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Background: The WHO is exploring the value of adding RSV testing to existing influenza surveillance systems to inform RSV control programs. We evaluate the usefulness of four commonly used influenza surveillance case-definitions for influenza and RSV surveillance., Methods: SHIVERS, a multi-institutional collaboration, conducted surveillance for influenza and RSV in four New Zealand hospitals. Nurses reviewed admission logs, enrolled patients with suspected acute respiratory infections (ARI), and obtained nasopharyngeal swabs for RT-PCR. We compared the performance characteristics for identifying laboratory-confirmed influenza and RSV severe acute respiratory infection (SARI), defined as persons admitted with measured or reported fever and cough within 10 days of illness, to three other case definitions: 1. reported fever and cough or shortness of breath, 2. cough and shortness of breath, or 3. cough., Results: During April-September 2012-2016, SHIVERS identified 16,055 admissions with ARI; of 6374 cases consented and tested for influenza or RSV, 5437 (85%) had SARI and 937 (15%) did not. SARI had the highest specificity in detecting influenza (40.6%) and RSV (40.8%) but the lowest sensitivity (influenza 78.8%, RSV 60.3%) among patients of all ages. Cough or shortness of breath had the highest sensitivity (influenza 99.3%, RSV 99.9%) but the lowest specificity (influenza 1.6%, RSV 1.9%). SARI sensitivity among children aged <3 months was 60.8% for influenza and 43.6% for RSV-both lower than in other age groups., Conclusions: While SARI had the highest specificity, its sensitivity was limited, especially among children aged <3 months. Cough or shortness of breath was the most sensitive., Competing Interests: Declaration of Competing Interest The authors on this paper have no conflicts of interest to declare., (Copyright © 2021. Published by Elsevier Ltd.)

Background: In contrast with respiratory disease caused by influenza, information on the risk of respiratory syncytial virus (RSV) disease among adults with chronic medical conditions (CMCs) is limited., Methods: We linked population-based surveillance of acute respiratory illness hospitalizations to national administrative data to estimate seasonal RSV hospitalization rates among adults aged 18-80 years with the following preexisting CMCs: chronic obstructive pulmonary disease (COPD), asthma, congestive heart failure (CHF), coronary artery disease (CAD), cerebrovascular accidents (CVA), diabetes mellitus (DM), and end-stage renal disease (ESRD). Age- and ethnicity-adjusted rates stratified by age group were estimated., Results: Among 883 999 adult residents aged 18-80 years, 281 RSV-positive hospitalizations were detected during 2012-2015 winter seasons. Across all ages, RSV hospitalization rates were significantly higher among adults with COPD, asthma, CHF, and CAD compared with those without each corresponding condition. RSV hospitalization rates were significantly higher among adults with ESRD aged 50-64 years and adults with DM aged 18-49 years and 65-80 years compared with adults in each age group without these conditions. No increased risk was seen for adults with CVA. The CMC with the highest risk of RSV hospitalization was CHF (incidence rate ratio [IRR] range, 4.6-36.5 across age strata) and COPD (IRR range, 9.6-9.7). Among RSV-positive adults, CHF and COPD were independently associated with increased length of hospital stay., Conclusions: Adults with specific CMCs are at increased risk of RSV hospitalizations. Age affects this relationship for some CMCs. Such populations maybe relevant for future RSV prevention strategies., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Despite evidence that antibodies targeting the influenza virus neuraminidase (NA) protein can be protective and are broadly cross-reactive, the immune response to NA during infection is poorly understood compared to the response to hemagglutinin (HA) protein. As such, we compared the antibody profile to HA and NA in two naturally infected human cohorts in Auckland, New Zealand: (i) a serosurvey cohort, consisting of pre- and post-influenza season sera from PCR-confirmed influenza cases ( n  = 50), and (ii) an immunology cohort, consisting of paired sera collected after PCR-confirmation of infection ( n  = 94). The induction of both HA and NA antibodies in these cohorts was influenced by age and subtype. Seroconversion to HA was more frequent in those <20 years old (yo) for influenza A (serosurvey, P  = 0.01; immunology, P  = 0.02) but not influenza B virus infection. Seroconversion to NA was not influenced by age or virus type. Adults ≥20 yo infected with influenza A viruses were more likely to show NA-only seroconversion compared to children (56% versus 14% [5 to 19 yo] and 0% [0 to 4 yo], respectively). Conversely, children infected with influenza B viruses were more likely than adults to show NA-only seroconversion (88% [0 to 4 yo] and 75% [5 to 19 yo] versus 40% [≥20 yo]). These data indicate a potential role for immunological memory in the dynamics of HA and NA antibody responses. A better mechanistic understanding of this phenomenon will be critical for any future vaccines aimed at eliciting NA immunity. IMPORTANCE Data on the immunologic responses to neuraminidase (NA) is lacking compared to what is available on hemagglutinin (HA) responses, despite growing evidence that NA immunity can be protective and broadly cross-reactive. Understanding these NA responses during natural infection is key to exploiting these properties for improving influenza vaccines. Using two community-acquired influenza cohorts, we showed that the induction of both HA and NA antibodies after infection is influenced by age and subtypes. Such response dynamics suggest the influence of immunological memory, and understanding how this process is regulated will be critical to any vaccine effort targeting NA immunity., (Copyright © 2020 Wong et al.)

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., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Understanding the attack rate of influenza infection and the proportion who become ill by risk group is key to implementing prevention measures. While population-based studies of antihemagglutinin antibody responses have been described previously, studies examining both antihemagglutinin and antineuraminidase antibodies are lacking., Methods: In 2015, we conducted a seroepidemiologic cohort study of individuals randomly selected from a population in New Zealand. We tested paired sera for hemagglutination inhibition (HAI) or neuraminidase inhibition (NAI) titers for seroconversion. We followed participants weekly and performed influenza polymerase chain reaction (PCR) for those reporting influenza-like illness (ILI)., Results: Influenza infection (either HAI or NAI seroconversion) was found in 321 (35% [95% confidence interval, 32%-38%]) of 911 unvaccinated participants, of whom 100 (31%) seroconverted to NAI alone. Young children and Pacific peoples experienced the highest influenza infection attack rates, but overall only a quarter of all infected reported influenza PCR-confirmed ILI, and one-quarter of these sought medical attention. Seroconversion to NAI alone was higher among children aged <5 years vs those aged ≥5 years (14% vs 4%; P < .001) and among those with influenza B vs A(H3N2) virus infections (7% vs 0.3%; P < .001)., Conclusions: Measurement of antineuraminidase antibodies in addition to antihemagglutinin antibodies may be important in capturing the true influenza infection rates.