Search

Objective To evaluate the consistency and quality of immunization monitoring systems in 27 countries during 2002-03 using standardized data quality audits (DQAs) that had been launched within the framework of the Global Alliance for Vaccines and Immunization. Methods The consistency of reporting systems was estimated by determining the proportion of third doses of diphtheria-tetanuspertussis (DTP-3) vaccine reported as being administered that could be verified by written documentation at health facilities and districts. The quality of monitoring systems was measured using quality indices for different components of the monitoring systems. These indices were applied to each level of the health service (health unit, district and national). Findings The proportion of verified DTP-3 doses was lower than 85% in 16 countries. Difficulties in verifying the doses administered often arose at the peripheral level of the health service, usually as the result of discrepancies in information between health units and their corresponding districts or because completed recording forms were not available from health units. All countries had weaknesses in their monitoring systems; these included the inconsistent use of monitoring charts; inadequate monitoring of vaccine stocks, injection supplies and adverse events; unsafe computer practices; and poor monitoring of completeness and timeliness of reporting. Conclusion Inconsistencies in immunization data occur in many countries, hampering their ability to manage their immunization programmes. Countries should use these findings to strengthen monitoring systems so that data can reliably guide programme activities. The DQA is an innovative tool that provides a way to independently assess the quality of immunization monitoring systems at all levels of a health service and serves as a point of entry to make improvements. It provides a useful example for other global health initiatives. Keywords Diphtheria-tetanus-pertussis vaccine/administration and dosage; Immunization programs/statistics; Data collection/ standards; Quality control (source: MeSH, NLM). Mots cles Vaccin diphterie-tetanos-coqueluche/administration et posologie; Programmes de vaccination/statistique; Collecte donnees/ normes; Controle qualite (source: MeSH, INSERM). Palabras dave Vacuna difteria-tetano-pertussis/administracion y dosificacion; Programas de inmunizacion/estadistica; Recoleccion de datos/normas; Control de calidad (fuente: DeCS, BIREME). Bulletin of the World Health Organization 2005;83:503-510., Introduction The Global Alliance for Vaccines and Immunization (GAVI) was launched in 2000, and since then it has provided annual financial support to improve childhood immunization services in 52 developing [...]

PURPOSE: The Health Plan Employer Data Information Set (HEDIS) provides comparative information across health plans to measure the quality of care and preventive services for health plan beneficiaries. We examined recent trends in adolescent immunizations recommended by the Advisory Committee for Immunization Practices (ACIP) measured through HEDIS and reported to the National Committee for Quality Assurance (NCQA). METHODS: The study was based on a longitudinal regression analysis of commercial managed care organizations' HEDIS measures from 1999-2002. HEDIS performance measures and plan characteristics include a sample of approximately 100-400 enrollees per plan each year. The outcome measures were the proportions of enrollees aged 13 years sampled in the plan who received measles-mumps-rubella vaccine (MMR), hepatitis B vaccine, and varicella vaccine. RESULTS: The immunization rates for all three antigens increased significantly from 1999 to 2002 (MMR: 57-68%; hepatitis B: 28-51%; and varicella: 21-38%). Factors in the final multivariable models that were found to be significantly associated with increased proportions immunized with MMR vaccine, hepatitis B vaccine, and varicella vaccine include year of report, presence of school entry laws, years in business up to 25 years, and operating in the northeastern U.S. region; the only factor associated with decreasing immunization rates for all antigens was the number of providers per 100 commercial enrollees. CONCLUSIONS: Consistent with previous reports, adolescent immunization rates are improving yet remain suboptimal. Strategies to increase immunization rates, as well as to improve documentation of immunization status, among commercial health insurance plans need to be developed and implemented. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine how child characteristics and immunization coverage levels differ among children using public and private providers. METHODS: Immunization coverage rates between 1996 and 2004 were compared among children aged 19-35 months, using data from the National Immunization Survey. Coverage was based on the 4:3:1:3:3 vaccine series: four or more doses of diphtheria, tetanus toxoids, acellular pertussis vaccine; three or more doses of poliovirus vaccine; one or more doses of measles-mumps-rubella vaccine; three or more doses of Haemophilus influenzae type b vaccine; and three or more doses of hepatitis B vaccine. Coverage differences were examined by provider types (child vaccinated by private, public, or a mix of providers), and stratified by child's race/ethnicity, area of residence, and household income level. RESULTS: Between 1996 and 2004, the proportion of children seeing exclusively private providers increased (58%-61%; P < .05); the proportion seeing only public providers decreased (19%-15%; P < .01). Coverage levels increased among children seeing all provider types. Coverage levels were higher for children using private providers than those using public providers in 2004 (83% vs 79%; P <.05). Except for White race (coverage was higher among those using private providers vs public providers), coverage levels by demographic variables did not significantly differ between children using only public or only private providers in 2004. CONCLUSIONS: Equal emphasis should be placed on the efforts of public providers and private providers to increase coverage among children of all race/ethnicity, income, and residential groups. [ABSTRACT FROM AUTHOR]

Abstract Background Detection of a retrovirus, xenotropic murine leukaemia virus-related virus (XMRV), has recently been reported in 67% of patients with chronic fatigue syndrome. We have studied a total of 170 samples from chronic fatigue syndrome patients from two UK cohorts and 395 controls for evidence of XMRV infection by looking either for the presence of viral nucleic acids using quantitative PCR (limit of detection Results We have not identified XMRV DNA in any samples by PCR (0/299). Some serum samples showed XMRV neutralising activity (26/565) but only one of these positive sera came from a CFS patient. Most of the positive sera were also able to neutralise MLV particles pseudotyped with envelope proteins from other viruses, including vesicular stomatitis virus, indicating significant cross-reactivity in serological responses. Four positive samples were specific for XMRV. Conclusions No association between XMRV infection and CFS was observed in the samples tested, either by PCR or serological methodologies. The non-specific neutralisation observed in multiple serum samples suggests that it is unlikely that these responses were elicited by XMRV and highlights the danger of over-estimating XMRV frequency based on serological assays. In spite of this, we believe that the detection of neutralising activity that did not inhibit VSV-G pseudotyped MLV in at least four human serum samples indicates that XMRV infection may occur in the general population, although with currently uncertain outcomes.

OBJECTIVE: Heptavalent pneumococcal conjugate vaccine was in short supply from December 2003 to August 2004. The Centers for Disease Control and Prevention with the American Academy of Pediatrics and the American Academy of Family Physicians made recommendations to providers to withhold third and fourth doses of heptavalent pneumococcal conjugate vaccine to ensure availability for those at highest risk. Previous studies of vaccine shortages have demonstrated that provider compliance with temporary recommendations is low. The objective of this study was to collect timely data about awareness and adherence to temporary recommendations and current supply status of heptavalent pneumococcal conjugate vaccine in pediatric practices. METHODS: A 2-phase telephone survey of pediatric practices was conducted during a 10-week period during the 2003-2004 heptavalent pneumococcal conjugate vaccine shortage. Immunization nurses at randomly selected sites with physician-members of the American Academy of Pediatrics were asked a series of questions. RESULTS: In both study phases, >90% of participating practices were aware of the recommendations and reported adhering to the recommendations. In phase 1, practices with insufficient supply were more likely to implement recommendations than practices with sufficient supply. Participants identified health departments and Wyeth Vaccines as the most common sources of information. At least 65% of the practices in each phase reported use of tracking systems for children who missed doses. CONCLUSIONS: Most pediatric practices surveyed were aware of the shortage and were implementing the heptavalent pneumococcal conjugate vaccine recommendations. Simplified recommendations and collaborative efforts to develop and widely disseminate interim recommendations may result in increased compliance by providers. [ABSTRACT FROM AUTHOR]

Objective To evaluate the consistency and quality of immunization monitoring systems in 27 countries during 2002-03 using standardized data quality audits (DQAs) that had been launched within the framework of the Global Alliance for Vaccines and Immunization. Methods The consistency of reporting systems was estimated by determining the proportion of third doses of diphtheria-tetanus-pertussis (DTP-3) vaccine reported as being administered that could be verified by written documentation at health facilities and districts. The quality of monitoring systems was measured using quality indices for different components of the monitoring systems. These indices were applied to each level of the health service (health unit, district and national). Findings The proportion of verified DTP-3 doses was lower than 85% in 16 countries. Difficulties in verifying the doses administered often arose at the peripheral level of the health service, usually as the result of discrepancies in information between health units and their corresponding districts or because completed recording forms were not available from health units. All countries had weaknesses in their monitoring systems; these included the inconsistent use of monitoring charts; inadequate monitoring of vaccine stocks, injection supplies and adverse events; unsafe computer practices; and poor monitoring of completeness and timeliness of reporting. Conclusion Inconsistencies in immunization data occur in many countries, hampering their ability to manage their immunization programmes. Countries should use these findings to strengthen monitoring systems so that data can reliably guide programme activities. The DQA is an innovative tool that provides a way to independently assess the quality of immunization monitoring systems at all levels of a health service and serves as a point of entry to make improvements. It provides a useful example for other global health initiatives. [ABSTRACT FROM AUTHOR]

Background: Norovirus-associated acute gastroenteritis (AGE) exacts a substantial disease burden, yet the health care utilization for and clinical management of norovirus-associated AGE are not well characterized., Methods: We describe the health care encounters and therapeutics used for patients with all-cause and norovirus-associated AGE in the Kaiser Permanente Northwest health system from 1 April 2014 through 30 September 2016. Medical encounters for patients with AGE were extracted from electronic health records, and encounters within 30 days of one another were grouped into single episodes. An age-stratified random sample of patients completed surveys and provided stool samples for norovirus testing., Results: In total, 40 348 individuals had 52 509 AGE episodes; 460 (14%) of 3310 participants in the substudy tested positive for norovirus. An overall 35% of all-cause AGE episodes and 29% of norovirus-associated AGE episodes had ≥2 encounters. While 80% of norovirus-associated AGE episodes had at least 1 encounter in the outpatient setting, all levels of the health care system were affected: 10%, 22%, 10%, and 2% of norovirus-associated AGE episodes had at least 1 encounter in virtual, urgent care, emergency department, and inpatient settings, respectively. Corresponding proportions of therapeutic use between norovirus-positive and norovirus-negative episodes were 13% and 10% for intravenous hydration ( P = .07), 65% and 50% for oral rehydration ( P < .001), 7% and 14% for empiric antibiotic therapy ( P < .001), and 33% and 18% for antiemetics ( P < .001)., Conclusions: Increased health care utilization and therapeutics are likely needed for norovirus-associated AGE episodes during peak norovirus winter seasons, and these data illustrate that effective norovirus vaccines will likely result in less health care utilization., Competing Interests: Potential conflicts of interest. A. L. N. has received research funding from Pfizer, Merck, and MedImmune (now AstraZeneca) for unrelated studies. All other authors report no potential conflicts., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Background: In the United States, public health surveillance systems often underestimate the burden of acute gastroenteritis (AGE) because they only identify disease among those who interact with the healthcare system., Objective: To identify factors associated with healthcare-seeking behavior among individuals experiencing community-acquired AGE., Methods: From October 2016 -September 2017, we conducted a weekly, age-stratified, random sample of Kaiser Permanente Northwest members located in northwest Oregon and southwest Washington, United States. Individuals who completed the online survey and experienced AGE were included in the analysis. Univariate and multivariable logistic regressions were performed to identify predictors of healthcare-seeking behavior., Results: Of the 3,894 survey respondents, 395 experienced an AGE episode and were eligible for analysis, of whom, 82 (21%) sought care for their AGE episode. In the final multivariable model, individuals with a concurrent fever (odds ratio [OR]: 4.76, 95% confidence interval [95% CI]: 2.48-9.13), increased diarrhea duration (≥6 days vs 1-4 days, OR: 4.22, 95% CI: 1.78-10.03), or increased vomiting duration (≥3 days vs 1 days, OR: 2.97, 95% CI: 1.22-7.26), were significantly more likely to seek healthcare. In the adjusted model, no sociodemographic or chronic disease variables were associated with healthcare-seeking behavior., Conclusion: These findings suggest that individuals with a short duration of AGE and those without concurrent fever are underrepresented in healthcare facility-based surveillance systems., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

HIV-1 remains a global health crisis 1 , highlighting the need to identify new targets for therapies. Here, given the disproportionate HIV-1 burden and marked human genome diversity in Africa 2 , we assessed the genetic determinants of control of set-point viral load in 3,879 people of African ancestries living with HIV-1 participating in the international collaboration for the genomics of HIV 3 . We identify a previously undescribed association signal on chromosome 1 where the peak variant associates with an approximately 0.3 log 10 -transformed copies per ml lower set-point viral load per minor allele copy and is specific to populations of African descent. The top associated variant is intergenic and lies between a long intergenic non-coding RNA (LINC00624) and the coding gene CHD1L, which encodes a helicase that is involved in DNA repair 4 . Infection assays in iPS cell-derived macrophages and other immortalized cell lines showed increased HIV-1 replication in CHD1L-knockdown and CHD1L-knockout cells. We provide evidence from population genetic studies that Africa-specific genetic variation near CHD1L associates with HIV replication in vivo. Although experimental studies suggest that CHD1L is able to limit HIV infection in some cell types in vitro, further investigation is required to understand the mechanisms underlying our observations, including any potential indirect effects of CHD1L on HIV spread in vivo that our cell-based assays cannot recapitulate., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the Food and Drug Administration in late 2020 for adults, authorisation for young children 6 months to <5 years of age did not occur until 2022. These authorisations were based on clinical trials, understanding real-world vaccine effectiveness (VE) in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 VE against infection among children aged >6 months and adults aged <50 years., Methods: CASCADIA is a 4-year community-based prospective study of SARS-CoV-2 VE among 3500 adults and paediatric populations aged 6 months to 49 years in Oregon and Washington, USA. At enrolment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrolment and annually thereafter, with optional blood draws every 6 months and after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by reverse transcription-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who test positive for SARS-CoV-2 undergo serial swab collection every 3 days for 21 days. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralisation assays., Analysis: The primary outcome is SARS-CoV-2 infection. Cox regression models will be used to estimate the incidence rate ratio associated with SARS-CoV-2 vaccination among the paediatric and adult population, controlling for demographic factors and other potential confounders., Ethics and Dissemination: All study materials including the protocol, consent forms, data collection instruments, participant communication and recruitment materials, were approved by the Kaiser Permanente Interregional Institutional Review Board, the IRB of record for the study. Results will be disseminated through peer-reviewed publications, presentations, participant newsletters and appropriate general news media., Competing Interests: Competing interests: HYC reports consulting with Ellume, Pfizer, The Bill and Melinda Gates Foundation, Glaxo Smith Kline, and Merck. HYC received research funding from Gates Ventures, Sanofi Pasteur, and support and reagents from Ellume and Cepheid outside of the submitted work. JAE reports research support from Gates Ventures, AstraZeneca, GlaxoSmithKline, Merck, and Pfizer, and consulting with Sanofi Pasteur, AstraZeneca, Teva Pharmaceuticals, and Meissa Vaccines, outside of the submitted work. ALN reports research funding from Pfizer and Vir Biotechnology, outside of the submitted work. JLK reports research funding from Vir Biotechnology, outside of the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Emerging data suggest that second-generation influenza vaccines with higher hemagglutinin (HA) antigen content and/or different production methods may induce stronger antibody responses to HA than standard-dose egg-based influenza vaccines in adults. We compared antibody responses to high-dose egg-based inactivated (HD-IIV3), recombinant (RIV4), and cell culture-based (ccIIV4) vs standard-dose egg-based inactivated influenza vaccine (SD-IIV4) among health care personnel (HCP) aged 18-65 years in 2 influenza seasons (2018-2019, 2019-2020)., Methods: In the second trial season, newly and re-enrolled HCPs who received SD-IIV4 in season 1 were randomized to receive RIV4, ccIIV4, or SD-IIV4 or were enrolled in an off-label, nonrandomized arm to receive HD-IIV3. Prevaccination and 1-month-postvaccination sera were tested by hemagglutination inhibition (HI) assay against 4 cell culture propagated vaccine reference viruses. Primary outcomes, adjusted for study site and baseline HI titer, were seroconversion rate (SCR), geometric mean titers (GMTs), mean fold rise (MFR), and GMT ratios that compared vaccine groups to SD-IIV4., Results: Among 390 HCP in the per-protocol population, 79 received HD-IIV3, 103 RIV4, 106 ccIIV4, and 102 SD-IIV4. HD-IIV3 recipients had similar postvaccination antibody titers compared with SD-IIV4 recipients, whereas RIV4 recipients had significantly higher 1-month-postvaccination antibody titers against vaccine reference viruses for all outcomes., Conclusions: HD-IIV3 did not induce higher antibody responses than SD-IIV4, but, consistent with previous studies, RIV4 was associated with higher postvaccination antibody titers. These findings suggest that recombinant vaccines rather than vaccines with higher egg-based antigen doses may provide improved antibody responses in highly vaccinated populations., Competing Interests: Potential conflicts of interest. Dr. Naleway received funding from Pfizer and Vir Biotechnology for unrelated studies. The other authors have no conflicts of interest to declare., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Antibody responses to non-egg-based standard-dose cell-culture influenza vaccine (containing 15 µg hemagglutinin [HA]/component) and recombinant vaccine (containing 45 µg HA/component) during consecutive seasons have not been studied in the United States., Methods: In a randomized trial of immunogenicity of quadrivalent influenza vaccines among healthcare personnel (HCP) aged 18-64 years over 2 consecutive seasons, HCP who received recombinant-HA influenza vaccine (RIV) or cell culture-based inactivated influenza vaccine (ccIIV) during the first season (year 1) were re-randomized the second season of 2019-2020 (year 2 [Y2]) to receive ccIIV or RIV, resulting in 4 ccIIV/RIV combinations. In Y2, hemagglutination inhibition antibody titers against reference cell-grown vaccine viruses were compared in each ccIIV/RIV group with titers among HCP randomized both seasons to receive egg-based, standard-dose inactivated influenza vaccine (IIV) using geometric mean titer (GMT) ratios of Y2 post-vaccination titers., Results: Y2 data from 414 HCP were analyzed per protocol. Compared with 60 IIV/IIV recipients, 74 RIV/RIV and 106 ccIIV/RIV recipients showed significantly elevated GMT ratios (Bonferroni corrected P < .007) against all components except A(H3N2). Post-vaccination GMT ratios for ccIIV/ccIIV and RIV/ccIIV were not significantly elevated compared with IIV/IIV except for RIV/ccIIV against A(H1N1)pdm09., Conclusions: In adult HCP, receipt of RIV in 2 consecutive seasons or the second season was more immunogenic than consecutive egg-based IIV for 3 of the 4 components of quadrivalent vaccine. Immunogenicity of ccIIV/ccIIV was similar to that of IIV/IIV. Differences in HA antigen content may play a role in immunogenicity of influenza vaccination in consecutive seasons., Clinical Trials Registration: NCT03722589., Competing Interests: Potential conflicts of interest. M. G. reports grants from the unrelated CDC (US Ambulatory Flu/COVID Vaccine Effectiveness Network, Hospitalized Adult Influenza Vaccine Effectiveness Network [HAIVEN], Refining Effectiveness Estimates of Influenza Vaccines Synergizing Epidemiolgy and Incidence Methods for Influenza and Other Acute Respiratory Viral Illness [SYNERGY] Studies), unrelated CDC-Abt Associates (Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel [RECOVER] and Pediatric Research Observing Trends and Exposures in COVID-19 Timelines [PROTECT] cohort studies), unrelated CDC–Vanderbilt University Medical Center (Influenza and Other Viruses in the Acutely Ill [IVY] Study), unrelated CDC-Westat (Virtual Network: Investigating the Risk of COVID-19-Associated Outcomes and COVID-19 Vaccine Effectiveness Using Integrated Medical and Public Health Records [VISION-COVID] Study), unrelated Janssen (RSV Severity Birth Cohort Study), and unrelated Pfizer (Education for Men B Vaccine in Adolescents); being the co-chair of the Texas Pediatric Society's (Texas Chapter of the American Academy of Pediatrics) Infectious Diseases and Immunization Committee (2016–2022). A. L. N. reports funding from Pfizer and Vir Biotechnology for unrelated studies. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

We assessed rotavirus vaccine impact using data on acute gastroenteritis (AGE) encounters within an integrated healthcare delivery system during 2000-2018. Following rotavirus vaccine introduction, all-cause AGE rates among children <5 years declined by 36% (95% confidence interval [CI]: 32%-40%) for outpatient and 54% (95% CI: 46%-60%) for inpatient encounters., (Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society 2022.)

Background: Healthcare personnel (HCP) are a priority group for annual influenza vaccination. Few studies have assessed the validity of recall of prior influenza vaccination status among HCP, especially for more than one preceding season., Methods: Using data from a randomized controlled trial of influenza vaccination among 947 HCP from two US healthcare systems, we assessed agreement between participant self-report and administrative record documentation of influenza vaccination status during the preceding five influenza seasons; kappa coefficients and sensitivity values were calculated. Administrative record documentation was considered the gold standard. Documented vaccination sources included electronic medical records, employee health records, outside immunization providers, and the state immunization information system., Results: Among 683 HCP with prior influenza immunization information, 89.7% (95% CI: 87.2%, 91.9%) of HCP were able to self-report their vaccination status for the season preceding the survey. By the fifth preceding season, 82.6% (95% CI: 79.5%, 85.3%) of HCP were able to self-report. Among HCP who self-reported their vaccination status, agreement between self-report and documented vaccination status ranged from 81.9% (95% CI: 77.2%, 86.7%) for the fifth season to 90.5% (95% CI: 87.2%, 93.9%) for the season preceding interview. HCP who received vaccine for only some of the preceding five seasons (18.3%) more commonly had ≥2 errors in their recall compared with those vaccinated all five preceding seasons (55.7% vs. 4.3%)., Conclusions: Self-reported vaccination status is a reliable source for historical influenza vaccination information among HCP who are consistently vaccinated but less reliable for those with a history of inconsistent vaccination., (© 2022 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Background: Data on the development of neutralizing antibodies (nAbs) against SARS-CoV-2 after SARS-CoV-2 infection and after vaccination with mRNA COVID-19 vaccines are limited., Methods: From a prospective cohort of 3975 adult essential and frontline workers tested weekly from August 2020 to March 2021 for SARS-CoV-2 infection by reverse transcription-polymerase chain reaction assay irrespective of symptoms, 497 participants had sera drawn after infection (170), vaccination (327), and after both infection and vaccination (50 from the infection population). Serum was collected after infection and each vaccine dose. Serum-neutralizing antibody titers against USA-WA1/2020-spike pseudotype virus were determined by the 50% inhibitory dilution. Geometric mean titers (GMTs) and corresponding fold increases were calculated using t tests and linear mixed-effects models., Results: Among 170 unvaccinated participants with SARS-CoV-2 infection, 158 (93%) developed nAbs with a GMT of 1003 (95% confidence interval, 766-1315). Among 139 previously uninfected participants, 138 (99%) developed nAbs after mRNA vaccine dose 2 with a GMT of 3257 (2596-4052). GMT was higher among those receiving mRNA-1273 vaccine (GMT, 4698; 3186-6926) compared with BNT162b2 vaccine (GMT, 2309; 1825-2919). Among 32 participants with prior SARS-CoV-2 infection, GMT was 21 655 (14 766-31 756) after mRNA vaccine dose 1, without further increase after dose 2., Conclusions: A single dose of mRNA vaccine after SARS-CoV-2 infection resulted in the highest observed nAb response. Two doses of mRNA vaccine in previously uninfected participants resulted in higher nAbs to SARS-CoV-2 than after 1 dose of vaccine or SARS-CoV-2 infection alone. nAb response also differed by mRNA vaccine product., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: In a multi-center prospective cohort of essential workers, we assessed knowledge, attitudes, and practices (KAP) by vaccine intention, prior SARS-CoV-2 positivity, and occupation, and their impact on vaccine uptake over time., Methods: Initiated in July 2020, the HEROES-RECOVER cohort provided socio-demographics and COVID-19 vaccination data. Using two follow-up surveys approximately three months apart, COVID-19 vaccine KAP, intention, and receipt was collected; the first survey categorized participants as reluctant, reachable, or endorser., Results: A total of 4,803 participants were included in the analysis. Most (70%) were vaccine endorsers, 16% were reachable, and 14% were reluctant. By May 2021, 77% had received at least one vaccine dose. KAP responses strongly predicted vaccine uptake, particularly positive attitudes about safety (aOR = 5.46, 95% CI: 1.4-20.8) and effectiveness (aOR = 5.0, 95% CI: 1.3-19.1). Participants' with prior SARS-CoV-2 infection were 22% less likely to believe the COVID-19 vaccine was effective compared with uninfected participants (aOR 0.78, 95% CI: 0.64-0.96). This was even more pronounced in first responders compared with other occupations, with first responders 42% less likely to believe in COVID-19 vaccine effectiveness (aOR = 0.58, 95% CI 0.40-0.84). Between administrations of the two surveys, 25% of reluctant, 56% reachable, and 83% of endorser groups received the COVID-19 vaccine. The reachable group had large increases in positive responses for questions about vaccine safety (10% of vaccinated, 34% of unvaccinated), and vaccine effectiveness (12% of vaccinated, 27% of unvaccinated)., Discussion: Our study demonstrates attitudes associated with COVID-19 vaccine uptake and a positive shift in attitudes over time. First responders, despite potential high exposure to SARS-CoV-2, and participants with a history of SARS-CoV-2 infection were more vaccine reluctant., Conclusions: Perceptions of the COVID-19 vaccine can shift over time. Targeting messages about the vaccine's safety and effectiveness in reducing SARS-CoV-2 virus infection and illness severity may increase vaccine uptake for reluctant and reachable participants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Allison L. Naleway reported funding from Pfizer for a meningococcal B vaccine study unrelated to the submitted work., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: RIV4 and cell-culture based inactivated influenza vaccine (ccIIV4) have not been compared to egg-based IIV4 in healthcare personnel, a population with frequent influenza vaccination that may blunt vaccine immune responses over time. We conducted a randomized trial among healthcare personnel (HCP) aged 18-64 years to compare humoral immune responses to ccIIV4 and RIV4 to IIV4., Methods: During the 2018-2019 season, participants were randomized to receive ccIIV4, RIV4, or IIV4 and had serum samples collected prevaccination, 1 and 6 months postvaccination. Serum samples were tested by hemagglutination inhibition (HI) for influenza A/H1N1, B/Yamagata, and B/Victoria and microneutralization (MN) for A/H3N2 against cell-grown vaccine reference viruses. Primary outcomes at 1 month were seroconversion rate (SCR), geometric mean titers (GMT), GMT ratio, and mean fold rise (MFR) in the intention-to-treat population., Results: In total, 727 participants were included (283 ccIIV4, 202 RIV4, and 242 IIV4). At 1 month, responses to ccIIV4 were similar to IIV4 by SCR, GMT, GMT ratio, and MFR. RIV4 induced higher SCRs, GMTs, and MFRs than IIV4 against A/H1N1, A/H3N2, and B/Yamagata. The GMT ratio of RIV4 to egg-based vaccines was 1.5 (95% confidence interval [CI] 1.2-1.9) for A/H1N1, 3.0 (95% CI: 2.4-3.7) for A/H3N2, 1.1 (95% CI: .9-1.4) for B/Yamagata, and 1.1 (95% CI: .9-1.3) for B/Victoria. At 6 months, ccIIV4 recipients had similar GMTs to IIV4, whereas RIV4 recipients had higher GMTs against A/H3N2 and B/Yamagata., Conclusions: RIV4 resulted in improved antibody responses by HI and MN compared to egg-based vaccines against 3 of 4 cell-grown vaccine strains 1 month postvaccination, suggesting a possible additional benefit from RIV4., Clinical Trials Registration: NCT03722589., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Genotoxicity data on commercial azo dyes and their components remain sparse, despite their widespread use. We have tested the mutagenicity of 2-cyano-4-nitroaniline (CNNA) and 2,6-dicyano-4-nitroaniline (CNCNNA), components of azo dyes such as Disperse Blue 165 and Disperse Red 73, in Ames test strains. Both compounds are extraordinarily potent frameshift mutagens, with much greater activity than structurally similar dihalonitroanilines and halodinitroanilines. Analysis of the responses of strains over-expressing or deficient in bioactivation enzymes shows that bacterial nitroreductase and acetyl CoA: arylamine N-acetyltransferase are important mediators of the mutagenicity of CNNA and CNCNNA., (© 2015 Wiley Periodicals, Inc.)

Evaluation of three subclasses of boron difluoride formazanate complexes bearing o-, m-, and p-anisole N-aryl substituents (Ar) as readily accessible alternatives to boron dipyrromethene (BODIPY) dyes for cell imaging applications is described. While the wavelengths of maximum absorption (λmax ) and emission (λem ) observed for each subclass of complexes, which differed by their carbon-bound substituents (R), were similar, the emission quantum yields for 7 a-c (R=cyano) were enhanced relative to 8 a-c (R=nitro) and 9 a-c (R=phenyl). Complexes 7 a-c and 8 a-c were also significantly easier to reduce electrochemically to their radical anion and dianion forms compared to 9 a-c. Within each subclass, the o-substituted derivatives were more difficult to reduce, had shorter λmax and λem , and lower emission quantum yields than the p-substituted analogues as a result of sterically driven twisting of the N-aryl substituents and a decrease in the degree of π-conjugation. The m-substituted complexes were the least difficult to reduce and possessed intermediate λmax , λem , and quantum yields. The complexes studied also exhibited large Stokes shifts (82-152 nm, 2143-5483 cm(-1) ). Finally, the utility of complex 7 c (Ar=p-anisole, R=cyano), which can be prepared for just a few dollars per gram, for fluorescence cell imaging was demonstrated. The use of 7 c and 4',6-diamino-2-phenylindole (DAPI) allowed for simultaneous imaging of the cytoplasm and nucleus of mouse fibroblast cells., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Context: Immunizations are the most effective way to reduce incidence of vaccine-preventable diseases. Immunization information systems (IISs) are confidential, population-based, computerized databases that record all vaccination doses administered by participating providers to people residing within a given geopolitical area. They facilitate consolidation of vaccination histories for use by health care providers in determining appropriate client vaccinations. Immunization information systems also provide aggregate data on immunizations for use in monitoring coverage and program operations and to guide public health action., Evidence Acquisition: Methods for conducting systematic reviews for the Guide to Community Preventive Services were used to assess the effectiveness of IISs. Reviewed evidence examined changes in vaccination rates in client populations or described expanded IIS capabilities related to improving vaccinations. The literature search identified 108 published articles and 132 conference abstracts describing or evaluating the use of IISs in different assessment categories., Evidence Synthesis: Studies described or evaluated IIS capabilities to (1) create or support effective interventions to increase vaccination rates, such as client reminder and recall, provider assessment and feedback, and provider reminders; (2) determine client vaccination status to inform decisions by clinicians, health care systems, and schools; (3) guide public health responses to outbreaks of vaccine-preventable disease; (4) inform assessments of vaccination coverage, missed vaccination opportunities, invalid dose administration, and disparities; and (5) facilitate vaccine management and accountability., Conclusions: Findings from 240 articles and abstracts demonstrate IIS capabilities and actions in increasing vaccination rates with the goal of reducing vaccine-preventable disease.

Context: A recent systematic review found that use of an immunization information system (IIS) is an effective intervention to increase vaccination rates. The purpose of this review was to evaluate costs and benefits associated with implementing, operating, and participating with an IIS. The speed of technology change has had an effect on costs and benefits of IIS and is considered in this review., Evidence Acquisition: An economic evaluation for IIS was conducted using methods developed for Community Guide systematic reviews. The literature search covered the period from January 1994 to March 2012 and identified 12 published articles and 2 government reports., Evidence Synthesis: Most studies involving cost data evaluated (1) system costs of building an IIS and (2) cost of exchanging immunization data; most economic benefits focused on administrative efficiency., Conclusions: A major challenge to evaluating a technology-based intervention is the evolution that comes with technology improvements and advancements. Although the cost and benefit data may be less applicable today due to changes in system technology, data exchange methods, availability of vendor support, system functionalities, and scope of IIS, it is likely that more up-to-date estimates and comprehensive estimates of benefits would support the findings of cost savings in this review. More research is needed to update and address limitations in the available evidence and to enable assessment of economic costs and benefits of present-day IIS.

Glutathione transferase (GST) enzymes catalyze the conjugation of glutathione with reactive functional groups of endogenous compounds and xenobiotics, including halonitroaromatics. 1-Chloro-2,4-dinitrobenzene (CDNB) is one of the most commonly used substrates for GST activity assays. We have studied the interactions of dinitronaphthalene analogues of CDNB with recombinant human GST enzymes (Alpha, Mu, and Pi classes) expressed in Escherichia coli. Dinitronaphthalene derivatives were found to be GST inhibitors. The highest potency of inhibition was observed towards Mu-class GSTs, M1-1 and M2-2; IC50 values for 1-methoxy- and 1-ethoxy-2,4-dinitronaphthalene were in the high nanomolar to low micromolar range. Inhibition accompanies the formation, at the enzyme active site, of very stable Meisenheimer complex intermediates., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Recent studies have described an increase in parental hesitancy regarding vaccines as well as increases in parental adoption of vaccine schedules that delay or limit receipt of recommended vaccines. This study quantifies potential prevalence and trends in alternative schedule compliance by measuring consistent shot-limiting in a metropolitan area of Oregon., Methods: Retrospective cohort analysis using the Oregon ALERT Immunization Information System to track children born between 2003 and 2009 in the Portland metropolitan area. Joinpoint regression was used to analyze prevalence trends in consistent shot-limiting during that time period. The 2007-2009 Haemophilus influenzae type b vaccine shortage and increased availability of combination vaccines were also examined for their effects on shot-limiting rates., Results: A total of 4502 of 97,711 (4.6%) children met the definition of consistent shot-limiters. The proportion of consistent shot-limiters in the population increased from 2.5% to 9.5% between 2006 and 2009. Compared with those with no or episodic limiting, consistent shot-limiters by 9 months of age had fewer injections (6.4 vs 10.4) but more visits when immunizations were administered (4.2 vs 3.3). However, only a small minority of shot-limiters closely adhered to published alternative schedules., Conclusions: The percentage of children consistently receiving 2 or fewer vaccine injections per visit between birth and age 9 months increased threefold within a 2-year period, suggesting an increase in acceptance of non-Advisory Committee on Immunization Practices vaccine schedules in this geographic area.

Despite record-high immunization coverage nationally, there is considerable variation across state and local immunization programs, which are responsible for the implementation of vaccine recommendations in their jurisdictions. The objectives of this study were to describe activities of state and local immunization programs that sustained high coverage levels across several years and to identify common themes and practical examples for sustaining childhood vaccination coverage rates that could be applied elsewhere. We conducted 95 semi-structured key informant interviews with internal staff members and external partners at the 10 immunization programs with the highest sustained childhood immunization coverage from 2000 to 2005, as measured by the National Immunization Survey. Interview transcripts were analyzed qualitatively using a general inductive approach. Common themes across the 10 programs included maintaining a strong program infrastructure, using available data to drive planning and decision making, a commitment to building and sustaining relationships, and a focus on education and communication. Given the challenges of an increasingly complex immunization system, the lessons learned from these programs may help inform others who are working to improve childhood immunization delivery and coverage in their own programs.

State and urban immunization programs are responsible for the implementation of comprehensive programs to vaccinate populations within their geographic area. Given the variability in immunization coverage rates between geographic areas, the purpose of this two-phase study was to first identify the state and urban areas that achieved the highest increases in coverage, and then those with the highest sustained coverage, between two designated periods, and to interview key program staff members and their community counterparts to capture their perspectives on what factors may have contributed to increasing and sustaining high rates. In this article, we describe phase 1, in which we visited the seven sites that achieved the largest increases in coverage from 2001 to 2004. Results describe outcomes from the 71 semistructured key informant interviews with internal staff and external partners at the site's immunization programs. Interview transcripts were analyzed qualitatively, using a general inductive approach. Common challenges encountered among the seven sites included increasing reluctance among parents and overcoming barriers to accessing care. Common strategies to address these and other challenges included collecting and using data on immunization coverage, developing communication and education efforts, and continuously reaching out and collaborating with immunization partners. Lessons learned from these programs may help inform others who are working to improve childhood immunization delivery and coverage in their own programs.

Introduction: Effective treatment regimens exist for the hepatitis C virus (HCV); however, clinicians are often resistant to evaluation or treatment of patients with alcohol or substance abuse problems. We describe a continuing medical education (CME) program for clinicians in a nationwide health care system, with emphasis on current treatment practices, multispecialty collaboration, and organizational change., Methods: Quantitative measures were used to assess changes in knowledge and treatment confidence, and site-specific organizational changes were qualitatively evaluated. The CME program included a preassessment of current HCV knowledge and care; a 2-day preceptorship; and follow-up with coaching calls at 1, 3, and 6 months. Program attendees included 54 medical and mental health providers from 28 Veterans Affairs Medical Centers., Results: Knowledge following the CME program increased significantly. In 93% of the sites, there were organizational changes such as HCV support group-initiated group education, in-service training, improvement in patient notification or scheduling processes, hiring of new clinical staff, development of a business plans, and discussions about changes with administration. Of all sites, 15 (54%) changed existing antiviral treatment protocols, 18 (64%) established collaborative relationships, and almost half (13/28) established regular use of depression and alcohol use screening tools. Major barriers to change included lack of administrative support or resources (or both) and difficulty collaborating with mental health colleagues., Discussion: This multifaceted CME program with follow-up coaching calls significantly increased individual knowledge and confidence scores and resulted in improved clinic processes and structures. Organizational change was facilitated by the development of an action plan. The major change agent was a nurse; the primary deterrent was an administrator.

Background: The three consensus elements at the 3' end of human introns--the branch point sequence, the polypyrimidine tract, and the 3' splice site AG dinucleotide--are usually closely spaced within the final 40 nucleotides of the intron. However, the branch point sequence and polypyrimidine tract of a few known alternatively spliced exons lie up to 400 nucleotides upstream of the 3' splice site. The extended regions between the distant branch points (dBPs) and their 3' splice site are marked by the absence of other AG dinucleotides. In many cases alternative splicing regulatory elements are located within this region., Results: We have applied a simple algorithm, based on AG dinucleotide exclusion zones (AGEZ), to a large data set of verified human exons. We found a substantial number of exons with large AGEZs, which represent candidate dBP exons. We verified the importance of the predicted dBPs for splicing of some of these exons. This group of exons exhibits a higher than average prevalence of observed alternative splicing, and many of the exons are in genes with some human disease association., Conclusion: The group of identified probable dBP exons are interesting first because they are likely to be alternatively spliced. Second, they are expected to be vulnerable to mutations within the entire extended AGEZ. Disruption of splicing of such exons, for example by mutations that lead to insertion of a new AG dinucleotide between the dBP and 3' splice site, could be readily understood even though the causative mutation might be remote from the conventional locations of splice site sequences.