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Background: The COVID-19 pandemic is reported to have affected the epidemiology of respiratory syncytial virus (RSV), which could have important implications for RSV prevention and control strategies. We aimed to assess the hospitalisation burden of RSV-associated acute lower respiratory infection (ALRI) in children younger than 5 years during the pandemic period and the possible changes in RSV epidemiology from a global perspective., Methods: We conducted a systematic literature search for studies published between Jan 1, 2020, and June 30, 2022, in MEDLINE, Embase, Global Health, Web of Science, the WHO COVID-19 Research Database, CINAHL, LILACS, OpenGrey, CNKI, WanFang, and CqVip. We included unpublished data on RSV epidemiology shared by international collaborators. Eligible studies reported data on at least one of the following measures for children (aged <5 years) hospitalised with RSV-associated ALRI: hospital admission rates, in-hospital case fatality ratio, and the proportion of hospitalised children requiring supplemental oxygen or requiring mechanical ventilation or admission to intensive care. We used a generalised linear mixed-effects model for data synthesis to measure the changes in the incidence, age distribution, and disease severity of children hospitalised with RSV-associated ALRI during the pandemic, compared with the year 2019., Findings: We included 61 studies from 19 countries, of which 14 (23%) studies were from the published literature (4052 identified records) and 47 (77%) were from unpublished datasets. Most (51 [84%]) studies were from high-income countries; nine (15%) were from upper-middle-income countries, one (2%) was from a lower-middle-income country (Kenya), and none were from a low-income country. 15 studies contributed to the estimates of hospitalisation rate and 57 studies contributed to the severity analyses. Compared with 2019, the rates of RSV-associated ALRI hospitalisation in all children (aged 0-60 months) in 2020 decreased by 79·7% (325 000 cases vs 66 000 cases) in high-income countries, 13·8% (581 000 cases vs 501 000 cases) in upper-middle-income countries, and 42·3% (1 378 000 cases vs 795 000 cases) in Kenya. In high-income countries, annualised rates started to rise in 2021, and by March, 2022, had returned to a level similar to 2019 (6·0 cases per 1000 children [95% uncertainty interval 5·4-6·8] in April, 2021, to March, 2022, vs 5·0 cases per 1000 children [3·6-6·8] in 2019). By contrast, in middle-income countries, rates remained lower in the latest period with data available than in 2019 (for upper-middle-income countries, 2·1 cases [0·7-6·1] in April, 2021, to March, 2022, vs 3·4 [1·2-9·7] in 2019; for Kenya, 2·2 cases [1·8-2·7] in 2021 vs 4·1 [3·5-4·7] in 2019). Across all time periods and income regions, hospitalisation rates peaked in younger infants (aged 0 to <3 months) and decreased with increasing age. A significantly higher proportion of children aged 12-24 months were hospitalised with RSV-associated ALRI in high-income and upper-middle-income countries during the pandemic years than in 2019, with odds ratios ranging from 1·30 (95% uncertainty interval 1·07-1·59) to 2·05 (1·66-2·54). No consistent changes in disease severity were observed., Interpretation: The hospitalisation burden of RSV-associated ALRI in children younger than 5 years was significantly reduced during the first year of the COVID-19 pandemic. The rebound in hospitalisation rates to pre-pandemic rates observed in the high-income region but not in the middle-income region by March, 2022, suggests a persistent negative impact of the pandemic on health-care systems and health-care access in the middle-income region. RSV surveillance needs to be established (or re-established) to monitor changes in RSV epidemiology, particularly in low-income and lower-middle-income countries., Funding: EU Innovative Medicines Initiative Preparing for RSV Immunisation and Surveillance in Europe (PROMISE), Bill & Melinda Gates Foundation, and WHO., Competing Interests: Declaration of interests UK is a current employee of Pfizer but took part in this project as a postgraduate student at the University of Edinburgh. NW has received grant funding from the Bill & Melinda Gates Foundation, Sanofi, and US Centers for Disease Control and Prevention. CFY reports grants from the National Medical Research Council Singapore and the Wellcome Trust, and fees from Sanofi, Pfizer, and Takeda, outside of the submitted work. HN reports grants from the Innovative Medicines Initiative related to the submitted work, and grants from WHO, the National Institute for Health Research, Pfizer, and Icosavax, and personal fees from the Bill & Melinda Gates Foundation, Pfizer, ReViral, GlaxoSmithKline, Merck, Icosavax, Sanofi, Novavax, and AbbVie, outside of the submitted work. YL reports grants from WHO, the Wellcome Trust, and GlaxoSmithKline, and personal fees from Pfizer, outside of the submitted work. All other authors declare no competing interests., (© 2024 World Health Organization. Published by Elsevier Ltd. All rights reserved. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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Background: Mathematical models of respiratory syncytial virus (RSV) transmission can help describe seasonal epidemics and assess the impact of potential vaccines and immunoprophylaxis with monoclonal antibodies (mAb)., Methods: We developed a deterministic, compartmental model for RSV transmission, which was fitted to population-based RSV hospital surveillance data from Auckland, New Zealand. The model simulated the introduction of either a maternal vaccine or a seasonal mAb among infants aged less than 6 months and estimated the reduction in RSV hospitalizations for a range of effectiveness and coverage values., Results: The model accurately reproduced the annual seasonality of RSV epidemics in Auckland. We found that a maternal vaccine with effectiveness of 30-40% in the first 90 days and 15-20% for the next 90 days could reduce RSV hospitalizations by 18-24% in children younger than 3 months, by 11-14% in children aged 3-5 months, and by 2-3% in children aged 6-23 months. A seasonal infant mAb with 40-60% effectiveness for 150 days could reduce RSV hospitalizations by 30-43%, 34-48% and by 14-21% in children aged 0-2 months, 3-5 months and 6-23 months, respectively., Conclusions: Our results suggest that either a maternal RSV vaccine or mAb would effectively reduce RSV hospitalization disease burden in New Zealand. Overall, a seasonal mAb resulted in a larger disease prevention impact than a maternal vaccine., Competing Interests: Declaration of Competing Interest NP, QSH, and ECN were contracted on a GlaxoSmithKline funded RSV surveillance project during manucript development. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Natural killer (NK) cells are a key component of the innate immune system and play pivotal roles as inflammatory regulators and in tumor surveillance. Human aspartyl β-hydroxylase (HAAH) is a plasma membrane and endoplasmic reticulum protein with hydroxylation activity, which is over-expressed in many malignant neoplasms and can be detected from the sera of tumor patients. HAAH is involved in regulating tumor cell infiltration and metastasis. Escaping from immune surveillance may help tumor cell infiltration and metastasis. However, the effects of HAAH on tumor immune surveillance have not yet been investigated carefully. The present study investigated the potential use of HAAH as an immune regulator of human NK cells. We assessed the effects of recombinant HAAH (r-HAAH) on primary human NK cell morphology, viability, cytotoxicity, apoptosis, receptors expression and cytokine/cytolytic proteins production. Our results demonstrated that r-HAAH negatively affects NK cell activity in a time and dose-dependent manner. It noticeably reduces the viability of the NK cells by increasing apoptosis and necrosis via caspase signaling pathways. Moreover, r-HAAH reduces the NK cell cytotoxicity by inhibiting surface expression of NKG2D, NKp44 and IFN-γ secretion. These findings suggest that one of the ways by which HAAH actively promotes tumor formation and proliferation is by inhibiting NK cell-surveillance activity., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Few studies report the effectiveness of trivalent inactivated influenza vaccine (TIV) in preventing hospitalisation for influenza-confirmed respiratory infections. Using a prospective surveillance platform, this study reports the first such estimate from a well-defined ethnically diverse population in New Zealand (NZ)., Methods: A case test-negative design was used to estimate propensity adjusted vaccine effectiveness. Patients with a severe acute respiratory infection (SARI), defined as a patient of any age requiring hospitalisation with a history of a fever or a measured temperature ≥38°C and cough and onset within the past 7 days, admitted to public hospitals in South and Central Auckland were eligible for inclusion in the study. Cases were SARI patients who tested positive for influenza, while non-cases (controls) were SARI patients who tested negative. Results were adjusted for the propensity to be vaccinated and the timing of the influenza season., Results: The propensity and season adjusted vaccine effectiveness (VE) was estimated as 39% (95% CI 16;56). The VE point estimate against influenza A (H1N1) was lower than for influenza B or influenza A (H3N2) but confidence intervals were wide and overlapping. Estimated VE was 59% (95% CI 26;77) in patients aged 45-64 years but only 8% (-78;53) in those aged 65 years and above., Conclusion: Prospective surveillance for SARI has been successfully established in NZ. This study for the first year, the 2012 influenza season, has shown low to moderate protection by TIV against influenza positive hospitalisation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: 18,500 laboratory-confirmed deaths caused by the 2009 pandemic influenza A H1N1 were reported worldwide for the period April, 2009, to August, 2010. This number is likely to be only a fraction of the true number of the deaths associated with 2009 pandemic influenza A H1N1. We aimed to estimate the global number of deaths during the first 12 months of virus circulation in each country., Methods: We calculated crude respiratory mortality rates associated with the 2009 pandemic influenza A H1N1 strain by age (0-17 years, 18-64 years, and >64 years) using the cumulative (12 months) virus-associated symptomatic attack rates from 12 countries and symptomatic case fatality ratios (sCFR) from five high-income countries. To adjust crude mortality rates for differences between countries in risk of death from influenza, we developed a respiratory mortality multiplier equal to the ratio of the median lower respiratory tract infection mortality rate in each WHO region mortality stratum to the median in countries with very low mortality. We calculated cardiovascular disease mortality rates associated with 2009 pandemic influenza A H1N1 infection with the ratio of excess deaths from cardiovascular and respiratory diseases during the pandemic in five countries and multiplied these values by the crude respiratory disease mortality rate associated with the virus. Respiratory and cardiovascular mortality rates associated with 2009 pandemic influenza A H1N1 were multiplied by age to calculate the number of associated deaths., Findings: We estimate that globally there were 201,200 respiratory deaths (range 105,700-395,600) with an additional 83,300 cardiovascular deaths (46,000-179,900) associated with 2009 pandemic influenza A H1N1. 80% of the respiratory and cardiovascular deaths were in people younger than 65 years and 51% occurred in southeast Asia and Africa., Interpretation: Our estimate of respiratory and cardiovascular mortality associated with the 2009 pandemic influenza A H1N1 was 15 times higher than reported laboratory-confirmed deaths. Although no estimates of sCFRs were available from Africa and southeast Asia, a disproportionate number of estimated pandemic deaths might have occurred in these regions. Therefore, efforts to prevent influenza need to effectively target these regions in future pandemics., Funding: None., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Recent innovations in dynamic devices have promised a reduction in stress shielding, protection of adjacent segment degeneration, and decreased implant failure. However, there have been few studies comparing the biomechanical properties of a rigid device in comparison to a dynamic posterior fixation device. The purpose of this study was to compare the immediate stability of a new dynamic pedicle screw fixation device with an equivalent rigid device., Methods: Six thoracolumbar cadaver spines (T10-L4) were fixed in a biomechanical testing frame. Pure moments of 10Nm were loaded in six directions: flexion, extension, right and left lateral bending, and right and left axial rotation. For each spine, four different stages were tested: intact, destabilization of the middle segment, fixation with the dynamic device, and fixation with the rigid device. Ranges of motion were measured using stereophotogrammetry. The specimens with each device were then subjected to flexion-compression loading for five cycles on a MTS 858 Universal Testing Machine. The average stiffness of the last three cycles was recorded., Findings: Both dynamic and rigid devices were found to provide stability for the injured segment in flexion-extension and lateral bending. In axial rotation, the devices could restore the stability to levels similar to those in an intact spine. Results also indicated a slight increase in range of motion in flexion-extension and significant reduction in stiffness of flexion-compression with the dynamic device (P < 0.01), in comparison to the rigid device., Interpretation: The dynamic device offers a system that may alter favorably the movement and load transmission of a spinal motion segment without sacrificing construct stability.