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Repeat vaccination with egg-based influenza vaccines could preferentially boost antibodies targeting the egg-adapted epitopes and reduce immunogenicity to circulating viruses. In this randomized trial (Clinicaltrials.gov: NCT03722589), sera pre- and post-vaccination with quadrivalent inactivated egg-based (IIV4), cell culture-based (ccIIV4), and recombinant (RIV4) influenza vaccines were collected from healthcare personnel (18-64 years) in 2018−19 ( N  = 723) and 2019−20 ( N  = 684) influenza seasons. We performed an exploratory analysis. Vaccine egg-adapted changes had the most impact on A(H3N2) immunogenicity. In year 1, RIV4 induced higher neutralizing and total HA head binding antibodies to cell- A(H3N2) virus than ccIIV4 and IIV4. In year 2, among the 7 repeat vaccination arms (IIV4-IIV4, IIV4-ccIIV4, IIV4-RIV4, RIV4-ccIIV4, RIV4-RIV4, ccIIV4-ccIIV4 and ccIIV4-RIV4), repeat vaccination with either RIV4 or ccIIV4 further improved antibody responses to circulating viruses with decreased neutralizing antibody egg/cell ratio. RIV4 also had higher post-vaccination A(H1N1)pdm09 and A(H3N2) HA stalk antibodies in year 1, but there was no significant difference in HA stalk antibody fold rise among vaccine groups in either year 1 or year 2. Multiple seasons of non-egg-based vaccination may be needed to redirect antibody responses from immune memory to egg-adapted epitopes and re-focus the immune responses towards epitopes on the circulating viruses to improve vaccine effectiveness. Here the authors report an exploratory analysis of a clinical trial that tested different influenza virus vaccination platforms. The results show that multiple seasons of recombinant or cell-based influenza vaccinations may be needed to redirect antibody responses away from immune memory to egg-adapted epitopes and refocus on epitopes on the circulating viruses.

Leukocyte adhesion to brain endothelial cells, the blood-brain barrier main component, is a critical step in the pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). Leukocyte adhesion is mediated mainly by selectins, cell adhesion molecules and chemokines induced by pro-inflammatory cytokines such as TNFα and IFNγ, but the regulation of this process is not fully clear. This study investigated the regulation of firm leukocyte adhesion to human brain endothelium by two different brain endothelial microRNAs (miRs), miR-126 and miR-126*, that are downregulated by TNFα and IFNγ in a human brain endothelial cell line, hCMEC/D3. Using a leukocyte adhesion in vitro assay under shear forces mimicking blood flow, we observed that reduction of endothelial miR-126 and miR-126* enhanced firm monocyte and T cell adhesion to hCMEC/D3 cells, whereas their increased expression partially prevented THP1, Jurkat and primary MS patient-derived PBMC firm adhesion. Furthermore, we observed that miR-126* and miR-126 downregulation increased E-selectin and VCAM1, respectively, while miR-126 overexpression reduced VCAM1 and CCL2 expression by hCMEC/D3 cells, suggesting that these miRs regulate leukocyte adhesion by modulating the expression of adhesion-associated endothelial mRNA targets. Hence, human brain endothelial miR-126 and miR-126* could be used as a therapeutic tool to reduce leukocyte adhesion and thus reduce neuroinflammation.

Avante Zambézia is an initiative of a Non-Governmental Organization (NGO), Friends in Global Health, LLC (FGH) and the Vanderbilt Institute for Global Health (VIGH) to provide technical assistance to the Mozambican Ministry of Health (MoH) in rural Zambézia Province. Avante Zambézia developed a district level Health Management Mentorship (HMM) program to strengthen health systems in ten of Zambézia's 17 districts. Our objective was to preliminarily analyze changes in four domains of health system capacity after the HMM's first year: accounting, Human Resources (HRs), Monitoring and Evaluation (M&E), and transportation management. Quantitative metrics were developed in each domain. During district visits for weeklong, on-site mentoring, the health management mentoring teams documented each indicator as a success ratio percentage. We analyzed data using linear regressions of each indicator's mean success ratio across all districts submitting a report over time. Of the four domains, district performance in the accounting domain was the strongest and most sustained. Linear regressions of mean monthly compliance for HR objectives indicated improvement in three of six mean success ratios. The M&E capacity domain showed the least overall improvement. The one indicator analyzed for transportation management suggested progress. Our outcome evaluation demonstrates improvement in health system performance during a HMM initiative. Evaluating which elements of our mentoring program are succeeding in strengthening district level health systems is vital in preparing to transition fiscal and managerial responsibility to local authorities.

Background The recent introduction of mobile phones into the rural Bandarban district of Bangladesh provided a resource to improve case detection and treatment of patients with malaria. Methods During studies to define the epidemiology of malaria in villages in south-eastern Bangladesh, an area with hypoendemic malaria, the project recorded 986 mobile phone calls from families because of illness suspected to be malaria between June 2010 and June 2012. Results Based on phone calls, field workers visited the homes with ill persons, and collected blood samples for malaria on 1,046 people. 265 (25%) of the patients tested were positive for malaria. Of the 509 symptomatic malaria cases diagnosed during this study period, 265 (52%) were detected because of an initial mobile phone call. Conclusion Mobile phone technology was found to be an efficient and effective method for rapidly detecting and treating patients with malaria in this remote area. This technology, when combined with local knowledge and field support, may be applicable to other hard-to-reach areas to improve malaria control.

Messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines have been shown to be effective in preventing symptomatic COVID-19 in randomized placebo-controlled Phase III trials (1,2); however, the benefits of these vaccines for preventing asymptomatic and symptomatic SARS-CoV-2 (the virus that causes COVID-19) infection, particularly when administered in real-world conditions, is less well understood. Using prospective cohorts of health care personnel, first responders, and other essential and frontline workers* in eight U.S. locations during December 14, 2020-March 13, 2021, CDC routinely tested for SARS-CoV-2 infections every week regardless of symptom status and at the onset of symptoms consistent with COVID-19-associated illness. Among 3,950 participants with no previous laboratory documentation of SARS-CoV-2 infection, 2,479 (62.8%) received both recommended mRNA doses and 477 (12.1%) received only one dose of mRNA vaccine. Among unvaccinated participants, 1.38 SARS-CoV-2 infections were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) per 1,000 person-days. In contrast, among fully immunized (≥14 days after second dose) persons, 0.04 infections per 1,000 person-days were reported, and among partially immunized (≥14 days after first dose and before second dose) persons, 0.19 infections per 1,000 person-days were reported. Estimated mRNA vaccine effectiveness for prevention of infection, adjusted for study site, was 90% for full immunization and 80% for partial immunization. These findings indicate that authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection, regardless of symptom status, among working-age adults in real-world conditions. COVID-19 vaccination is recommended for all eligible persons.

Protection from Covid-19 after Third Vaccine DoseIn a cohort of frontline health care workers, a third dose of an mRNA vaccine provided 91% protection against SARS-CoV-2 infection with the delta variant and 60% against the omicron variant.

The BNT162b2 (Pfizer-BioNTech) mRNA COVID-19 vaccine was recommended by CDC's Advisory Committee on Immunization Practices for persons aged 12-15 years (referred to as adolescents in this report) on May 12, 2021, and for children aged 5-11 years on November 2, 2021 (1-4). Real-world data on vaccine effectiveness (VE) in these age groups are needed, especially because when the B.1.1.529 (Omicron) variant became predominant in the United States in December 2021, early investigations of VE demonstrated a decline in protection against symptomatic infection for adolescents aged 12-15 years and adults* (5). The PROTECT prospective cohort of 1,364 children and adolescents aged 5-15 years was tested weekly for SARS-CoV-2, irrespective of symptoms, and upon COVID-19-associated illness during July 25, 2021-February 12, 2022. Among unvaccinated participants (i.e., those who had received no COVID-19 vaccine doses) with any laboratory-confirmed SARS-CoV-2 infection, those with B.1.617.2 (Delta) variant infections were more likely to report COVID-19 symptoms (66%) than were those with Omicron infections (49%). Among fully vaccinated children aged 5-11 years, VE against any symptomatic and asymptomatic Omicron infection 14-82 days (the longest interval after dose 2 in this age group) after receipt of dose 2 of the Pfizer-BioNTech vaccine was 31% (95% CI = 9%-48%), adjusted for sociodemographic characteristics, health information, frequency of social contact, mask use, location, and local virus circulation. Among adolescents aged 12-15 years, adjusted VE 14-149 days after dose 2 was 87% (95% CI = 49%-97%) against symptomatic and asymptomatic Delta infection and 59% (95% CI = 22%-79%) against Omicron infection. Fully vaccinated participants with Omicron infection spent an average of one half day less sick in bed than did unvaccinated participants with Omicron infection. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations.

•Mothers in Albania, Nicaragua, Philippines, and Jordan completed a survey.•Influenza vaccine is not routinely given in these countries.•Many mothers were unaware of the disease or vaccine.•Perceived safety was an important predictor of vaccine intentions. Despite a large burden of influenza in middle income countries, pediatric vaccination coverage remains low. The aims of this study were to (1) describe mothers’ knowledge and attitudes about influenza illnesses and vaccination, and (2) identify characteristics associated with mothers’ intent to vaccinate their child. From 2015 to 2017, infants 0–11 months old in Nicaragua, Philippines, Jordan, and Albania were enrolled from community settings and hospitals. Interviewers administered a questionnaire to their mothers. Mothers of infants aged 6–11 months rated their intention (small-to-moderate vs. large chance) to accept pediatric vaccination if it was offered at no-cost. The importance of knowledge, attitudes, and sociodemographic characteristics in predicting influenza vaccination intention was measured as the mean decrease in Gini index when that factor was excluded from 1000 decision trees in a random forest analysis. In total, 1,308 mothers were enrolled from the community setting and 3,286 from the hospital setting. Prevalence of at least some knowledge of influenza illness ranged from 34% in Philippines to 88% in Albania (in the community sample), and between 23% in Philippines to 88% in Jordan (in the hospital sample). In the community sample, most mothers in Albania (69%) and Philippines (58%) would accept the influenza vaccine, and these proportions were higher in the hospital sample for all countries except Albania (48%) (P < 0.0001). Perceived vaccine safety (mean decrease in Gini index = 61) and effectiveness (55), and perceived knowledge of influenza vaccine (45) were the most important predictors of influenza vaccination intention in models that also included country and community versus hospital sample. Intent to vaccinate infants aged 6–11 months in four middle income countries was tied primarily to knowledge of the vaccine and perceptions of vaccine safety and effectiveness. These findings were noted among mothers interviewed in the community and mothers of recently hospitalized infants.

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.

An estimated 1% to 3% of children with SARS-CoV-2 infection will develop post-COVID-19 condition (PCC). To evaluate the odds of PCC among children with COVID-19 vaccination prior to SARS-CoV-2 infection compared with odds among unvaccinated children. In this case-control study, children were enrolled in a multisite longitudinal pediatric cohort from July 27, 2021, to September 1, 2022, and followed up through May 2023. Analysis used a case (PCC reported)-control (no PCC reported) design and included children aged 5 to 17 years whose first real time-polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection occurred during the study period, who were COVID-19 vaccine age-eligible at the time of infection, and who completed a PCC survey at least 60 days after infection. From December 1, 2022, to May 31, 2023, children had weekly SARS-CoV-2 testing and were surveyed regarding PCC (≥1 new or ongoing symptom lasting ≥1 month after infection). COVID-19 mRNA vaccination status at time of infection was the exposure of interest; participants were categorized as vaccinated (≥2-dose series completed ≥14 days before infection) or unvaccinated. Vaccination status was verified through vaccination cards or vaccine registry and/or medical records when available. Main outcomes were estimates of the odds of PCC symptoms. Multivariate logistic regression was performed to estimate the odds of PCC among vaccinated children compared with odds of PCC among unvaccinated children. A total of 622 participants were included, with 28 (5%) case participants and 594 (95%) control participants. Median (IQR) age was 10.0 (7.0-11.9) years for case participants and 10.3 (7.8-12.7) years for control participants (P = .37). Approximately half of both groups reported female sex (13 case participants [46%] and 287 control participants [48%]). Overall, 57% of case participants (16 children) and 77% of control participants (458 children) were vaccinated (P = .05). After adjusting for demographic characteristics, number of acute COVID-19 symptoms, and baseline health, COVID-19 vaccination was associated with decreased odds of 1 or more PCC symptom (adjusted odds ratio [aOR], 0.43; 95% CI, 0.19-0.98) and 2 or more PCC symptoms (aOR, 0.27; 95% CI, 0.10-0.69). In this study, mRNA COVID-19 vaccination was associated with reduced odds of PCC in children. The aORs correspond to an estimated 57% and 73% reduced likelihood of 1 or more and 2 or more PCC symptoms, respectively, among vaccinated vs unvaccinated children. These findings suggest benefits of COVID-19 vaccination beyond those associated with protection against acute COVID-19 and may encourage increased pediatric uptake.