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Background Annual influenza vaccination is recommended for older adults but repeated vaccination with standard-dose influenza vaccine has been linked to reduced immunogenicity and effectiveness, especially against A(H3N2) viruses. Methods Community-dwelling Hong Kong adults aged 65–82 years were randomly allocated to receive 2017–2018 standard-dose quadrivalent, MF59-adjuvanted trivalent, high-dose trivalent, and recombinant-HA quadrivalent vaccination. Antibody response to unchanged A(H3N2) vaccine antigen was compared among participants with and without self-reported prior year (2016–2017) standard-dose vaccination. Results Mean fold rise (MFR) in antibody titers from day 0 to day 30 by hemagglutination inhibition and virus microneutralization assays were lower among 2017–2018 standard-dose and enhanced vaccine recipients with (range, 1.7–3.0) versus without (range, 4.3–14.3) prior 2016–2017 vaccination. MFR was significantly reduced by about one-half to four-fifths for previously vaccinated recipients of standard-dose and all 3 enhanced vaccines (β range,.21–.48). Among prior-year vaccinated older adults, enhanced vaccines induced higher 1.43 to 2.39-fold geometric mean titers and 1.28 to 1.74-fold MFR versus standard-dose vaccine by microneutralization assay. Conclusions In the context of unchanged A(H3N2) vaccine strain, prior-year vaccination was associated with reduced antibody response among both standard-dose and enhanced influenza vaccine recipients. Enhanced vaccines improved antibody response among older adults with prior-year standard-dose vaccination. [ABSTRACT FROM AUTHOR]

Background Understanding respiratory syncytial virus (RSV) global epidemiology is important to inform future prevention strategies. Methods Hospitalized infants <1-year-old with acute illness were enrolled prospectively in Albania, Jordan, Nicaragua, and Philippines during respiratory seasons in 2015–2017. Medical chart review, parental interview, and post-discharge follow up were conducted. Respiratory specimens were tested using real-time RT-PCR for RSV. Infant characteristics associated with very severe illness (intensive care unit [ICU] admission or receipt of supplemental oxygen) were assessed using logistic regression to adjust for potential confounders (age, sex, study site, and preterm birth). Results Of 3634 enrolled hospitalized infants, 1129 (31%) tested positive for RSV. The median age of RSV-positive infants was 2.7 (IQR: 1.4–6.1) months and 665 (59%) were male. Very severe illness in 583 (52%) RSV-positive infants was associated with younger age (aOR 4.1, 95% CI: 2.6–6.5 for 0–2 compared to 9–11-months; P <.01), low weight-for-age z -score (aOR 1.9, 95% CI: 1.2–2.8; P <.01), ICU care after birth (aOR 1.6, 95% CI: 1.0–2.5; P =.048), and cesarean delivery (aOR 1.4, 95% CI: 1.0–1.8; P =.03). RSV subgroups A and B co-circulated at all sites with alternating predominance by year; subgroup was not associated with severity (aOR 1.0, 95% CI: 0.8–1.4). Nine (0.8%) RSV-positive infants died during admission or within ≤30 days of discharge, of which 7 (78%) were <6-months-old. Conclusions RSV was associated with nearly a third of infant acute illness hospitalizations in four middle-income countries during the respiratory season, where, in addition to young age, factors including low weight-for-age might be important predictors of severity. RSV prevention strategies targeting young infants could substantially reduce RSV-associated hospitalizations in middle-income countries. [ABSTRACT FROM AUTHOR]

Background: We assessed COVID-19 vaccination impact on illness severity among adults hospitalized with COVID-19 August 2021-March 2022.Methods: We evaluated differences in intensive care unit (ICU) admission, in-hospital death, and length of stay among vaccinated (2 or 3 mRNA vaccine doses) versus unvaccinated patients aged ≥18 years hospitalized for ≥24 hours with COVID-19-like illness (CLI) and positive SARS-CoV-2 molecular testing. We calculated odds ratios for ICU admission and death and subdistribution hazard ratios (SHR) for time to hospital discharge adjusted for age, geographic region, calendar time, and local virus circulation.Results: We included 27,149 SARS-CoV-2 positive hospitalizations. During both Delta and Omicron-predominant periods, protection against ICU admission was strongest among 3-dose vaccinees compared with unvaccinated patients (Delta OR [CI]: 0.52 [0.28-0.96]); Omicron OR [CI]: 0.69 [0.54-0.87]). During both periods, risk of in-hospital of death was lower among vaccinated compared with unvaccinated but ORs were overlapping; during Omicron, lowest among 3-dose vaccinees (OR [CI] 0.39 [0.28-0.54]). We observed SHR >1 across all vaccination strata in both periods indicating faster discharge for vaccinated patients.Conclusions: COVID-19 vaccination was associated with lower rates of ICU admission and in-hospital death in both Delta and Omicron periods compared with being unvaccinated. [ABSTRACT FROM AUTHOR]

Background: We analyzed data from a randomized controlled trial on the reactogenicity of 3 enhanced influenza vaccines compared with standard-dose (SD) inactivated influenza vaccine.Methods: We enrolled community-dwelling older adults in Hong Kong, and we randomly allocated them to receive 2017-2018 northern hemisphere formulations of SD vaccine (FluQuadri; Sanofi Pasteur), MF59-adjuvanted vaccine (FLUAD; Seqirus), high-dose (HD) vaccine (Fluzone High-Dose; Sanofi Pasteur), or recombinant hemagglutinin vaccine (Flublok; Sanofi Pasteur). Local and systemic reactions were evaluated at days 1, 3, 7, and 14 after vaccination.Results: Reported reactions were generally mild and short-lived. Systemic reactions occurred in similar proportions of participants by vaccine. Some local reactions were slightly more frequently reported among recipients of the MF59-adjuvanted and HD vaccines than among SD vaccine recipients. Participants reporting feverishness 1 day after vaccination had mean fold rises in postvaccination hemagglutination inhibition titers that were 1.85-fold higher (95% confidence interval, 1.01-3.38) for A(H1N1) than in those who did not report feverishness.Conclusions: Some acute local reactions were more frequent after vaccination with MF59-adjuvanted and HD influenza vaccines, compared with SD inactivated influenza vaccine, whereas systemic symptoms occurred at similar frequencies in all groups. The association between feverishness and immunogenicity should be further investigated in a larger population.Clinical Trials Registration: NCT03330132. [ABSTRACT FROM AUTHOR]

Background Enhanced influenza vaccines may improve protection for older adults, but comparative immunogenicity data are limited. Our objective was to examine immune responses to enhanced influenza vaccines, compared to standard-dose vaccines, in community-dwelling older adults. Methods Community-dwelling older adults aged 65–82 years in Hong Kong were randomly allocated (October 2017–January 2018) to receive 2017–2018 Northern hemisphere formulations of a standard-dose quadrivalent vaccine, MF59-adjuvanted trivalent vaccine, high-dose trivalent vaccine, or recombinant-hemagglutinin (rHA) quadrivalent vaccine. Sera collected from 200 recipients of each vaccine before and at 30-days postvaccination were assessed for antibodies to egg-propagated vaccine strains by hemagglutination inhibition (HAI) and to cell-propagated A/Hong Kong/4801/2014(H3N2) virus by microneutralization (MN). Influenza-specific CD4+ and CD8+ T cell responses were assessed in 20 participants per group. Results Mean fold rises (MFR) in HAI titers to egg-propagated A(H1N1) and A(H3N2) and the MFR in MN to cell-propagated A(H3N2) were statistically significantly higher in the enhanced vaccine groups, compared to the standard-dose vaccine. The MFR in MN to cell-propagated A(H3N2) was highest among rHA recipients (4.7), followed by high-dose (3.4) and MF59-adjuvanted (2.9) recipients, compared to standard-dose recipients (2.3). Similarly, the ratio of postvaccination MN titers among rHA recipients to cell-propagated A(H3N2) recipients was 2.57-fold higher than the standard-dose vaccine, which was statistically higher than the high-dose (1.33-fold) and MF59-adjuvanted (1.43-fold) recipient ratios. Enhanced vaccines also resulted in the boosting of T-cell responses. Conclusions In this head-to-head comparison, older adults receiving enhanced vaccines showed improved humoral and cell-mediated immune responses, compared to standard-dose vaccine recipients. Clinical Trials Registration NCT03330132. [ABSTRACT FROM AUTHOR]

Background: Pregnant women are at increased risk of seasonal influenza hospitalizations, but data about the epidemiology of severe influenza among pregnant women remain largely limited to pandemics.Methods: To describe the epidemiology of hospitalizations for acute respiratory infection or febrile illness (ARFI) and influenza-associated ARFI among pregnant women, administrative and electronic health record data were analyzed from retrospective cohorts of pregnant women hospitalized with ARFI who had testing for influenza viruses by reverse-transcription polymerase chain reaction (RT-PCR) in Australia, Canada, Israel, and the United States during 2010-2016.Results: Of 18 048 ARFI-coded hospitalizations, 1064 (6%) included RT-PCR testing for influenza viruses, 614 (58%) of which were influenza positive. Of 614 influenza-positive ARFI hospitalizations, 35% were in women with low socioeconomic status, 20% with underlying conditions, and 67% in their third trimesters. The median length of influenza-positive hospitalizations was 2 days (interquartile range, 1-4), 18% (95% confidence interval [CI], 15%-21%) resulted in delivery, 10% (95% CI, 8%-12%) included a pneumonia diagnosis, 5% (95% CI, 3%-6%) required intensive care, 2% (95% CI, 1%-3%) included a sepsis diagnosis, and <1% (95% CI, 0%-1%) resulted in respiratory failure.Conclusions: Our findings characterize seasonal influenza hospitalizations among pregnant women and can inform assessments of the public health and economic impact of seasonal influenza on pregnant women. [ABSTRACT FROM AUTHOR]

Background: Severe influenza illness is presumed more common in adults with chronic medical conditions (CMCs), but evidence is sparse and often combined into broad CMC categories.Methods: Residents (aged 18-80 years) of Central and South Auckland hospitalized for World Health Organization-defined severe acute respiratory illness (SARI) (2012-2015) underwent influenza virus polymerase chain reaction testing. The CMC statuses for Auckland residents were modeled using hospitalization International Classification of Diseases, Tenth Revision codes, pharmaceutical claims, and laboratory results. Population-level influenza rates in adults with congestive heart failure (CHF), coronary artery disease (CAD), cerebrovascular accidents (CVA), chronic obstructive pulmonary disease (COPD), asthma, diabetes mellitus (DM), and end-stage renal disease (ESRD) were calculated by Poisson regression stratified by age and adjusted for ethnicity.Results: Among 891 276 adults, 2435 influenza-associated SARI hospitalizations occurred. Rates were significantly higher in those with CMCs compared with those without the respective CMC, except for older adults with DM or those aged <65 years with CVA. The largest effects occurred with CHF (incidence rate ratio [IRR] range, 4.84-13.4 across age strata), ESRD (IRR range, 3.30-9.02), CAD (IRR range, 2.77-10.7), and COPD (IRR range, 5.89-8.78) and tapered with age.Conclusions: Our findings support the increased risk of severe, laboratory-confirmed influenza disease among adults with specific CMCs compared with those without these conditions. [ABSTRACT FROM AUTHOR]

Background: Pregnant women are prioritized for seasonal influenza vaccination, but the evidence on the risk of influenza during pregnancy that is used to inform these policies is limited.Methods: Individual-level administrative data sets and active surveillance data were joined to estimate influenza-associated hospitalization and outpatient visit rates by pregnancy, postpartum, and trimester status.Results: During 2012-2015, 46 of 260 (17.7%) influenza-confirmed hospitalizations for acute respiratory infection and 13 of 294 (4.4%) influenza-confirmed outpatient visits were among pregnant and postpartum women. Pregnant and postpartum women experienced higher rates of influenza-associated hospitalization than nonpregnant women overall (rate ratio [RR], 3.4; 95% confidence interval [CI], 2.5-4.7) and by trimester (first, 2.5 [95% CI, 1.2-5.4]; second, 3.9 [95% CI, 2.4-6.3]; and third, 4.8 [95% CI, 3.0-7.7]); the RR for the postpartum period was 0.7 (95% CI, 3.0-7.7). Influenza A viruses were associated with an increased risk (RR for 2009 pandemic influenza A[H1N1] virus, 5.3 [95% CI, 3.2-8.7]; RR for influenza A(H3N2) virus, 3.0 [95% CI, 1.8-5.0]), but influenza B virus was not (RR, 1.8; 95% CI, .7-4.6). Influenza-associated hospitalization rates in pregnancy were significantly higher for Māori women (RR, 3.2; 95% CI, 1.3-8.4), compared with women of European or other ethnicity. Similar risks for influenza-confirmed outpatient visits were not observed.Conclusion: Seasonal influenza poses higher risks of hospitalization among pregnant women in all trimesters, compared with nonpregnant women. Hospitalization rates vary by influenza virus type and ethnicity among pregnant women. [ABSTRACT FROM AUTHOR]

Background: A number of enhanced influenza vaccines have been developed for use in older adults, including high-dose, MF59-adjuvanted, and intradermal vaccines.Methods: We conducted a systematic review examining the improvements in antibody responses measured by the hemagglutination inhibition assay associated with these enhanced vaccines, compared with each other and with the standard-dose (SD) vaccine using random effects models.Results: Thirty-nine trials were included. Compared with adults aged ≥60 years receiving SD vaccines, those receiving enhanced vaccines had significantly higher postvaccination titers (for all vaccine strains) and higher proportions with elevated titers ≥40 (for most vaccine strains). High-dose vaccine elicited 82% higher postvaccination titer to A(H3N2) compared with SD vaccine; this was significantly higher than the 52% estimated for MF59-adjuvanted versus SD vaccines (P = .04), which was higher than the 32% estimated for intradermal versus SD vaccines (P < .01).Conclusions: Overall, by summarizing current evidence, we found that enhanced vaccines had greater antibody responses than the SD vaccine. Indications of differences among enhanced vaccines highlight the fact that further research is needed to compare new vaccine options, especially during seasons with mismatched circulating strains and for immune outcomes other than hemagglutination inhibition titers as well as vaccine efficacy. [ABSTRACT FROM AUTHOR]

Background To date, no study has examined influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza-associated hospitalizations during pregnancy. Methods The Pregnancy Influenza Vaccine Effectiveness Network (PREVENT) consisted of public health or healthcare systems with integrated laboratory, medical, and vaccination records in Australia, Canada (Alberta and Ontario), Israel, and the United States (California, Oregon, and Washington). Sites identified pregnant women aged 18 through 50 years whose pregnancies overlapped with local influenza seasons from 2010 through 2016. Administrative data were used to identify hospitalizations with acute respiratory or febrile illness (ARFI) and clinician-ordered real-time reverse transcription polymerase chain reaction (rRT-PCR) testing for influenza viruses. Overall IVE was estimated using the test-negative design and adjusting for site, season, season timing, and high-risk medical conditions. Results Among 19450 hospitalizations with an ARFI discharge diagnosis (across 25 site-specific study seasons), only 1030 (6%) of the pregnant women were tested for influenza viruses by rRT-PCR. Approximately half of these women had pneumonia or influenza discharge diagnoses (54%). Influenza A or B virus infections were detected in 598/1030 (58%) of the ARFI hospitalizations with influenza testing. Across sites and seasons, 13% of rRT-PCR-confirmed influenza-positive pregnant women were vaccinated compared with 22% of influenza-negative pregnant women; the adjusted overall IVE was 40% (95% confidence interval = 12%–59%) against influenza-associated hospitalization during pregnancy. Conclusion Between 2010 and 2016, influenza vaccines offered moderate protection against laboratory-confirmed influenza-associated hospitalizations during pregnancy, which may further inform the benefits of maternal influenza vaccination programs. [ABSTRACT FROM AUTHOR]

Background. During the 2012-2013 influenza season, there was cocirculation of influenza A(H3N2) and 2 influenza B lineage viruses in the United States. Methods. Patients with acute cough illness for ⩽7 days were prospectively enrolled and had swab samples obtained at outpatient clinics in 5 states. Influenza vaccination dates were confirmed by medical records. The vaccine effectiveness (VE) was estimated as [100% × (1 - adjusted odds ratio)] for vaccination in cases versus test-negative controls. Results. Influenza was detected in 2307 of 6452 patients (36%); 1292 (56%) had influenza A(H3N2), 582 (25%) had influenza B/Yamagata, and 303 (13%) had influenza B/Victoria. VE was 49% (95% confidence interval [CI], 43%-55%) overall, 39% (95% CI, 29%-47%) against influenza A(H3N2), 66% (95% CI, 58%-73%) against influenza B/Yamagata (vaccine lineage), and 51% (95% CI, 36%-63%) against influenza B/Victoria. VE against influenza A(H3N2) was highest among persons aged 50-64 years (52%; 95% CI, 33%-65%) and persons aged 6 months- 8 years (51%; 95% CI, 32%-64%) and lowest among persons aged ⩾65 years (11%; 95% CI, -41% to 43%). In younger age groups, there was evidence of residual protection from receipt of the 2011-2012 vaccine 1 year earlier. Conclusions. The 2012-2013 vaccines were moderately effective in most age groups. Cross-lineage protection and residual effects from prior vaccination were observed and warrant further investigation. [ABSTRACT FROM AUTHOR]

Background. There are recognized needs to identify determinants of influenza vaccine effectiveness (VE), including the effect of repeated annual vaccination. Methods. We recruited 321 households with 1426 members, including 833 children, and followed them during the 2012-2013 influenza season; specimens were collected from subjects with reported acute respiratory illnesses.We estimated the effectiveness of documented influenza vaccination in preventing laboratory-confirmed influenza, using adjusted Cox proportional hazards models. Antibody titers in a subset of subjects were determined by a hemagglutination inhibition assay to determine the subjects' preseason susceptibility to influenza. Results. Influenza was identified in 76 (24%) households and 111 (8%) individuals. VE point estimates indicated significant protection in adults (48%; 95% confidence interval [CI], 1%-72%), similar protection in children aged 9- 17 years (49%; 95% CI, -16% to 78%), but no evidence of effectiveness in children aged <9 years (-4%; 95% CI, -110% to 49%). Lower VE was observed in those vaccinated in both the current and prior seasons, compared with those vaccinated in the current season only; susceptibility titers against type A but not type B were consistent with this observation. Residual protection from vaccination in the prior season was indicated by both VE and serologic results. Conclusions. Prior vaccination appears to modify VE by both residual protection and reduced vaccine response. [ABSTRACT FROM AUTHOR]

Background. The household has traditionally been the site for studying acute respiratory illnesses (ARIs). Most studies were conducted many years ago, and more broadly sensitive laboratory methods to determine ARI etiology are now available.Methods. We recruited and followed households with children over 3 annual surveillance periods and collected respiratory tract specimens from subjects with reported ARI. Virus etiology was determined by real-time reverse-transcription polymerase chain reaction (RT-PCR) analysis.Results. Individuals in larger households (defined as households with >4 members) and those in households with children aged <5 years had significantly higher ARI frequencies than others. ARI frequency generally declined with increasing age. Virus etiology was most likely to be determined in young children, who were also most likely to have virus coinfection. Overall, 16% of ARIs with 1 virus identified had ≥1 coinfecting virus. Rhinoviruses and coronaviruses were the most frequently identified agents of ARI in all age categories. Influenza virus and adenovirus were less frequently identified but were most likely to cause ARI that required medical attention.Conclusions. Longitudinal studies in families remain a valuable way to study respiratory infections. RT-PCR has increased the sensitivity of virus detection, including coinfecting viruses, and expanded our ability to detect viruses now known to cause ARI. [ABSTRACT FROM AUTHOR]

The effect of prior influenza vaccination history on vaccine effectiveness was assessed in a community cohort over 8 seasons. Current- and previous-season vaccination generated similar levels of protection; vaccine-induced protection was greatest for individuals with no recent vaccination history.Background. Recent studies suggest that influenza vaccination in the previous season may influence the effectiveness of current-season vaccination, but this has not been assessed in a single population over multiple years.Methods. Patients presenting with acute respiratory illness were prospectively enrolled during the 2004–2005 through 2012–2013 influenza seasons. Respiratory swabs were tested for influenza and vaccination dates obtained from a validated registry. Vaccination status was determined for the current, previous, and prior 5 seasons. Vaccine effectiveness (VE) was calculated for participants aged ≥9 years using logistic regression models with an interaction term for vaccination history.Results. There were 7315 enrollments during 8 seasons; 1056 (14%) and 650 (9%) were positive for influenza A(H3N2) and B, respectively. Vaccination during current only, previous only, or both seasons yielded similar protection against H3N2 (adjusted VE range, 31%–36%) and B (52%–66%). In the analysis using 5 years of historical vaccination data, current season VE against H3N2 was significantly higher among vaccinated individuals with no prior vaccination history (65%; 95% confidence interval [CI], 36%–80%) compared with vaccinated individuals with a frequent vaccination history (24%; 95% CI, 3%–41%; P = .01). VE against B was 75% (95% CI, 50%–87%) and 48% (95% CI, 29%–62%), respectively (P = .05). Similar findings were observed when analysis was restricted to adults 18–49 years.Conclusions. Current- and previous-season vaccination generated similar levels of protection, and vaccine-induced protection was greatest for individuals not vaccinated during the prior 5 years. Additional studies are needed to understand the long-term effects of annual vaccination. [ABSTRACT FROM PUBLISHER]

During the 2012–2013 influenza season, antiviral treatment was underutilized and antibiotics may have been overused among clinicians providing care to outpatients with laboratory-confirmed influenza.Background. Early antiviral treatment (≤2 days since illness onset) of influenza reduces the probability of influenza-associated complications. Early empiric antiviral treatment is recommended for those with suspected influenza at higher risk for influenza complications regardless of their illness severity. We describe antiviral receipt among outpatients with acute respiratory illness (ARI) and antibiotic receipt among patients with influenza.Methods. We analyzed data from 5 sites in the US Influenza Vaccine Effectiveness Network Study during the 2012–2013 influenza season. Subjects were outpatients aged ≥6 months with ARI defined by cough of ≤7 days’ duration; all were tested for influenza by polymerase chain reaction (PCR). Medical history and prescription information were collected by medical and pharmacy records. Four sites collected prescribing data on 3 common antibiotics (amoxicillin-clavulanate, amoxicillin, and azithromycin).Results. Of 6766 enrolled ARI patients, 509 (7.5%) received an antiviral prescription. Overall, 2366 (35%) had PCR-confirmed influenza; 355 (15%) of those received an antiviral prescription. Among 1021 ARI patients at high risk for influenza complications (eg, aged <2 years or ≥65 years or with ≥1 chronic medical condition) presenting to care ≤2 days from symptom onset, 195 (19%) were prescribed an antiviral medication. Among participants with PCR-confirmed influenza and antibiotic data, 540 of 1825 (30%) were prescribed 1 of 3 antibiotics; 297 of 1825 (16%) were prescribed antiviral medications.Conclusions. Antiviral treatment was prescribed infrequently among outpatients with influenza for whom therapy would be most beneficial; in contrast, antibiotic prescribing was more frequent. Continued efforts to educate clinicians on appropriate antibiotic and antiviral use are essential to improve healthcare quality. [ABSTRACT FROM AUTHOR]

Influenza vaccination reduced the risk of acute respiratory illness associated with laboratory-confirmed influenza among pregnant women by one-half during the 2010–2011 and 2011–2012 seasons, similar to influenza vaccine effectiveness observed among all adults during these seasons.Background. Although vaccination with trivalent inactivated influenza vaccine (TIV) is recommended for all pregnant women, no vaccine effectiveness (VE) studies of TIV in pregnant women have assessed laboratory-confirmed influenza outcomes.Methods. We conducted a case-control study over 2 influenza seasons (2010–2011 and 2011–2012) among Kaiser Permanente health plan members in 2 metropolitan areas in California and Oregon. We compared the proportion vaccinated among 100 influenza cases (confirmed by reverse transcription polymerase chain reaction) with the proportions vaccinated among 192 controls with acute respiratory illness (ARI) who tested negative for influenza and 200 controls without ARI (matched by season, site, and trimester).Results. Among influenza cases, 42% were vaccinated during the study season compared to 58% and 63% vaccinated among influenza-negative controls and matched ARI-negative controls, respectively. The adjusted VE of the current season vaccine against influenza A and B was 44% (95% confidence interval [CI], 5%–67%) using the influenza-negative controls and 53% (95% CI, 24%–72%) using the ARI-negative controls. Receipt of the prior season's vaccine, however, had an effect similar to receipt of the current season's vaccine. As such, vaccination in either or both seasons had statistically similar adjusted VE using influenza-negative controls (VE point estimates range = 51%–76%) and ARI-negative controls (48%–76%).Conclusions. Influenza vaccination reduced the risk of ARI associated with laboratory-confirmed influenza among pregnant women by about one-half, similar to VE observed among all adults during these seasons. [ABSTRACT FROM PUBLISHER]

Influenza vaccine effectiveness in preventing medically attended influenza in the 2011–2012 season was modest overall, with low effectiveness against the predominant A (H3N2) virus. This may be related to antigenic drift, but past history of vaccination might also play a role.Background. Each year, the US Influenza Vaccine Effectiveness Network examines the effectiveness of influenza vaccines in preventing medically attended acute respiratory illnesses caused by influenza.Methods. Patients with acute respiratory illnesses of ≤7 days’ duration were enrolled at ambulatory care facilities in 5 communities. Specimens were collected and tested for influenza by real-time reverse-transcriptase polymerase chain reaction. Receipt of influenza vaccine was defined based on documented evidence of vaccination in medical records or immunization registries. Vaccine effectiveness was estimated in adjusted logistic regression models by comparing the vaccination coverage in those who tested positive for influenza with those who tested negative.Results. The 2011–2012 season was mild and peaked late, with circulation of both type A viruses and both lineages of type B. Overall adjusted vaccine effectiveness was 47% (95% confidence interval [CI], 36–56) in preventing medically attended influenza; vaccine effectiveness was 65% (95% CI, 44–79) against type A (H1N1) pdm09 but only 39% (95% CI, 23–52) against type A (H3N2). Estimates of vaccine effectiveness against both type B lineages were similar (overall, 58%; 95% CI, 35–73). An apparent negative effect of prior year vaccination on current year effectiveness estimates was noted, particularly for A (H3N2) outcomes.Conclusions. Vaccine effectiveness in the 2011–2012 season was modest overall, with lower effectiveness against the predominant A (H3N2) virus. This may be related to antigenic drift, but past history of vaccination might also play a role. [ABSTRACT FROM PUBLISHER]

During 2009–2010, we examined 217 patients hospitalized with laboratory-confirmed pandemic influenza in 9 Influenza Hospitalization Surveillance Network sites and 413 age- and community-matched controls and found that a single dose of monovalent nonadjuvanted influenza A(H1N1)pdm09 vaccine was 50% (95% confidence interval, 13%–71%) effective in preventing hospitalization associated with A(H1N1)pdm09 virus infection. [ABSTRACT FROM AUTHOR]

During the 2011–2012 influenza season, we enrolled hospitalized adults with acute respiratory illness and tested each for influenza using reverse transcription polymerase chain reaction. Influenza vaccination was verified in 35% (6/17) of adults with influenza-associated hospitalizations compared to 64% (97/152) of test-negative controls; adjusted vaccine effectiveness was 71.4% (95% confidence interval, 17.1%–94.9%). [ABSTRACT FROM AUTHOR]

We examined influenza vaccine effectiveness in preventing community- and household-acquired influenza. Estimates were lower than those demonstrated in other observational studies carried out the same season, with unexpected findings of lower effectiveness with repeated vaccination and no protection with household exposure.Background. There is a recognized need to determine influenza vaccine effectiveness on an annual basis and a long history of studying respiratory illnesses in households.Methods. We recruited 328 households with 1441 members, including 839 children, and followed them during the 2010–2011 influenza season. Specimens were collected from subjects with reported acute respiratory illnesses and tested by real-time reverse transcriptase polymerase chain reaction. Receipt of influenza vaccine was defined based on documented evidence of vaccination in medical records or an immunization registry. The effectiveness of 2010–2011 influenza vaccination in preventing laboratory-confirmed influenza was estimated using Cox proportional hazards models adjusted for age and presence of high-risk condition, and stratified by prior season (2009–2010) vaccination status.Results. Influenza was identified in 78 (24%) households and 125 (9%) individuals; the infection risk was 8.5% in the vaccinated and 8.9% in the unvaccinated (P = .83). Adjusted vaccine effectiveness in preventing community-acquired influenza was 31% (95% confidence interval [CI], −7% to 55%). In vaccinated subjects with no evidence of prior season vaccination, significant protection (62% [95% CI, 17%–82%]) against community-acquired influenza was demonstrated. Substantially lower effectiveness was noted among subjects who were vaccinated in both the current and prior season. There was no evidence that vaccination prevented household transmission once influenza was introduced; adults were at particular risk despite vaccination.Conclusions. Vaccine effectiveness estimates were lower than those demonstrated in other observational studies carried out during the same season. The unexpected findings of lower effectiveness with repeated vaccination and no protection given household exposure require further study. [ABSTRACT FROM AUTHOR]

Background. Although children <5 years old in sub-Saharan Africa are vulnerable to both malaria and influenza, little is known about coinfection.Methods. This retrospective, cross-sectional study in rural western Kenya examined outpatient visits and hospitalizations associated with febrile acute respiratory illness (ARI) during a 2-year period (July 2009–June 2011) in children <5 years old.Results. Across sites, 45% (149/331) of influenza-positive patients were coinfected with malaria, whereas only 6% (149/2408) of malaria-positive patients were coinfected with influenza. Depending on age, coinfection was present in 4%–8% of outpatient visits and 1%–3% of inpatient admissions for febrile ARI. Children with influenza were less likely than those without to have malaria (risk ratio [RR], 0.57–0.76 across sites and ages), and children with malaria were less likely than those without to have influenza (RR, 0.36–0.63). Among coinfected children aged 24–59 months, hospital length of stay was 2.7 and 2.8 days longer than influenza-only-infected children at the 2 sites, and 1.3 and 3.1 days longer than those with malaria only (all P < .01).Conclusions. Coinfection with malaria and influenza was uncommon but associated with longer hospitalization than single infections among children 24–59 months of age. [ABSTRACT FROM AUTHOR]

In a case-control study at 4 US centers, the effectiveness of influenza vaccine against medically attended polymerase chain reaction–confirmed influenza was 60% (95% confidence interval, 53%–66%). Significant effectiveness was demonstrated in young children, adolescents, and adults, with a lower estimate for those aged ≥65.Background. Influenza vaccines may be reformulated annually because of antigenic drift in influenza viruses. However, the relationship between antigenic characteristics of circulating viruses and vaccine effectiveness (VE) is not well understood. We conducted an assessment of the effectiveness of US influenza vaccines during the 2010–2011 season.Methods. We performed a case–control study comparing vaccination histories between subjects with acute respiratory illness with positive real-time reverse transcription polymerase chain reaction for influenza and influenza test-negative controls. Subjects with acute respiratory illness of ≤7 days duration were enrolled in hospitals, emergency departments, or outpatient clinics in communities in 4 states. History of immunization with the 2010–2011 vaccine was ascertained from vaccine registries or medical records. Vaccine effectiveness was estimated in logistic regression models adjusted for study community, age, race, insurance status, enrollment site, and presence of a high-risk medical condition.Results. A total of 1040 influenza-positive cases and 3717 influenza-negative controls were included from the influenza season, including 373 cases of influenza A(H1N1), 334 cases of influenza A(H3N2), and 333 cases of influenza B. Overall adjusted VE was 60% (95% confidence interval [CI], 53%–66%). Age-specific VE estimates ranged from 69% (95% CI, 56%–77%) in children aged 6 months–8 years to 38% (95% CI, −16% to 67%) in adults aged ≥65 years.Conclusions. The US 2010–2011 influenza vaccines were moderately effective in preventing medically attended influenza during a season when all 3 vaccine strains were antigenically similar to circulating viruses. Continued monitoring of influenza vaccines in all age groups is important, particularly as new vaccines are introduced. [ABSTRACT FROM PUBLISHER]

Background Respiratory syncytial virus (RSV) is the most commonly identified viral pathogen among young children with acute lower respiratory tract infection. Understanding global RSV epidemiology and risk factors for severe illness in low- and middle-income settings is critical as new vaccine candidates become available. Methods We prospectively enrolled infants aged < 1 year hospitalized with any acute illness from sites in Albania, Jordan, Nicaragua and Philippines during 2015–2017. Standardized parental interviews and medical record review were conducted. Respiratory specimens collected during enrollment were tested for RSV using rRT–PCR. RSV A or B subgroup was determined using a CDC-developed rRT–PCR assay. Very severe RSV illness was defined as requiring ICU admission or supplemental oxygen. Factors potentially associated with severity were assessed using individual logistic regression models to adjust for age and study site. Results Overall, 1,129 (31%) of 3634 enrolled infants had RSV infection. The median age of RSV-positive infants was 2.7 (range: < 1 to 11.9) months, 665 (59%) were male, and 63 (6%) had ≥1 underlying medical condition. RSV subgroup was determined for 1,028 (91%); RSV A and B co-circulated at all sites with alternating predominance by study year (figure). 583 (52%) infants had very severe RSV illness, which was significantly associated with younger age (median: 2.0 vs. 4.3 months; P < 0.01), study site (aOR: Jordan 5.0, Albania 2.9, Philippines 1.2, Nicaragua reference; P < 0.01), birth by cesarean section (aOR: 1.4; 95% CI [CI] 1.0–1.8; P = 0.03), having received ICU care after birth (aOR: 1.6; CI 1.0–2.4; P = 0.03), chronic heart or respiratory tract disease (aOR: 1.9; CI 1.0–3.4; P = 0.04), and a low weight-for-age Z score (aOR: 1.8; CI 1.3–2.7; P < 0.01). RSV subgroup was not associated with severity (aOR: 1.0; CI: 0.7–1.3; P = 0.72). Conclusion RSV was associated with a substantial proportion of acute illness among hospitalized infants in middle-income countries. Subgroups co-circulated across sites and study years with varying predominance and resulted in similar illness severity. Significant comorbidities were uncommon, but factors including younger age, low weight-for-age and chronic heart or respiratory tract disease were associated with more severe illness. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Studies have demonstrated that optimal protection against childhood influenza requires two "priming" doses of influenza vaccine in the first season of vaccination. Two doses of influenza vaccine are recommended for US children aged 6 months-8 years who received ≤1 dose in prior seasons. We examined risk of influenza among children fully or partially vaccinated during study seasons and vaccine effectiveness (VE) by the number of priming doses. Methods Analyses included children aged 6 months-17 years enrolled during outpatient visits for acute illness for ≤7 days with cough in the US Influenza Vaccine Effectiveness Network during 2014–2015 through 2017–2018. Participants' respiratory specimens were tested for influenza by rRT-PCR. Vaccination histories back to birth year were obtained from electronic immunization records. VE was calculated by comparing vaccination odds among influenza-positive cases to test-negative controls, as 100 × (1 − odds ratio) adjusted for season, site, age, high-risk status, and calendar time. Results Of 7,583 children, 6,362 (84%) had received ≥1 dose in their lifetime. Among vaccinated children, 90% were primed prior to the enrollment season, and 80% were primed prior to age 2 years. Most (55%) received two priming doses in their first season. Among children recommended to receive two priming doses in the enrollment season, receipt of two doses vs. one was associated with a lower risk of influenza illness (aOR: 0.60; 95% CL: 0.36, 1.00). VE of ≥1 dose in the enrollment season against any influenza among unprimed children was 53% (95% CL: 36, 66). VE of ≥1 dose in the enrollment season was similar among children primed with one dose in their first season (46%; 95% CL: 34, 55) and among those primed with two doses (46%; 95% CL: 35, 55). Overall results were similar when stratified by age and for A/H3N2 viruses, which predominated during study years. Conclusion Among the US children recommended to receive two priming doses of vaccine in the enrollment season, receipt of two doses provided optimal protection. VE in seasons after the priming did not differ by the number of priming doses. Results were driven by predominance of A/H3N2 viruses and may not be similar for A/H1N1pdm09 or B viruses. Current US influenza vaccine recommendations for children are effective and appropriate. Disclosures All Authors: No reported Disclosures. [ABSTRACT FROM AUTHOR]

Background. Most inactivated influenza vaccines contain purified and standardized hemagglutinin (HA) and residual neuraminidase (NA) antigens. Vaccine-associated HA antibody responses (hemagglutination inhibition [HAI]) are well described, but less is known about the immune response to the NA.Methods. Serum of 1349 healthcare personnel (HCP) electing or declining the 2010–2011 trivalent-inactivated influenza vaccine ([IIV3], containing A/California/7/2009 p(H1N1), A/Perth/16/2009 [H3N2], B/Brisbane/60/2008 strains) were tested for NA-inhibiting (NAI) antibody by a modified lectin-based assay using pseudotyped N1 and N2 influenza A viruses with an irrelevant (H5) HA. Neuraminidase-inhibiting and HAI antibody titers were evaluated approximately 30 days after vaccination and end-of-season for those with polymerase chain reaction (PCR)-confirmed influenza infection.Results. In 916 HCP (68%) receiving IIV3, a 2-fold increase in N1 and N2 NAI antibody occurred in 63.7% and 47.3%, respectively. Smaller responses occurred in HCP age >50 years and those without prior 2009–2010 IIV3 nor monovalent A(H1N1)pdm09 influenza vaccinations. Forty-four PCR-confirmed influenza infections were observed, primarily affecting those with lower pre-exposure HAI and NAI antibodies. Higher pre-NAI titers correlated with shorter duration of illness for A(H1N1)pdm09 virus infections.Conclusions. Trivalent-inactivated influenza vaccine is modestly immunogenic for N1 and N2 antigens in HCP. Vaccines eliciting robust NA immune responses may improve efficacy and reduce influenza-associated morbidity. [ABSTRACT FROM PUBLISHER]

Background. Because little is known about attitudes toward influenza and influenza vaccine among pregnant women in West Africa, before local distribution of A(H1N1)pdm09 vaccine in Ivory Coast we assessed knowledge of the pandemic and acceptance of the A(H1N1)pdm09 vaccine in a diverse population of pregnant women.Methods. A cross-sectional intercept survey of 411 pregnant women in 4 prenatal care settings was conducted during 15–28 February 2010 in Abidjan, Ivory Coast.Results. The majority (64.5%) of pregnant women said they had heard of the influenza pandemic, and of these, the majority (61.3%) were aware of the A(H1N1)pdm09 vaccine. However, awareness varied significantly by clinical setting, education level, and access to media (P < .001 for all comparisons). After adjustment for other sociodemographic factors, college-educated women were 16.8 (95% confidence interval [CI], 3.3–85.2) times as likely as women without formal education to be aware of the pandemic. After controlling for both education and demographic characteristics, women with televisions were 5 times as likely as women without television to be aware of the pandemic (adjusted odds ratio [aOR], 4.94; 95% CI, 1.34–18.17). Of those aware of the influenza pandemic, 69.8% said they would accept the A(H1N1)pdm09 vaccine while they were pregnant. Although awareness was highest in private prenatal care clinics, compared with public outpatient clinics (90.6% vs 37.5%), acceptance of vaccine was significantly lower in private settings, compared with public outpatient settings (57.3% vs 87.2%; P < .001 for each comparison).Conclusions. Gaps in knowledge about the influenza pandemic and vaccine highlight the challenges of pandemic preparedness in poorer countries, where substantial disparities in education and media access are evident. [ABSTRACT FROM AUTHOR]