Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-30 (of 113 Records) |
Query Trace: Schmid G[original query] |
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Building Evidence, Building Community: The Physical Activity Policy Research and Evaluation Network (PAPREN)
Lemon SC , Goins KV , Ussery EN , Rose KM , Chriqui JF . J Healthy Eat Act Living 12/28/2021 1 (4) 165-168 Regular physical activity is an essential action people can take to improve their health (U.S. Department of Health and Human Services, 2018). Despite well-established benefits, only 1 in 4 U.S. adults meet the combined aerobic and muscle-strengthening physical activity guidelines (Centers for Disease Control and Prevention). The built environment, defined as the physical makeup of where people live, learn, work, and play, can support or inhibit physical activity. The Community Preventive Services Task Force (CPSTF) recommends built environment strategies that combine new or improved pedestrian, bicycle, or transit transportation systems (i.e., activity-friendly routes) with land use components (i.e., connecting everyday destinations) (Community Preventive Services Task Force, 2016). Active People, Healthy NationSM is a national initiative led by the Centers for Disease Control and Prevention (CDC) to help 27 million Americans become more physically active by 2027 (Fulton et al., 2018). To reach this goal, states and communities can implement strategies for increasing physical activity (Schmid et al., 2021) across sectors and settings. Each strategy can be designed to ensure equitable access to opportunities for physical activity. However, implementation of physical activity–supportive policies across the United States remains low. The National Complete Streets Coalition reports that only 1,600 jurisdictions (mainly cities) have adopted Complete Streets policies (Smart Growth America); this is a fraction of all U.S. jurisdictions, and the quality of policies varies. There remains a need for applied research to translate knowledge into practice for implementing evidence-based policies to increase physical activity. Best practices that inform the implementation of these strategies are also needed to support communities and states. |
Effect of high dose vitamin D supplementation on subsequent immune responses to administration of the live herpes zoster vaccine to long-term care residents
Levin MJ , Ginde AA , Schmid DS , Lang N , Canniff J , Schwartz RS , Weinberg A . Vaccine 2024 Thirty-three long-term care residents (mean age 76.5 years), who were participating in a study in which they were randomized to receive either oral daily standard dose (400-1000 IU/day) 25-hydroxy vitamin D (vitamin D3) (SD) or high dose (3000-4000 IU/day) (HD) vitamin D3, were vaccinated with the live, attenuated herpes zoster vaccine. Blood was drawn at vaccination and three weeks later to determine varicella-zoster virus (VZV) antibody and T-cell mediated immune responses. ELISA and neutralizing antibodies increased significantly, but to the same extent, in both groups. The antibody avidity significantly increased from pre- to post-vaccination only in the HD group. VZV-CMI, as measured by FLUOROSPOT significantly increased post-vaccination in both groups, but the difference in interferon-γ spot-forming cells (SFC) and interleukin-2 SFC was lower in the HD than SD group. The increase in VZV-CMI correlated inversely with circulating regulatory T cells in the HD group. We conclude that pre-treatment with HD vitamin D3 does not appreciably enhance the antibody response to a live vaccine and that VZV-CMI responses were diminished in HD vitamin D3 recipients. |
Primary series COVID-19 vaccine effectiveness among healthcare workers in Albania, February-December 2021
Rubin-Smith JE , Castro MYR , Preza I , Hasibra I , Sulo J , Fico A , Daja R , Vasili A , Kota M , Schmid A , Sridhar S , Guseinova A , Boshevska G , Bejtja G , Mühlemann B , Drosten C , Jorgensen P , Pebody R , Kissling E , Lafond KE , Katz MA , Bino S . IJID Reg 2023 8 19-27 BACKGROUND: Healthcare workers have experienced high rates of morbidity and mortality from coronavirus disease 2019 (COVID-19). METHODS: A prospective cohort study was conducted in three Albanian hospitals between 19 February and 14 December 2021. All participants underwent polymerase chain reaction (PCR) and serological testing at enrolment, regular serology throughout, and PCR testing when symptomatic.Vaccine effectiveness (VE) against COVID-19 and against all severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections (symptomatic or asymptomatic) was estimated. VE was estimated using a Cox regression model, with vaccination status as a time-varying variable. FINDINGS: In total, 1504 HCWs were enrolled in this study; 70% had evidence of prior SARS-CoV-2 infection. VE was 65.1% [95% confidence interval (CI) 37.7-80.5] against COVID-19, 58.2% (95% CI 15.7-79.3) among participants without prior SARS-CoV-2 infection, and 73.6% (95% CI 24.3-90.8) among participants with prior SARS-CoV-2 infection. For BNT162b2 alone, VE was 69.5% (95% CI 44.5-83.2). During the period when the Delta variant was predominant, VE was 67.1% (95% CI 38.3-82.5). VE against SARS-CoV-2 infection for the full study period was 36.9% (95% CI 15.8-52.7). INTERPRETATION: This study found moderate primary series VE against COVID-19 among healthcare workers in Albania. These results support the continued promotion of COVID-19 vaccination in Albania, and highlight the benefits of vaccination in populations with high levels of prior infection. |
Predictors of Five-Year Persistence of Antibody Responses to Zoster Vaccines
Weinberg A , Schmid DS , Leung J , Johnson MJ , Miao C , Levin MJ . J Infect Dis 2023 BACKGROUND: Protection against herpes zoster (HZ) is primarily conferred by cell-mediated immunity (CMI). However, anti-VZV-glycoprotein (anti-gp) antibody responses to Zoster Vaccine Live (ZVL) correlate with protection, suggesting a potential protective role for antibody. Detailed studies of antibody responses to the Recombinant Zoster Vaccine (RZV) are lacking. METHODS: We compared ELISA-measured anti-gp and anti-glycoprotein E (anti-gE) antibodies and avidity in 159 participants randomized to RZV (n = 80) or ZVL (n = 79) recipients over 5 years post-vaccination and identified predictors of antibody persistence. RESULTS: The comparison between vaccine groups showed higher anti-gE and anti-gp antibody levels after RZV than ZVL over the 5-year study duration. RZV recipients also had higher anti-gE avidity for 5 years and higher anti-gp avidity in the first year post-vaccination. Compared with pre-vaccination, RZV recipients maintained higher levels of anti-gE antibodies and avidity for 5 years, whereas ZVL recipients only maintained higher anti-gE avidity. Anti-gp antibody levels and avidity decreased to pre-vaccination levels or below after 1-year post-vaccination in both groups. Independent predictors of persistence of antibody levels and avidity were the following: vaccine type, pre-vaccination and peak antibody levels and avidity, pre-vaccination and peak CMI, and age. Sex or prior ZVL administration did not affect persistence. CONCLUSION: Antibody responses and avidity were higher and more persistent in RZV than ZVL recipients. The effect of age on antibody persistence in RZV recipients is novel. |
Using Tribal Data Linkages to Improve the Quality of American Indian Cancer Data in Michigan
Weber TL , Copeland G , Pingatore N , Schmid KK , Jim MA , Watanabe-Galloway S . J Health Care Poor Underserved 2019 30 (3) 1237-1247 This study examines the extent to which data linkages between Indian Health Service, tribal data, and cancer registries affect cancer incidence rates among American Indians/Alaska Natives (AI/ANs) in Michigan. The incidence of tobacco- and alcohol-associated cancers for 1995-2012 was analyzed to compare rates of the Upper Peninsula (UP) and Lower Peninsula (LP) in Michigan and among AI/ANs and non-Hispanic Whites (NHWs). Complete linkage resulted in 1,352 additional AI/AN cases; 141 cases were linked via IHS records alone, while 373 were linked via tribal records alone; 838 were linked through both IHS and tribal records. Age-adjusted incidence rates for AI/ANs increased from 214.39 per 100,000 to 405.41 per 100,000, similar to that of NHWs after complete linkage (421.46 per 100,000). In the UP, AI/ANs had age-adjusted incidence rates 1.67 times higher than NHWs (596.69 per 100,000 vs. 356.32 per 100,000 respectively). This study indicates a substantial number of AI/AN cancer cases remain misclassified in Michigan. |
Factors associated with receipt of COVID-19 vaccination and SARS-CoV-2 seropositivity among healthcare workers in Albania (February 2021June 2022): secondary analysis of a prospective cohort study
Jorgensen P , Schmid A , Sulo J , Preza I , Hasibra I , Kissling E , Fico A , Sridhar S , Rubin-Smith JE , Kota M , Vasili A , Daja R , Nika M , Pebody R , Lafond KE , Katz MA , Bino S . Lancet Reg Health Eur 2023 27 100584 Background: Healthcare workers (HCWs) have been disproportionally affected by COVID-19. We investigated factors associated with two- and three-dose COVID-19 vaccine uptake and SARS-CoV-2 seropositivity among 1504 HCWs enrolled (19 February-7 May 2021) in a prospective COVID-19 vaccine effectiveness cohort in Albania through a secondary analysis. Methods: We collected sociodemographic, occupational, health, prior SARS-CoV-2 infection, and COVID-19 vaccination data from all HCWs at enrollment. Vaccination status was assessed weekly through June 2022. A serum sample was collected from all participants at enrollment and tested for anti-spike SARS-CoV-2 antibodies. We analyzed HCWs characteristics and outcomes using multivariable logistic regression. Findings: By 11 June 2022, 1337 (88.9%) HCWs had received two COVID-19 vaccine doses, of whom 255 (19.1%) received a booster. Factors significantly associated with receiving three doses (adjusted odds ratio (aOR), 95% CIs) were being ≥35 years (35–44 years: 1.76 (1.05–2.97); 45–54 years: 3.11 (1.92–5.05); ≥55 years: 3.38 (2.04–5.59)) and vaccinated against influenza (1.78; 1.20–2.64). Booster dose receipt was lower among females (0.58; 0.41–0.81), previously infected (0.67; 0.48–0.93), nurses and midwives (0.31; 0.22–0.45), and support staff (0.19; 0.11–0.32). Overall 1076 (72%) were SARS-CoV-2 seropositive at enrollment. Nurses and midwifes (1.45; 1.05–2.02), support staff (1.57; 1.03–2.41), and HCWs performing aerosol-generating procedures (AGPs) (1.40; 1.01–1.94) had higher odds of being seropositive, while smokers had reduced odds (0.55; 0.40–0.75). Interpretation: In a large cohort of Albanian HCWs, COVID-19 vaccine booster dose uptake was very low, particularly among younger, female, and non-physician HCWs, despite evidence demonstrating the added benefit of boosters in preventing infection and severe disease. Reasons behind these disparities should be explored to develop targeted strategies in order to promote uptake in this critical population. SARS-CoV-2 seroprevalence was higher among non-physicians and HCWs performing APGs. A better understanding of the factors contributing to these differences is needed to inform interventions that could reduce infections in the future. Funding: This study was funded by the Task Force for Global Health (US Centers for Disease Control (CDC) cooperative agreement # NU51IP000873) and the World Health Organization, Regional Office for Europe. © 2023 World Health Organization |
Selective retention of virus-specific tissue-resident T cells in healed skin after recovery from herpes zoster
Laing KJ , Ouwendijk WJD , Campbell VL , McClurkan CL , Mortazavi S , Elder Waters M , Krist MP , Tu R , Nguyen N , Basu K , Miao C , Schmid DS , Johnston C , Verjans Gmgm , Koelle DM . Nat Commun 2022 13 (1) 6957 Herpes zoster is a localized skin infection caused by reactivation of latent varicella-zoster virus. Tissue-resident T cells likely control skin infections. Zoster provides a unique opportunity to determine if focal reinfection of human skin boosts local or disseminated antigen-specific tissue-resident T cells. Here, we show virus-specific T cells are retained over one year in serial samples of rash site and contralateral unaffected skin of individuals recovered from zoster. Consistent with zoster resolution, viral DNA is largely undetectable on skin from day 90 and virus-specific B and T cells decline in blood. In skin, there is selective infiltration and long-term persistence of varicella-zoster virus-specific T cells in the rash site relative to the contralateral site. The skin T cell infiltrates express the canonical tissue-resident T cell markers CD69 and CD103. These findings show that zoster promotes spatially-restricted long-term retention of antigen-specific tissue-resident T cells in previously infected skin. |
Development of antibody-dependent cellular cytotoxicity in response to recombinant and live-attenuated herpes zoster vaccines
Park SY , Levin MJ , Canniff J , Johnson M , Schmid DS , Weinberg A . NPJ Vaccines 2022 7 (1) 123 Zoster vaccines generate antibody responses against varicella-zoster virus (VZV). We compared antibody-dependent cell cytotoxicity (ADCC) elicited by zoster vaccine live (ZVL) and recombinant zoster vaccine (RZV). ADCC mediated by antibodies against VZV lysate (VZV-ADCC) and recombinant glycoprotein E (gE-ADCC) was measured using plasma from 20 RZV- and 20 ZVL-recipients, including half 50-60-years-old and half 70-years-old. Solid phase-bound anti-VZV antibodies stimulated TNF in NK cells as measured by flow cytometry or ELISA. VZV-ADCC pre- and post-immunization was higher in younger vaccinees. ZVL did not appreciably increase VZV-ADCC, whereas RZV increased VZV-ADCC in older vaccinees. ELISA-measured gE-ADCC was similar across groups pre-immunization; significantly increased after ZVL; and RZV and was higher in younger RZV than ZVL recipients. IgG3 antibodies increased after RZV and ZVL, with greater anti-gE than anti-VZV responses. Moreover, gE-ADCC strongly correlated with anti-gE antibody avidity, but there were no appreciable correlations between VZV-ADCC and avidity. NK cells stimulated by anti-gE antibodies showed increased IFN and CD107a expression, which was not observed with anti-VZV antibodies. In conclusion, anti-gE antibodies generated more robust ADCC than anti-VZV antibodies. RZV induced higher ADCC antibodies than ZVL depending on the antigen and age of vaccinees. Older adults had lower ADCC antibodies before and after vaccination than younger adults. |
COVID-19 vaccine effectiveness among healthcare workers in Albania (COVE-AL): protocol for a prospective cohort study and cohort baseline data.
Sridhar S , Fico A , Preza I , Hatibi I , Sulo J , Kissling E , Daja R , Ibrahim R , Lemos D , Rubin-Smith J , Schmid A , Vasili A , Valenciano M , Jorgensen P , Pebody R , Lafond KE , Katz MA , Bino S . BMJ Open 2022 12 (3) e057741 INTRODUCTION: Critical questions remain about COVID-19 vaccine effectiveness (VE) in real-world settings, particularly in middle-income countries. We describe a study protocol to evaluate COVID-19 VE in preventing laboratory-confirmed SARS-CoV-2 infection in health workers (HWs) in Albania, an upper-middle-income country. METHODS AND ANALYSIS: In this 12-month prospective cohort study, we enrolled HWs at three hospitals in Albania. HWs are vaccinated through the routine COVID-19 vaccine campaign. Participants completed a baseline survey about demographics, clinical comorbidities, and infection risk behaviours. Baseline serology samples were also collected and tested against the SARS-CoV-2 spike protein, and respiratory swabs were collected and tested for SARS-CoV-2 by RT-PCR. Participants complete weekly symptom questionnaires and symptomatic participants have a respiratory swab collected, which is tested for SARS-CoV-2. At 3, 6, 9 months and 12 months of the study, serology will be collected and tested for antibodies against the SARS-CoV-2 nucleocapsid protein and spike protein. VE will be estimated using a piecewise proportional hazards model (VE=1-HR). BASELINE DATA: From February to May 2021, 1504 HWs were enrolled. The median age was 44 (range: 22-71) and 78% were female. At enrolment, 72% of participants were seropositive for SARS-CoV-2. 56% of participants were vaccinated with one dose, of whom 98% received their first shot within 4days of enrolment. All HWs received the Pfizer BNT162b2 mRNA COVID-19 vaccine. ETHICS AND DISSEMINATION: The study protocol and procedures were reviewed and approved by the WHO Ethical Review Board, reference number CERC.0097A, and the Albanian Institute of Public Health Ethical Review Board, reference number 156. All participants have provided written informed consent to participate in this study. The primary results of this study will be published in a peer-reviewed journal at the time of completion. TRIAL REGISTRATION NUMBER: NCT04811391. |
ICTV Virus Taxonomy Profile: Herpesviridae 2021.
Gatherer D , Depledge DP , Hartley CA , Szpara ML , Vaz PK , Benkő M , Brandt CR , Bryant NA , Dastjerdi A , Doszpoly A , Gompels UA , Inoue N , Jarosinski KW , Kaul R , Lacoste V , Norberg P , Origgi FC , Orton RJ , Pellett PE , Schmid DS , Spatz SJ , Stewart JP , Trimpert J , Waltzek TB , Davison AJ . J Gen Virol 2021 102 (10) Members of the family Herpesviridae have enveloped, spherical virions with characteristic complex structures consisting of symmetrical and non-symmetrical components. The linear, double-stranded DNA genomes of 125-241 kbp contain 70-170 genes, of which 43 have been inherited from an ancestral herpesvirus. In general, herpesviruses have coevolved with and are highly adapted to their hosts, which comprise many mammalian, avian and reptilian species. Following primary infection, they are able to establish lifelong latent infection, during which there is limited viral gene expression. Severe disease is usually observed only in the foetus, the very young, the immunocompromised or following infection of an alternative host. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Herpesviridae, which is available at ictv.global/report/herpesviridae. |
Humoral and cellular immune responses to recombinant herpes zoster vaccine in patients with chronic lymphocytic leukemia and monoclonal B cell lymphocytosis
Muchtar E , Koehler AB , Johnson MJ , Rabe KG , Ding W , Call TG , Leis JF , Kenderian SS , Hayman SR , Wang Y , Hampel PJ , Holets MA , Darby HC , Slager SL , Kay NE , Miao C , Canniff J , Whitaker JA , Levin MJ , Schmid DS , Kennedy RB , Weinberg A , Parikh SA . Am J Hematol 2021 97 (1) 90-98 Monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL) are clonal B cell disorders associated with increased risk of infections and impaired vaccination responses. We investigated the immunogenicity of recombinant zoster vaccine (RZV) in these patients. Individuals with MBL/untreated CLL and Bruton tyrosine kinase inhibitor (BTKi)-treated CLL patients were given two doses of RZV separated by two months. Responses assessed at 3-months and 12-months from the first dose of RZV by an anti-glycoprotein E ELISA antibody assay and by dual-color IFN-γ and IL-2 FLUOROSPOT assays were compared to historic controls matched by age and sex. Sixty-two patients (37 MBL/untreated CLL and 25 BTKi-treated CLL) were enrolled with a median age of 68 years at vaccination. An antibody response at 3 months was seen in 45% of participants, which was significantly lower compared to historic controls (63%, P=0.03). The antibody response did not significantly differ between MBL/untreated CLL and BTKi-treated CLL (51% vs 36%, respectively, P=0.23). The CD4+ T cell response to vaccination was significantly lower in study participants compared to controls (54% vs 96%, P<0.001), mainly due to lower responses among BTKi-treated patients compared to untreated MBL/CLL (32% vs 73%, P=0.008). Overall, only 29% of participants achieved combined antibody and cellular responses to RZV. Among participants with response assessment at 12 months (n=47), 24% had antibody titers below response threshold. Hypogammaglobulinemia and BTKi therapy were associated with reduced T cell responses in a univariate analysis. Strategies to improve vaccine response to RZV among MBL/CLL patients are needed. This article is protected by copyright. All rights reserved. |
Communicability of varicella before rash onset: a literature review
Marin M , Leung J , Lopez AS , Shepersky L , Schmid DS , Gershon AA . Epidemiol Infect 2021 149 1-18 Varicella poses an occupational risk and a nosocomial risk for susceptible healthcare personnel and patients, respectively. Patients with varicella are thought to be infectious from 1 to 2 days before rash onset until all lesions are crusted, typically 4-7 days after onset of rash. We searched Medline, Embase, Cochrane Library and CINAHL databases to assess evidence of varicella-zoster virus (VZV) transmission before varicella rash onset. Few articles (7) contributed epidemiologic evidence; no formal studies were found. Published articles reported infectiousness at variable intervals before rash onset, between <1 day to 4 days prior to rash, with 1-2 patients for each interval. Laboratory assessment of transmission before rash was also limited (10 articles). No culture-positive results were reported. VZV DNA was identified by PCR before rash onset in only one study however, PCR does not indicate infectivity of the virus. Based on available medical literature, VZV transmission before rash onset seems unlikely, although the possibility of pre-rash, respiratory transmission cannot be entirely ruled out. |
Comparative antibody responses to the live-attenuated and recombinant herpes zoster vaccines
Schmid DS , Miao C , Leung J , Johnson M , Weinberg A , Levin MJ . J Virol 2021 95 (12) Two herpes zoster (HZ) vaccines licensed in the United States are recommended by the Advisory Committee on Immunization Practices (ACIP): 1) live-attenuated vaccine (ZVL) using vOka strain varicella-zoster virus (VZV), and 2) recombinant adjuvanted vaccine (RZV) containing recombinant VZV glycoprotein E (gE). Two phase 3 clinical trials of RZV led the Advisory Committee on Immunization Practices (ACIP) to recommend it with preferred status.VZV T cell-mediated immunity (CMI), but not humoral immunity, are considered essential for protection against HZ. Published studies of humoral immunity focused on VZV-specific IgG concentration. To complement reports comparing the CMI responses to these vaccines, we compared humoral responses in ZVL and RZV recipients, emphasizing functional qualities (avidity and neutralization). Baseline avidities to a VZV glycoprotein mixture (gp) were near the upper limit of detection, but avidity to gE was much lower. Small increases in gp avidity were observed for both RZV and ZVL vaccination [19 and 12 avidity index units (AIU), respectively]. RZV boosted both gE avidity and VZV neutralizing antibody significantly more than ZVL (mean gE avidity boost: 47 AIU versus 22 AIU; mean neutralizing antibody boost: 22-fold versus 8-fold). Increases in neutralizing antibodies strongly correlated with gE avidity increases (r=0.5) and moderately with gp avidity increases (r=0.23). After 1 year, 81% of RZV recipients and only 18% of ZVL recipients retained >50% of their peak avidity boosts. These results are consistent with the CMI responses to these vaccines: RZV responses are skewed to long-term memory, whereas ZVL preferentially induces transient effector responses.IMPORTANCEThese observations further distinguish the immunogenicity and duration of the immune response of the two vaccines. In addition, measurements of functional humoral immunity (IgG avidity, neutralizing antibody) in response to zoster immunization, alone or combined with other immune markers, might contribute to practical in vitro correlates of protection. Finally, combined with previous observations of the cell-mediated response to these vaccines, this study suggests that vaccine development could benefit from more expansive and granular assessments of acquired immunity during early phase 1 immunogenicity trials. |
Clinical and epidemiologic findings from enhanced monkeypox surveillance in Tshuapa Province, Democratic Republic of the Congo during 2011-2015
Whitehouse ER , Bonwitt J , Hughes CM , Lushima RS , Likafi T , Nguete B , Kabamba J , Monroe B , Doty JB , Nakazawa Y , Damon I , Malekani J , Davidson W , Wilkins K , Li Y , Radford KW , Schmid DS , Pukuta E , Muyamuna E , Karhemere S , Tamfum JM , Okitolonda EW , McCollum AM , Reynolds MG . J Infect Dis 2021 223 (11) 1870-1878 BACKGROUND: Monkeypox is a poorly described emerging zoonosis endemic to Central and Western Africa. METHODS: Using surveillance data from Tshuapa Province, Democratic Republic of the Congo during 2011-2015, we evaluated differences in incidence, exposures, and clinical presentation of PCR-confirmed cases by sex and age. RESULTS: We report 1,057 confirmed cases. Average annual incidence was 14·1 per 100,000 (95% CI: 13·3-15·0). Incidence was higher in males (incidence rate ratio [IRR] males: females: 1·21, 95% CI 1·07-1·37), except among 20-29-year-old (IRR: 0·70, 95% CI: 0·51-0·95). Females aged 20-29 years also reported a high frequency of exposures (26·2%) to people with monkeypox-like symptoms. Highest incidence was among 10-19-year-old males, the cohort reporting the highest proportion of animal exposures (37·5%). Incidence was lower among those presumed to have received smallpox vaccination versus those presumed unvaccinated. No differences were observed by age group in lesion count or lesion severity score. CONCLUSIONS: Monkeypox incidence was twice that reported during 1980-1985, an increase possibly linked to declining immunity provided by smallpox vaccination. The high proportion of cases attributed to human exposures suggests changing exposure patterns. Cases were distributed across age and sex, suggesting frequent exposures that follow socio-cultural norms. |
Safety and immunogenicity of adjuvanted recombinant subunit herpes zoster vaccine in lung transplant recipients
Hirzel C , L'Huillier AG , Ferreira VH , Marinelli T , Ku T , Ierullo M , Miao C , Schmid DS , Juvet S , Humar A , Kumar D . Am J Transplant 2021 21 (6) 2246-2253 Lung transplant recipients are at high risk for herpes zoster and preventive measures are a significant unmet need. We investigated the safety and immunogenicity of two doses of a recombinant zoster vaccine (RZV) in lung transplant recipients (≥50 years). We enrolled 50 patients of which 49 received at least one vaccine dose. Anti-glycoprotein E (gE) antibody levels (n=43) increased significantly compared to baseline (median optical density [OD] 1.96; interquartile range [IQR]: 1.17-2.89) after the first (median OD 3.41, IQR 2.54-3.81, p<0.0001) and second vaccine dose (median OD 3.63, IQR 3.39-3.86, p<0.0001). gE-specific polyfunctional CD4+ T-cell frequencies (n=38) also increased from baseline (median 85 per 10(6) CD4+ T-cells; IQR: 46-180) to the first (median 128 per 10(6) CD4+ T-cells; IQR: 82-353; p=0.023) and after the second dose (median 361 per 10(6) CD4+ T-cells; IQR: 146-848; p<0.0001). Tenderness (83.0%; 95%CI:69.2-92.4%) and redness (31.9%; 95%CI:19.1-47.1%) at injection site were common. One rejection episode within three weeks of vaccination was observed. This is the first study demonstrating that RZV was safe and elicited significant humoral and cell mediated immunity in lung transplant recipients. RZV is a new option for the prevention of shingles in this population. |
Evaluation of recombinant herpes zoster vaccine for primary immunization of varicella-seronegative transplant recipients
LʼHuillier AG , Hirzel C , Ferreira VH , Ierullo M , Ku T , Selzner N , Schiff J , Juvet S , Miao C , Schmid DS , Humar A , Kumar D . Transplantation 2021 105 (10) 2316-2323 BACKGROUND: Immunization of VZV-seronegative solid organ transplant (SOT) patients using the live-attenuated varicella vaccine is generally contraindicated, leaving no widely applicable immunization option. The recombinant subunit herpes zoster vaccine (RZV) is indicated for VZV seropositive persons to prevent shingles but could potentially also protect VZV-seronegative persons against varicella. We performed a safety and immunogenicity evaluation of RZV in VZV-seronegative SOT recipients as an option for protection. METHODS: VZV-seronegative adult SOT patients with no history of varicella/shingles vaccine or disease were given 2 doses of RZV vaccine 2-6 months apart. Blood was drawn prevaccination (V1), prior to the second dose (V2) and 4 weeks after second dose (V3). Humoral (anti-gE) and cell-mediated immunity was evaluated, with polyfunctional cells defined as cells producing ≥2 cytokines. RESULTS: Among 31 eligible VZV-seronegative SOT patients screened, 23 were enrolled. Median age was 38 years and median time since transplant procedure was 38 years. The most frequent transplant types were liver (35%) and lung (30%). Median anti-gE levels significantly increased from V1 to V3 (p=0001) and V2 to V3 (p<0001), even though only 55% had a positive seroresponse. Median polyfunctional CD4 T-cells counts increased from V1 to V2 (54/10 vs 104/10 cells; p=0041), and from V2 to V3 (380/10; p=0002). Most adverse events were mild with no rejection episodes. CONCLUSION: RZV was safe and elicited significant humoral and cellular responses in VZV-seronegative SOT patients, and has the potential to be considered as a preventive strategy against primary varicella. |
A tale of two viruses: Coinfections of monkeypox and varicella zoster virus in the Democratic Republic of Congo
Hughes CM , Liu L , Davidson WB , Radford KW , Wilkins K , Monroe B , Metcalfe MG , Likafi T , Lushima RS , Kabamba J , Nguete B , Malekani J , Pukuta E , Karhemere S , Muyembe Tamfum JJ , Wemakoy EO , Reynolds MG , Schmid DS , McCollum AM . Am J Trop Med Hyg 2020 104 (2) 604-611 Recent enhanced monkeypox (MPX) surveillance in the Democratic Republic of Congo, where MPX is endemic, has uncovered multiple cases of MPX and varicella zoster virus (VZV) coinfections. The purpose of this study was to verify if coinfections occur and to characterize the clinical nature of these cases. Clinical, epidemiological, and laboratory results were used to investigate MPX/VZV coinfections. A coinfection was defined as a patient with at least one Orthopoxvirus/MPX-positive sample and at least one VZV-positive sample within the same disease event. Between September 2009 and April 2014, 134 of the 1,107 (12.1%) suspected MPX cases were confirmed as MPX/VZV coinfections. Coinfections were more likely to report symptoms than VZV-alone cases and less likely than MPX-alone cases. Significantly higher lesion counts were observed for coinfection cases than for VZV-alone but less than MPX-alone cases. Discernible differences in symptom and rash severity were detected for coinfection cases compared with those with MPX or VZV alone. Findings indicate infection with both MPX and VZV could modulate infection severity. Collection of multiple lesion samples allows for the opportunity to detect coinfections. As this program continues, it will be important to continue these procedures to assess variations in the proportion of coinfected cases over time. |
Amylin, Abeta42, and amyloid in VZV vasculopathy cerebrospinal fluid and infected vascular cells
Bubak AN , Beseler C , Como CN , Coughlan CM , Johnson NR , Hassell JE , Burnet AM , Mescher T , Schmid DS , Coleman C , Mahalingam R , Cohrs RJ , Boyd TD , Potter H , Shilleh AH , Russ HA , Nagel MA . J Infect Dis 2020 223 (7) 1284-1294 BACKGROUND: VZV vasculopathy is characterized by persistent arterial inflammation leading to stroke. Studies show that VZV induces amyloid formation that may aggravate vasculitis. Thus, we determined if VZV central nervous system (CNS) infection produces amyloid. METHODS: Aβ peptides, amylin, and amyloid were measured in CSF from 16 VZV vasculopathy subjects and 36 stroke controls. To determine if infection induced amyloid deposition, mock- and VZV-infected quiescent primary human perineurial cells (qHPNCs), present in vasculature, were analyzed for intracellular amyloidogenic transcripts/proteins and amyloid. Supernatants were assayed for amyloidogenic peptides and ability to induce amyloid formation. To determine amylin's function during infection, amylin was knocked down with siRNA and viral cDNA quantitated. RESULTS: Compared to controls, VZV vasculopathy CSF had increased amyloid that positively correlated with amylin and anti-VZV antibody levels; Aβ40 was reduced and Aβ42 unchanged. Intracellular amylin, Aβ42, and amyloid were seen only in VZV-infected qHPNCs. VZV-infected supernatant formed amyloid fibrils following addition of amyloidogenic peptides. Amylin knockdown decreased viral cDNA. CONCLUSIONS: VZV infection increased levels of amyloidogenic peptides and amyloid in CSF and qHPNCs, indicating that VZV-induced amyloid deposition may contribute to persistent arterial inflammation in VZV vasculopathy. In addition, we identified a novel proviral function of amylin. |
Analysis of the reiteration regions (R1 to R5) of varicella-zoster virus.
Jensen NJ , Depledge DP , Ng TFF , Leung J , Quinlivan M , Radford KW , Folster J , Tseng HF , LaRussa P , Jacobsen SJ , Breuer J , Schmid DS . Virology 2020 546 38-50 The varicella-zoster virus (VZV) genome, comprises both unique and repeated regions. The genome also includes reiteration regions, designated R1 to R5, which are tandemly repeating sequences termed elements. These regions represent an understudied feature of the VZV genome. The R4 region is duplicated, with one copy in the internal repeat short (IRs) which we designated R4A and a second copy in the terminal repeat short (TRs) termed R4B. We developed primers to amplify and Sanger sequence these regions, including independent amplification of both R4 regions. Reiteration regions from >80 cases of PCR-confirmed shingles were sequenced and analyzed. Complete genome sequences for the remaining portions of these viruses were determined using Illumina MiSeq. We identified 28 elements not previously reported, including at least one element for each R region. Length heterogeneity was substantial in R3, R4A and R4B. Length heterogeneity between the two copies of R4 was common. |
Persistence of varicella zoster virus specific plasma cells in adult human bone marrow following childhood vaccination
Eberhardt CS , Wieland A , Nasti TH , Grifoni A , Wilson E , Schmid DS , Pulendran B , Sette A , Waller EK , Rouphael N , Ahmed R . J Virol 2020 94 (13) Childhood immunization with the live-attenuated varicella zoster virus (VZV) vaccine induces protective immune responses. Routine VZV vaccination started only two decades ago and thus there are few studies examining the longevity of vaccine-induced immunity. Herein, we analyzed the quantity of VZV-specific plasma cells (PCs) and CD4 T cells in the bone marrow (BM) of healthy young adults (n=15) following childhood VZV immunization. Long-lived BM resident plasma cells constitutively secrete antibodies and we detected VZV-specific PCs in the BM of all subjects. Anti-VZV plasma antibody titers correlated positively with the number of VZV-specific BM PCs. Furthermore, we quantified the number of IFNgamma-producing CD4 T cells specific for VZV glycoprotein E and all other structural and non-structural VZV proteins in both BM and blood (PBMCs). The frequency of VZV-specific IFNgamma-producing CD4 T cells was significantly higher in PBMCs compared to BM. Our study shows that VZV-specific PCs and VZV-specific CD4 memory T cells persist up to 20 years after vaccination. These findings indicate that childhood VZV vaccination can elicit long-lived immune memory responses in the bone marrow.IMPORTANCE Childhood varicella zoster virus (VZV) immunization induces immune memory responses that protect against primary VZV infection, chickenpox. In the US, routine childhood VZV vaccination has been introduced only two decades ago. Hence, there is limited information on the longevity of B and CD4 T cell memory which are both important for protection. Here we show in fifteen healthy young adults that VZV-specific B and CD4 T cell responses are detectable in bone marrow (BM) and blood up to 20 years after vaccination. Specifically, we measured antibody-secreting plasma cells in the BM and VZV-specific CD4 T cells in BM and blood. These findings suggest that childhood VZV vaccination induces long-lived immunity. |
Clinical diagnostic testing for human cytomegalovirus infections
Razonable RR , Inoue N , Pinninti SG , Boppana SB , Lazzarotto T , Gabrielli L , Simonazzi G , Pellett PE , Schmid DS . J Infect Dis 2020 221 S74-s85 Human cytomegalovirus (HCMV) infections are among the most common complications arising in transplant patients, elevating the risk of various complications including loss of graft and death. HCMV infections are also responsible for more congenital infections worldwide than any other agent. Congenital HCMV (cCMV) infections are the leading nongenetic cause of sensorineural hearing loss and a source of significant neurological disabilities in children. While there is overlap in the clinical and laboratory approaches to diagnosis of HCMV infections in these settings, the management, follow-up, treatment, and diagnostic strategies differ considerably. As yet, no country has implemented a universal screening program for cCMV. Here, we summarize the issues, limitations, and application of diagnostic strategies for transplant recipients and congenital infection, including examples of screening programs for congenital HCMV that have been implemented at several centers in Japan, Italy, and the United States. |
Notes from the field: Monkey bite in a public park and possible exposure to herpes B virus - Thailand, 2018
Wu AC , Rekant SI , Baca ER , Jenkins RM , Perelygina LM , Hilliard JK , Schmid DS , Leman RF . MMWR Morb Mortal Wkly Rep 2020 69 (9) 247-248 On January 7, 2019, the Oregon Public Health Division (OPHD) was contacted by a local health department regarding an Oregon teen who, on December 24, 2018, was bitten by a macaque monkey (Figure) in a public park in Phuket, Thailand. The bleeding wound was immediately rinsed with bottled water without soap. Subsequently, hotel staff members applied a topical pain reliever. The following day, the teen went to a local clinic in Thailand and received the first dose of rabies postexposure prophylaxis vaccine; rabies immune globulin was not administered. She received 2 additional doses of rabies vaccine while in Thailand. | | On January 5, 2019, the patient left Thailand and was evaluated by a physician in Oregon on January 7. The physician contacted the local health department, seeking guidance about when to administer the final dose of rabies vaccine. Upon learning about the macaque bite, the local health department contacted OPHD, where staff members expressed concern about possible exposure to Macacine herpesvirus 1 (B virus). This virus, commonly found in macaques,* can, in rare cases, cause severe encephalitic infection in humans if not treated promptly (1). The case fatality rate of untreated B virus infection approaches 80% (2). OPHD contacted CDC, and the National B Virus Resource Center (NBVRC) in Atlanta, Georgia, to discuss testing.† |
Vaccine Oka varicella meningitis in two adolescents
Harrington WE , Mato S , Burroughs L , Carpenter PA , Gershon A , Schmid DS , Englund JA . Pediatrics 2019 144 (6) The live-attenuated varicella vaccine, a routine immunization in the United States since 1995, is both safe and effective. Like wild-type varicella-zoster virus, however, vaccine Oka (vOka) varicella can establish latency and reactivate as herpes zoster, rarely leading to serious disease, particularly among immunocompromised hosts. Previous cases of reactivated vOka resulting in meningitis have been described in young children who received a single dose of varicella vaccine; less is known about vOka reactivation in older children after the 2-dose vaccine series. We present 2 adolescents with reactivated vOka meningitis, 1 immunocompetent and 1 immunocompromised, both of whom received 2 doses of varicella vaccine many years before as children. Pediatricians should be aware of the potential of vOka varicella to reactivate and cause clinically significant central nervous system disease in vaccinated children and adolescents. |
Recurrent herpes zoster in the Shingles Prevention Study: Are second episodes caused by the same varicella-zoster virus strain?
Harbecke R , Jensen NJ , Depledge DP , Johnson GR , Ashbaugh ME , Schmid DS , Breuer J , Levin MJ , Oxman MN . Vaccine 2019 38 (2) 150-157 Herpes zoster (HZ) is caused by reactivation of varicella zoster virus (VZV) that established latency in sensory and autonomic neurons during primary infection. In the Shingles Prevention Study (SPS), a large efficacy trial of live attenuated Oka/Merck zoster vaccine (ZVL), PCR-confirmed second episodes of HZ occurred in two of 660 placebo and one of 321 ZVL recipients with documented HZ during a mean follow-up of 3.13years. An additional two ZVL recipients experienced a second episode of HZ in the Long-Term Persistence Substudy. All episodes of HZ were caused by wild-type VZV. The first and second episodes of HZ occurred in different dermatomes in each of these five participants, with contralateral recurrences in two. Time between first and second episodes ranged from 12 to 28months. One of the five participants, who was immunocompetent on study enrollment, was immunocompromised at the onset of his first and second episodes of HZ. VZV DNA isolated from rash lesions from the first and second episodes of HZ was used to sequence the full-length VZV genomes. For the unique-sequence regions of the VZV genome, we employed target enrichment of VZV DNA, followed by deep sequencing. For the reiteration regions, we used PCR amplification and Sanger sequencing. Our analysis and comparison of the VZV genomes from the first and second episodes of HZ in each of the five participants indicate that both episodes were caused by the same VZV strain. This is consistent with the extraordinary stability of VZV during the replication phase of varicella and the subsequent establishment of latency in sensory ganglia throughout the body. Our observations also indicate that VZV is stable during the persistence of latency and the subsequent reactivation and replication that results in HZ. |
Genotypes of clinical varicella-zoster virus isolates from Manaus, Brazil.
Bastos MS , Folster J , Alvarenga OP , Sampaio DA , Rabelo RMP , Joao GAP , Lacerda MVG , Schmid DS . Rev Soc Bras Med Trop 2019 52 e20180166 INTRODUCTION: Vaccination against varicella-zoster virus (VZV) has been effective and safe in countries that routinely administer the vaccine. Brazil began universal VZV vaccination in 2013. This study aimed to identify VZV genotypes present in Manaus, Brazil prior to widespread immunization. METHODS: Vesicular lesions or cerebral-spinal-fluid samples were collected from patients diagnosed with VZV, herpes zoster, or meningitis/encephalitis. DNA was extracted, amplified, and sequenced. RESULTS: Half the isolates were clade-5 viruses and the remaining were divided between the European clades 1 and 3. CONCLUSIONS: This study provides insights into the circulating VZV genotypes in Manaus prior to widespread vaccination. |
Challenges and solutions for instituting an efficient maintenance program for laboratory equipment in Central Asian, and developing world, countries
Ikranbegiin R , Schmid G , Hoos D , Young A , Della-Latta P , Spearman P , Ramos A , Alemayehu B , Achmetova B , Nauryzova G , Albetkova A . BMC Public Health 2019 19 476 We review the current state of quality assurance in laboratories of the five Central Asia Republics (CARs), focusing on laboratory equipment, and compare quality assurance approaches with CLSI standards. The laboratories of the CARs faced exceptional challenges including highly-structured laboratory systems that retain centralized and outmoded Soviet-era approaches to quality assurance, considerably jeopardizing the validity of laboratory tests. The relative isolation of the CARs, based on geography and almost exclusive use of the Russian language, further hamper change. CARs must make high-level government decisions to widely implement quality assurance programs within their laboratory systems, within which approaches to the management of laboratory equipment will be a prominent part. |
Mixing it up: New insights into interspecies recombination between herpes simplex virus type 1 and 2
Schmid DS . J Infect Dis 2019 221 (8) 1208-1209 Herpes simplex viruses (HSV-1 and HSV-2) are closely related alphaherpesviruses, with more than 80% identity at the deoxyribonucleic acid (DNA) sequence level [1]. More than two thirds of the world's population is estimated to have been infected with one or both viruses. The divergence of the common ancestor to these viruses is thought to have coincided with the separation of the human and chimpanzee lineages approximately 6 million years ago, leading to separate evolution of HSV-1 and HSV-2, respectively. Zoonotic transmission of HSV-2 to an extinct early hominid occurred approximately one and a half million years ago [2]. No other primate species are known to serve as common hosts for 2 distinct herpes simplex species. |
Patient report of herpes zoster pain: Incremental benefits of zoster vaccine live
Bruxvoort KJ , Liang AS , Harpaz R , Qian L , Sy LS , LaRussa P , Schmid DS , Luo Y , Takhar H , Tseng HF . Vaccine 2019 37 (26) 3478-3484 INTRODUCTION: Pain following herpes zoster (HZ) can persist for months and negatively impact quality of life. To evaluate the effect of zoster vaccine live (ZVL) on progression of pain following HZ, we conducted a prospective cohort study of HZ cases at Kaiser Permanente Southern California. METHODS: ZVL vaccinated and unvaccinated members aged >/=60years with laboratory-confirmed HZ from January 18, 2012 to February 26, 2015 were followed up within 5days of HZ diagnosis, and at 30, 60, and 90days after diagnosis. Pain was assessed with the Zoster Brief Pain Inventory (ZBPI) on a 0-10 scale, using cut-points of >/=3, >/=5, and >/=7, with postherpetic neuralgia (PHN) defined as pain >/=3 at 90days. Log binomial regression was used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) associated with pain, comparing vaccinated versus unvaccinated HZ patients. RESULTS: We interviewed 509 vaccinated and 509 unvaccinated HZ patients. ZVL was associated with significantly lower risks of HZ-related pain at all time-points. The risk of PHN in vaccinated and unvaccinated patients, respectively, was 9.2% and 15.4% (aRR=0.594, 95% CI: 0.413, 0.854); 2.0% and 4.8% of these patients reported pain >/=7 (aRR=0.332, 95% CI: 0.153, 0.721). Irrespective of vaccination, the risk of PHN was lower in adults aged <70years versus those >/=70years and was similar or lower in females versus males. CONCLUSION: We used laboratory confirmation of HZ cases and patient survey to show that aside from preventing HZ, ZVL reduced HZ-related pain and prevented PHN among vaccine recipients who experienced HZ. Observational studies will be needed to evaluate long-term effectiveness of the new recombinant zoster vaccine and its benefits in protecting patients against PHN. |
Varicella in Tshuapa Province, Democratic Republic of Congo, 2009-2014
Leung J , McCollum AM , Radford K , Hughes C , Lopez AS , Guagliardo SAJ , Nguete B , Likafi T , Kabamba J , Malekani J , Lushima RS , Pukuta E , Karhemere S , Tamfum JJM , Reynolds MG , Okitolonda EW , Schmid DS , Marin M . Trop Med Int Health 2019 24 (7) 839-848 OBJECTIVE: To describe varicella cases in Tshuapa Province of the Democratic Republic of the Congo identified during monkeypox surveillance. METHODS: Demographic, clinical, and epidemiological data were collected from each suspected monkeypox case 2009-2014. Samples were tested by PCR for both Orthopoxviruses and varicella-zoster virus (VZV); a subset of VZV positive samples were genotyped. We defined a varicella case as a rash illness with laboratory-confirmed VZV. RESULTS: 366 varicella cases were identified; 66% were </=19 years old. Most patients had non-typical varicella rash with lesions reported as the same size and stage of evolution (86%), deep and profound (91%), on palms of hands and/or soles of feet (86%), and not itchy (49%). Many had non-typical signs and symptoms, such as lymphadenopathy (70%) and sensitivity to light (23%). A higher proportion of persons aged >/=20 years than persons aged </=19 years had >/=50 lesions (79% versus 65%, p = 0.007) and were bedridden (15% versus 9%, p = 0.056). All VZV isolates genotyped from 79 varicella cases were clade 5. During the surveillance period, one possible VZV-related death occurred in a 7 year-old child. CONCLUSIONS: A large proportion of patients presented with nontypical varicella rash and clinical signs and symptoms, highlighting challenges identifying varicella in an area with endemic monkeypox. Continued surveillance and laboratory diagnosis will help in rapid identification and control of both monkeypox and varicella and improve our understanding of varicella epidemiology in Africa. This article is protected by copyright. All rights reserved. |
Systematic review of how Play Streets impact opportunities for active play, physical activity, neighborhoods, and communities
Umstattd Meyer MR , Bridges CN , Schmid TL , Hecht AA , Pollack Porter KM . BMC Public Health 2019 19 (1) 335 BACKGROUND: Active play and physical activity are important for preventing childhood obesity, building healthy bones and muscles, reducing anxiety and stress, and increasing self-esteem. Unfortunately, safe and accessible play places are often lacking in under-resourced communities. Play Streets (temporary closure of streets) are an understudied intervention that provide safe places for children, adolescents, and their families to actively play. This systematic review examines how Play Streets impact opportunities for children and adolescents to engage in safe active play and physical activity, and for communities and neighborhoods. Methods for evaluating Play Streets were also examined. METHODS: A systematic literature review was conducted in Academic Search Complete, CINHAL, PsycINFO, PubMED, Web of Science, and Google Scholar. Peer-reviewed intervention studies published worldwide were included if they were published in English, through December 2017 and documented free-to-access Play Streets or other temporary spaces that incorporated a designated area for children and/or adolescents to engage in active play. Systematic data extraction documented sample, implementation, and measurement characteristics and outcomes. RESULTS: Of 180 reviewed abstracts, 6 studies met inclusion criteria. Studies were conducted in five different countries (n = 2 in U.S.), using mostly cross-sectional study designs (n = 4). Physical activity outcomes were measured in half of the studies; one used observational and self-report measures, and two used device-based and self-report measures. In general, Play Streets provided safe places for child play, increased sense of community, and when measured, data suggest increased physical activity overall and during Play Streets. CONCLUSIONS: Play Streets can create safe places for children to actively play, with promise of increasing physical activity and strengthening community. Given the popularity of Play Streets and the potential impact for active play, physical activity, and community level benefits, more rigorous evaluations and systematic reporting of Play Streets' evaluations are needed. |
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