Background Hemagglutination inhibition (HAI) titers to the live-attenuated influenza vaccine (LAIV4) are typically lower than its counterpart egg-based inactivated influenza vaccines (IIV). Similar comparisons have not been made between LAIV4 and the 4-strain, cell-culture inactivated influenza vaccine (ccIIV4). We compared healthy children and young adult HAI titers against the 2019-2020 LAIV4 and ccIIV4.Methods Participants aged 4-21 years were randomized 1:1 to receive ccIIV4 (n =100) or LAIV4 (n=98). Blood was drawn prevaccination and on day 28 (21-35) post vaccination. HAI assays against egg-grown A/H1N1, A/H3N2, both vaccine B strains and cell-grown A/H3N2 antigens were conducted. Outcomes were geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers.Results GMTs to A/H1N1, A/H3N2 and B/Victoria increased following both ccIIV and LAIV and to B/Yamagata following ccIIV (p<0.05). The GMFR range was 2.4-3.0 times higher for ccIIV4 than for LAIV4 (p<0.001). Within vaccine types, egg-grown A/H3N2 GMTs were higher (p<0.05) than cell-grown GMTs [ccIIV4 day 28: egg=205 (95% CI: 178-237); cell=136 (95% CI:113-165); LAIV4 day 28: egg=96 (95% CI: 83-112); cell=63 (95% CI: 58-74)]. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar. Pre-vaccination titers inversely predicted GMFR.Conclusion The HAI response to ccIIV4 was greater than LAIV4 in this study of mostly older children, and day 0 HAI titers inversely predicted GMFR for both vaccines. For both vaccines, the A/H3N2 cell-grown antigen levels were lower than egg-grown, but the GMFR for cell-grown and egg-grown did not differ significantly within vaccine type.Clinical Trials No NCT03982069Competing Interest StatementConflict of Interest: RKZ has received funding by Sanofi for an unrelated study. MPN has research funding from Merck & Co., Inc. for an unrelated study. JMM has received funding from Merck, Sharp and Dohme for an unrelated study.Clinical TrialClinical Trials No.: NCT03982069Funding StatementThis work was supported by the Centers for Disease Control and Prevention (CDC) [5U01IP001035] and by National Institutes of Health (NIH) [UL1TR001857], [KL2 TR001856], and/or [TL1 TR001858]. This work represents the views of the authors and not the CDC or NIH. Pennsylvania Statewide Immunization Information System (PA-SIIS) vaccine registry was used to verify vaccination status. These data were supplied in part by the Bureau of Health Statistics & Registries, Pennsylvania Department of Health, Harrisburg, Pennsylvania. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations, or conclusions. REDCap and the Department of Biomedical Informatics grant support (Clinical and Translational Sciences Institute at the University of Pittsburgh Grant Number UL1-TR-001857). Study data were collected and managed using REDCap electronic data capture tools hosted at the University of Pittsburgh. Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The Institutional Review Boards at the University of Pittsburgh and the Centers for Disease Control and Prevention (CDC) approved this study. Written informed consent and assent, where appropriate, were obtained from all participants and/or their parents/legal guardians prior to beginning study procedures.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field expla ning why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData can be made available upon request.HAIhemagglutination inhibition assayIIVinactivated influenza vaccineccIIV4cell-culture-based inactivated influenza vaccine quadrivalentLAIV4Egg-based live attenuated influenza vaccine quadrivalentEMRElectronic medical recordRDEReceptor-destroying enzymePBSPhosphate-buffered salineCDCCenters for Disease Control and PreventionFDAFood and Drug AdministrationGMTGeometric mean titersGMFRGeometric mean fold riseACIPAdvisory Committee on Immunization PracticePA-SIISPennsylvania Statewide Immunization Information System

BACKGROUND: Few studies have focused on the immune response to more recent influenza vaccine formulations such as cell-cultured inactivated influenza vaccine (ccIIV4) or live-attenuated influenza vaccine (LAIV4) in older children and young adults, or differences in immunoglobulin response using newer antibody landscape technology. METHODS: Participants ages 4-21 were randomized to receive ccIIV4 (n = 112) or LAIV4 (n = 118). A novel high-throughput multiplex influenza antibody detection assay was used to provide detailed IgG, IgA, and IgM antibody isotypes, along with hemagglutination inhibition levels (HAI), measured pre- and 28 days post-vaccination. RESULTS: The HAI and immunoglobulin isotype response to ccIIV4 was greater than LAIV4, with significant increases in IgG but not IgA or IgM. The youngest participants had the highest LAIV4 response. Prior LAIV4 vaccination was associated with a higher response to current season ccIIV4. Cross-reactive A/Delaware/55/2019(H1N1)pdm09 antibodies were present pre-vaccination and increased in response to ccIIV4, but not LAIV4. Immunoglobulin assays strongly correlated with and confirmed the findings of HAI titers to measure immune response. CONCLUSIONS: Age and prior season vaccination may play a role in the immune response in children and young adults to ccIIV4 and LAIV4. While immunoglobulin isotypes provide high-level antigen-specific information, HAI titers alone can provide a meaningful representation of day 28 post-vaccination response. CLINICAL TRIALS NO: NCT03982069.

BACKGROUND: Hemagglutination inhibition (HAI) titers to the live-attenuated influenza vaccine (LAIV4) are typically lower than its counterpart egg-based inactivated influenza vaccines (IIV). Similar comparisons have not been made between LAIV4 and the 4-strain, cell-culture inactivated influenza vaccine (ccIIV4). We compared healthy children's and young adults' HAI titers against the 2019-2020 LAIV4 and ccIIV4. METHODS: Participants aged 4-21 years were randomized 1:1 to receive ccIIV4 (n = 100) or LAIV4 (n = 98). Blood was drawn prevaccination and on day 28 (21-35) post vaccination. HAI assays against egg-grown A/H1N1, A/H3N2, both vaccine B strains and cell-grown A/H3N2 antigens were conducted. Primary outcomes were geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers. RESULTS: GMTs to A/H1N1, A/H3N2 and B/Victoria increased following both ccIIV and LAIV and to B/Yamagata following ccIIV (p < 0.05). The GMFR range was 2.4-3.0 times higher for ccIIV4 than for LAIV4 (p < 0.001). Within vaccine types, egg-grown A/H3N2 GMTs were higher (p < 0.05) than cell-grown GMTs [ccIIV4 day 28: egg = 205 (95% CI: 178-237); cell = 136 (95% CI:113-165); LAIV4 day 28: egg = 96 (95% CI: 83-112); cell = 63 (95% CI: 58-74)]. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar. Pre-vaccination titers inversely predicted GMFR. CONCLUSION: The HAI response to ccIIV4 was greater than LAIV4 in this study of mostly older children, and day 0 HAI titers inversely predicted GMFR for both vaccines. Lower prevaccination titers were associated with greater GMFR in both vaccine groups.

In March 2021, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by four families (Aliusviridae, Crepuscuviridae, Myriaviridae, and Natareviridae), three subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae), 42 genera, and 200 species. Thirty-nine species were renamed and/or moved and seven species were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.

Physical frailty's impact on hemagglutination inhibition antibody titers (HAI) and peripheral blood mononuclear cell (PBMC) transcriptional responses after influenza vaccination is unclear. Physical frailty was assessed using the 5-item Fried frailty phenotype in 168 community- and assisted-living adults ≥55 years of age during an observational study. Blood was drawn before, 3, 7, and 28 days post-vaccination with the 2017-2018 inactivated influenza vaccine. HAI response to the A/H1N1 strain was measured at Days 0 and 28 using seropositivity, seroconversion, log(2) HAI titers, and fold-rise in log(2) HAI titers. RNA sequencing of PBMCs from Days 0, 3 and 7 was measured in 28 participants and compared using pathway analyses. Frailty was not significantly associated with any HAI outcome in multivariable models. Compared with non-frail participants, frail participants expressed decreased cell proliferation, metabolism, antibody production, and interferon signaling genes. Conversely, frail participants showed elevated gene expression in IL-8 signaling, T-cell exhaustion, and oxidative stress pathways compared with non-frail participants. These results suggest that reduced effectiveness of influenza vaccine among older, frail individuals may be attributed to immunosenescence-related changes in PBMCs that are not reflected in antibody levels.

Influenza vaccination is the primary way to prevent influenza, yet influenza vaccination coverage remains low in the United States. Previous studies have shown that children residing in rural areas have less access to healthcare and lower vaccination coverage for some vaccines. Influenza vaccination coverage among children 6 months-17 years by rural/urban residence during the 2011-12 through 2018-19 influenza seasons was examined using National Immunization Survey-Flu data. The Council of American Survey Research Organizations response rates for National Immunization Survey-Flu ranged from 48% to 65% (2011-12 through the 2017-18 seasons) for the landline sample and 20%-39% (2011-12 through the 2018-19 seasons) for the cellular telephone sample. Children residing in rural areas had influenza vaccination coverage that ranged from 7.9 (2012-13 season) to 12.6 (2016-17 season) percentage points lower than children residing in urban areas, and ranged from 4.5 (2012-13 season) to 7.4 (2016-17 season) percentage points lower than children residing in suburban areas. The differences in influenza vaccination coverage among rural, suburban, and urban children were consistent over the eight seasons studied. Lower influenza vaccination coverage was observed among rural children regardless of child's age, mother's education, household income, or number of children under 18 years of age in the household. Rural versus urban and suburban differences in influenza vaccination coverage remained statistically significant while adjusting for selected sociodemographic characteristics. A better understanding of the reasons for lower childhood influenza vaccination coverage for children in rural and suburban areas is needed.

OBJECTIVE: The objective was to compare estimates of childhood influenza vaccination across 7 consecutive influenza seasons based on 2 survey systems. METHODS: We analyzed data from the National Health Interview Survey (NHIS) and the National Immunization Survey-Flu (NIS-Flu) using Kaplan-Meier survival analysis to estimate receipt, based on parental report, of at least 1 dose of influenza vaccine among children aged 6 months to 17 years. RESULTS: We found no significant increasing trend in influenza vaccination coverage among children overall from 2012 to 2018 based on the NHIS or from 2012 to 2019 based on the NIS-Flu. We found 4 seasons with a significant increase in influenza vaccination coverage compared with the previous season (2012-2013 [NHIS, NIS-Flu], 2013-2014 [NIS-Flu], 2017-2018 [NHIS], and 2018-2019 [NIS-Flu]). As of the 2018-2019 season, based on NIS-Flu, influenza vaccination coverage was only 62.6%. Children with health conditions that put them at increased risk for complications from influenza had higher influenza vaccination coverage than children without these health conditions for all the seasons studied except 2014-2015. For all seasons studied, influenza vaccination coverage estimates for children were higher based on NIS-Flu data compared with NHIS data. Trends across seasons and differences in vaccination coverage between age groups were similar between the 2 surveys. CONCLUSIONS: Influenza vaccination coverage among children appears to have plateaued. Only about half of the children in the United States were vaccinated against influenza. Improvements in measurement of influenza vaccination and development and review of strategies to increase childhood influenza vaccination coverage are needed.

Influenza D virus (IDV) of the Orthomyxoviridae family has a wide host range and a broad geographical distribution. Recent IDV outbreaks in swine along with serological and genetic evidence of IDV infection in humans have raised concerns regarding the zoonotic potential of this virus. To better study IDV at the molecular level, a reverse-genetics system (RGS) is urgently needed, but to date, no RGS had been described for IDV. In this study, we rescued the recombinant influenza D/swine/Oklahoma/1314/2011 (D/OK) virus by using a bidirectional seven-plasmid-based system and further characterized rescued viruses in terms of growth kinetics, replication stability, and receptor-binding capacity. Our results collectively demonstrated that RGS-derived viruses resembled the parental viruses for these properties, thereby supporting the utility of this RGS to study IDV infection biology. In addition, we developed an IDV minigenome replication assay and identified the E697K mutation in PB1 and the L462F mutation in PB2 that directly affected the activity of the IDV ribonucleoprotein (RNP) complex, resulting in either attenuated or replication-incompetent viruses. Finally, by using the minigenome replication assay, we demonstrated that a single nucleotide polymorphism at position 5 of the 3' conserved noncoding region in IDV and influenza C virus (ICV) resulted in the inefficient cross-recognition of the heterotypic promoter by the viral RNP complex. In conclusion, we successfully developed a minigenome replication assay and a robust reverse-genetics system that can be used to further study replication, tropism, and pathogenesis of IDV.IMPORTANCE Influenza D virus (IDV) is a new type of influenza virus that uses cattle as the primary reservoir and infects multiple agricultural animals. Increased outbreaks in pigs and serological and genetic evidence of human infection have raised concerns about potential IDV adaptation in humans. Here, we have developed a plasmid-based IDV reverse-genetics system that can generate infectious viruses with replication kinetics similar to those of wild-type viruses following transfection of cultured cells. Further characterization demonstrated that viruses rescued from the described RGS resembled the parental viruses in biological and receptor-binding properties. We also developed and validated an IDV minireplicon reporter system that specifically measures viral RNA polymerase activity. In summary, the reverse-genetics system and minireplicon reporter assay described in this study should be of value in identifying viral determinants of cross-species transmission and pathogenicity of novel influenza D viruses.

Objective Asian Americans' food purchasing, cooking, and eating patterns are not well understood. Greater insight into these behaviors is urgently needed to guide public health interventions of dietary behaviors in this population. The present study aims to examine the effects of a community-level intervention on food purchasing and preparation, nutrition knowledge, and health awareness in Asian Americans. Methods From 2015 to 2017, we conducted the Improving Diets with an Ecological Approach for Lifestyle (IDEAL-REACH) intervention to increase access to healthy food or beverage options for the Asian-American population in the Philadelphia metropolitan area. Participants (1110 at pre- and 1098 at post-assessment) were recruited from 31 community-based organizations (CBOs). We assessed Asian Americans' dietary behaviors, nutrition knowledge, and awareness of heart health. Results The results of pre-post intervention comparisons showed that the IDEAL-REACH intervention was successful in promoting whole grains consumption, reducing sodium consumption, and raising knowledge and awareness related to nutrition and heart health. Conclusions To our knowledge, this is one of the first initiatives in the U.S. to engage CBOs to promote healthier dietary behaviors. The findings show that CBOs serve as a powerful platform for community-level interventions to improve healthy nutrition behaviors in Asian-American communities.

BACKGROUND: Patient reminders are recommended to increase vaccination rates. The objectives of this study were to estimate the percentage of children 6months-17years for whom a patient reminder for influenza vaccination was received by a child's parent or guardian, estimate influenza vaccination coverage by receipt of a patient reminder, and identify factors associated with receipt of a patient reminder. METHODS: National Immunization Survey-Flu (NIS-Flu) data for the 2013-14 influenza season were analyzed. Tests of association between patient reminders and demographic characteristics were conducted using Wald chi-square tests and pairwise comparison t-tests. Multivariable logistic regression was used to determine variables independently associated with receiving a patient reminder. RESULTS: Approximately 22% of children had a parent or guardian report receiving a patient reminder for influenza vaccination for their child, ranging from 12.9% in Idaho to 41.2% in Mississippi. Children with a patient reminder were more likely to be vaccinated compared with children without a patient reminder (73.7% versus 55.5%). In the multivariable model, reminder receipt was higher for children 6-23months compared with children 13-17years, black children compared with white children, and children whose parent completed the survey in English compared with children whose parent completed the survey in a language other than English or Spanish. CONCLUSIONS: Although patient reminders are associated with a higher likelihood of influenza vaccination, nationally, less than one-fourth of children had a parent report receiving one. Despite being based on parental report, with its limitations, this study suggests that increasing the number of parents who receive patient reminders for their children may improve vaccination coverage among children.

INTRODUCTION: Staying home when sick can reduce the spread of influenza. The objectives of this study were to quantify the percentage of workers who had paid sick leave (PSL) benefits, examine sociodemographic characteristics that may be associated with having these benefits, and examine the association between having PSL benefits and use of sick days and influenza vaccination status. METHODS: The public-use dataset from the 2009 National H1N1 Flu Survey (NHFS) were analyzed in 2017. Wald chi-square tests and t-tests were used to test for associations between having PSL benefits and sociodemographic characteristics and industry and occupation groups, the associations between having PSL benefits and seeking treatment when sick with influenza-like illness (ILI), and taking days off work when sick with ILI. Logistic regression was used to determine variables associated with having PSL benefits and the association between having PSL benefits and influenza vaccination status. RESULTS: Sixty-one percent of employed adults reported having PSL benefits during the 2009-10 influenza season. Being younger, female, Hispanic, less educated, or a farm/blue collar worker were associated with reduced likelihood of having PSL benefits. Not having PSL benefits was associated with a lower likelihood of receiving an influenza vaccination and visiting a health professional when sick with ILI. CONCLUSIONS: The percentage of workers who have PSL benefits differs by sociodemographic characteristics and industry/occupation groups. Offering PSL benefits along with promoting influenza vaccination and encouraging employees with ILI to stay home can increase influenza vaccination coverage and help control the spread of influenza.

BACKGROUND: Provider recommendation is associated with influenza vaccination receipt. The objectives of this study were to estimate the percentage of children 6months-17years for whom a provider recommendation for influenza vaccination was received, identify factors associated with receipt of provider recommendation, and evaluate the association between provider recommendation and influenza vaccination status among children. METHODS: National Immunization Survey-Flu (NIS-Flu) parentally reported data for the 2013-14, 2014-15, and 2015-16 seasons were analyzed. Tests of association between provider recommendation and demographic characteristics were conducted using Wald chi-square tests and pairwise comparison t-tests. Multivariable logistic regression was used to determine variables independently associated with receiving provider recommendation and the association between provider recommendation and influenza vaccination status. RESULTS: Approximately 70% of children had a parent report receiving a provider recommendation for influenza vaccination for their child. The strongest association between receipt of provider recommendation and demographic characteristics was with child's age, with younger children (6-23months, 2-4years, and 5-12years) being more likely to have a provider recommendation than older children (13-17years). In addition, children living in a household above poverty with household income >$75,000 were more likely to have a parent report receipt of a provider recommendation than children living below poverty. Children with a provider recommendation were twice as likely to be vaccinated than those without. CONCLUSIONS: This study affirms the importance of provider recommendation for influenza vaccination among children. Ensuring that parents of all children receive a provider recommendation may improve vaccination coverage.

INTRODUCTION: Depending upon influenza vaccination history, children aged 6 months-8 years need one or two doses of influenza vaccine to be considered fully vaccinated. The objectives of this study were to quantify the percentage of children aged 6 months-8 years who were fully vaccinated against influenza based on parental report, overall, by state, and by sociodemographic characteristics, and to examine sociodemographic characteristics associated with being fully vaccinated. METHODS: Data from the National Immunization Survey-Flu for the 2012-2013 and 2013-2014 influenza seasons were analyzed in 2015 using the Kaplan-Meier method to produce vaccination coverage estimates. Wald chi-square tests were used to test for bivariate associations, and Cox proportional hazards models were used to test for demographic characteristics independently associated with the child being fully vaccinated. RESULTS: The percentages of children aged 6 months-8 years who were fully vaccinated during the 2012-2013 and 2013-2014 influenza seasons were 41.0% and 45.2%, respectively. Full vaccination varied widely by state and was more likely for children requiring only one dose. Based on the statistical models, children likely to be fully vaccinated were older, non-black, had a mother with an education >12 years, or lived in a high-income household. CONCLUSIONS: Most children in the U.S. are not fully vaccinated against influenza. Reminder systems and interventions that reduce or remove barriers to children receiving their second doses of influenza vaccine may improve full influenza vaccination coverage among all children.

OBJECTIVE: Prevention of influenza among infants and young children is a public health priority because of their high risk for influenza-related complications. Depending on a child's age and previous influenza vaccination history, they are recommended to receive either 1 dose or 2 doses of influenza vaccine to be considered fully vaccinated against influenza for the season. We compared estimates of full (complete) influenza vaccination coverage of children 6 to 23 months across 10 consecutive influenza seasons (2002-2012), by race/ethnicity, age group, and by number of doses required to be fully vaccinated given child's vaccination history. METHODS: National Immunization Survey data were used to estimate full influenza vaccination status among children 6 to 23 months on the basis of provider report. Estimates were computed by using Kaplan-Meier survival analysis methods. RESULTS: Full influenza vaccination coverage among children 6 to 23 months increased from 4.8% in the 2002-2003 influenza season to 44.7% in the 2011-2012 season. In all 10 influenza seasons studied, non-Hispanic black children and Hispanic children had lower full influenza vaccination coverage than non-Hispanic white children. For all 10 influenza seasons, full influenza vaccination coverage was higher among children requiring only 1 dose compared with those requiring 2 doses. CONCLUSIONS: Less than half of children 6 to 23 months in the United States, and an even a smaller percentage of Hispanic and non-Hispanic black children, are fully vaccinated against influenza. More implementation of evidence-based strategies that increase the percentage of children who are fully vaccinated is needed.

BACKGROUND: Studies are published on settings adults receive influenza vaccination but few have reported on settings children are vaccinated and how this might be changing over time or vary by socio-demographics. METHODS: Data from the National Immunization Survey-Flu were analyzed to assess place of influenza vaccination among vaccinated children 6 months-17 years during the 2010-11, 2011-12, 2012-13, and 2013-14 influenza seasons. The percentage of children vaccinated at each place was calculated overall and by age, race/ethnicity, income, and Metropolitan Statistical Area (MSA). RESULTS: The places children received influenza vaccination varied little over four recent influenza seasons. From the 2010-11 through 2013-14 influenza seasons the percentage of vaccinated children receiving influenza vaccination at a doctor's office was 64.1%, 65.1%, 65.3%, and 65.3%, respectively with no differences from one season to the next. Likewise, for vaccination at clinics or health centers (17.8%, 17.5%, 17.0%. 18.0%), health departments (3.2%, 3.6%, 3.0%, 2.8%), and other non-medical places (1.6%, 1.4%, 1.2%, 1.1%), there were no differences from one season to the next. There were some differences for vaccinations at hospitals, pharmacies, and schools. There was considerable variability in the place of influenza vaccination by age, race/ethnicity, income, and MSA. Fewer Hispanic children were vaccinated at a doctor's office than black, white, and other or multiple race children and fewer black children and children of other or multiple races were vaccinated at a doctor's office than white children. More children at or below the poverty level were vaccinated at a clinic or health center than all of the other income groups. CONCLUSION: Most vaccinated children receive their influenza vaccination at a doctor's office. Place of vaccination changed little over four recent influenza seasons. Large variability in place of vaccination exists by age, race/ethnicity, income, and MSA. Monitoring place of vaccination can help shape future immunization programs.

BACKGROUND: Influenza vaccines available for children in the United States include inactivated influenza vaccine (IIV) and live, attenuated influenza vaccine (LAIV). Objectives of this study were to quantify proportions of IIV and LAIV received by vaccinated children, and examine associations between vaccine type received and demographic characteristics. METHODS: National Immunization Survey-Flu (NIS-Flu) parental reported data for the 2011-12 through 2013-14 influenza seasons were used to estimate proportions of vaccinated children 2-17 years who received IIV and LAIV. Tests of association between vaccination type and demographic variables were conducted using Wald chi-square tests and pair-wise comparison t-tests. Multivariable logistic regression was used to determine variables independently associated with receipt of LAIV versus IIV. RESULTS: In the 2013-14 season, 33.3% of vaccinated children received LAIV, similar to the proportion in the 2011-12 (32.2%) and 2012-13 (32.1%) seasons. Across all seasons studied, the strongest observed association was between vaccination type and child's age, with children 2-8 years (Adjusted Prevalence Ratio (95% confidence interval) [APR(95% CI)] 1.41(1.27-1.56), 1.46(1.34-1.59), and 1.50(1.38-1.63) for 2011-12, 2012-13, and 2013-14) and 9-12 years (APR(95% CI) 1.37(1.23-1.54), 1.38(1.26-1.51), and 1.50(1.38-1.63) for 2011-12, 2012-13, and 2013-14) being more likely to have received LAIV than children 13-17 years. Among those vaccinated, whites were more likely to have received LAIV compared with blacks (APR(95% CI) 1.19(1.05-1.35), 1.24(1.10-1.39), and 1.22(1.11-1.34) for 2011-12, 2012-13, and 2013-14), and children living above poverty (annual income >$75,000) were more likely to have received LAIV than those living at or below poverty (APR(95% CI) 1.43(1.23-1.67), 1.13(1.02-1.26), and 1.16(1.06-1.28) for 2011-12, 2012-13, and 2013-14). CONCLUSIONS: This study provides a baseline of the extent and patterns of LAIV uptake that can be used to measure the impact of relevant public health policy. Additional research is needed to investigate parental and provider preferences and barriers regarding LAIV.

BACKGROUND: The Vaccines for Children (VFC) program provides vaccines at no cost to children who are Medicaid-eligible, uninsured, American Indian or Alaska Native (AI/AN), or underinsured and vaccinated at Federally Qualified Health Centers or Rural Health Clinics. The objective of this study was to compare influenza vaccination coverage of VFC-entitled to privately insured children in the United States, nationally, by state, and by selected socio-demographic variables. METHODS: Data from the National Immunization Survey-Flu (NIS-Flu) surveys were analyzed for the 2011-2012 and 2012-2013 influenza seasons for households with children 6 months-17 years. VFC-entitlement and private insurance status were defined based upon questions asked of the parent during the telephone interview. Influenza vaccination coverage estimates of children VFC-entitled versus privately insured were compared by t-tests, both nationally and within state, and within selected socio-demographic variables. RESULTS: For both seasons studied, influenza coverage for VFC-entitled children did not significantly differ from coverage for privately insured children (2011-2012: 52.0%+/-1.9% versus 50.7%+/-1.2%; 2012-2013: 56.0%+/-1.6% versus 57.2%+/-1.2%). Among VFC-entitled children, uninsured children had lower coverage (2011-2012: 38.9%+/-4.7%; 2012-2013: 44.8%+/-3.5%) than Medicaid-eligible (2011-2012: 55.2%+/-2.1%; 2012-2013: 58.6%+/-1.9%) and AI/AN children (2011-2012: 54.4%+/-11.3%; 2012-2013: 54.6%+/-7.0%). Significant differences in vaccination coverage among VFC-entitled and privately insured children were observed within some subgroups of race/ethnicity, income, age, region, and living in a metropolitan statistical area principle city. CONCLUSIONS: Although finding few differences in influenza vaccination coverage among VFC-entitled versus privately insured children was encouraging, nearly half of all children were not vaccinated for influenza and coverage was particularly low among uninsured children. Additional public health interventions are needed to ensure that more children are vaccinated such as a strong recommendation from health care providers, utilization of immunization information systems, provider reminders, standing orders, and community-based interventions such as educational activities and expanded access to vaccination services.

BACKGROUND: Varicella vaccine is available in the private sector in China, with a single dose currently recommended for children aged ≥12 months. We investigated a varicella outbreak in a school in Beijing with high varicella vaccination coverage to describe the outbreak, examine risk factors for vaccine failure, and calculate vaccine effectiveness. METHODS: A varicella case was defined as an acute generalized maculopapular rash without other apparent cause in a student without prior varicella attending the elementary school during August 30-December 28, 2010. Varicella among vaccinated students (breakthrough varicella) was defined as varicella occurring >42 days after vaccination. Students' vaccination status was verified with immunization records and clinical presentations were collected from health care practitioners. RESULTS: Of the 951 students, 934 (98%) had no prior varicella history. Among these students, 916 had received 1 dose of varicella vaccine and 2 had received 2 doses (98% vaccination coverage) before the outbreak. A total of 87 cases occurred during the outbreak; most had breakthrough varicella (86/87, 99%) and mild disease (83/87, 95%). Age at vaccination (<15 months vs. ≥15 months) and time since vaccination before outbreak (<5 years vs. ≥5 years) were not associated with development of breakthrough varicella. Single-dose varicella vaccination was 89% effective in preventing any varicella and 99% in preventing moderate/severe varicella. CONCLUSION: Single-dose varicella vaccination is highly effective in reducing varicella incidence and mitigating disease severity, but not high enough to prevent outbreak. A two-dose program might help to prevent varicella outbreaks in Beijing.

Genetic analysis of hepatitis B virus (HBV) frequently involves study of intra-host variants, identification of which is commonly achieved using short regions of the HBV genome. However, the use of short sequences significantly limits evaluation of genetic relatedness among HBV strains. Although analysis of HBV complete genomes using genetic cloning has been developed, its application is highly labor intensive and practiced only infrequently. We describe here a novel approach to whole genome (WG) HBV quasispecies analysis based on end-point, limiting-dilution real-time PCR (EPLD-PCR) for amplification of single HBV genome variants, and their subsequent sequencing. EPLD-PCR was used to analyze WG quasispecies from serum samples of patients (n = 38) infected with HBV genotypes A, B, C, D, E and G. Phylogenetic analysis of the EPLD-isolated HBV-WG quasispecies showed the presence of mixed genotypes, recombinant variants and sub-populations of the virus. A critical observation was that HBV-WG consensus sequences obtained by direct sequencing of PCR fragments without EPLD are genetically close, but not always identical to the major HBV variants in the intra-host population, thus indicating that consensus sequences should be judiciously used in genetic analysis. Sequence-based studies of HBV WG quasispecies should afford a more accurate assessment of HBV evolution in various clinical and epidemiological settings.

Genotyping of hepatitis B virus (HBV) is important for tracking HBV infections, prognosticating the development of severe liver disease and predicting outcomes of therapy. Current genotyping methods can be laborious, costly and rely on subjective data interpretation. To identify less expensive but equally reliable alternatives, we compared gold standard sequencing to a novel mass spectrometry approach. Sera from individuals with acute or chronic HBV infection (n=756), representing all genotypes, were used to PCR-amplify the HBV S gene. All amplicons were subject to base-specific cleavage and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The resulting mass peak patterns were used to identify HBV genotype by automated comparison to peak patterns simulated from reference sets of HBV sequences of known genotypes. The MALDI-TOF MS data and phylogenetic analysis of HBV sequences produced completely concordant results. Several parameters such as genetic relatedness of tested HBV variants to the reference set, chronic infections, as well as the quality of PCR products, can lower the MS score but never affected the accuracy of the genotype call. This new streamlined MS-based method provides for rapid and accurate HBV genotyping, produces automated data reports and is therefore suitable for routine use in diagnostic settings.

From July to September in 2005 and 2006, a survey was conducted to identify mosquito species and mosquito-borne arboviruses at elevations ranging from 900-3280 m between 24 degrees 00' N and 29 degrees 00' N latitude in the northwestern part of Yunnan Province, China. A total of 54,879 mosquitoes representing 15 species and 4 genera was collected using UV light traps at 59 sites. Culex tritaeniorhynchus and Anopheles sinensis were the most abundant species. The density of mosquitoes as well as the diversity of species decreased with increasing altitude. A total of 21,008 mosquitoes in 281 pools representing all of the 15 species was tested for the presence of viruses using cell culture. Viruses identified included Japanese encephalitis virus (13 isolates), Getah virus (five isolates), Banna virus (three isolates), Kadipiro virus (five isolates), and Densovirus (seven isolates). These isolates were obtained from Culex tritaeniorhynchus (20 isolates), Anopheles sinensis (three isolates), Armigeres subalbatus (six isolates), Culex pipiens quinquefasciatus (two isolates), and from unidentified, mixed mosquitoes (two isolates). Most of the isolates were from collections made at elevations below 2,500 m. Vector Borne Zoonotic Dis. 0, 000-000.