Publications by authors named "Sue Huang"

60 Publications

Global burden of influenza-associated lower respiratory tract infections and hospitalizations among adults: A systematic review and meta-analysis.

PLoS Med 2021 Mar 1;18(3):e1003550. Epub 2021 Mar 1.

Division of Global Health Protection, US Centers for Disease Control and Prevention, Nairobi, Kenya.

Background: Influenza illness burden is substantial, particularly among young children, older adults, and those with underlying conditions. Initiatives are underway to develop better global estimates for influenza-associated hospitalizations and deaths. Knowledge gaps remain regarding the role of influenza viruses in severe respiratory disease and hospitalizations among adults, particularly in lower-income settings.

Methods And Findings: We aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza viruses among adults. We searched 9 online databases (Medline, Embase, CINAHL, Cochrane Library, Scopus, Global Health, LILACS, WHOLIS, and CNKI; 1 January 1996-31 December 2016) to identify observational studies of influenza-associated hospitalizations in adults, and assessed eligible papers for bias using a simplified Newcastle-Ottawa scale for observational data. We applied meta-analytic proportions to global estimates of lower respiratory infections (LRIs) and hospitalizations from the Global Burden of Disease study in adults ≥20 years and by age groups (20-64 years and ≥65 years) to obtain the number of influenza-associated LRI episodes and hospitalizations for 2016. Data from 63 sources showed that influenza was associated with 14.1% (95% CI 12.1%-16.5%) of acute respiratory hospitalizations among all adults, with no significant differences by age group. The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast Asia, n = 11; Western Pacific, n = 18). Data quality for published data sources was predominantly moderate or high (75%, n = 56/75). We estimate 32,126,000 (95% CI 20,484,000-46,129,000) influenza-associated LRI episodes and 5,678,000 (95% CI 3,205,000-9,432,000) LRI hospitalizations occur each year among adults. While adults <65 years contribute most influenza-associated LRI hospitalizations and episodes (3,464,000 [95% CI 1,885,000-5,978,000] LRI hospitalizations and 31,087,000 [95% CI 19,987,000-44,444,000] LRI episodes), hospitalization rates were highest in those ≥65 years (437/100,000 person-years [95% CI 265-612/100,000 person-years]). For this analysis, published articles were limited in their inclusion of stratified testing data by year and age group. Lack of information regarding influenza vaccination of the study population was also a limitation across both types of data sources.

Conclusions: In this meta-analysis, we estimated that influenza viruses are associated with over 5 million hospitalizations worldwide per year. Inclusion of both published and unpublished findings allowed for increased power to generate stratified estimates, and improved representation from lower-income countries. Together, the available data demonstrate the importance of influenza viruses as a cause of severe disease and hospitalizations in younger and older adults worldwide.
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http://dx.doi.org/10.1371/journal.pmed.1003550DOI Listing
March 2021

Impact of the COVID-19 nonpharmaceutical interventions on influenza and other respiratory viral infections in New Zealand.

Nat Commun 2021 02 12;12(1):1001. Epub 2021 Feb 12.

WHO Collaborating Centre, St Jude Children's Research Hospital, Memphis, TN, USA.

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.
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http://dx.doi.org/10.1038/s41467-021-21157-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881137PMC
February 2021

Genomic Evidence of In-Flight Transmission of SARS-CoV-2 Despite Predeparture Testing.

Emerg Infect Dis 2021 03 5;27(3):687-693. Epub 2021 Jan 5.

Since the first wave of coronavirus disease in March 2020, citizens and permanent residents returning to New Zealand have been required to undergo managed isolation and quarantine (MIQ) for 14 days and mandatory testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of October 20, 2020, of 62,698 arrivals, testing of persons in MIQ had identified 215 cases of SARS-CoV-2 infection. Among 86 passengers on a flight from Dubai, United Arab Emirates, that arrived in New Zealand on September 29, test results were positive for 7 persons in MIQ. These passengers originated from 5 different countries before a layover in Dubai; 5 had negative predeparture SARS-CoV-2 test results. To assess possible points of infection, we analyzed information about their journeys, disease progression, and virus genomic data. All 7 SARS-CoV-2 genomes were genetically identical, except for a single mutation in 1 sample. Despite predeparture testing, multiple instances of in-flight SARS-CoV-2 transmission are likely.
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http://dx.doi.org/10.3201/eid2703.204714DOI Listing
March 2021

Genomic epidemiology reveals transmission patterns and dynamics of SARS-CoV-2 in Aotearoa New Zealand.

Nat Commun 2020 12 11;11(1):6351. Epub 2020 Dec 11.

Institute of Environmental Science and Research, Wellington, New Zealand.

New Zealand, a geographically remote Pacific island with easily sealable borders, implemented a nationwide 'lockdown' of all non-essential services to curb the spread of COVID-19. Here, we generate 649 SARS-CoV-2 genome sequences from infected patients in New Zealand with samples collected during the 'first wave', representing 56% of all confirmed cases in this time period. Despite its remoteness, the viruses imported into New Zealand represented nearly all of the genomic diversity sequenced from the global virus population. These data helped to quantify the effectiveness of public health interventions. For example, the effective reproductive number, R of New Zealand's largest cluster decreased from 7 to 0.2 within the first week of lockdown. Similarly, only 19% of virus introductions into New Zealand resulted in ongoing transmission of more than one additional case. Overall, these results demonstrate the utility of genomic pathogen surveillance to inform public health and disease mitigation.
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http://dx.doi.org/10.1038/s41467-020-20235-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733492PMC
December 2020

Impact of the COVID-19 nonpharmaceutical interventions on influenza and other respiratory viral infections in New Zealand.

medRxiv 2020 Nov 13. Epub 2020 Nov 13.

WHO Collaborating Centre, St Jude Children's Research Hospital, Memphis, USA.

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.
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http://dx.doi.org/10.1101/2020.11.11.20228692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668762PMC
November 2020

Respiratory syncytial virus hospitalisations among young children: a data linkage study - Erratum.

Epidemiol Infect 2020 08 28;148:e179. Epub 2020 Aug 28.

Department of Paediatrics: Child &Youth Health, University of Auckland, Auckland, New Zealand.

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http://dx.doi.org/10.1017/S0950268820001612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482036PMC
August 2020

Respiratory Virus-related Emergency Department Visits and Hospitalizations Among Infants in New Zealand.

Pediatr Infect Dis J 2020 08;39(8):e176-e182

From the Institute of Environmental Science and Research, Wellington, New Zealand.

Background: Estimates of the contribution of respiratory viruses to emergency department (ED) utilization remain limited.

Methods: We conducted surveillance of infants with acute respiratory infection (ARI) associated ED visits, which then resulted in either hospital admission or discharge home. Seasonal rates of specific viruses stratified by age, ethnicity, and socioeconomic status were estimated for both visits discharged directly from ED and hospitalizations using rates of positivity for each virus.

Results: During the 2014-2016 winter seasons, 3585 (66%) of the 5412 ARI ED visits were discharged home directly and 1827 (34%) were admitted to hospital. Among visits tested for all respiratory viruses, 601/1111 (54.1%) of ED-only and 639/870 (73.4%) of the hospital-admission groups were positive for at least one respiratory virus. Overall, respiratory virus-associated ED visit rates were almost twice as high as hospitalizations. Respiratory syncytial virus was associated with the highest ED (34.4 per 1000) and hospitalization rates (24.6 per 1000) among infants. ED visit and hospitalization rates varied significantly by age and virus. Māori and Pacific children had significantly higher ED visit and hospitalization rates for all viruses compared with children of other ethnicities.

Conclusions: Many infants with acute respiratory virus infections are managed in the ED rather than admitted to the hospital. Higher rates of ED-only versus admitted acute respiratory virus infections occur among infants living in lower socioeconomic households, older infants and infants of Māori or Pacific versus European ethnicity. Respiratory virus infections resulting in ED visits should be included in measurements of ARI disease burden.
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http://dx.doi.org/10.1097/INF.0000000000002681DOI Listing
August 2020

Respiratory syncytial virus associated hospitalizations among adults with chronic medical conditions.

Clin Infect Dis 2020 Jun 12. Epub 2020 Jun 12.

Institute of Environmental Science and Research, Wallaceville, NZ.

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 certain pre-existing 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 to those without each corresponding condition. RSV hospitalization rates were significantly higher among adults with ESRD aged 50-64 years and adults with DM aged 65-80 years compared to 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.
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http://dx.doi.org/10.1093/cid/ciaa730DOI Listing
June 2020

The health and economic burden of respiratory syncytial virus associated hospitalizations in adults.

PLoS One 2020 11;15(6):e0234235. Epub 2020 Jun 11.

Department of Paediatrics: Child & Youth Health, University of Auckland, Auckland, New Zealand.

Background: Respiratory syncytial virus (RSV) is increasingly recognized as an important cause of illness in adults; however, data on RSV disease and economic burden in this age group remain limited. We aimed to provide comprehensive estimates of RSV disease burden among adults aged ≥18 years.

Methods: During 2012-2015, population-based, active surveillance of acute respiratory infection (ARI) hospitalizations enabled estimation of the seasonal incidence of RSV hospitalizations and direct health costs in adults aged ≥18 years in Auckland, New Zealand.

Results: Of 4,600 ARI hospitalizations tested for RSV, 348 (7.6%) were RSV positive. The median (interquartile range) length of hospital stay for RSV positive patients was 4 (2-6) days. The seasonal incidence rate (IR) of RSV hospitalizations, corrected for non-testing, was 23.6 (95% confidence intervals [CI] 21.0-26.1) per 100,000 adults aged ≥18 years. Hospitalization risk increased with age with the highest incidence among adults aged ≥80 years (IR 190.8 per 100,000, 95% CI 137.6-244.0). Being of Māori or Pacific ethnicity or living in a neighborhood with low socioeconomic status (SES) were independently associated with increased RSV hospitalization rates. We estimate RSV-associated hospitalizations among adults aged ≥18 years to cost on average NZD $4,758 per event.

Conclusions: RSV infection is associated with considerable disease and economic cost in adults. RSV disproportionally affects adult sub-groups defined by age, ethnicity, and neighborhood SES. An effective RSV vaccine or RSV treatment may offer benefits for older adults.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234235PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289360PMC
August 2020

Hemagglutinin and Neuraminidase Antibodies Are Induced in an Age- and Subtype-Dependent Manner after Influenza Virus Infection.

J Virol 2020 03 17;94(7). Epub 2020 Mar 17.

Institute of Environmental Science and Research, Ltd., NCBID-Wallaceville, Wallaceville, New Zealand.

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 ( = 50), and (ii) an immunology cohort, consisting of paired sera collected after PCR-confirmation of infection ( = 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,  = 0.01; immunology,  = 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. 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.
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http://dx.doi.org/10.1128/JVI.01385-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081922PMC
March 2020

Heterogeneity in influenza seasonality and vaccine effectiveness in Australia, Chile, New Zealand and South Africa: early estimates of the 2019 influenza season.

Euro Surveill 2019 Nov;24(45)

Health Intelligence Team, Institute of Environmental Science and Research, Wellington, New Zealand.

We compared 2019 influenza seasonality and vaccine effectiveness (VE) in four southern hemisphere countries: Australia, Chile, New Zealand and South Africa. Influenza seasons differed in timing, duration, intensity and predominant circulating viruses. VE estimates were also heterogeneous, with all-ages point estimates ranging from 7-70% (I2: 33%) for A(H1N1)pdm09, 4-57% (I2: 49%) for A(H3N2) and 29-66% (I2: 0%) for B. Caution should be applied when attempting to use southern hemisphere data to predict the northern hemisphere influenza season.
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http://dx.doi.org/10.2807/1560-7917.ES.2019.24.45.1900645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852316PMC
November 2019

Risk of Severe Influenza Among Adults With Chronic Medical Conditions.

J Infect Dis 2020 01;221(2):183-190

Health Intelligence Team, Institute of Environmental Science and Research, Porirua, New Zealand.

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.
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http://dx.doi.org/10.1093/infdis/jiz570DOI Listing
January 2020

The epidemiological signature of influenza B virus and its B/Victoria and B/Yamagata lineages in the 21st century.

PLoS One 2019 12;14(9):e0222381. Epub 2019 Sep 12.

Netherlands Institute for Health Services Research (Nivel), Utrecht, The Netherlands.

We describe the epidemiological characteristics, pattern of circulation, and geographical distribution of influenza B viruses and its lineages using data from the Global Influenza B Study. We included over 1.8 million influenza cases occurred in thirty-one countries during 2000-2018. We calculated the proportion of cases caused by influenza B and its lineages; determined the timing of influenza A and B epidemics; compared the age distribution of B/Victoria and B/Yamagata cases; and evaluated the frequency of lineage-level mismatch for the trivalent vaccine. The median proportion of influenza cases caused by influenza B virus was 23.4%, with a tendency (borderline statistical significance, p = 0.060) to be higher in tropical vs. temperate countries. Influenza B was the dominant virus type in about one every seven seasons. In temperate countries, influenza B epidemics occurred on average three weeks later than influenza A epidemics; no consistent pattern emerged in the tropics. The two B lineages caused a comparable proportion of influenza B cases globally, however the B/Yamagata was more frequent in temperate countries, and the B/Victoria in the tropics (p = 0.048). B/Yamagata patients were significantly older than B/Victoria patients in almost all countries. A lineage-level vaccine mismatch was observed in over 40% of seasons in temperate countries and in 30% of seasons in the tropics. The type B virus caused a substantial proportion of influenza infections globally in the 21st century, and its two virus lineages differed in terms of age and geographical distribution of patients. These findings will help inform health policy decisions aiming to reduce disease burden associated with seasonal influenza.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222381PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742362PMC
March 2020

Respiratory syncytial virus hospitalisations among young children: a data linkage study.

Epidemiol Infect 2019 01;147:e246

Department of Paediatrics: Child & Youth Health,University of Auckland,Auckland,New Zealand.

We aimed to provide comprehensive estimates of laboratory-confirmed respiratory syncytial virus (RSV)-associated hospitalisations. Between 2012 and 2015, active surveillance of acute respiratory infection (ARI) hospitalisations during winter seasons was used to estimate the seasonal incidence of laboratory-confirmed RSV hospitalisations in children aged <5 years in Auckland, New Zealand (NZ). Incidence rates were estimated by fine age group, ethnicity and socio-economic status (SES) strata. Additionally, RSV disease estimates determined through active surveillance were compared to rates estimated from hospital discharge codes. There were 5309 ARI hospitalisations among children during the study period, of which 3923 (73.9%) were tested for RSV and 1597 (40.7%) were RSV-positive. The seasonal incidence of RSV-associated ARI hospitalisations, once corrected for non-testing, was 6.1 (95% confidence intervals 5.8-6.4) per 1000 children <5 years old. The highest incidence was among children aged <3 months. Being of indigenous Māori or Pacific ethnicity or living in a neighbourhood with low SES independently increased the risk of an RSV-associated hospitalisation. RSV hospital discharge codes had a sensitivity of 71% for identifying laboratory-confirmed RSV cases. RSV infection is a leading cause of hospitalisation among children in NZ, with significant disparities by ethnicity and SES. Our findings highlight the need for effective RSV vaccines and therapies.
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http://dx.doi.org/10.1017/S0950268819001377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805750PMC
January 2019

A Modular Cytokine Analysis Method Reveals Novel Associations With Clinical Phenotypes and Identifies Sets of Co-signaling Cytokines Across Influenza Natural Infection Cohorts and Healthy Controls.

Front Immunol 2019 18;10:1338. Epub 2019 Jun 18.

National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Be'er-Sheva, Israel.

Cytokines and chemokines are key signaling molecules of the immune system. Recent technological advances enable measurement of multiplexed cytokine profiles in biological samples. These profiles can then be used to identify potential biomarkers of a variety of clinical phenotypes. However, testing for such associations for each cytokine separately ignores the highly context-dependent covariation in cytokine secretion and decreases statistical power to detect associations due to multiple hypothesis testing. Here we present CytoMod-a novel data-driven approach for analysis of cytokine profiles that uses unsupervised clustering and regression to identify putative functional modules of co-signaling cytokines. Each module represents a biosignature of co-signaling cytokines. We applied this approach to three independent clinical cohorts of subjects naturally infected with influenza in which cytokine profiles and clinical phenotypes were collected. We found that in two out of three cohorts, cytokine modules were significantly associated with clinical phenotypes, and in many cases these associations were stronger than the associations of the individual cytokines within them. By comparing cytokine modules across datasets, we identified cytokine "cores"-specific subsets of co-expressed cytokines that clustered together across the three cohorts. Cytokine cores were also associated with clinical phenotypes. Interestingly, most of these cores were also co-expressed in a cohort of healthy controls, suggesting that in part, patterns of cytokine co-signaling may be generalizable. CytoMod can be readily applied to any cytokine profile dataset regardless of measurement technology, increases the statistical power to detect associations with clinical phenotypes and may help shed light on the complex co-signaling networks of cytokines in both health and infection.
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http://dx.doi.org/10.3389/fimmu.2019.01338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594355PMC
October 2020

Influenza-Associated Outcomes Among Pregnant, Postpartum, and Nonpregnant Women of Reproductive Age.

J Infect Dis 2019 05;219(12):1893-1903

Institute of Environmental Science and Research, Upper Hutt, New Zealand.

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.
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http://dx.doi.org/10.1093/infdis/jiz035DOI Listing
May 2019

Influenza vaccine effectiveness in preventing influenza-associated intensive care admissions and attenuating severe disease among adults in New Zealand 2012-2015.

Vaccine 2018 09 1;36(39):5916-5925. Epub 2018 Aug 1.

Auckland District Health Board, Auckland, New Zealand.

Background: Little is known about inactivated influenza vaccine effectiveness (IVE) in preventing very severe disease, including influenza-associated intensive care unit (ICU) admissions.

Methods: The Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance (SHIVERS) project enrolled adults (aged ≥ 18 years) with acute respiratory illness (ARI) in general ward (GW) hospital settings (n = 3034) and ICUs (n = 101) during 2012-2015. IVE was assessed using a test-negative design comparing the odds of influenza vaccination among influenza positives vs. negatives (confirmed by real-time reverse transcription polymerase chain reaction). All models were adjusted for season, weeks from season peak, and a vaccination propensity score.

Results: Influenza virus infection was confirmed in 28% of GW hospital and 41% of ICU patients; influenza vaccination was documented for 56% and 41%, respectively. Across seasons, IVE was 37% (95% confidence intervals [CI] = 23-48%) among GW patients and 82% (95% CI = 45-94%) among ICU patients. IVE point estimates were > 70% against ICU influenza and consistently higher than IVE against GW influenza when stratified by season, by virus (sub)types, and for adults with or without chronic medical conditions and for both adults aged <65 and ≥65 years old. Among hospitalized influenza positives, influenza vaccination was associated with a 59% reduction in the odds of ICU admission (aOR = 0.41, 95% CI = 0.18-0.96) and with shorter ICU lengths of stay (LOS), but not with radiograph-confirmed pneumonia or GW hospital LOS.

Conclusion: Inactivated influenza vaccines prevented influenza-associated ICU admissions, may have higher effectiveness in ICU than GW hospital settings, and appeared to reduce the risk of severe disease among those who are infected despite vaccination.
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http://dx.doi.org/10.1016/j.vaccine.2018.07.028DOI Listing
September 2018

Risk Factors and Attack Rates of Seasonal Influenza Infection: Results of the Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance (SHIVERS) Seroepidemiologic Cohort Study.

J Infect Dis 2019 01;219(3):347-357

Centers for Disease Control and Prevention, Atlanta, Georgia.

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.
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http://dx.doi.org/10.1093/infdis/jiy443DOI Listing
January 2019

Distribution of influenza virus types by age using case-based global surveillance data from twenty-nine countries, 1999-2014.

BMC Infect Dis 2018 06 8;18(1):269. Epub 2018 Jun 8.

Netherlands Institute for Health Services Research (NIVEL), Otterstraat 118-124, 3513, CR, Utrecht, The Netherlands.

Background: Influenza disease burden varies by age and this has important public health implications. We compared the proportional distribution of different influenza virus types within age strata using surveillance data from twenty-nine countries during 1999-2014 (N=358,796 influenza cases).

Methods: For each virus, we calculated a Relative Illness Ratio (defined as the ratio of the percentage of cases in an age group to the percentage of the country population in the same age group) for young children (0-4 years), older children (5-17 years), young adults (18-39 years), older adults (40-64 years), and the elderly (65+ years). We used random-effects meta-analysis models to obtain summary relative illness ratios (sRIRs), and conducted meta-regression and sub-group analyses to explore causes of between-estimates heterogeneity.

Results: The influenza virus with highest sRIR was A(H1N1) for young children, B for older children, A(H1N1)pdm2009 for adults, and (A(H3N2) for the elderly. As expected, considering the diverse nature of the national surveillance datasets included in our analysis, between-estimates heterogeneity was high (I>90%) for most sRIRs. The variations of countries' geographic, demographic and economic characteristics and the proportion of outpatients among reported influenza cases explained only part of the heterogeneity, suggesting that multiple factors were at play.

Conclusions: These results highlight the importance of presenting burden of disease estimates by age group and virus (sub)type.
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http://dx.doi.org/10.1186/s12879-018-3181-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994061PMC
June 2018

Severe Influenza Is Characterized by Prolonged Immune Activation: Results From the SHIVERS Cohort Study.

J Infect Dis 2018 01;217(2):245-256

Department of Immunology, St. Jude Children's Research Hospital, Memphis.

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.
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http://dx.doi.org/10.1093/infdis/jix571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335675PMC
January 2018

Modelled seasonal influenza mortality shows marked differences in risk by age, sex, ethnicity and socioeconomic position in New Zealand.

J Infect 2017 09 1;75(3):225-233. Epub 2017 Jun 1.

Department of Public Health, University of Otago, Wellington, New Zealand.

Objectives: Influenza is responsible for a large number of deaths which can only be estimated using modelling methods. Such methods have rarely been applied to describe the major socio-demographic characteristics of this disease burden.

Methods: We used quasi Poisson regression models with weekly counts of deaths and isolates of influenza A, B and respiratory syncytial virus for the period 1994 to 2008.

Results: The estimated average mortality rate was 13.5 per 100,000 people which was 1.8% of all deaths in New Zealand. Influenza mortality differed markedly by age, sex, ethnicity and socioeconomic position. Relatively vulnerable groups were males aged 65-79 years (Rate ratio (RR) = 1.9, 95% CI: 1.9, 1.9 compared with females), Māori (RR = 3.6, 95% CI: 3.6, 3.7 compared with European/Others aged 65-79 years), Pacific (RR = 2.4, 95% CI: 2.4, 2.4 compared with European/Others aged 65-79 years) and those living in the most deprived areas (RR = 1.8, 95% CI: 1.3, 2.4) for New Zealand Deprivation (NZDep) 9&10 (the most deprived) compared with NZDep 1&2 (the least deprived).

Conclusions: These results support targeting influenza vaccination and other interventions to the most vulnerable groups, in particular Māori and Pacific people and men aged 65-79 years and those living in the most deprived areas.
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http://dx.doi.org/10.1016/j.jinf.2017.05.017DOI Listing
September 2017

Influenza in the Asia-Pacific region: Findings and recommendations from the Global Influenza Initiative.

Vaccine 2017 02 9;35(6):856-864. Epub 2017 Jan 9.

University of Pennsylvania, Doylestown, PA, USA.

The fourth roundtable meeting of the Global Influenza Initiative (GII) was held in Hong Kong, China, in July 2015. An objective of this meeting was to gain a broader understanding of the epidemiology, surveillance, vaccination policies and programs, and obstacles to vaccination of influenza in the Asia-Pacific region through presentations of data from Australia, Hong Kong, India, Indonesia, Malaysia, New Zealand, the Philippines, Taiwan, Thailand, and Vietnam. As well as a need for improved levels of surveillance in some areas, a range of factors were identified that act as barriers to vaccination in some countries, including differences in climate and geography, logistical challenges, funding, lack of vaccine awareness and education, safety concerns, perceived lack of vaccine effectiveness, and lack of inclusion in national guidelines. From the presentations at the meeting, the GII discussed a number of recommendations for easing the burden of influenza and overcoming the current challenges in the Asia-Pacific region. These recommendations encompass the need to improve surveillance and availability of epidemiological data; the development and publication of national guidelines, where not currently available and/or that are in line with those proposed by the World Health Organization; the requirement for optimal timing of vaccination programs according to local or country-specific epidemiology; and calls for advocacy and government support of vaccination programs in order to improve availability and uptake and coverage. In conclusion, in addition to the varied epidemiology of seasonal influenza across this diverse region, there are a number of logistical and resourcing issues that present a challenge to the development of optimally effective vaccination strategies and that need to be overcome to improve access to and uptake of seasonal influenza vaccines. The GII has developed a number of recommendations to address these challenges and improve the control of influenza.
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http://dx.doi.org/10.1016/j.vaccine.2016.12.064DOI Listing
February 2017

Pandemic Seasonal H1N1 Reassortants Recovered from Patient Material Display a Phenotype Similar to That of the Seasonal Parent.

J Virol 2016 09 12;90(17):7647-56. Epub 2016 Aug 12.

St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Unlabelled: We have previously shown that 11 patients became naturally coinfected with seasonal H1N1 (A/H1N1) and pandemic H1N1 (pdm/H1N1) during the Southern hemisphere winter of 2009 in New Zealand. Reassortment of influenza A viruses is readily observed during coinfection of host animals and in vitro; however, reports of reassortment occurring naturally in humans are rare. Using clinical specimen material, we show reassortment between the two coinfecting viruses occurred with high likelihood directly in one of the previously identified patients. Despite the lack of spread of these reassortants in the community, we did not find them to be attenuated in several model systems for viral replication and virus transmission: multistep growth curves in differentiated human bronchial epithelial cells revealed no growth deficiency in six recovered reassortants compared to A/H1N1 and pdm/H1N1 isolates. Two reassortant viruses were assessed in ferrets and showed transmission to aerosol contacts. This study demonstrates that influenza virus reassortants can arise in naturally coinfected patients.

Importance: Reassortment of influenza A viruses is an important driver of virus evolution, but little has been done to address humans as hosts for the generation of novel influenza viruses. We show here that multiple reassortant viruses were generated during natural coinfection of a patient with pandemic H1N1 (2009) and seasonal H1N1 influenza A viruses. Though apparently fit in model systems, these reassortants did not become established in the wider population, presumably due to herd immunity against their seasonal H1 antigen.
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http://dx.doi.org/10.1128/JVI.00772-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988147PMC
September 2016

Temporal Patterns of Influenza A and B in Tropical and Temperate Countries: What Are the Lessons for Influenza Vaccination?

PLoS One 2016 31;11(3):e0152310. Epub 2016 Mar 31.

Netherlands Institute for Health Services Research (NIVEL), Utrecht, The Netherlands.

Introduction: Determining the optimal time to vaccinate is important for influenza vaccination programmes. Here, we assessed the temporal characteristics of influenza epidemics in the Northern and Southern hemispheres and in the tropics, and discuss their implications for vaccination programmes.

Methods: This was a retrospective analysis of surveillance data between 2000 and 2014 from the Global Influenza B Study database. The seasonal peak of influenza was defined as the week with the most reported cases (overall, A, and B) in the season. The duration of seasonal activity was assessed using the maximum proportion of influenza cases during three consecutive months and the minimum number of months with ≥80% of cases in the season. We also assessed whether co-circulation of A and B virus types affected the duration of influenza epidemics.

Results: 212 influenza seasons and 571,907 cases were included from 30 countries. In tropical countries, the seasonal influenza activity lasted longer and the peaks of influenza A and B coincided less frequently than in temperate countries. Temporal characteristics of influenza epidemics were heterogeneous in the tropics, with distinct seasonal epidemics observed only in some countries. Seasons with co-circulation of influenza A and B were longer than influenza A seasons, especially in the tropics.

Discussion: Our findings show that influenza seasonality is less well defined in the tropics than in temperate regions. This has important implications for vaccination programmes in these countries. High-quality influenza surveillance systems are needed in the tropics to enable decisions about when to vaccinate.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152310PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816507PMC
August 2016

A chest radiograph scoring system in patients with severe acute respiratory infection: a validation study.

BMC Med Imaging 2015 Dec 29;15:61. Epub 2015 Dec 29.

Starship Children's Hospital, Auckland, New Zealand.

Background: The term severe acute respiratory infection (SARI) encompasses a heterogeneous group of respiratory illnesses. Grading the severity of SARI is currently reliant on indirect disease severity measures such as respiratory and heart rate, and the need for oxygen or intensive care. With the lungs being the primary organ system involved in SARI, chest radiographs (CXRs) are potentially useful for describing disease severity. Our objective was to develop and validate a SARI CXR severity scoring system.

Methods: We completed validation within an active SARI surveillance project, with SARI defined using the World Health Organization case definition of an acute respiratory infection with a history of fever, or measured fever of ≥ 38 °C; and cough; and with onset within the last 10 days; and requiring hospital admission. We randomly selected 250 SARI cases. Admission CXR findings were categorized as: 1 = normal; 2 = patchy atelectasis and/or hyperinflation and/or bronchial wall thickening; 3 = focal consolidation; 4 = multifocal consolidation; and 5 = diffuse alveolar changes. Initially, four radiologists scored CXRs independently. Subsequently, a pediatrician, physician, two residents, two medical students, and a research nurse independently scored CXR reports. Inter-observer reliability was determined using a weighted Kappa (κ) for comparisons between radiologists; radiologists and clinicians; and clinicians. Agreement was defined as moderate (κ > 0.4-0.6), good (κ > 0.6-0.8) and very good (κ > 0.8-1.0).

Results: Agreement between the two pediatric radiologists was very good (κ = 0.83, 95% CI 0.65-1.00) and between the two adult radiologists was good (κ = 0.75, 95% CI 0.57-0. 93). Agreement of the clinicians with the radiologists was moderate-to-good (pediatrician:κ = 0.65; pediatric resident:κ = 0.69; physician:κ = 0.68; resident:κ = 0.67; research nurse:κ = 0.49, medical students: κ = 0.53 and κ = 0.56). Agreement between clinicians was good-to-very good (pediatrician vs. physician:κ = 0.85; vs. pediatric resident:κ = 0.81; vs. medicine resident:κ = 0.76; vs. research nurse:κ = 0.75; vs. medical students:κ = 0.63 and 0.66). Following review of discrepant CXR report scores by clinician pairs, κ values for radiologist-clinician agreement ranged from 0.59 to 0.70 and for clinician-clinician agreement from 0.97 to 0.99.

Conclusions: This five-point CXR scoring tool, suitable for use in poorly- and well-resourced settings and by clinicians of varying experience levels, reliably describes SARI severity. The resulting numerical data enables epidemiological comparisons of SARI severity between different countries and settings.
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http://dx.doi.org/10.1186/s12880-015-0103-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696329PMC
December 2015

Influenza vaccine effectiveness for hospital and community patients using control groups with and without non-influenza respiratory viruses detected, Auckland, New Zealand 2014.

Vaccine 2016 Jan 10;34(4):503-509. Epub 2015 Dec 10.

The University of Auckland, Private Bag 92019, Victoria St West, Auckland, New Zealand. Electronic address:

Background: We aimed to estimate the protection afforded by inactivated influenza vaccine, in both community and hospital settings, in a well characterised urban population in Auckland during 2014.

Methods: We used two different comparison groups, all patients who tested negative for influenza and only those patients who tested negative for influenza and had a non-influenza respiratory virus detected, to calculate the vaccine effectiveness in a test negative study design. Estimates were made separately for general practice outpatient consultations and hospitalised patients, stratified by age group and by influenza type and subtype. Vaccine status was confirmed by electronic record for general practice patients and all respiratory viruses were detected by real time polymerase chain reaction.

Results: 1039 hospitalised and 1154 general practice outpatient consultations met all the study inclusion criteria and had a respiratory sample tested for influenza and other respiratory viruses. Compared to general practice patients, hospitalised patients were more likely to be very young or very old, to be Māori or Pacific Islander, to have a low income and to suffer from chronic disease. Vaccine effectiveness (VE) adjusted for age and other participant characteristics using all influenza negative controls was 42% (95% CI: 16 to 60%) for hospitalised and 56% (95% CI: 35 to 70%) for general practice patients. The vaccine appeared to be most effective against the influenza A(H1N1)pdm09 strain with an adjusted VE of 62% (95% CI:38 to 77%) for hospitalised and 59% (95% CI:36 to 74%) for general practice patients, using influenza virus negative controls. Similar results found when patients testing positive for a non-influenza respiratory virus were used as the control group.

Conclusion: This study contributes to validation of the test negative design and confirms that inactivated influenza vaccines continue to provide modest but significant protection against laboratory-confirmed influenza.
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http://dx.doi.org/10.1016/j.vaccine.2015.11.073DOI Listing
January 2016

Epidemiological and virological characteristics of influenza B: results of the Global Influenza B Study.

Influenza Other Respir Viruses 2015 Aug;9 Suppl 1:3-12

Netherlands Institute for Health Services Research (NIVEL), Utrecht, The Netherlands.

Introduction: Literature on influenza focuses on influenza A, despite influenza B having a large public health impact. The Global Influenza B Study aims to collect information on global epidemiology and burden of disease of influenza B since 2000.

Methods: Twenty-six countries in the Southern (n = 5) and Northern (n = 7) hemispheres and intertropical belt (n = 14) provided virological and epidemiological data. We calculated the proportion of influenza cases due to type B and Victoria and Yamagata lineages in each country and season; tested the correlation between proportion of influenza B and maximum weekly influenza-like illness (ILI) rate during the same season; determined the frequency of vaccine mismatches; and described the age distribution of cases by virus type.

Results: The database included 935 673 influenza cases (2000-2013). Overall median proportion of influenza B was 22·6%, with no statistically significant differences across seasons. During seasons where influenza B was dominant or co-circulated (>20% of total detections), Victoria and Yamagata lineages predominated during 64% and 36% of seasons, respectively, and a vaccine mismatch was observed in ≈25% of seasons. Proportion of influenza B was inversely correlated with maximum ILI rate in the same season in the Northern and (with borderline significance) Southern hemispheres. Patients infected with influenza B were usually younger (5-17 years) than patients infected with influenza A.

Conclusion: Influenza B is a common disease with some epidemiological differences from influenza A. This should be considered when optimizing control/prevention strategies in different regions and reducing the global burden of disease due to influenza.
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http://dx.doi.org/10.1111/irv.12319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549097PMC
August 2015

Strengthening the influenza vaccine virus selection and development process: Report of the 3rd WHO Informal Consultation for Improving Influenza Vaccine Virus Selection held at WHO headquarters, Geneva, Switzerland, 1-3 April 2014.

Vaccine 2015 Aug 3;33(36):4368-82. Epub 2015 Jul 3.

National Influenza Center, Helsinki, Finland.

Despite long-recognized challenges and constraints associated with their updating and manufacture, influenza vaccines remain at the heart of public health preparedness and response efforts against both seasonal and potentially pandemic influenza viruses. Globally coordinated virological and epidemiological surveillance is the foundation of the influenza vaccine virus selection and development process. Although national influenza surveillance and reporting capabilities are being strengthened and expanded, sustaining and building upon recent gains has become a major challenge. Strengthening the vaccine virus selection process additionally requires the continuation of initiatives to improve the timeliness and representativeness of influenza viruses shared by countries for detailed analysis by the WHO Global Influenza Surveillance and Response System (GISRS). Efforts are also continuing at the national, regional, and global levels to better understand the dynamics of influenza transmission in both temperate and tropical regions. Improved understanding of the degree of influenza seasonality in tropical countries of the world should allow for the strengthening of national vaccination policies and use of the most appropriate available vaccines. There remain a number of limitations and difficulties associated with the use of HAI assays for the antigenic characterization and selection of influenza vaccine viruses by WHOCCs. Current approaches to improving the situation include the more-optimal use of HAI and other assays; improved understanding of the data produced by neutralization assays; and increased standardization of serological testing methods. A number of new technologies and associated tools have the potential to revolutionize influenza surveillance and response activities. These include the increasingly routine use of whole genome next-generation sequencing and other high-throughput approaches. Such approaches could not only become key elements in outbreak investigations but could drive a new surveillance paradigm. However, despite the advances made, significant challenges will need to be addressed before next-generation technologies become routine, particularly in low-resource settings. Emerging approaches and techniques such as synthetic genomics, systems genetics, systems biology and mathematical modelling are capable of generating potentially huge volumes of highly complex and diverse datasets. Harnessing the currently theoretical benefits of such bioinformatics ("big data") concepts for the influenza vaccine virus selection and development process will depend upon further advances in data generation, integration, analysis and dissemination. Over the last decade, growing awareness of influenza as an important global public health issue has been coupled to ever-increasing demands from the global community for more-equitable access to effective and affordable influenza vaccines. The current influenza vaccine landscape continues to be dominated by egg-based inactivated and live attenuated vaccines, with a small number of cell-based and recombinant vaccines. Successfully completing each step in the annual influenza vaccine manufacturing cycle will continue to rely upon timely and regular communication between the WHO GISRS, manufacturers and regulatory authorities. While the pipeline of influenza vaccines appears to be moving towards a variety of niche products in the near term, it is apparent that the ultimate aim remains the development of effective "universal" influenza vaccines that offer longer-lasting immunity against a broad range of influenza A subtypes.
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http://dx.doi.org/10.1016/j.vaccine.2015.06.090DOI Listing
August 2015

Estimating the contribution of influenza to hospitalisations in New Zealand from 1994 to 2008.

Vaccine 2015 Aug 2;33(33):4087-92. Epub 2015 Jul 2.

Department of Public Health, University of Otago, Wellington, New Zealand.

Background: Influenza has a substantially but poorly measured impact on population health. Estimating its true contribution to hospitalisations remains a challenge.

Methods: We used simple and comprehensive negative binomial regression models with weekly counts of hospitalisations and isolates of influenza A, B and respiratory syncytial virus for the period 1994- 2008.

Results: The estimated annual national average number of hospitalisations attributable to influenza was 822.1(95% CI: 815.3, 828.9) for pneumonia and influenza, 1861.3 (95% CI: 1842.9, 1879.7) for respiratory illness, 12.1 (95% CI: 2.6, 21.6) for circulatory illness, 2260.0 (95% CI: 2212.2, 2307.8) for all medical illness and 2419.9 (95% CI: 2356.4, 2483.4) for all causes. The contribution of influenza to total hospitalisations was about nine times larger than indicated by routine discharge data. New Zealanders 80 years of age and older had the highest annual excess rates of influenza-related hospitalisations (327.8 per 100,000); followed by infants under 1 year (244.5 per 100,000). Estimated influenza hospitalisation rates were also markedly higher in Pacific (83.3 per 100,000) and Māori (80.0 per 100,000) compared with European/Others (58.1 per 100,000). Respiratory illness was the major contributor to all cause hospitalisations attributed to influenza accounting for 77%. Influenza hospitalisations included only a negligible contribution from circulatory illness.

Conclusion: These findings support efforts to reduce the impact of influenza, particularly for the most vulnerable population groups highlighted here. Analysis of the cost-effectiveness of such interventions needs to consider these higher modelled estimates of disease impact.
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http://dx.doi.org/10.1016/j.vaccine.2015.06.080DOI Listing
August 2015