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Both vector and mRNA vaccines were an important part of the response to the COVID-19 pandemic and may be required in future outbreaks and pandemics. The aim of this study was to validate whether immunogenicity differs for adenoviral vectored (AdV) versus mRNA vaccines against SARS-CoV-2, and to investigate how anti-vector immunity and B cell dynamics modulate immunogenicity. We enrolled SARS-CoV-2 infection-naïve health care workers who had received two doses of either AdV AZD1222 (n = 184) or mRNA BNT162b2 vaccine (n = 274) between April and October 2021. Blood was collected at least once, 10-48 days after vaccine dose 2 for antibody and B cell analyses. Median ages were 42 and 39 years, for AdV and mRNA vaccinees, respectively. Surrogate virus neutralization test (sVNT) and spike binding antibody titres were a median of 4.2 and 2.2 times lower, respectively, for AdV compared to mRNA vaccinees (p < 0.001). Median percentages of memory B cells that recognized fluorescent-tagged spike and RBD were 2.9 and 8.3 times lower, respectively for AdV compared to mRNA vaccinees. Titres of IgG reactive with human adenovirus type 5 hexon protein rose a median of 2.2-fold after AdV vaccination but were not correlated with anti-spike antibody titres. Together the results show that mRNA induced substantially more sVNT antibody than AdV vaccine, which reflected greater B cell expansion and targeting of the RBD rather than an attenuating effect of anti-vector antibodies. ClinicalTrials.gov Identifier: NCT05110911.

Test negative studies have been used extensively for the estimation of COVID-19 vaccine effectiveness (VE). Such studies are able to estimate VE against medically-attended illness under certain assumptions. Selection bias may be present if the probability of participation is associated with vaccination or COVID-19, but this can be mitigated through use of a clinical case definition to screen patients for eligibility, which increases the likelihood that cases and non-cases come from the same source population. We examined the extent to which this type of bias could harm COVID-19 VE through systematic review and simulation. A systematic review of test-negative studies was re-analysed to identify studies ignoring the need for clinical criteria. Studies using a clinical case definition had a lower pooled VE estimate compared with studies that did not. Simulations varied the probability of selection by case and vaccination status. Positive bias away from the null (i.e., inflated VE consistent with the systematic review) was observed when there was a higher proportion of healthy, vaccinated non-cases, which may occur if a dataset contains many results from asymptomatic screening in settings where vaccination coverage is high. We provide an html tool for researchers to explore site-specific sources of selection bias in their own studies. We recommend all groups consider the potential for selection bias in their vaccine effectiveness studies, particularly when using administrative data.

BACKGROUND: Large-scale evaluation of COVID-19 is likely to rely on the quality of ICD coding. However, little is known about the validity of ICD-coded COVID-19 diagnoses. OBJECTIVES: To evaluate the performance of diagnostic codes in detecting COVID-19 during pregnancy. METHODS: We used data from a national cohort of 78,283 individuals with a pregnancy ending between 11 March 2020 and 31 January 2021 in the OptumLabs® Data Warehouse (OLDW). OLDW is a longitudinal, real-world data asset with de-identified administrative claims and electronic health record data. We identified all services with an ICD-10-CM diagnostic code of U07.1 and all laboratory claims records for COVID-19 diagnostic testing. We compared ICD-coded diagnoses to testing results to estimate positive and negative predictive values (PPV and NPV). To evaluate impact on risk estimation, we estimated risk of adverse pregnancy outcomes by source of exposure information. RESULTS: Of 78,283 pregnancies, 5644 had a laboratory test result for COVID-19. Testing was most common among older individuals, Hispanic individuals, those with higher socioeconomic status and those with a diagnosed medical condition or pregnancy complication; 52% of COVID-19 cases was identified through ICD-coded diagnosis alone, 19% from laboratory test results alone and 29% from both sources. Agreement between ICD-coded diagnosis and laboratory testing records was high 91% (95% confidence interval [CI] 90, 92). However, the PPV of ICD-code diagnosis was low (36%; 95% CI 33, 39). We observed up to a 50% difference in risk estimates of adverse pregnancy outcomes when exposure was based on laboratory testing results or diagnostic coding alone. CONCLUSIONS: More than one-in-five COVID-19 cases would be missed by using ICD-coded diagnoses alone to identify COVID-19 during pregnancy. Epidemiological studies exclusively relying on diagnostic coding or laboratory testing results are likely to be affected by exposure misclassification. Research

BACKGROUND: When new vaccine components or platforms are developed, they will typically need to demonstrate noninferiority or superiority over existing products, resulting in the assessment of relative vaccine effectiveness (rVE). This review aims to identify how rVE evaluation is being performed in studies of influenza to inform a more standardized approach. METHODS: We conducted a systematic search on PubMed, Google Scholar, and Web of Science for studies reporting rVE comparing vaccine components, dose, or vaccination schedules. We screened titles, abstracts, full texts, and references to identify relevant articles. We extracted information on the study design, relative comparison made, and the definition and statistical approach used to estimate rVE in each study. RESULTS: We identified 63 articles assessing rVE in influenza virus. Studies compared multiple vaccine components (n = 38), two or more doses of the same vaccine (n = 17), or vaccination timing or history (n = 9). One study compared a range of vaccine components and doses. Nearly two-thirds of all studies controlled for age, and nearly half for comorbidities, region, and sex. Assessment of 12 studies presenting both absolute and relative effect estimates suggested proportionality in the effects, resulting in implications for the interpretation of rVE effects. CONCLUSIONS: Approaches to rVE evaluation in practice is highly varied, with improvements in reporting required in many cases. Extensive consideration of methodologic issues relating to rVE is needed, including the stability of estimates and the impact of confounding structure on the validity of rVE estimates.

Human respiratory syncytial virus (RSV) is an important cause of acute respiratory infection with the most severe disease in the young and elderly. Non-pharmaceutical interventions and travel restrictions for controlling COVID-19 have impacted the circulation of most respiratory viruses including RSV globally, particularly in Australia, where during 2020 the normal winter epidemics were notably absent. However, in late 2020, unprecedented widespread RSV outbreaks occurred, beginning in spring, and extending into summer across two widely separated regions of the Australian continent, New South Wales (NSW) and Australian Capital Territory (ACT) in the east, and Western Australia. Through genomic sequencing we reveal a major reduction in RSV genetic diversity following COVID-19 emergence with two genetically distinct RSV-A clades circulating cryptically, likely localised for several months prior to an epidemic surge in cases upon relaxation of COVID-19 control measures. The NSW/ACT clade subsequently spread to the neighbouring state of Victoria and to cause extensive outbreaks and hospitalisations in early 2021. These findings highlight the need for continued surveillance and sequencing of RSV and other respiratory viruses during and after the COVID-19 pandemic, as mitigation measures may disrupt seasonal patterns, causing larger or more severe outbreaks.

During the coronavirus disease pandemic, international travel controls have been widely adopted. To determine the effectiveness of these measures, we analyzed data from 165 countries and found that early implementation of international travel controls led to a mean delay of 5 weeks in the first epidemic peak of cases.

Prior vaccination can alternately enhance or attenuate influenza vaccine immunogenicity and effectiveness. Analogously, we found that vaccine immunogenicity was enhanced by prior A(H3N2) virus infection among participants of the Ha Nam Cohort, Viet Nam, but was attenuated by prior vaccination among Australian Health Care Workers (HCWs) vaccinated in the same year. Here, we combined these studies to directly compare antibody titers against 35 A(H3N2) viruses spanning 1968-2018. Participants received licensed inactivated vaccines containing A/HongKong/4801/2014 (H3N2). The analysis was limited to participants aged 18-65 Y, and compared those exposed to A(H3N2) viruses circulating since 2009 by infection (Ha Nam) or vaccination (HCWs) to a reference group who had no recent A(H3N2) infection or vaccination (Ha Nam). Antibody responses were compared by fitting titer/titer-rise landscapes across strains, and by estimating titer ratios to the reference group of 2009-2018 viruses. Pre-vaccination, titers were lowest against 2009-2014 viruses among the reference (no recent exposure) group. Post-vaccination, titers were, on average, two-fold higher among participants with prior infection and two-fold lower among participants with 3-5 prior vaccinations compared to the reference group. Titer rise was negligible among participants with 3-5 prior vaccinations, poor among participants with 1-2 prior vaccinations, and equivalent or better among those with prior infection compared to the reference group. The enhancing effect of prior infection versus the incrementally attenuating effect of prior vaccinations suggests that these exposures may alternately promote and constrain the generation of memory that can be recalled by a new vaccine strain.

AIMS: Public health responses to reduce SARS-CoV-2 transmission have profoundly affected the epidemiology and management of other infections. We examined the impact of COVID-19 restrictions on antibiotic dispensing in Australia. METHODS: We used national claims data to investigate antibiotic dispensing trends from November 2015 to October 2020 and whether changes reflected reductions in primary care consultations. We used interrupted time series analysis to quantify changes in monthly antibiotic dispensing and face-to-face and telehealth GP consultations and examined changes by recipient age, pharmacy State and prescriber specialty. RESULTS: Over the study period, an estimated 19 921 370 people had 125 495 137 antibiotic dispensings, 71% prescribed by GPs. Following COVID-19 restrictions, we observed a sustained 36% (95% CI: 33-40%) reduction in antibiotic dispensings from April 2020. Antibiotics recommended for managing respiratory tract infections showed large reductions (range 51-69%), whereas those recommended for non-respiratory infections were unchanged. Dispensings prescribed by GPs decreased from 63.5 per 1000 population for April-October 2019 to 37.0 per 1000 for April-October 2020. Total GP consultation rates remained stable, but from April 2020, 31% of consultations were telehealth. CONCLUSION: In a setting with a low COVID-19 incidence, restrictions were associated with a substantial reduction in community dispensings of antibiotics primarily used to treat respiratory infections, coincident with reported reductions in respiratory viral infections. Our findings are informative for post-pandemic antimicrobial stewardship and highlight the potential to reduce inappropriate prescribing by GPs and specialists for respiratory viral infections.

Outbreaks of influenza in swine can result in potential threats to human public health. A notable occurrence was the emergence of swine-origin H1N1 influenza viruses in 2009. Since then, there have been several documented outbreaks of swine-origin influenza infecting humans in several countries. Sustained events have occurred when H1N1v, H1N2v, and H3N2v swine-origin viruses have infected humans visiting agricultural shows in the US. The predominant H3N2v viruses gained the matrix protein from the A(H1N1)pdm09 viruses, with reported human-to-human transmission raising fears of another pandemic. Current vaccines do not induce secondary cell-mediated immune responses, which may provide cross-protection against novel influenza A subtypes, however, population susceptibility to infection with seasonal influenza is likely to be influenced by cross-reactive CD8+ T-cells directed towards immunogenic peptides derived from viral proteins. This study involved a retrospective review of historical influenza viruses circulating in human populations from 1918 to 2020 to identify evidence of prior circulation of H3N3v immunogenic CD8+ T-cells peptides found in the NP and M1 proteins. We found evidence of prior circulation of H3N2v NP and M1 immunogenic peptides in historical influenza viruses. This provides insight into the population context in which influenza viruses emerge and may help inform immunogenic peptide selection for cytotoxic T-cell lymphocytes (CTL)-inducing influenza vaccines. Next-generation vaccines capable of eliciting CD8+ T-cell-mediated cross-protective immunity may offer a long-term alternative strategy for influenza vaccines.

Natural infection with the influenza virus is believed to generate cross-protective immunity across both types and subtypes. However, less is known about the persistence of this immunity and thus the susceptibility of individuals to repeat infection. We used 13 years (2005-2017) of surveillance data from Queensland, Australia, to describe the incidence and distribution of repeat influenza infections. Consecutive infections that occurred within 14 days of prior infection were considered a mixed infection; those that occurred more than 14 days later were considered separate (repeat) infections. Kaplan-Meier plots were used to investigate the probability of reinfection over time and the Prentice, Williams and Peterson extension of the Cox proportional hazards model was used to assess the association of age and gender with reinfection. Among the 188 392 notifications received during 2005-2017, 6165 were consecutively notified for the same individual (3.3% of notifications), and 2958 were mixed infections (1.6%). Overall, the probability of reinfection was low: the cumulative incidence was <1% after one year, 4.6% after five years, and 9.6% after ten years. The majority of consecutive infections were the result of two type A infections (43%) and were most common among females (adjusted hazard ratio (aHR): 1.15, 95% confidence interval (CI) 1.09-1.21), children aged less than 5 years (relative to adults aged 18-64 years aHR: 1.58, 95% CI 1.47-1.70) and older adults aged at least 65 years (aHR: 1.35; 95% CI 1.24-1.47). Our study suggests consecutive infections are possible but rare. These findings have implications for our understanding of population immunity to influenza.

BACKGROUND: The extent to which influenza recurrence depends upon waning immunity from prior infection is undefined. We used antibody titers of Ha-Nam cohort participants to estimate protection curves and decay trajectories. METHODS: Households (270) participated in influenza-like-illness (ILI) surveillance and provided blood at intervals spanning laboratory-confirmed virus transmission. Sera were tested in hemagglutination inhibition assay. Infection was defined as influenza virus-positive ILI and/or seroconversion. Median protective titers were estimated using scaled-logistic regression to model pretransmission titer against infection status in that season, limiting analysis to households with infection(s). Titers were modelled against month since infection using mixed-effects linear regression to estimate decay and when titers fell below protection thresholds. RESULTS: From December 2008-2012, 295 and 314 participants were infected with H1N1pdm09-like and A/Perth/16/09-like (H3N2Pe09) viruses, respectively. The proportion protected rose more steeply with titer for H1N1pdm09 than for H3N2Pe09, and estimated 50% protection titers were 19.6 and 37.3, respectively. Postinfection titers started higher against H3N2Pe09 but decayed more steeply than against H1N1pdm09. Seroprotection was estimated to be sustained against H1N1pdm09 but to wane by 8-months for H3N2Pe09. CONCLUSIONS: Estimates indicate that infection induces durable seroprotection against H1N1pdm09 but not H3N2Pe09, which could in part account for the younger age of A(H1N1) versus A(H3N2) cases.

Aims: Public health responses to reduce SARS-CoV-2 transmission have profoundly affected the epidemiology and management of other infections. We examined the impact of COVID-19 restrictions on antibiotic dispensing in Australia. Methods: We used national claims data to investigate antibiotic dispensing trends from November 2015 to October 2020 and whether changes reflected reductions in primary care consultations. We used interrupted time series analysis to quantify changes in monthly antibiotic dispensing and face-to-face and telehealth GP consultations and examined changes by recipient age, pharmacy State and prescriber specialty. Results: Over the study period, an estimated 19 921 370 people had 125 495 137 antibiotic dispensings, 71% prescribed by GPs. Following COVID-19 restrictions, we observed a sustained 36% (95% CI: 33–40%) reduction in antibiotic dispensings from April 2020. Antibiotics recommended for managing respiratory tract infections showed large reductions (range 51–69%), whereas those recommended for non-respiratory infections were unchanged. Dispensings prescribed by GPs decreased from 63.5 per 1000 population for April–October 2019 to 37.0 per 1000 for April–October 2020. Total GP consultation rates remained stable, but from April 2020, 31% of consultations were telehealth. Conclusion: In a setting with a low COVID-19 incidence, restrictions were associated with a substantial reduction in community dispensings of antibiotics primarily used to treat respiratory infections, coincident with reported reductions in respiratory viral infections. Our findings are informative for post-pandemic antimicrobial stewardship and highlight the potential to reduce inappropriate prescribing by GPs and specialists for respiratory viral infections.

BACKGROUND: Infectious diseases are a leading cause of hospitalization during childhood. The various mitigation strategies implemented to control the coronavirus disease (COVID-19) pandemic could have additional, unintended benefits for limiting the spread of other infectious diseases and their associated burden on the health care system. METHODS: We conducted an interrupted time-series analysis using population-wide hospitalization data for the state of Victoria, Australia. Infection-related hospitalizations for children and adolescents (aged <18 years, total source population ∼1.4 million) were extracted using pre-defined International Classification of Diseases 10th Revision Australian Modification (ICD-10-AM) codes. The change in weekly hospitalization rates (incidence rate ratio, IRR) for all infections following the introduction of pandemic-related restrictions from 15 March 2020 was estimated. RESULTS: Over 2015-19, the mean annual incidence of hospitalization with infection among children less than 18 years was 37 per 1000 population. There was an estimated 65% (95% CI 62-67%) reduction in the incidence of overall infection-related hospitalizations associated with the introduction of pandemic restrictions. The reduction was most marked in younger children (at least 66% in those less than 5 years of age) and for lower respiratory tract infections (relative reduction 85%, 95% CI 85-86%). CONCLUSIONS: The wider impacts of pandemic mitigation strategies on non-COVID-19 infection-related hospitalizations are poorly understood. We observed marked and rapid decreases in hospitalized childhood infection. In tandem with broader consequences, sustainable measures, such as improved hand hygiene, could reduce the burden of severe childhood infection post-pandemic and the social and economic costs of hospitalization.

BACKGROUND: Victoria experienced the greatest burden of COVID-19 in Australia in 2020. This report describes key epidemiological characteristics and corresponding control measures between 17 January 2020 and 26 March 2021. METHODS: COVID-19 notifications made to the State Government Department of Health were used in this analysis. Epidemiological features are described over 4 phases, including enhancements to testing, contact tracing and public health interventions. Demographic and clinical features of cases are described. FINDINGS: Victoria recorded 20,483 cases of COVID-19, of which 1073 (5•2%) were acquired overseas and 19,360 (95%) were locally acquired. The initial epidemic (Phase I) was well-contained through public health interventions and was followed by relaxation of restrictions and low-level community transmission (Phase II). However, an outbreak in a hotel used to quarantine returned travellers led to wide-scale community transmission accounting for a majority (91%) of cases (Phase III). Outbreaks occurred in vulnerable settings including aged care and hospitals, contributing to high hospitalisation (12%) and case fatality rates (3•7%). Aggressive restrictions ultimately led to local elimination, and subsequent outbreaks have been swiftly managed with improved processes (Phase IV). The demographic composition of cases evolved across phases from an older, wealthier population to a less advantaged younger population, with many from culturally and linguistically diverse backgrounds. INTERPRETATION: Over time, adaptations to the public health response have strengthened capacity to respond to new cases and outbreaks in a more effective manner. The Victorian experience underscores the importance of authentic engagement with diverse communities and balancing restrictions with livelihoods.

BACKGROUND: Many countries/regions implemented strict border measures (e.g., 14-day quarantines) as a blanket policy to prevent COVID-19 importations, while proposed "travel bubbles" as an alternative to reduce the impact of border controls. We aim to examine the differential importation risks with departure origins and post-arrival controls. METHODS: We developed a Bayesian framework to model disease progress of COVID-19 and the effectiveness of travel measures and inferred the origin-specific disease prevalence among inbound travellers, using data on passengers arriving in Hong Kong and laboratory-confirmed imported cases. We estimated the origin-specific risks of releasing infectious travellers under different control strategies and traveller volumes. We also estimated the risk of having released infectious travellers when a resurgence occurs in departure locations with no imported cases during a certain period. FINDINGS: Under the then strict controls of 14-day quarantine and testing on day 12, the Philippines imposed the greatest importation risk among the studied countries/regions (95.8% of releasing at least one infectious traveller, 95% credible interval (CrI), 94.8-96.6%). This was higher than that from low prevalence countries/regions (e.g., 23.4%, 95% CrI, 21.6-25.3% for Taiwan) if controls relaxed (i.e., 7-day quarantine and test on day 5). Increased traveller volumes and resurgence in departure locations with low prevalence under relaxed controls did not impose a greater importation risk than high prevalence locations under stricter controls. INTERPRETATION: Moderate relaxation of control measures for travellers arriving from low prevalence locations did not impose higher risks of community outbreaks than strict controls on travellers from high prevalence locations. FUNDING: Health and Medical Research Fund, Hong Kong.

BACKGROUND: Mongolia is a vast, sparsely populated country in central Asia. Its harsh climate and nomadic lifestyle make the population vulnerable to acute respiratory infections, particularly influenza. Evidence on the morbidity, mortality and socioeconomic impact of influenza in Mongolia is scarce; however, routine surveillance for influenza-like illness (ILI), severe acute respiratory infection (SARI) and laboratory-detected influenza is conducted. This paper describes the epidemiology of influenza and the estimated burden of influenza-associated illness in Mongolia in the five influenza seasons between 2013-2014 and 2017-2018. METHODS: Demographic and laboratory data from 152 sentinel surveillance sites on all patients who met the case definitions of ILI and SARI between October 2013 and May 2018 were extracted and analysed as described in A Manual for Estimating Disease Burden Associated with Seasonal Influenza. RESULTS: The estimated annual influenza-associated ILI and SARI rates, presented as ranges, were 1279-2798 and 81-666 cases per 100 000 population, respectively. Children aged < 5 years accounted for 67% of all ILI cases and 79% of all SARI cases. The annual specimen positivity for influenza was highest (11-30% for ILI and 8-31% for SARI) for children aged 5- < 15 years and children < 2 years old, respectively. The annual mortality rate due to pneumonia and SARI was highest among children aged < 2 years (15.8-54.0 per 100 000 population). Although the incidence of influenza-associated ILI and SARI was lowest for people aged 365 years, the mortality rate due to pneumonia and SARI (1.2-5.1 per 100 000) was higher than that for those aged 15-64 years. CONCLUSION: The estimated influenza-associated ILI and SARI incidence rates are high in Mongolia, and children, especially those aged < 5 years, have the highest influenza-associated burden in Mongolia. These findings provide evidence for decision-makers in Mongolia to consider targeted influenza vaccination

Much of our current understanding about novel coronavirus disease 2019 (COVID-19) comes from hospitalised patients. However, the spectrum of mild and subclinical disease has implications for population-level screening and control. Forty-nine participants were recruited from a group of 99 adults repatriated from a cruise ship with a high incidence of COVID-19. Respiratory and rectal swabs were tested by polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sera were tested for anti-SARS-CoV-2 antibodies by enzyme-linked immunosorbent assay (ELISA) and microneutralisation assay. Symptoms, viral shedding and antibody response were examined. Forty-five participants (92%) were considered cases based on either positive PCR or positive ELISA for immunoglobulin G. Forty-two percent of cases were asymptomatic. Only 15% of symptomatic cases reported fever. Serial respiratory and rectal swabs were positive for 10% and 5% of participants respectively about 3 weeks after median symptom onset. Cycle threshold values were high (range 31-45). Attempts to isolate live virus were unsuccessful. The presence of symptoms was not associated with demographics, comorbidities or antibody response. In closed settings, incidence of COVID-19 could be almost double that suggested by symptom-based screening. Serology may be useful in diagnosis of mild disease and in aiding public health investigations.

BACKGROUND: Allocation of scarce resources during a pandemic extends to the allocation of vaccines when they eventually become available. We describe a framework for priority vaccine allocation that employed a cross-disciplinary approach, guided by ethical considerations and informed by local risk assessment. METHODS: Published and grey literature was reviewed, and augmented by consultation with key informants, to collate past experience, existing guidelines and emerging strategies for pandemic vaccine deployment. Identified ethical issues and decision-making processes were also included. Concurrently, simulation modelling studies estimated the likely impacts of alternative vaccine allocation approaches. Assembled evidence was presented to a workshop of national experts in pandemic preparedness, vaccine strategy, implementation and ethics. All of this evidence was then used to generate a proposed ethical framework for vaccine priorities best suited to the Australian context. FINDINGS: Published and emerging guidance for priority pandemic vaccine distribution differed widely with respect to strategic objectives, specification of target groups, and explicit discussion of ethical considerations and decision-making processes. Flexibility in response was universally emphasised, informed by real-time assessment of the pandemic impact level, and identification of disproportionately affected groups. Model outputs aided identification of vaccine approaches most likely to achieve overarching goals in pandemics of varying transmissibility and severity. Pandemic response aims deemed most relevant for an Australian framework were: creating and maintaining trust, promoting equity, and reducing harmful outcomes. INTERPRETATION: Defining clear and ethically-defendable objectives for pandemic response in context aids development of flexible and adaptive decision support frameworks and facilitates clear communication and engagement activities.

BACKGROUND: The Northern Territory (NT) of Australia has a mix of climates, sparsely distributed population and a large proportion of the populace are Indigenous Australians, and influenza is known to have a disproportionate impact upon this group. Understanding the epidemiology of influenza in this region would inform public health strategies. OBJECTIVES: To assess if there are consistent patterns in characteristics of influenza outbreaks in the NT. METHODS: Laboratory confirmed influenza cases in the NT are notified to the NT Centre for Disease Control. We conducted analyses on notified cases from 2007-2016 to determine incidence rates (by age group, Indigenous status and area), seasonality of cases and spatial distribution of influenza types. Notified cases were linked to laboratory datasets to update information on influenza type or subtype RESULTS: The disparity in Indigenous and non-Indigenous notification rates varied by age group, with rate ratios for Indigenous versus non-Indigenous ranging from 1.58 (95% CI:1.39, 1.80) for ages 15-24 to 5.56 (95% CI: 4.71, 6.57) for ages 55-64. The disparity between Indigenous and non-Indigenous notification rates appeared higher in the Central Australia region. Indigenous versus non-Indigenous hospitalisation and mortality rate ratios were 6.51 (95% CI: 5.91, 7.18) and 5.46 (95% CI: 2.40, 12.71) respectively. Inter-seasonal peaks during February and March occurred in 2011, 2013 and 2014, and were due to influenza activity in the tropical north of the NT. CONCLUSIONS: Our results highlight the importance of influenza vaccination across all age groups for Indigenous Australians. An early vaccination campaign targeted against outbreaks in February-March would be best focused on the tropical north.

BACKGROUND: The test-negative design is an increasingly popular approach for estimating vaccine effectiveness (VE) due to its efficiency. This review aims to examine published test-negative design studies of VE and to explore similarities and differences in methodological choices for different diseases and vaccines. METHODS: We conducted a systematic search on PubMed, Web of Science, and Medline, for studies reporting the effectiveness of any vaccines using a test-negative design. We screened titles and abstracts and reviewed full texts to identify relevant articles. We created a standardized form for each included article to extract information on the pathogen of interest, vaccine(s) being evaluated, study setting, clinical case definition, choices of cases and controls, and statistical approaches used to estimate VE. RESULTS: We identified a total of 348 articles, including studies on VE against influenza virus (n = 253), rotavirus (n = 48), pneumococcus (n = 24), and nine other pathogens. Clinical case definitions used to enroll patients were similar by pathogens of interest but the sets of symptoms that defined them varied substantially. Controls could be those testing negative for the pathogen of interest, those testing positive for nonvaccine type of the pathogen of interest, or a subset of those testing positive for alternative pathogens. Most studies controlled for age, calendar time, and comorbidities. CONCLUSIONS: Our review highlights similarities and differences in the application of the test-negative design that deserve further examination. If vaccination reduces disease severity in breakthrough infections, particular care must be taken in interpreting vaccine effectiveness estimates from test-negative design studies.

The coronavirus disease pandemic was declared in March 2020, as the southern hemisphere's winter approached. Australia expected co-circulation of severe acute respiratory syndrome coronavirus 2, influenza and other seasonal respiratory viruses. However, influenza notifications were 7,029 (March-September) compared with an average 149,832 for the same period in 2015-2019 [corrected], despite substantial testing. Restrictions on movement within and into Australia may have temporarily eliminated influenza. Other respiratory pathogens also showed remarkably changed activity in 2020.

Several studies have reported evidence of interference between respiratory viruses: respiratory viruses rarely reach their epidemic peak concurrently and there appears to be a negative association between infection with one respiratory virus and co-infection with another. We used results spanning 16 years (2002–2017) of a routine diagnostic multiplex panel that tests for nine respiratory viruses to further investigate these interactions in Victoria, Australia. Time series analyses were used to plot the proportion positive for each virus. The seasonality of all viruses included was compared with respiratory syncytial virus (RSV) and influenza A virus using cross-correlations. Logistic regression was used to explore the likelihood of co-infection with one virus given infection with another. Seasonal peaks were observed each year for influenza A and RSV and less frequently for influenza B, coronavirus and parainfluenza virus. RSV circulated an average of 6 weeks before influenza A. Co-infection with another respiratory virus was less common with picornavirus, RSV or influenza A infection. Our findings provide further evidence of a temporal relationship in the circulation of respiratory viruses. A greater understanding of the interaction between respiratory viruses may enable better prediction of the timing and magnitude of respiratory virus epidemics.

Vaccination is the most practical means available for preventing influenza. Influenza vaccines require frequent updates to keep pace with antigenic drift of the virus, and the effectiveness, and sometimes the safety, of the vaccine can therefore vary from season to season. Three key populations that the World Health Organization recommends should be prioritized for influenza vaccination are pregnant women, children younger than 5 years of age and the elderly. This review discusses the burden of influenza and the safety and effectiveness profile of influenza vaccines recommended for these groups.

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.

The epidemiology of H5N1 and H7N9 avian viruses of humans infected in China differs despite both viruses being avian reassortants that have inherited six internal genes from a common ancestor, H9N2. The median age of infected populations is substantially younger for H5N1 virus (26 years) compared with H7N9 virus (63 years). Population susceptibility to infection with seasonal influenza is understood to be influenced by cross-reactive CD8+ T cells directed towards immunogenic peptides derived from internal viral proteins which may provide some level of protection against further influenza infection. Prior exposure to seasonal influenza peptides may influence the age-related infection patterns observed for H5N1 and H7N9 viruses. A comparison of relatedness of immunogenic peptides between historical human strains and the two avian emerged viruses was undertaken for a possible explanation in the differences in age incidence observed. There appeared to be some relationship between past exposure to related peptides and the lower number of H5N1 virus cases in older populations, however the relationship between prior exposure and older populations among H7N9 virus patients was less clear.

The continuous improvement in laboratory capacity for influenza surveillance has helped drive the development of diagnostic and virology laboratories in the Global Influenza Surveillance and Response System (GISRS) in the Western Pacific Region, at the same time strengthening their ability to detect and respond to infectious threats beyond influenza.

Surveillance for influenza-like illness (ILI) and laboratory-confirmed influenza in Victoria, Australia is undertaken jointly by the Victorian Infectious Diseases Reference Laboratory and the Victorian Government Department of Health and Human Services from May to October each year. Surveillance data comprise notifiable laboratory-confirmed influenza and ILI reporting from from two sources - a general practice sentinel surveillance programme and a locum service. The magnitude of the 2017 influenza season was high in Victoria with widespread circulation of influenza type A(H3N2), which peaked in September. A record number of laboratory-confirmed influenza cases were notified, and the proportion of ILI cases to total consultations from both the general practice and locum service were higher than previous years. Notified cases of influenza A were older than influenza B cases with 25% compared to 17% aged more than 65 years, respectively. The proportion of swabs that were positive for influenza peaked at 58%. Antigenic characterization suggested a good match between the circulating and vaccine strains of influenza A(H3N2). Most of the increases observed in notified cases of laboratory-confirmed influenza in recent years in Victoria have been attributed to increases in testing. However, that cases of ILI also increased in Victoria in 2017 is suggestive that 2017 was a relatively severe season. The dominance of influenza type A(H3N2), the extended duration of elevated activity, and a potential phylogenetic mismatch of vaccine to circulating strains are likely to have contributed to the relative severity of the 2017 season. Victoria is Australia's second most populous state and is the mainland's southernmost state. It has a temperate climate with an influenza season usually occurring in the cooler months between May and October. The Victorian Infectious Diseases Reference Laboratory (VIDRL), in partnership with the Victorian Government Department of Health and Human Servic

The use of seasonal influenza vaccine remains an important factor of influenza prevention as well as for pandemic preparedness. This was demonstrated in Fiji in 2016, where a strong global influenza network was able to detect and respond to an unusual seasonal influenza event. However, despite the known importance of seasonal influenza vaccination, in the World Health Organization Western Pacific Region, the number of doses distributed per 1000 population has decreased over the past years. There are several efforts ongoing to address this gap in use of seasonal influenza vaccine and continued collaboration is needed to ensure we are best prepared for the next pandemic.

INTRODUCTION: The burden of influenza in Cambodia is not well known, but it would be useful for understanding the impact of seasonal epidemics and pandemics and to design appropriate policies for influenza prevention and control. The severe acute respiratory infection (SARI) surveillance system in Cambodia was used to estimate the national burden of SARI hospitalizations in Cambodia. METHODS: We estimated age-specific influenza-associated SARI hospitalization rates in three sentinel sites in Svay Rieng, Siem Reap and Kampong Cham provinces. We used influenza-associated SARI surveillance data for one year to estimate the numerator and hospital admission surveys to estimate the population denominator for each site. A national influenza-associated SARI hospitalization rate was calculated using the pooled influenza-associated SARI hospitalizations for all sites as a numerator and the pooled catchment population of all sites as denominator. National influenza-associated SARI case counts were estimated by applying hospitalization rates to the national population. RESULTS: The national annual rates of influenza-associated hospitalizations per 100 000 population was highest for the two youngest age groups at 323 for < 1 year and 196 for 1-4 years. We estimated 7547 influenza-associated hospitalizations for Cambodia with almost half of these represented by children younger than 5 years. DISCUSSION: We present national estimates of influenza-associated SARI hospitalization rates for Cambodia based on sentinel surveillance data from three sites. The results of this study indicate that the highest burden of severe influenza infection is borne by the younger age groups. These findings can be used to guide future strategies to reduce influenza morbidity.

Viral respiratory tract infection (vRTI) is a significant cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to assess the epidemiologic characteristics, risk factors, and outcomes of vRTI occurring in the period from conditioning to 100 days after allo-HSCT in the era of molecular testing. This study was a retrospective record review of patients who underwent allo-HSCT at Royal Melbourne Hospital between January 2010 and December 2015. Symptomatic patients were tested using respiratory multiplex polymerase chain reaction (PCR). Logistic regression and Kaplan-Meier analysis were used to identify risk factors for vRTI and the risk of death or intensive care unit (ICU) admission, respectively. A total of 382 patients were reviewed, and 65 episodes of vRTI were identified in 56 patients (14.7%). Rhinovirus accounted for the majority of infections (69.2%). The majority of episodes presented initially with upper respiratory tract infection (58.5%), with 28.9% of them progressing to lower respiratory tract infection. Eleven episodes (16.9%) were associated with ICU admission. There were no deaths directly due to vRTI. Previous autologous HSCT was associated with an increased risk of vRTI (odds ratio, 2.1; 95% confidence interval, 1.0 to 4.1). The risks of death (P = .47) or ICU admission (P = .65) were not significantly different by vRTI status. vRTI is common in the first 100 days after allo-HSCT and is associated with ICU admission.

In 2017, influenza seasonal activity was high in the southern hemisphere. We present interim influenza vaccine effectiveness (VE) estimates from Australia. Adjusted VE was low overall at 33% (95% confidence interval (CI): 17 to 46), 50% (95% CI: 8 to 74) for A(H1)pdm09, 10% (95% CI: -16 to 31) for A(H3) and 57% (95% CI: 41 to 69) for influenza B. For A(H3), VE was poorer for those vaccinated in the current and prior seasons.

This study investigates the improvement of the prevention of mother-to-child transmission (PMTCT) of Human Immunodeficiency Virus (HIV) in China during 2004-2011. A clinic-based prospective study was conducted among HIV-positive pregnant women and their children in eight counties across China. Associated factors of mother-to-child transmission were analyzed using regression analysis. A total of 1,387 HIV+ pregnant women and 1,377 HIV-exposed infants were enrolled. The proportion of pregnant women who received HIV testing increased significantly from 45.1% to 98.9% during 2004-2011. Among whom, the proportion that received antiretroviral (ARV) prophylaxis increased from 61% to 96%, and the corresponding coverage in children increased from 85% to 97% during the same period. In contrast, single-dose nevirapine treatment during delivery declined substantially from 97.9% to 12.7%. Vertical transmission of HIV declined from 11.1% (95% confidence interval [CI]: 5.7-23.3%) in 2004 to 1.2% (95% CI: 0.1-5.8%) in 2011. Women who had a vaginal delivery (compared to emergency caesarian section (odds ratio [OR] = 0.46; 0.23-0.96)) and mothers on multi-ARVs (OR = 0.11; 0.04-0.29) were less likely to transmit HIV to their newborns. Increasing HIV screening enabled timely HIV care and prophylaxis to reduce vertical transmission of HIV. Early and consistent treatment with multi-ARVs during pregnancy is vital for PMTCT.

The factors that determine the characteristic seasonality of influenza remain enigmatic. Current models predict that occurrences of influenza outside the normal surveillance season within a temperate region largely reflect the importation of viruses from the alternate hemisphere or from equatorial regions in Asia. To help reveal the drivers of seasonality we investigated the origins and evolution of influenza viruses sampled during inter-seasonal periods in Australia. To this end we conducted an expansive phylogenetic analysis of 9912, 3804, and 3941 hemagglutinnin (HA) sequences from influenza A/H1N1pdm, A/H3N2, and B, respectively, collected globally during the period 2009-2014. Of the 1475 viruses sampled from Australia, 396 (26.8% of Australian, or 2.2% of global set) were sampled outside the monitored temperate influenza surveillance season (1 May - 31 October). Notably, rather than simply reflecting short-lived importations of virus from global localities with higher influenza prevalence, we documented a variety of more complex inter-seasonal transmission patterns including "stragglers" from the preceding season and "heralds" of the forthcoming season, and which included viruses sampled from clearly temperate regions within Australia. We also provide evidence for the persistence of influenza B virus between epidemic seasons, in which transmission of a viral lineage begins in one season and continues throughout the inter-seasonal period into the following season. Strikingly, a disproportionately high number of inter-seasonal influenza transmission events occurred in tropical and subtropical regions of Australia, providing further evidence that climate plays an important role in shaping patterns of influenza seasonality.

OBJECTIVES: The emergence of the pandemic influenza A(H1N1)pdm09 virus in 2009 saw a significant increase in the therapeutic and prophylactic use of neuraminidase inhibitors (NAIs) to mitigate the impact of this highly transmissible virus. Prior to the pandemic, many countries stockpiled NAIs and developed pandemic plans for the use of antiviral drugs, based on either treatment of high-risk individuals and/or prophylaxis of contacts. However, to date there has been a lack of in vivo models to test the efficacy of treatment or prophylaxis with NAIs, for influenza-infected individuals or exposed contacts, in a household setting. METHODS: A ferret model of household contact was developed to study the efficacy of different prophylaxis regimens in preventing infection in contact ferrets exposed to influenza A(H1N1)pdm09-infected index ferrets. RESULTS: Among the different prophylactic regimens, contact ferrets receiving oseltamivir prophylaxis twice daily showed better outcomes than those receiving oseltamivir once daily. Benefits included a significant delay in the time to secondary infection, lower weight loss and higher activity levels. The treatment of index ferrets at 36 h post-infection did not influence either secondary infection rates or clinical symptoms in exposed contact ferrets. Neither prophylaxis nor treatment prevented infection or reduced the duration of viral shedding, although clinical symptoms did improve in infected animals receiving prophylaxis. CONCLUSIONS: Different oseltamivir prophylaxis regimens did not prevent infections, but consistently resulted in a reduction in symptoms in infected ferrets. However, oseltamivir prophylaxis failed to reduce viral titres, which warrants further investigation in humans.

Influenza viruses collected from regions of Asia, Africa and Oceania between 2009 and 2012 were tested for their susceptibility to two new neuraminidase inhibitors, peramivir and laninamivir. All viruses tested had normal laninamivir inhibition. However, 3·2% (19/599) of A(H1N1)pdm09 viruses had highly reduced peramivir inhibition (due to H275Y NA mutation) and <1% (6/1238) of influenza B viruses had reduced or highly reduced peramivir inhibition, with single occurrence of variants containing I221T, A245T, K360E, A395E, D432G and a combined G145R+Y142H mutation. These data demonstrate that despite an increase in H275Y variants in 2011, there was no marked change in the frequency of peramivir- or laninamivir-resistant variants following the market release of the drugs in Japan in 2010.

BACKGROUND: Influenza vaccines are licensed annually based on immunogenicity studies. We used five sequential years of data to estimate influenza vaccine effectiveness (VE), the critical outcome in the field. METHODS: Between 2007 and 2011, we performed annual prospective test-negative design case-control studies among adults aged 20-64 years recruited from sentinel general practices in the Australian state of Victoria. We used PCR-confirmed influenza as the endpoint to estimate influenza VE for all years. We compared annual VE estimates with the match between circulating and vaccine strains, determined by haemagglutination inhibition assays. RESULTS: The adjusted VE estimate for all years (excluding 2009) was 62% (95% CI 43, 75). By type and subtype, the point estimates of VE by year ranged between 31% for seasonal influenza A(H1N1) and 88% for influenza A(H1N1)pdm09. In 2007, when circulating strains were assessed as incompletely matched, the point estimate of the adjusted VE against all influenza was 58%. The point estimate was 59% in 2011 when all strains were assessed as well matched. CONCLUSION: Trivalent inactivated vaccines provided moderate protection against laboratory-confirmed influenza in adults of working age, although VE estimates were sensitive to the model used. VE estimates correlated poorly with circulating strain match, as assessed by haemagglutination inhibition assays, suggesting a need for VE studies that incorporate antigenic characterization data.

BACKGROUND: Since 2007, sex has been the major mode of HIV transmission in China, accounting for 75% of new infections in 2009. Reducing sexual transmission is a major challenge for China in controling the HIV epidemic. METHODS: This article discusses the pilot programmes that have guided the expansion of sex education and behavioural interventions to reduce the sexual transmission of HIV in China. RESULTS: Commercial sex became prevalent across China in the early 1980s, prompting some health officials to become concerned that this would fuel an HIV epidemic. Initial pilot intervention projects to increase condom use among sex workers were launched in 1996 on a small scale and, having demonstrated their effectiveness, were expanded nationwide during the 2000s. Since then, supportive policies to expand sex education to other groups and throughout the country have been introduced and the range of targets for education programmes and behavioural interventions has broadened considerably to also include school children, college students, married couples, migrant workers and men who have sex with men. CONCLUSIONS: Prevention programmes for reducing sexual transmission of HIV have reasonable coverage, but can still improve. The quality of intervention needs to be improved in order to have a meaningful impact on changing behaviour to reducing HIV sexual transmission. Systematic evaluation of the policies, guidelines and intervention programmes needs to be conducted to understand their impact and to maintain adherence.

China's methadone maintenance treatment program was initiated in 2004 as a small pilot project in just eight sites. It has since expanded into a nationwide program encompassing more than 680 clinics covering 27 provinces and serving some 242 000 heroin users by the end of 2009. The agencies that were tasked with the program's expansion have been confronted with many challenges, including high drop-out rates, poor cooperation between local governing authorities and poor service quality at the counter. In spite of these difficulties, ongoing evaluation has suggested reductions in heroin use, risky injection practices and, importantly, criminal behaviours among clients, which has thus provided the impetus for further expansion. Clinic services have been extended to offer clients a range of ancillary services, including HIV, syphilis and hepatitis C testing, information, education and communication, psychosocial support services and referrals for treatment of HIV, tuberculosis and sexually transmitted diseases. Cooperation between health and public security officials has improved through regular meetings and dialogue. However, institutional capacity building is still needed to deliver sustainable and standardized services that will ultimately improve retention rates. This article documents the steps China made in overcoming the many barriers to success of its methadone program. These lessons might be useful for other countries in the region that are scaling-up their methadone programs.

Four factors have driven China's response to the HIV/AIDS pandemic: (1) existing government structures and networks of relationships; (2) increasing scientific information; (3) external influences that underscored the potential consequences of an HIV/AIDS pandemic and thus accelerated strategic planning; and (4) increasing political commitment at the highest levels. China's response culminated in legislation to control HIV/AIDS-the AIDS Prevention and Control Regulations. Three major initiatives are being scaled up concurrently. First, the government has prioritised interventions to control the epidemic in injection drug users, sex workers, men who have sex with men, and plasma donors. Second, routine HIV testing is being implemented in populations at high risk of infection. Third, the government is providing treatment for infected individuals. These bold programmes have emerged from a process of gradual and prolonged dialogue and collaboration between officials at every level of government, researchers, service providers, policymakers, and politicians, and have led to decisive action.

The first cases of severe acute respiratory syndrome (SARS) were identified in November 2002, in Guangdong Province, China. The epidemic spread rapidly within China and internationally, with 8454 recorded infections and 792 deaths by June 15, 2003. Temperature, relative humidity, and wind velocity were the three key meteorological determinants affecting the transmission of SARS. The peak spread of SARS occurred at a mean temperature of 16.9 degrees C (95% CI, 10.7 degrees C to 23.1 degrees C), with a mean relative humidity of 52.2% (95% CI, 33.0% to 71.4%) and wind speed of 2.8 ms(-1) (95% CI, 2.0 to 3.6 ms(-1)). In northern China, these conditions are most likely to occur in the spring and suggest that SARS has a seasonal nature akin to viruses such as influenza and the common cold. A regression equation (Y=218.692-0.698X(t)-2.043X(h)+2.282X(w)) was derived to represent the optimal climatic conditions for the 2003 SARS epidemic. Further investigations in other regions are necessary to verify these results.