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Pandemic (H1N1) 2009 virus was first identified in mid-April 2009 (1), near the beginning of the Southern Hemisphere influenza season. The potential for reassortment of cocirculating seasonal influenza A viruses [...]

Stringent nonpharmaceutical interventions (NPIs) such as lockdowns and border closures are not currently recommended for pandemic influenza control. New Zealand used these NPIs to eliminate coronavirus disease 2019 during its first wave. Using multiple surveillance systems, we observed a parallel and unprecedented reduction of influenza and other respiratory viral infections in 2020. This finding supports the use of these NPIs for controlling pandemic influenza and other severe respiratory viral threats. New Zealand has been relatively successful in controlling COVID-19 due to implementation of strict non-pharmaceutical interventions. Here, the authors demonstrate a striking decline in reports of influenza and other non-influenza respiratory pathogens over winter months in which the interventions have been in place. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The immunologic factors underlying severe influenza are poorly understood. To address this, we compared the immune responses of influenza-confirmed hospitalized individuals with severe acute respiratory illness (SARI) to those of nonhospitalized individuals with influenza-like illness (ILI).Methods: Peripheral blood lymphocytes were collected from 27 patients with ILI and 27 with SARI, at time of enrollment and then 2 weeks later. Innate and adaptive cellular immune responses were assessed by flow cytometry, and serum cytokine levels were assessed by a bead-based assay.Results: During the acute phase, SARI was associated with significantly reduced numbers of circulating myeloid dendritic cells, CD192+ monocytes, and influenza virus-specific CD8+ and CD4+ T cells as compared to ILI. By the convalescent phase, however, most SARI cases displayed continued immune activation characterized by increased numbers of CD16+ monocytes and proliferating, and influenza virus-specific, CD8+ T cells as compared to ILI cases. SARI was also associated with reduced amounts of cytokines that regulate T-cell responses (ie, interleukin 4, interleukin 13, interleukin 12, interleukin 10, and tumor necrosis factor β) and hematopoiesis (interleukin 3 and granulocyte-macrophage colony-stimulating factor) but increased amounts of a proinflammatory cytokine (tumor necrosis factor α), chemotactic cytokines (MDC, MCP-1, GRO, and fractalkine), and growth-promoting cytokines (PDGFBB/AA, VEGF, and EGF) as compared to ILI.Conclusions: Severe influenza cases showed a delay in the peripheral immune activation that likely led prolonged inflammation, compared with mild influenza cases. [ABSTRACT FROM AUTHOR]

Introduction: Oseltamivir (Tamiflu®) is an important pharmaceutical intervention against the influenza virus. The importance of surveillance for resistance to oseltamivir has been highlighted by two global events: the emergence of an oseltamivir-resistant seasonal influenza A(H1N1) virus in 2008, and emergence of the influenza A(H1N1)pdm09 virus in 2009. Oseltamivir is a prescription medicine in New Zealand, but more timely access has been provided since 2007 by allowing pharmacies to directly dispense oseltamivir to patients with influenza-like illness. Objective: To determine the frequency of oseltamivir-resistance in the context of a medicine reclassification in 2007, the importation of an oseltamivir-resistant seasonal influenza virus in 2008, and the emergence of a pandemic in 2009. Methods: A total of 1795 influenza viruses were tested for oseltamivir-resistance using a fluorometric neuraminidase inhibition assay. Viruses were collected as part of a sentinel influenza surveillance programme between the years 2006 and 2010. Results: All influenza B, influenza A(H3N2) and influenza A(H1N1)pdm09 viruses tested between 2006 and 2010 were shown to be sensitive to oseltamivir. Seasonal influenza A(H1N1) viruses from 2008 and 2009 were resistant to oseltamivir. Sequencing of the neuraminidase gene showed that the resistant viruses contained an H275Y mutation, and S247N was also identified in the neuraminidase gene of one seasonal influenza A(H1N1) virus that exhibited enhanced resistance. Discussion: No evidence was found to suggest that increased access to oseltamivir has promoted resistance. A probable importation event was documented for the global 2008 oseltamivir-resistant seasonal A(H1N1) virus nine months after it was first reported in Europe in January 2008. [ABSTRACT FROM AUTHOR]

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; a serosurvey cohort, consisting of pre- and post-influenza season sera from PCR- confirmed influenza cases (n=50), and 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% vs 14% [5 - 19 yo] and 0% [0 - 4 yo] respectively). Conversely, children infected with influenza B viruses were more likely than adults to show NA- only seroconversion (88% [0 - 4 yo] and 75% [5 - 19 yo] vs 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. [ABSTRACT FROM AUTHOR]

The failure to mount an antibody response following viral infection or seroconversion failure is a largely underappreciated and poorly understood phenomenon. Here, we identified immunologic markers associated with robust antibody responses after influenza virus infection in two independent human cohorts, SHIVERS and FLU09, based in Auckland, New Zealand and Memphis, Tennessee, USA, respectively. In the SHIVERS cohort, seroconversion significantly associates with (1) hospitalization, (2) greater numbers of proliferating, activated CD4 + T cells, but not CD8 + T cells, in the periphery during the acute phase of illness, and (3) fewer inflammatory monocytes (CD14 hi CD16 + ) by convalescence. In the FLU09 cohort, fewer CD14 hi CD16 + monocytes during early illness in the nasal mucosa were also associated with the generation of influenza-specific mucosal immunoglobulin A (IgA) and IgG antibodies. Our study demonstrates that seroconversion failure after infection is a definable immunological phenomenon, associated with quantifiable cellular markers that can be used to improve diagnostics, vaccine efficacy, and epidemiologic efforts., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Background: The immunologic factors underlying severe influenza are poorly understood. To address this, we compared the immune responses of influenza-confirmed hospitalized individuals with severe acute respiratory illness (SARI) to those of nonhospitalized individuals with influenza-like illness (ILI)., Methods: Peripheral blood lymphocytes were collected from 27 patients with ILI and 27 with SARI, at time of enrollment and then 2 weeks later. Innate and adaptive cellular immune responses were assessed by flow cytometry, and serum cytokine levels were assessed by a bead-based assay., Results: During the acute phase, SARI was associated with significantly reduced numbers of circulating myeloid dendritic cells, CD192+ monocytes, and influenza virus-specific CD8+ and CD4+ T cells as compared to ILI. By the convalescent phase, however, most SARI cases displayed continued immune activation characterized by increased numbers of CD16+ monocytes and proliferating, and influenza virus-specific, CD8+ T cells as compared to ILI cases. SARI was also associated with reduced amounts of cytokines that regulate T-cell responses (ie, interleukin 4, interleukin 13, interleukin 12, interleukin 10, and tumor necrosis factor β) and hematopoiesis (interleukin 3 and granulocyte-macrophage colony-stimulating factor) but increased amounts of a proinflammatory cytokine (tumor necrosis factor α), chemotactic cytokines (MDC, MCP-1, GRO, and fractalkine), and growth-promoting cytokines (PDGFBB/AA, VEGF, and EGF) as compared to ILI., Conclusions: Severe influenza cases showed a delay in the peripheral immune activation that likely led prolonged inflammation, compared with mild influenza cases., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)