovery of varicella zoster virus (VZV) in the temporal arteries of patients with GCA are reviewed.RECENT FINDINGS: GCA is characterized by severe headache/head pain and scalp tenderness. Many patients also have a history of vision loss, jaw claudication, polymyalgia rheumatica, fever, night sweats, weight loss, and fatigue. The erythrocyte sedimentation rate and C-reactive protein are usually elevated. Diagnosis is confirmed by temporal artery biopsy, which reveals vessel wall damage and inflammation, with multinucleated giant cells and/or epithelioid macrophages. Skip lesions are common. Importantly, temporal artery biopsies are pathologically negative in many clinically suspect cases. The present review highlights recent virological findings in temporal arteries from patients with pathologically verified GCA and in temporal arteries from patients who manifest clinical and laboratory features of GCA but whose temporal artery biopsies are pathologically negative for GCA. Virological analysis revealed that VZV is present in most GCA-positive and GCA-negative temporal artery biopsies, particularly in skip areas that correlate with adjacent GCA disease.SUMMARY: The presence of VZV in GCA-positive and GCA-negative temporal arteries reflects the possible role of VZV in triggering the immunopathology of GCA and indicates that both groups of patients should be treated with antivirals in addition to corticosteroids. Whether oral antiviral agents and steroids are as effective as intravenous acyclovir and steroids, and the dosage and duration of treatment, remain to be determined.

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PMID: 

Pediatr Infect Dis J. 2016 09 ;35(9):e275-84. PMID: 27187755

Abstract Title: 

The Cost-effectiveness of Varicella Zoster Virus Vaccination Considering Late Onset Asthma.

Abstract: 

BACKGROUND: Recent studies reported that infection by varicella zoster virus (VZV) may lead to delayed onset of asthma in children/adolescents. This information will likely alter the cost-effectiveness of the US. VZV vaccination program. We created a decision analysis model to estimate the costs and health-related effects of VZV 2-dose vaccination, assuming VZV infection delays asthma onset.METHODS: The Markov model considered a birth cohort of 3,957,577 individuals entering the population from a societal perspective. We predicted the number of asthma/VZV cases, asthma-/VZV-related mortality and costs associated with asthma/VZV. Comparison arms included (1) VZV vaccination program without delayed asthma onset, (2) VZV vaccination program with delayed asthma onset and (3) no VZV vaccination program with delayed asthma onset. We considered delayed onset ranging from 3 to 12 years.RESULTS: The vaccination program proved cost-effective without an assumed delay in asthma onset. When the vaccination and no-vaccination arms were compared assuming delayed asthma onset, vaccination remained less costly despite increased savings related to asthma without vaccination. With delayed asthma onset of 9 years post VZV infection, cost savings due to vaccination were $914.09 million, with 9984 cases of asthma averted and 9 greater overall deaths with vaccination.CONCLUSION: VZV vaccination program was less costly than the"no-vaccination"scenario, despite delayed onset of asthma post VZV infection. However, vaccination resulted in increased asthma morbidity and mortality. This adds to current evidence that VZV vaccination is cost-effective, and may alter asthma-related health-care outcomes. VZV's effect on asthma symptoms still needs further evaluation before firm conclusions can be reached.

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PMID: 

Allergy Asthma Immunol Res. 2019 Sep ;11(5):632-643. PMID: 31332975

Abstract Title: 

Short-term Haze Exposure Predisposes Healthy Volunteers to Nasal Inflammation.

Abstract: 

PURPOSE: This study aimed to investigate the impact of short-term haze exposure on nasal inflammation in healthy volunteers.METHODS: Thirty-three healthy university students were assessed for nasal symptoms, nasal patency, upper and lower respiratory tract nitric oxide (NO) as well as inflammatory mediators and neuropeptides in nasal secretions before and after a 5-day haze episode. Peripheral blood mononuclear cells (PBMCs) were stimulated with particulate matter with an aerodynamic diameter of less than 2.5μm (PM), and cytokines in the supernatants were examined.RESULTS: Mild nasal symptoms were reported by some participants during the haze episode. Objective measures of nasal patency demonstrated that nasal airway resistance was significantly increased from baseline levels, while nasal cavity volume and minimum cross-sectional area were significantly decreased. Similarly, the levels of nasal and exhaled NO, eotaxin, interleukin (IL)-5, chemokine (C-C motif) ligand 17, IL-8, substance P, nerve growth factor and vasoactive intestinal peptides in nasal secretions were significantly increased from baseline values following the haze episode. In contrast, the levels of interferon-γ, IL-10, transforming growth factor-β and neuropeptide Y were significantly decreased. Incubation with 0.1-10 μg/mL PM2.5 significantly increased release of IL-1β, IL-4, IL-5, IL-8 and IL-10 from PBMCs.CONCLUSIONS: Short-term haze exposure may lead to nasal inflammation and hypersensitivity in healthy subjects predominantly by Th2 cytokine-mediated immune responses.

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PMID: 

Pediatr Infect Dis J. 2016 11 ;35(11):e348-e352. PMID: 27753768

Abstract Title: 

Varicella Vaccination of Children With Leukemia Without Interruption of Maintenance Therapy: A Danish Experience.

Abstract: 

BACKGROUND: Varicella-zoster virus (VZV) can be fatal or cause severe complications in children with acute lymphoblastic leukemia (ALL). This analysis set out to investigate the morbidity and mortality of VZV vaccination without interruption of maintenance therapy in children with ALL.METHODS: Files of 73 seronegative children with ALL were examined for data regarding VZV vaccination and infection, and long-term seroconversion was measured. Criteria before VZV vaccination were (1) seronegative, (2) in complete remission, (3) age≥ 1.0 year, (4) lymphocyte count ≥ 0.6 × 10/L at time of vaccination and (5) receiving maintenance therapy.RESULTS: Forty-five children were vaccinated. No child died or experienced serious adverse events due to VZV vaccination. Nine children developed late chickenpox despite vaccination. Long-term protection was found in 86% of children not receiving acyclovir and 78% of the entire population. Long-term seroconversion was found in 52% of the children. There were no severe cases of varicella infection. Acyclovir prophylaxis postvaccination was associated with an increased risk of late chickenpox [hazard ratio = 5.40 (1.43, 20.41), P = 0.01]. In contrast, a vaccine-induced rash reduced the risk of late chickenpox [hazard ratio = 0.08 (0.01, 0.66), P = 0.02]. No child had interruption of maintenance therapy at the time of vaccination, but 33% experienced discontinuation of therapy due to vaccine-induced rash. Dexamethasone was associated with an increased risk of vaccine-induced rash [hazard ratio = 2.9 (1.21, 6.90), P = 0.02].CONCLUSIONS: This analysis indicates that VZV vaccination is feasible and justified in seronegative children with ALL, in countries where VZV vaccination is not part of the national vaccination program.

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