Since April 2024, sporadic infections with highly pathogenic avian influenza (HPAI) A(H5) viruses have been detected among dairy farm workers in the United States. To date, infections have mostly been detected through worker monitoring, and have been mild despite the possibility of more severe illness. During June-August 2024, CDC collaborated with the Michigan Department of Health and Human Services and the Colorado Department of Public Health and Environment to implement cross-sectional serologic surveys to ascertain the prevalence of recent infection with HPAI A(H5) virus among dairy workers. In both states, a convenience sample of persons who work in dairies was interviewed, and blood specimens were collected. Among 115 persons, eight (7%; 95% CI = 3.6%-13.1%) had serologic evidence of recent infection with A(H5) virus; all reported milking cows or cleaning the milking parlor. Among persons with serologic evidence of infection, four recalled being ill around the time cows were ill; symptoms began before or within a few days of A(H5) virus detections among cows. This finding supports the need to identify and implement strategies to prevent transmission among dairy cattle to reduce worker exposures and for education and outreach to dairy workers concerning prevention, symptoms, and where to seek medical care if the workers develop symptoms. Timely identification of infected herds can support rapid initiation of monitoring, testing, and treatment for human illness, including mild illness, among exposed dairy workers.

Background The 2017-2018 US influenza season was severe with low vaccine effectiveness. Circulating A(H3N2) viruses from multiple genetic groups were antigenically similar to cell-grown vaccine strains. However, most influenza vaccines are egg-propagated.Methods Serum was collected shortly after illness onset from 15 PCR confirmed A(H3N2) infected cases and 15 uninfected (controls) hospitalized adults enrolled in an influenza vaccine effectiveness study.Geometric mean titers against egg- and cell-grown A/Hong Kong/4801/2014 A(H3N2) vaccine strains and representative circulating viruses (including A/Washington/16/2017) were determined by microneutralization (MN) assays. Independent effects of strain-specific titers on susceptibility were estimated by logistic regression.Results MN titers against egg-A/Hong Kong were significantly higher among those who were vaccinated (MN GMT: 173 vs 41; P = 0.01). However, antibody titers to cell-grown viruses were much lower in all individuals (P>0.05) regardless of vaccination. In unadjusted models, a 2-fold increase in MN titers against egg-A/Hong Kong was not significantly protective against infection (29% reduction; p=0.09), but a similar increase in cell-A/Washington titer (3C.2a2) was protective (60% reduction; p=0.02). A similar increase in egg-A/Hong Kong titer was not significantly associated with odds of infection when adjusting for MN titers against A/Washington (15% reduction; P=0.61). A 54% reduction of odds of infection was observed with a 2-fold increase in A/Washington (not significant; P=0.07), adjusted for egg-A/Hong Kong titer.Conclusion Although individuals vaccinated in 2017-2018 had high antibody titers against the egg-adapted vaccine strain, antibody responses to cell-grown circulating viruses may not be sufficient to provide protection, likely due to egg-adaptation in the vaccine.We thank Maryna Eichelberger, Hongquan Wan, Jin Gao, and Laura Couzens (Food and Drug Administration) for technical support and providing reassortant influenza viruses for use in the enzyme-linked lectin assays. St Jude Children’s Research Hospital provided plasmids that were used to generate these reassortant influenza viruses. We thank Mrs F Liaini Gross, Lauren Horner and Makeda Kay from Influenza Division, Centers for Disease Control and Prevention for technical support for virus propagation and specimen management.

Juneteenth, a federal holiday officially recognized in 2021, is celebrated annually in the United States to honor the emancipation of enslaved Black Americans. As a symbol of racial justice, equality, and equity, Juneteenth represents an opportunity to pay tribute to the achievements of a wide range of Black chemistry students and the initiatives taken to promote the success of every student within an environment that has historically not been inclusive. | | While the U.S. STEM workforce has become more diverse in the past 10 years, Black people continue to be underrepresented in science, and in chemistry, in particular. The recent National Science Foundation report Diversity and STEM: Women, Minorities and Persons with Disabilities 2023 shows that only 9% of the STEM workforce identifies as Black, 3 percentage points (roughly 7.7M people (1)) lower than their overall representation in the adult U.S. population. (2) The U.S. Bureau of Labor Statistics paints a similar picture─in 2022 only 10% of the chemical manufacturing workforce was Black. (3) Chemical & Engineering News culled the chemistry data from the 2023 NSF report revealing even bleaker figures─in 2021, Black people comprised only 4.4% of employed chemists, (4) and were more likely to occupy lower paying STEM jobs that do not require a college degree. (2) | | Recent publications have emphasized the importance of scientists and scientific institutions welcoming and supporting the development of individuals from groups historically marginalized in fields such as chemistry, biology, mathematics, computer science, and physics. (5) Not only is such intentional support a moral imperative, but numerous reports have demonstrated that increasing diversity and inclusion in these fields leads to a more innovative and productive scientific community. (6) | | Marginalized groups often face systemic barriers to accessing education and career opportunities, resulting in a chemical workforce that lacks diversity. To address this, chemists and chemistry organizations have taken steps to actively support and mentor individuals from historically excluded groups, providing access to resources and opportunities, and promoting a culture of inclusivity in academia and the workplace. For instance, since 1965, the American Chemical Society (ACS) Project Seed program has provided summer research experiences for more than 11,000 high school students, while the ACS Scholars program has provided renewable scholarships for more than 3,500 undergraduates interested in chemistry-related careers.

Influenza A(H7N9) viruses remain as a high pandemic threat. The continued evolution of the A(H7N9) viruses poses major challenges in pandemic preparedness strategies through vaccination. We assessed the breadth of the heterologous neutralizing antibody responses against the 3rd and 5th wave A(H7N9) viruses using the 1st wave vaccine sera from 4 vaccine groups: 1. inactivated vaccine with 2.8 μg hemagglutinin (HA)/dose + AS03(A); 2. inactivated vaccine with 5.75 μg HA/dose + AS03(A;) 3. inactivated vaccine with 11.5 μg HA/dose + MF59; and 4. recombinant virus like particle (VLP) vaccine with 15 μg HA/dose + ISCOMATRIX™. Vaccine group 1 had the highest antibody responses to the vaccine virus and the 3rd/5th wave drifted viruses. Notably, the relative levels of cross-reactivity to the drifted viruses as measured by the antibody GMT ratios to the 5th wave viruses were similar across all 4 vaccine groups. The 1st wave vaccines induced robust responses to the 3rd and Pearl River Delta lineage 5th wave viruses but lower cross-reactivity to the highly pathogenic 5th wave A(H7N9) virus. The population in the United States was largely immunologically naive to the A(H7N9) HA. Seasonal vaccination induced cross-reactive neuraminidase inhibition and binding antibodies to N9, but minimal cross-reactive antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies to A(H7N9).

Although some adults infected with influenza 2009 A(H1N1)pdm09 viruses mounted high hemagglutination inhibition (HAI) antibody response, they still suffered from severe disease, or even death. Here, we analyzed antibody profiles in patients (n = 31, 17-65 years) admitted to intensive care units (ICUs) with lung failure and invasive mechanical ventilation use due to infection with A(H1N1)pdm09 viruses during 2009-2011. We performed a comprehensive analysis of the quality and quantity of antibody responses using HAI, virus neutralization, biolayer interferometry, enzyme-linked-lectin and enzyme-linked immunosorbent assays. At time of the ICU admission, 45% (14/31) of the patients had HAI antibody titers ≥ 80 in the first serum (S1), most (13/14) exhibited narrowly-focused HAI and/or anti-HA-head binding antibodies targeting single epitopes in or around the receptor binding site. In contrast, 42% (13/31) of the patients with HAI titers ≤ 10 in S1 had non-neutralizing anti-HA-stem antibodies against A(H1N1)pdm09 viruses. Only 19% (6/31) of the patients showed HA-specific IgG1-dominant antibody responses. Three of 5 fatal patients possessed highly focused cross-type HAI antibodies targeting the (K130 + Q223)-epitopes with extremely low avidity. Our findings suggest that narrowly-focused low-quality antibody responses targeting specific HA-epitopes may have contributed to severe infection of the lower respiratory tract.

BACKGROUND: Studies of thunderstorm asthma to understand risk factors using high-resolution climate data and asthma outcomes on a large scale are scarce. Moreover, thunderstorm asthma is not well studied in the United States. OBJECTIVES: We examined whether climate parameters involved in thunderstorms are associated with emergency department (ED) visits for acute asthma attacks in the United States. METHODS: We analyzed 63,789 asthma-related, daily ED visits for all age groups, and thunderstorm-associated climate data in Louisiana during 2010 through 2012. We performed time-series analyses using quasi-Poisson regression models with natural cubic splines of date, parish, holiday, day of week, season, daily maximum concentrations of ozone (O3) and fine particulate matter [PM 2.5 m in aerodynamic diameter (PM2.5)], and daily mean pressure, precipitation, and temperature. Because of a significant interaction effect between temperature and lightning days on asthma-related visits, we performed stratified analyses by days with/without lightning or thunderstorm (defined by any lightning and precipitation). RESULTS: On thunderstorm days, higher asthma-related ED visits were associated with higher daily mean precipitation [relative risk(RR) =1.145per1g/m2/s (95% CI: 1.009, 1.300)] and lower daily mean temperature [RR =1.011 per 1C change (1.000-1.021)] without carry-over effect to the next non-thunderstorm day. These higher risks were found mainly among children and adults <65years of age. We observed similar results on lightning days. However, we did not find similar associations for non-thunderstorm or non-lightning days. Daily maximum O3 and PM2.5 levels were not significantly associated with asthma ED visits on thunderstorm days. DISCUSSION: Higher precipitation and lower temperature on thunderstorm days appear to contribute to asthma attacks among people with asthma, suggesting they should consider taking precautions during thunderstorms. EDs should consider preparing for a potential increase of asthma-related visits and ensuring sufficient stock of emergency medication and supplies for forecasted severe thunderstorm days. https://doi.org/10.1289/EHP10440.

Gatherings where people are eating and drinking can increase the risk of getting and spreading SARS-CoV-2 among people who are not fully vaccinated; prevention strategies like wearing masks and physical distancing continue to be important for some groups. We conducted an online survey to characterise fall/winter 2020-2021 holiday gatherings, decisions to attend and prevention strategies employed during and before gatherings. We determined associations between practicing prevention strategies, demographics and COVID-19 experience. Among 502 respondents, one-third attended in person holiday gatherings; 73% wore masks and 84% practiced physical distancing, but less did so always (29% and 23%, respectively). Younger adults were 44% more likely to attend gatherings than adults >/=35 years. Younger adults (adjusted prevalence ratio (aPR) 1.53, 95% CI 1.19-1.97), persons who did not experience COVID-19 themselves or have relatives/close friends experience severe COVID-19 (aPR 1.56, 95% CI 1.18-2.07), and non-Hispanic White persons (aPR 1.57, 95% CI 1.13-2.18) were more likely to not always wear masks in public during the 2 weeks before gatherings. Public health messaging emphasizing consistent application of COVID-19 prevention strategies is important to slow the spread of COVID-19.

We sought to determine which Salmonella serotypes cause illness related to the Thanksgiving holiday in the United States and to foods disproportionately eaten then (e.g., turkey). Using routine surveillance for 1998-2018 and a case-crossover design, we found serotype Reading to be most strongly associated with Thanksgiving.

Prevention behaviors represent important public health tools to limit spread of SARS-CoV-2. Adherence with recommended public health prevention behaviors among 20000 + members of a COVID-19 syndromic surveillance cohort from the mid-Atlantic and southeastern United States was assessed via electronic survey following the 2020 Thanksgiving and winter holiday (WH) seasons. Respondents were predominantly non-Hispanic Whites (90%), female (60%), and ≥ 50 years old (59%). Non-household members (NHM) were present at 47.1% of Thanksgiving gatherings and 69.3% of WH gatherings. Women were more likely than men to gather with NHM (p < 0.0001). Attending gatherings with NHM decreased with older age (Thanksgiving: 60.0% of participants aged < 30 years to 36.3% aged ≥ 70 years [p-trend < 0.0001]; WH: 81.6% of those < 30 years to 61.0% of those ≥ 70 years [p-trend < 0.0001]). Non-Hispanic Whites were more likely to gather with NHM than were Hispanics or non-Hispanic Blacks (p < 0.0001). Mask wearing, reported by 37.3% at Thanksgiving and 41.9% during the WH, was more common among older participants, non-Hispanic Blacks, and Hispanics when gatherings included NHM. In this survey, most people did not fully adhere to recommended public health safety behaviors when attending holiday gatherings. It remains unknown to what extent failure to observe these recommendations may have contributed to the COVID-19 surges observed following Thanksgiving and the winter holidays in the United States.

A(H3N2) Influenza vaccine effectiveness (VE) were low during 2016-2019 seasons and varied by age. We analyzed neutralizing antibody responses to egg- and cell-propagated vaccine and circulating viruses following vaccination in 375 individuals (aged 7 months to 82 years) across all vaccine eligible age groups in 3 influenza seasons. Antibody responses to cell- compared to egg-propagated vaccine viruses were significantly reduced due to egg-adapted changes T160K, D225G, and L194P in the vaccine hemagglutinins. Vaccine egg-adaptation had differential impact on antibody responses across different age groups. Immunologically naive children immunized with egg-adapted vaccines mostly mounted antibodies targeting egg-adapted epitopes, whereas those previously primed with infection produced broader responses even when vaccinated with egg-based vaccines. In elderly, repeated boost of vaccine egg-adapted epitopes significantly reduced antibody responses to the wild type cell-grown viruses. Analysis with reverse genetics viruses suggested that the response to each egg-adapted substitution varied by age. Antibody responses did not differ in male versus female vaccinees. Here, the combination of age-specific responses to vaccine egg-adapted substitutions, diverse host immune priming histories and virus antigenic drift impacted antibody responses following vaccination and may have led to the low and variable VE against A(H3N2) viruses across different age groups.

Public health and law are inextricably intertwined. Law is the foundation of governmental public health practice, delineating the duties and authority to protect and promote conditions necessary for population health. 1 Law is also a social and structural determinant of health, because laws shape the physical, social, and economic environments that directly impact population health. 2 Public health laws at all levels of government enshrine public health strategies, are critical to addressing emerging issues, and are the means through which interventions are implemented and enforced.

In the 10 months since the first confirmed case of coronavirus disease 2019 (COVID-19) was reported in the United States on January 20, 2020 (1), approximately 13.8 million cases and 272,525 deaths have been reported in the United States. On October 30, the number of new cases reported in the United States in a single day exceeded 100,000 for the first time, and by December 2 had reached a daily high of 196,227.* With colder weather, more time spent indoors, the ongoing U.S. holiday season, and silent spread of disease, with approximately 50% of transmission from asymptomatic persons (2), the United States has entered a phase of high-level transmission where a multipronged approach to implementing all evidence-based public health strategies at both the individual and community levels is essential. This summary guidance highlights critical evidence-based CDC recommendations and sustainable strategies to reduce COVID-19 transmission. These strategies include 1) universal face mask use, 2) maintaining physical distance from other persons and limiting in-person contacts, 3) avoiding nonessential indoor spaces and crowded outdoor spaces, 4) increasing testing to rapidly identify and isolate infected persons, 5) promptly identifying, quarantining, and testing close contacts of persons with known COVID-19, 6) safeguarding persons most at risk for severe illness or death from infection with SARS-CoV-2, the virus that causes COVID-19, 7) protecting essential workers with provision of adequate personal protective equipment and safe work practices, 8) postponing travel, 9) increasing room air ventilation and enhancing hand hygiene and environmental disinfection, and 10) achieving widespread availability and high community coverage with effective COVID-19 vaccines. In combination, these strategies can reduce SARS-CoV-2 transmission, long-term sequelae or disability, and death, and mitigate the pandemic's economic impact. Consistent implementation of these strategies improves health equity, preserves health care capacity, maintains the function of essential businesses, and supports the availability of in-person instruction for kindergarten through grade 12 schools and preschool. Individual persons, households, and communities should take these actions now to reduce SARS-CoV-2 transmission from its current high level. These actions will provide a bridge to a future with wide availability and high community coverage of effective vaccines, when safe return to more everyday activities in a range of settings will be possible.

BACKGROUND: Current influenza vaccine effectiveness (VE) improvement efforts focus on minimizing egg adaptation mutations during manufacture. This study compared immune response of two FDA-approved quadrivalent inactivated influenza vaccines in an unblinded randomized controlled trial. METHODS: Participants were 144 community dwelling, healthy children/adolescents aged 4-20 years, randomized 1:1 in blocks of 4 to a vaccine grown in cell culture (ccIIV4 [Flucelvax(R)]; n = 85); or in egg medium (IIV4 [Fluzone (R)]; n = 83). Blood was drawn at day 0 prevaccination and at day 28 (19-35 days) post vaccination. Hemagglutination inhibition (HI) assays against A/H1N1 and both B strains and microneutralization (MN) assays against egg-based and cell-based A/H3N2 strains were conducted. The primary outcome measure was seroconversion (day 28/day 0 titer ratio >/= 4 with day 28 titer >/= 40). Secondary outcomes were elevated titers (day 28 HI titer >/= 1:110), geometric mean titers (GMTs) and mean fold rise (MFR) in titers. Outcomes were compared for 74 ccIIV4 recipients and 70 IIV4 recipients, and for those vaccinated and unvaccinated the previous year. Only the HI and MN laboratory analysis team was blinded to group assignment. RESULTS: In this racially diverse (81% non-white) group of children with a median age of 14 years, baseline demographics did not differ between vaccine groups. At day 0, half or more in each vaccine group had elevated HI or MN titers. Low seroconversion rates (14%-35%) were found; they did not differ between groups. Among 2018-19 ccIIV4 recipients, those unvaccinated in the previous season showed significantly higher MFR against A/H1N1 and A/H3N2 cell-grown virus than the previously vaccinated. Similar results were found for MFR against B/Victoria among 2018-2019 IIV4 recipients. CONCLUSION: In mostly older children with high baseline titers, no differences in seroconversion or other measures of antibody titers were found between ccIIV4 and IIV4 recipients against egg- and cell-grown influenza vaccine viruses. CLINICAL TRIALS NO: NCT03614975.

This report summarizes the design and outcomes of randomized controlled operational research trials performed by the Bill & Melinda Gates Foundation-funded Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) from 2009 to 2019. Their goal was to define the effectiveness and test the limitations of current WHO-recommended schistosomiasis control protocols by performing large-scale pragmatic trials to compare the impact of different schedules and coverage regimens of praziquantel mass drug administration (MDA). Although there were limitations to study designs and performance, analysis of their primary outcomes confirmed that all tested regimens of praziquantel MDA significantly reduced local Schistosoma infection prevalence and intensity among school-age children. Secondary analysis suggested that outcomes in locations receiving four annual rounds of MDA were better than those in communities that had treatment holiday years, in which no praziquantel MDA was given. Statistical significance of differences was obscured by a wider-than-expected variation in community-level responses to MDA, defining a persistent hot spot obstacle to MDA success. No MDA schedule led to elimination of infection, even in those communities that started at low prevalence of infection, and it is likely that programs aiming for elimination of transmission will need to add supplemental interventions (e.g., snail control, improvement in water, sanitation and hygiene, and behavior change interventions) to achieve that next stage of control. Recommendations for future implementation research, including exploration of the value of earlier program impact assessment combined with intensification of intervention in hot spot locations, are discussed.

BACKGROUND: The development of serologic assays that can rapidly assess human exposure to novel influenza viruses remains a public health need. Previously, we developed an 11-plex magnetic fluorescence microsphere immunoassay (MAGPIX) by using globular head domain recombinant hemagglutinins (rHAs) with serum adsorption using two ectodomain rHAs. METHODS: We compared sera collected from two cohorts with novel influenza exposures: animal shelter staff during an A(H7N2) outbreak in New York City in 2016-2017 (n = 119 single sera) and poultry workers from a live bird market in Bangladesh in 2012-2014 (n = 29 pairs). Sera were analyzed by microneutralization (MN) assay and a 20-plex MAGPIX assay with rHAs from 19 influenza strains (11 subtypes) combined with serum adsorption using 8 rHAs from A(H1N1) and A(H3N2) viruses. Antibody responses were analyzed to determine the novel influenza virus exposure. RESULTS: Among persons with novel influenza virus exposures, the median fluorescence intensity (MFI) against the novel rHA from exposed influenza virus had the highest correlation with MN titers to the same viruses and could be confirmed by removal of cross-reactivity from seasonal H1/H3 rHAs following serum adsorption. Interestingly, in persons with exposures to novel influenza viruses, age and MFIs against exposed novel HA were negatively correlated, whereas in persons without exposure to novel influenza viruses, age and MFI against novel HAs were positively correlated. CONCLUSIONS: This 20-plex high-throughput assay with serum adsorption will be a useful tool to detect novel influenza virus infections during influenza outbreak investigations and surveillance, especially when well-paired serum samples are not available.

BACKGROUND: Since influenza often presents non-specifically in infancy, we aimed to assess the extent to which existing respiratory surveillance platforms might underestimate the frequency of severe influenza disease among infants. METHODS: The Influenza and Respiratory Syncytial Virus in Infants (IRIS) study was a prospective observational study done at four hospitals in Albania, Jordan, Nicaragua, and the Philippines. We included acutely ill infants aged younger than 1 year admitted to hospital within 10 days or less of illness onset during two influenza seasons (2015-16 and 2016-17) in Albania, Jordan, and Nicaragua, and over a continuous 34 week period (2015-16) in the Philippines. We assessed the frequency of influenza virus infections by real-time RT-PCR (rRT-PCR) and serology. The main study outcome was seroconversion, defined as convalescent antibody titres more than or equal to four-fold higher than acute sera antibody titres, and convalescent antibody titres of 40 or higher. Seroconverison was confirmed by haemagglutination inhibition assay for influenza A viruses, and by hemagglutination inhibition assay and microneutralisation for influenza B viruses. FINDINGS: Between June 27, 2015, and April 21, 2017, 3634 acutely ill infants were enrolled, of whom 1943 were enrolled during influenza seasons and had complete acute-convalescent pairs and thus were included in the final analytical sample. Of the 1943 infants, 94 (5%) were influenza-positive by both rRT-PCR and serology, 58 (3%) were positive by rRT-PCR-only, and 102 (5%) were positive by serology only. Seroconversion to at least one of the influenza A or B viruses was observed among 196 (77%) of 254 influenza-positive infants. Of the 254 infants with influenza virus, 84 (33%) only had non-respiratory clinical discharge diagnoses (eg, sepsis, febrile seizures, dehydration, or other non-respiratory viral illness). A focus on respiratory diagnoses and rRT-PCR-confirmed influenza underdetects influenza-associated hospital admissions among infants by a factor of 2.6 (95% CI 2.0-3.6). Findings were unchanged when syndromic severe acute respiratory infection criteria were applied instead of clinical diagnosis. INTERPRETATION: If the true incidence of laboratory-confirmed influenza-associated hospital admissions among infants is at least twice that of previous estimates, this substantially increases the global burden of severe influenza and expands our estimates of the preventive value of maternal and infant influenza vaccination programmes. FUNDING: US Centers for Disease Control and Prevention.

Highly pathogenic avian influenza (HPAI) A(H5Nx) viruses continue to pose a pandemic threat. US national vaccine stockpiles are a cornerstone of the influenza pandemic preparedness plans. However, continual genetic and antigenic divergence of A(H5Nx) viruses requires the development of effective vaccination strategies using stockpiled vaccines and adjuvants for pandemic preparedness. Human sera collected from healthy adults who received either homologous (2 doses of a AS03A-adjuvanted A/turkey/Turkey/1/2005, A/Turkey), or heterologous (primed with AS03A-adjuvanted A/Indonesia/5/2005, A/Indo, followed by A/Turkey boost) prime-boost vaccination regimens were analyzed by hemagglutination inhibition and microneutralization assays against 8 wild-type HPAI A(H5Nx) viruses from 6 genetic clades. Molecular, structural and antigenic features of the A(H5Nx) viruses that could influence the cross-clade antibody responses were also explored. Compared with homologous prime-boost vaccinations, priming with a clade 2.1.3.2 antigen (A/Indo) followed by one booster dose of a clade 2.2.1 antigen (A/Turkey) administered 18 months apart did not compromise the antibody responses to the booster vaccine (A/Turkey), it also broadened the cross-clade antibody responses to several antigenically drifted variants from 6 heterologous clades, including an antigenically distant A(H5N8) virus (A/gyrfalcon/Washington/410886/2014, clade 2.3.4.4) that caused recent outbreaks in US poultry. The magnitude and breadth of the cross-clade antibody responses against emerging HPAI A(H5Nx) viruses are associated with genetic, structural and antigenic differences from the vaccine viruses and enhanced by the inclusion of an adjuvant. Heterologous prime-boost vaccination with AS03A adjuvanted vaccine offers a vaccination strategy to use existing stockpiled vaccines for pandemic preparedness against new emerging HPAI A(H5Nx) viruses.

Background: Influenza vaccine effectiveness was low in 2017-2018, yet circulating A(H3N2) viruses were antigenically similar to cell-grown vaccine strains. Notably, most influenza vaccines are egg-propagated. Methods: Serum was collected shortly after illness onset from 15 A(H3N2) infected cases and 15 uninfected hospitalized adults. Geometric mean titers against egg- and cell-grown A/Hong Kong/4801/2014 A(H3N2) vaccine strains and representative circulating viruses (including A/Washington/16/2017) were determined by microneutralization (MN). Independent effects of strain-specific titers on susceptibility were estimated by logistic regression. Results: MN titers against egg-A/Hong Kong were significantly higher among vaccinated individuals (173 vs 41; p=0.01). In unadjusted models, a 2-fold increase in titers against egg-A/Hong Kong was not significantly protective (29% reduction; p=0.09), but a similar increase in cell-A/Washington titer (3C.2a2) was protective (60% reduction; p=0.02). Higher egg-A/Hong Kong titers were not significantly associated with infection, when adjusted for titers against A/Washington (15% reduction; p=0.61). A 54% reduction of odds of infection was observed with a 2-fold increase in A/Washington (not significant), adjusted for egg-A/Hong Kong titer. Conclusion: Individuals vaccinated in 2017-2018 had high antibody titers against the egg-adapted vaccine strain and lower titers against circulating viruses. Titers against circulating, but not egg-adapted strains, were correlated with protection.

Kitchen, a painting completed in 1580 by Italian artist Vincenzo Campi, celebrates the chaotic workspace that was devoted to keeping a noble family’s house supplied with food and drink. The kitchen workers are preparing an assortment and quantity of meats, pies and breads, sauces, and side dishes as a special meal for a celebration or holiday. | | Invisible to the viewer and unknown to Campi, his subjects, or his patrons, this kitchen would have been permeated by numerous unwelcome microorganisms that could cause zoonotic foodborne diseases. Such a setting would provide many opportunities for transmission of potentially pathogenic bacteria, viruses, and parasites in the raw meat and poultry, in the blood and viscera spattered on the workers’ skin and clothing, on floors and shared work surfaces, knives, and other utensils, and from domestic pets, rodents, and insects. | | Campi’s Kitchen is alive with activity. Near the top of the painting, demonstrating the artist’s mastery of the technique of perspective, the viewer sees a dining room containing a long table festooned with a white tablecloth and tended by a young girl. Half a dozen colorfully dressed women are busy preparing the food, seemingly using every available surface. An older woman is working on the floor and appears to react negatively to the taste or smell of whatever is covering the bottom of a large pestle. A small child is sitting on a colander, amusing himself by inflating an animal’s stomach. On the upper left periphery, a pair of men are butchering a deer carcass, while across the kitchen, a young man is carefully skewering raw, uncooked game birds on a spit. A cat and dog scrap for entrails plucked from the poultry carcass in the foreground, cooking pans dangle near rows of stacked plates in the upper right, and a small fire smolders in the fireplace near the center.

Neutralizing antibodies against hemagglutinin (HA) of influenza viruses are considered the main immune mechanism that correlates with protection for influenza infections. Microneutralization (MN) assays are often used to measure neutralizing antibody responses in human sera after influenza vaccination or infection. Madine Darby Canine Kidney (MDCK) cells are the commonly used cell substrate for MN assays. However, currently circulating 3C.2a and 3C.3a A(H3N2) influenza viruses have acquired altered receptor binding specificity. The MDCK-SIAT1 cell line with increased α-2,6 sialic galactose moieties on the surface has proven to provide improved infectivity and more faithful replications than conventional MDCK cells for these contemporary A(H3N2) viruses. Here, we describe a MN assay using MDCK-SIAT1 cells that has been optimized to quantify neutralizing antibody titers to these contemporary A(H3N2) viruses. In this protocol, heat inactivated sera containing neutralizing antibodies are first serially diluted, then incubated with 100 TCID50/well of influenza A(H3N2) viruses to allow antibodies in the sera to bind to the viruses. MDCK-SIAT1 cells are then added to the virus-antibody mixture, and incubated for 18 - 20 h at 37 °C, 5% CO2 to allow A(H3N2) viruses to infect MDCK-SIAT1 cells. After overnight incubation, plates are fixed and the amount of virus in each well is quantified by an enzyme-linked immunosorbent assay (ELISA) using anti-influenza A nucleoprotein (NP) monoclonal antibodies. Neutralizing antibody titer is defined as the reciprocal of the highest serum dilution that provides ≥50% inhibition of virus infectivity. © 2017 Journal of Visualized Experiments.

Recently, novel highly pathogenic avian influenza H5Nx viruses (clade 2.3.4.4) caused outbreaks in US poultry. We evaluated the potential of a stockpiled A(H5N1) A/Anhui/1/2005 (clade 2.3.4) vaccine to elicit cross-reactive antibody responses to these emerging viruses. Sera from subjects who received 2 doses of MF59-adjuvanted A/Anhui/1/2005, or 1 dose of MF59-adjuvanted A/Anhui/1/2005 following priming with a clade 1 vaccine were characterized by microneutralization assays and modified hemagglutination inhibition (HI) assays. Only heterologous prime-boost vaccination induced modest cross-reactive HI antibody responses to H5Nx viruses. Heterologous prime-boost may provide a more effective vaccination strategy to broaden the antibody responses to emerging viruses.

Avian influenza viruses of the H7 hemagglutinin (HA) subtype present a significant public health threat, as evidenced by the ongoing outbreak of human A(H7N9) infections in China. When evaluated by hemagglutinin inhibition (HI) and micro-neutralization (MN) assays, H7 viruses and vaccines induce lower level of neutralizing antibodies (nAb) than do their seasonal counterparts, making it difficult to develop and evaluate pre-pandemic vaccines. We have previously shown that purified recombinant H7 hemagglutinin (HA) appear to be poorly immunogenic in that they induce low levels of HI and MN antibodies. Here, we immunized mice with whole inactivated reverse genetics reassortant (RG) viruses expressing HA and NA from 3 different H7 viruses [A/Shanghai/2/2013 (H7N9), A/Netherlands/219/2003 (H7N7) and A/New York/107/2003 (H7N2)], or with human A(H1N1)pdm09 [A/California/07/2009-like] or A(H3N2) [A/Perth16/2009] viruses. Mice produced equivalent titers of antibodies to all viruses as measured by ELISA. However, the antibody titers induced by H7 viruses were significantly lower when measured by HI and MN assays. Despite inducing very low levels of nAb, H7 vaccines conferred complete protection against homologous virus challenge in mice, and the serum antibodies directed against the HA head region were capable of mediating protection. The apparently low immunogenicity associated with H7 viruses and vaccines may be at least partly related to measuring antibody titers with the traditional HI and MN assays, which may not provide a true measure of protective immunity associated with H7 immunization. This study underscores the need for development of additional correlates of protection for pre-pandemic vaccines.IMPORTANCE H7 avian influenza viruses present a serious risk to human health. Preparedness efforts include development of pre-pandemic vaccines. For seasonal influenza viruses, protection is correlated with antibody titers measured by hemagglutination inhibition (HI) and virus microneutralization (MN) assays. Since H7 vaccines typically induce low HI and MN titers, they have been considered to be poorly immunogenic. We show that in mice H7 whole inactivated virus (WIV) vaccines were as immunogenic as seasonal WIVs, as they induced similar levels of overall serum antibodies. However, a larger fraction of the antibodies induced by H7 WIV was non-neutralizing in vitro. Nevertheless, the H7 WIV completely protected mice against homologous viral challenge, and antibodies directed against the HA-head were the major contributor toward immune protection. Vaccines against H7 avian influenza viruses may be more effective than HI and virus neutralization assays suggest, and such vaccines may need other methods for evaluation.

BACKGROUND: We determined influenza A(H1N1)pdm09 antibody levels before and after the first wave of the pandemic in an urban community in Dhaka, Bangladesh. METHODS: We identified a cohort of households by stratified random sampling. We collected baseline serum specimens during July-August 2009, just prior to the initial wave of the 2009 pandemic in this community and a second specimen during November 2009, after the pandemic peak. Paired sera was tested for antibodies against A(H1N1)pdm09 virus using microneutralization assay and hemagglutinin inhibition (HI) assay. A four-fold increase in antibody titer by either assay with a titer of ≥40 in the convalescent sera was considered a seroconversion. At baseline, an HI titer of >40 was considered seropositive. We collected information on clinical illness from weekly home visits. RESULTS: We tested 779 paired sera from the participants. At baseline, before the pandemic wave, 1% overall and 3% of persons >60 years old were seropositive. After the first wave of the pandemic, 211 (27%) individuals seroconverted against A(H1N1)pdm09. Children aged 5-17 years had the highest proportion (37%) of seroconversion. Among 264 (34%) persons with information on clinical illness, 191 (72%) had illness >3 weeks prior to collection of the follow-up sera and 73 (38%) seroconverted. Sixteen (22%) of these 73 seroconverted participants reported no clinical illness. CONCLUSION: After the first pandemic wave in Dhaka, one in four persons were infected by A(H1N1)pdm09 virus and the highest burden of infection was among the school-aged children. Seroprevalence studies supplement traditional surveillance systems to estimate infection burden. This article is protected by copyright. All rights reserved.

Background. Detection of neutralizing antibodies (nAbs) to influenza A virus hemagglutinin (HA) antigens by conventional serological assays is currently the main immune correlate of protection for influenza vaccines However, current prepandemic avian influenza vaccines are poorly immunogenic in inducing nAbs despite considerable protection conferred. Recent studies show that Ab-dependent cell-mediated cytotoxicity (ADCC) to HA antigens are readily detectable in the sera of healthy individuals and patients with influenza infection. Methods. Virus neutralization and ADCC activities of serum samples from individuals who received either seasonal or a stock-piled H5N1 avian influenza vaccine were evaluated by hemagglutination inhibition assay, microneutralization assay, and an improved ADCC natural killer (NK) cell activation assay. Results. Immunization with inactivated seasonal influenza vaccine led to strong expansion of both nAbs and ADCC-mediating antibodies (adccAbs) to H3 antigen of the vaccine virus in 24 postvaccination human sera. In sharp contrast, 18 individuals vaccinated with the adjuvanted H5N1 avian influenza vaccine mounted H5-specific antibodies with strong ADCC activities despite moderate virus neutralization capacity. Strength of HA-specific ADCC activities is largely associated with the titers of HA-binding antibodies and not with the fine antigenic specificity of anti-HA nAbs. Conclusions. Detection of both nAbs and adccAbs may better reflect protective capacity of HA-specific antibodies induced by avian influenza vaccines.

There is no research investigating indoor tanning advertising on social media. We assessed the use of social media to promote indoor tanning. We subscribed to social media platforms in six US cities and content-analyzed promotional messages received. We captured 662 messages on Twitter and Facebook, through salon emails, and in daily deal coupons. Salon postings were most frequent on Twitter and Facebook, with an average of 2-3 postings per week. National chains posted more frequently than local businesses. Forty percent of messages were devoid of tanning content and included photos, jokes, or popular references. Thirty percent mentioned price reductions, and 28 % referenced an upcoming holiday. Sunless tanning (17 %) was promoted more often than ultraviolet tanning (9 %). Tanning salons actively use social media as a strategy for maintaining relationships with customers and offer pricing deals that promote loyalty and high-frequency tanning.

It is well established that virus neutralizing (VN) antibodies to hemagglutinin (HA) antigens of influenza A viruses provide optimal protection against antigenically matched strains of influenza A viruses. In contrast, little is known about the potential role of HA-specific, non-neutralizing antibodies in protection against human influenza illness at present. In this study, we show that individuals vaccinated with the 2014-15 seasonal inactivated influenza vaccine displayed strong A/H3N2 HA-specific antibody-dependent cell-mediated cytotoxicity (ADCC) activities against an antigenically drifted H3N2 virus, despite poor induction of cross-reactive neutralizing antibodies against the antigenic variant. Given that passive transfer of influenza HA-monospecific immune sera with negligible levels of HA-specific VN antibodies can often confer considerable cross protection against lethal challenge with heterologous influenza viruses in animal models, it is conceivable that HA-specific, non-neutralizing antibodies may provide certain degree of cross protection against antigenically drifted influenza A viruses through ADCC in case of influenza vaccine mismatches. This may have important implications for public health.

In the United States, influenza season typically begins in October or November, peaks in February, and tapers off in April. During the winter holiday break, from the end of December to the beginning of January, changes in social mixing patterns, healthcare-seeking behaviors, and surveillance reporting could affect influenza-like illness (ILI) rates. We compared predicted with observed weekly ILI to examine trends around the winter break period. We examined weekly rates of ILI by region in the United States from influenza season 2003-2004 to 2012-2013. We compared observed and predicted ILI rates from week 44 to week 8 of each influenza season using the auto-regressive integrated moving average (ARIMA) method. Of 1,530 region, week, and year combinations, 64 observed ILI rates were significantly higher than predicted by the model. Of these, 21 occurred during the typical winter holiday break period (weeks 51-52); 12 occurred during influenza season 2012-2013. There were 46 observed ILI rates that were significantly lower than predicted. Of these, 16 occurred after the typical holiday break during week 1, eight of which occurred during season 2012-2013. Of 90 (10 HHS regions x 9 seasons) predictions during the peak week, 78 predicted ILI rates were lower than observed. Out of 73 predictions for the post-peak week, 62 ILI rates were higher than observed. There were 53 out of 73 models that had lower peak and higher post-peak predicted ILI rates than were actually observed. While most regions had ILI rates higher than predicted during winter holiday break and lower than predicted after the break during the 2012-2013 season, overall there was not a consistent relationship between observed and predicted ILI around the winter holiday break during the other influenza seasons.

National syndromic surveillance systems require optimal anomaly detection methods. For method performance comparison, we injected multi-day signals stochastically drawn from lognormal distributions into time series of aggregated daily visit counts from the U.S. Centers for Disease Control and Prevention's BioSense syndromic surveillance system. The time series corresponded to three different syndrome groups: rash, upper respiratory infection, and gastrointestinal illness. We included a sample of facilities with data reported every day and with median daily syndromic counts 1 over the entire study period. We compared anomaly detection methods of five control chart adaptations, a linear regression model and a Poisson regression model. We assessed sensitivity and timeliness of these methods for detection of multi-day signals. At a daily background alert rate of 1% and 2%, the sensitivities and timeliness ranged from 24%-77% and 3.3-6.1 days, respectively. The overall sensitivity and timeliness increased substantially after stratification by weekday versus weekend and holiday. Adjusting the baseline syndromic count by the total number of facility visits gave consistently improved sensitivity and timeliness without stratification, but it provided better performance when combined with stratification. The daily syndrome/total-visit proportion method did not improve the performance. In general, alerting based on linear regression outperformed control chart based methods. A Poisson regression model obtained the best sensitivity in the series with high-count data.