A surge in human metapneumovirus paediatric respiratory admissions in Western Australia following the reduction of SARS-CoV-2 non-pharmaceutical interventions.

AIM: Western Australian laboratory data demonstrated a decrease in human metapneumovirus (hMPV) detections through 2020 associated with SARS-CoV-2-related non-pharmaceutical interventions (NPIs), followed by a subsequent surge in metropolitan region in mid-2021. We aimed to assess the impact of the surge in hMPV on paediatric hospital admissions and the contribution of changes in testing. METHODS: All respiratory-coded admissions of children aged <16 years at a tertiary paediatric centre between 2017 and 2021 were matched with respiratory virus testing data. Patients were grouped by age at presentation and by ICD-10 AM codes into bronchiolitis, other acute lower respiratory infection (OALRI), wheeze and upper respiratory tract infection (URTI). For analysis, 2017-2019 was utilised as a baseline period. RESULTS: hMPV-positive admissions in 2021 were more than 2.8 times baseline. The largest increase in incidence was observed in the 1-4 years group (incidence rate ratio (IRR) 3.8; 95% confidence interval (CI): 2.5-5.9) and in OALRI clinical phenotype (IRR 2.8; 95% CI: 1.8-4.2). The proportion of respiratory-coded admissions tested for hMPV in 2021 doubled (32-66.2%, P < 0.001), with the greatest increase in wheeze (12-75% in 2021, P < 0.001). hMPV test percentage positivity in 2021 was higher than in the baseline period (7.6% vs. 10.1% in 2021, P = 0.004). CONCLUSION: The absence and subsequent surge underline the susceptibility of hMPV to NPIs. Increased hMPV-positive admissions in 2021 can be partially attributable to testing, but test-positivity remained high, consistent with a genuine increase. Continued comprehensive testing will help ascertain true burden of hMPV respiratory diseases.

Impact of Coronavirus Disease 2019 Public Health Measures on Detections of Influenza and Respiratory Syncytial Virus in Children During the 2020 Australian Winter.

Public health measures targeting coronavirus disease 2019 have potential to impact transmission of other respiratory viruses. We found 98.0% and 99.4% reductions in respiratory syncytial virus and influenza detections, respectively, in Western Australian children through winter 2020 despite schools reopening. Border closures have likely been important in limiting external introductions.

Epidemiology and Clinical Outcomes of Hospitalizations for Acute Respiratory or Febrile Illness and Laboratory-Confirmed Influenza Among Pregnant Women During Six Influenza Seasons, 2010-2016.

BACKGROUND: Pregnant women are at increased risk of seasonal influenza hospitalizations, but data about the epidemiology of severe influenza among pregnant women remain largely limited to pandemics. METHODS: To describe the epidemiology of hospitalizations for acute respiratory infection or febrile illness (ARFI) and influenza-associated ARFI among pregnant women, administrative and electronic health record data were analyzed from retrospective cohorts of pregnant women hospitalized with ARFI who had testing for influenza viruses by reverse-transcription polymerase chain reaction (RT-PCR) in Australia, Canada, Israel, and the United States during 2010-2016. RESULTS: Of 18 048 ARFI-coded hospitalizations, 1064 (6%) included RT-PCR testing for influenza viruses, 614 (58%) of which were influenza positive. Of 614 influenza-positive ARFI hospitalizations, 35% were in women with low socioeconomic status, 20% with underlying conditions, and 67% in their third trimesters. The median length of influenza-positive hospitalizations was 2 days (interquartile range, 1-4), 18% (95% confidence interval [CI], 15%-21%) resulted in delivery, 10% (95% CI, 8%-12%) included a pneumonia diagnosis, 5% (95% CI, 3%-6%) required intensive care, 2% (95% CI, 1%-3%) included a sepsis diagnosis, and <1% (95% CI, 0%-1%) resulted in respiratory failure. CONCLUSIONS: Our findings characterize seasonal influenza hospitalizations among pregnant women and can inform assessments of the public health and economic impact of seasonal influenza on pregnant women.

Flight-Associated Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 Corroborated by Whole-Genome Sequencing.

To investigate potential transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during a domestic flight within Australia, we performed epidemiologic analyses with whole-genome sequencing. Eleven passengers with PCR-confirmed SARS-CoV-2 infection and symptom onset within 48 hours of the flight were considered infectious during travel; 9 had recently disembarked from a cruise ship with a retrospectively identified SARS-CoV-2 outbreak. The virus strain of those on the cruise and the flight was linked (A2-RP) and had not been previously identified in Australia. For 11 passengers, none of whom had traveled on the cruise ship, PCR-confirmed SARS-CoV-2 illness developed between 48 hours and 14 days after the flight. Eight cases were considered flight associated with the distinct SARS-CoV-2 A2-RP strain; the remaining 3 cases (1 with A2-RP) were possibly flight associated. All 11 passengers had been in the same cabin with symptomatic persons who had culture-positive A2-RP virus strain. This investigation provides evidence of flight-associated SARS-CoV-2 transmission.

Influenza Vaccine Effectiveness in Preventing Influenza-associated Hospitalizations During Pregnancy: A Multi-country Retrospective Test Negative Design Study, 2010-2016.

BACKGROUND: To date, no study has examined influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza-associated hospitalizations during pregnancy. METHODS: The Pregnancy Influenza Vaccine Effectiveness Network (PREVENT) consisted of public health or healthcare systems with integrated laboratory, medical, and vaccination records in Australia, Canada (Alberta and Ontario), Israel, and the United States (California, Oregon, and Washington). Sites identified pregnant women aged 18 through 50 years whose pregnancies overlapped with local influenza seasons from 2010 through 2016. Administrative data were used to identify hospitalizations with acute respiratory or febrile illness (ARFI) and clinician-ordered real-time reverse transcription polymerase chain reaction (rRT-PCR) testing for influenza viruses. Overall IVE was estimated using the test-negative design and adjusting for site, season, season timing, and high-risk medical conditions. RESULTS: Among 19450 hospitalizations with an ARFI discharge diagnosis (across 25 site-specific study seasons), only 1030 (6%) of the pregnant women were tested for influenza viruses by rRT-PCR. Approximately half of these women had pneumonia or influenza discharge diagnoses (54%). Influenza A or B virus infections were detected in 598/1030 (58%) of the ARFI hospitalizations with influenza testing. Across sites and seasons, 13% of rRT-PCR-confirmed influenza-positive pregnant women were vaccinated compared with 22% of influenza-negative pregnant women; the adjusted overall IVE was 40% (95% confidence interval = 12%-59%) against influenza-associated hospitalization during pregnancy. CONCLUSION: Between 2010 and 2016, influenza vaccines offered moderate protection against laboratory-confirmed influenza-associated hospitalizations during pregnancy, which may further inform the benefits of maternal influenza vaccination programs.

Divergent Human-Origin Influenza Viruses Detected in Australian Swine Populations.

Global swine populations infected with influenza A viruses pose a persistent pandemic risk. With the exception of a few countries, our understanding of the genetic diversity of swine influenza viruses is limited, hampering control measures and pandemic risk assessment. Here we report the genomic characteristics and evolutionary history of influenza A viruses isolated in Australia from 2012 to 2016 from two geographically isolated swine populations in the states of Queensland and Western Australia. Phylogenetic analysis with an expansive human and swine influenza virus data set comprising >40,000 sequences sampled globally revealed evidence of the pervasive introduction and long-term establishment of gene segments derived from several human influenza viruses of past seasons, including the H1N1/1977, H1N1/1995, H3N2/1968, and H3N2/2003, and the H1N1 2009 pandemic (H1N1pdm09) influenza A viruses, and a genotype that contained gene segments derived from the past three pandemics (1968, reemerged 1977, and 2009). Of the six human-derived gene lineages, only one, comprising two viruses isolated in Queensland during 2012, was closely related to swine viruses detected from other regions, indicating a previously undetected circulation of Australian swine lineages for approximately 3 to 44 years. Although the date of introduction of these lineages into Australian swine populations could not be accurately ascertained, we found evidence of sustained transmission of two lineages in swine from 2012 to 2016. The continued detection of human-origin influenza virus lineages in swine over several decades with little or unpredictable antigenic drift indicates that isolated swine populations can act as antigenic archives of human influenza viruses, raising the risk of reemergence in humans when sufficient susceptible populations arise.IMPORTANCE We describe the evolutionary origins and antigenic properties of influenza A viruses isolated from two separate Australian swine populations from 2012 to 2016, showing that these viruses are distinct from each other and from those isolated from swine globally. Whole-genome sequencing of virus isolates revealed a high genotypic diversity that had been generated exclusively through the introduction and establishment of human influenza viruses that circulated in past seasons. We detected six reassortants with gene segments derived from human H1N1/H1N1pdm09 and various human H3N2 viruses that circulated during various periods since 1968. We also found that these swine viruses were not related to swine viruses collected elsewhere, indicating independent circulation. The detection of unique lineages and genotypes in Australia suggests that isolated swine populations that are sufficiently large can sustain influenza virus for extensive periods; we show direct evidence of a sustained transmission for at least 4 years between 2012 and 2016.

Respiratory Syncytial Virus Hospitalization During Pregnancy in 4 High-income Countries, 2010-2016.

Few studies have addressed respiratory syncytial virus (RSV) infection during pregnancy. Among 846 pregnant women hospitalized with respiratory illness and tested for RSV, 21 (2%) were RSV positive, of whom 8 (38%) were diagnosed with pneumonia. Despite study limitations, these data can help inform decisions about RSV prevention strategies.

Using record linkage to validate notification and laboratory data for a more accurate assessment of notifiable infectious diseases.

BACKGROUND: Infectious disease burden is commonly assessed using notification data. Using retrospective record linkage in Western Australia, we described how well notification data captures laboratory detections of influenza, pertussis and invasive pneumococcal disease (IPD). METHODS: We linked data from the Western Australian Notifiable Infectious Diseases Database (WANIDD) and the PathWest Laboratory Database (PathWest) pertaining to the Triple I birth cohort, born in Western Australia in 1996-2012. These were combined to calculate the number of unique cases captured in each dataset alone or in both datasets. To assess the impact of under-ascertainment, we compared incidence rates calculated using WANIDD data alone and using combined data. RESULTS: Overall, there were 5550 influenza, 513 IPD (2001-2012) and 4434 pertussis cases (2000-2012). Approximately 2% of pertussis and IPD cases and 7% of influenza cases were solely recorded in PathWest. Notification of influenza and pertussis cases to WANIDD improved over time. Overall incidence rates of influenza in children aged <5 years using both datasets was 10% higher than using WANIDD data alone (IRR = 1.1, 95% CI = 1.1-1.2). CONCLUSIONS: This is the first time WANIDD data have been validated against routinely collected laboratory data. We anticipated all cases would be captured in WANIDD but found additional laboratory-confirmed cases that were not notified. Studies investigating pathogen-specific infectious disease would benefit from using multiple data sources.

An observational study of febrile seizures: the importance of viral infection and immunization.

BACKGROUND: Febrile seizures are common in young children. Annual peaks in incidence mirror increased respiratory virus activity during winter. Limited virological data are available using modern diagnostic techniques for children with febrile seizures. We aimed to determine the frequency of detection of specific viral pathogens in children with febrile seizures, to describe risk factors including recent vaccination and clinical features associated with specific etiologies. METHODS: An observational study was performed. Children aged 6 months to 5 years presenting to the Emergency Department of a tertiary children's hospital in Western Australia with febrile seizures were enrolled between March 2012 and October 2013. Demographic, clinical data and vaccination history were collected, and virological testing was performed on per-nasal and per-rectal samples. RESULTS: One hundred fifty one patients (72 female; median age 1.7y; range 6 m-4y9m) were enrolled. Virological testing was completed for 143/151 (95%). At least one virus was detected in 102/143 patients (71%). The most commonly identified were rhinoviruses (31/143, 22%), adenovirus (30/151, 21%), enteroviruses, (28/143, 20%), influenza (19/143, 13%) and HHV6 (17/143, 12%). More than one virus was found in 48/143 (34%). No significant clinical differences were observed when children with a pathogen identified were compared with those with no pathogen detected. Febrile seizures occurred within 14 days of vaccine administration in 16/151 (11%). CONCLUSION: At least one virus was detected in over two thirds of cases tested (commonly picornaviruses, adenovirus and influenza). Viral co-infections were frequently identified. Febrile seizures occurred infrequently following immunization.

Metatranscriptomic Sequencing of Medically Important Mosquitoes Reveals Extensive Diversity of RNA Viruses and Other Microbial Communities in Western Australia.

Mosquitoes harbor a wide diversity of microorganisms, including viruses that are human pathogens, or that are insect specific. We used metatranscriptomics, an unbiased high-throughput molecular approach, to describe the composition of viral and other microbial communities in six medically important mosquito species from across Western Australia: Aedes vigilax, Culex annulirostris, Cx. australicus, Cx. globocoxitus, Cx. pipiens biotype molestus, and Cx. quinquefasciatus. We identified 42 viral species, including 13 novel viruses, from 19 families. Culex mosquitoes exhibited a significantly higher diversity of viruses than Aedes mosquitoes, and no virus was shared between the two genera. Comparison of mosquito populations revealed a heterogenous distribution of viruses between geographical regions and between closely related species, suggesting that geography and host species may play a role in shaping virome composition. We also detected bacterial and parasitic microorganisms, among which Wolbachia bacteria were detected in three members of the Cx. pipiens complex, Cx. australicus, Cx. pipiens biotype molestus, and Cx. quinquefasciatus. In summary, our unbiased metatranscriptomics approach provides important insights into viral and other microbial diversity in Western Australian mosquitoes that vector medically important viruses.

The Changing Detection Rate of Respiratory Syncytial Virus in Adults in Western Australia between 2017 and 2023.

The incidence of respiratory syncytial virus (RSV) in adults is inadequately defined and the impact of SARS-CoV-2-related non-pharmaceutical interventions (NPIs) is underexplored. Using laboratory data, we described the detection rate of RSV in adults ≥16 years in Western Australia (WA) between 2017 and 2023. With the exception of 2020, RSV detections rose annually between 2017 and 2023, reaching 50.7 per 100,000 in 2023 (95% confidence interval [CI], 47.9-53.8). RSV testing expanded considerably across the study period, with the testing in 2023 more than five times the 2017 total. The detection rate was highest in adults ≥60 years between 2017 and 2019, particularly those ≥75 years. Following 2020, the detections in all age groups increased, with the highest detection rate in 2023 in those ≥75-years (199.5 per 100,000; 95% CI, 180.5-220). NPIs significantly impacted RSV seasonality; the preceding winter pattern was disrupted, resulting in an absent 2020 winter season and two major summer seasons in 2020/21 and 2021/22. The RSV season began to realign in 2022, reverting to a winter seasonal pattern in 2023 and the largest season in the study period. Ongoing surveillance will be required to understand the stability of these increases and to delineate the impact of new immunisation strategies.

Defining the phylogenetics and resistome of the major Clostridioides difficile ribotypes circulating in Australia.

Clostridioides difficile infection (CDI) remains a significant public health threat globally. New interventions to treat CDI rely on an understanding of the evolution and epidemiology of circulating strains. Here we provide longitudinal genomic data on strain diversity, transmission dynamics and antimicrobial resistance (AMR) of C. difficile ribotypes (RTs) 014/020 (n=169), 002 (n=77) and 056 (n=36), the three most prominent C. difficile strains causing CDI in Australia. Genome scrutiny showed that AMR was uncommon in these lineages, with resistance-conferring alleles present in only 15/169 RT014/020 strains (8.9 %), 1/36 RT056 strains (2.78 %) and none of 77 RT002 strains. Notably, ~90 % of strains were resistant to MLSB agents in vitro, but only ~5.9 % harboured known resistance alleles, highlighting an incongruence between AMR genotype and phenotype. Core genome analyses revealed all three RTs contained genetically heterogeneous strain populations with limited evidence of clonal transmission between CDI cases. The average number of pairwise core genome SNP (cgSNP) differences within each RT group ranged from 23.3 (RT056, ST34, n=36) to 115.6 (RT002, ST8, n=77) and 315.9 (RT014/020, STs 2, 13, 14, 49, n=169). Just 19 clonal groups (encompassing 40 isolates), defined as isolates differing by ≤2 cgSNPs, were identified across all three RTs (RT014/020, n=14; RT002, n=3; RT056, n=2). Of these clonal groups, 63 % (12/19) comprised isolates from the same Australian State and 37 % (7/19) comprised isolates from different States. The low number of plausible transmission events found for these major RTs (and previously documented populations in animal and environmental sources/reservoirs) points to widespread and persistent community sources of diverse C. difficile strains as opposed to ongoing nationwide healthcare outbreaks dominated by a single clone. Together, these data provide new insights into the evolution of major lineages causing CDI in Australia and highlight the urgent need for enhanced surveillance, and for public health interventions to move beyond the healthcare setting and into a One Health paradigm to effectively combat this complex pathogen.

Factors Predicting Secondary Respiratory Morbidity Following Early-Life Respiratory Syncytial Virus Infections: Population-Based Cohort Study.

Background: The association between early-life respiratory syncytial virus (RSV) infections and later respiratory morbidity is well established. However, there is limited evidence on factors that influence this risk. We examined sociodemographic and perinatal factors associated with later childhood respiratory morbidity requiring secondary care following exposure to a laboratory-confirmed RSV episode in the first 2 years. Methods: We used a probabilistically linked whole-of-population-based birth cohort including 252 287 children born in Western Australia between 2000 and 2009 with follow-up to the end of 2012. Cox proportional hazards models estimated adjusted hazard ratios (aHRs) of the association of various risk factors with the first respiratory episode for asthma, wheezing, and unspecified acute lower respiratory infection beyond the age of 2 years. Results: The analytic cohort included 4151 children with a confirmed RSV test before age 2 years. The incidence of subsequent respiratory morbidity following early-life RSV infection decreased with child age at outcome (highest incidence in 2-<4-year-olds: 41.8 per 1000 child-years; 95% CI, 37.5-46.6), increased with age at RSV infection (6-<12-month-olds: 23.6/1000 child-years; 95% CI, 19.9-27.8; 12-<24-month-olds: 22.4/1000 child-years; 95% CI, 18.2-22.7) and decreasing gestational age (50.8/1000 child-years; 95% CI, 33.5-77.2 for children born extremely preterm, <28 weeks gestation). Risk factors included age at first RSV episode (6-<12 months: aHR, 1.42; 95% CI, 1.06-1.90), extreme prematurity (<28 weeks: aHR, 2.22; 95% CI, 1.40-3.53), maternal history of asthma (aHR, 1.33; 95% CI, 1.04-1.70), and low socioeconomic index (aHR, 1.76; 95% CI, 1.03-3.00). Conclusions: Our results suggest that in addition to preterm and young infants, children aged 12-<24 months could also be potential target groups for RSV prevention to reduce the burden of later respiratory morbidities associated with RSV.

The seasonality of respiratory syncytial virus in Western Australia prior to implementation of SARS-CoV-2 non-pharmaceutical interventions.

Background: Respiratory syncytial virus (RSV) seasonality is dependent on the local climate. We assessed the stability of RSV seasonality prior to the SARS-CoV-2 pandemic in Western Australia (WA), a state spanning temperate and tropical regions. Method: RSV laboratory testing data were collected from January 2012 to December 2019. WA was divided into three regions determined by population density and climate: Metropolitan, Northern and Southern. Season threshold was calculated per region at 1.2% annual cases, with onset the first of ≥2 weeks above this threshold and offset as the last week before ≥2 weeks below. Results: The detection rate of RSV in WA was 6.3/10,000. The Northern region had the highest detection rate (15/10,000), more than 2.5 times the Metropolitan region (detection rate ratio 2.7; 95% CI, 2.6-2.9). Test percentage positive was similar in the Metropolitan (8.6%) and Southern (8.7%) regions, with the lowest in the Northern region (8.1%). RSV seasons in the Metropolitan and Southern regions occurred annually, with a single peak and had consistent timing and intensity. The Northern tropical region did not experience a distinct season. Proportion of RSV A to RSV B in the Northern region differed from the Metropolitan region in 5 of the 8 years studied. Conclusions: Detection rate of RSV in WA is high, especially in the Northern region, where climate, an expanded at-risk population and increased testing may have contributed to greater numbers. Before the SARS-CoV-2 pandemic, RSV seasonality in WA was consistent in timing and intensity for the Metropolitan and Southern regions.

Determining the true incidence of seasonal respiratory syncytial virus-confirmed hospitalizations in preterm and term infants in Western Australia.

Respiratory syncytial virus contributes to significant global infant morbidity and mortality. We applied a previously developed statistical prediction model incorporating pre-pandemic RSV testing data and hospital admission data to estimate infant RSV-hospitalizations by birth month and prematurity, focused on infants aged <1 year. The overall predicted RSV-hospitalization incidence rates in infants <6 months were 32.7/1,000 child-years (95 % CI: 31.8, 33.5) and 3.1/1,000 child-years (95 % CI: 3.0, 3.1) in infants aged 6-<12 months. Predicted RSV-hospitalization rates for infants aged <6 months were highest for infants born in April/May. Predicted rates for preterm infants born 29-32 weeks gestation were highest in March-May, whereas infants born >33 weeks had peak RSV-hospitalization rates from May-June, similar to late preterm or term births. RSV-hospitalization rates in the pre-pandemic era were highly seasonal, and seasonality varied with degree of prematurity. Accurate estimates of RSV-hospitalization in high-risk sub-groups are essential to understand preventable burden of RSV especially given the current prevention landscape.

Respiratory Syncytial Virus Reinfections in Children in Western Australia.

Respiratory syncytial virus (RSV) reinfection in children is poorly understood. We examined the incidence, characteristics, and outcomes of hospital-attended RSV reinfections in children <16 years in Western Australia between 2012 and 2022. Individuals with repeat RSV detections ≥56 days apart were identified using laboratory data. The incidence of reinfection in the first five years of life was estimated using the total birth population from 2012 to 2017. Clinical data on a subset of reinfection episodes were obtained from two metropolitan pediatric centers. A total of 466 children with hospital-attended reinfections were identified. The median interval between RSV detections was 460 days (interquartile range: 324, 812), with a reinfection rate of 95 per 100,000 individuals (95% confidence interval: 82, 109). Reinfection was most common in children who experienced their first RSV detection <6 months of age. Predisposing factors were identified in 56% of children; children with predisposing factors were older at first and second detections, were more likely to be admitted, and had a longer length of stay. This study highlights the significant burden of hospital-attended RSV reinfections in children with and without predisposing factors. Expanded surveillance with in-depth clinical data is required to further characterize the impact of RSV reinfection.

Circulation of influenza and other respiratory viruses during the COVID-19 pandemic in Australia and New Zealand, 2020-2021.

Objective: Circulation patterns of influenza and other respiratory viruses have been globally disrupted since the emergence of coronavirus disease (COVID-19) and the introduction of public health and social measures (PHSMs) aimed at reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Methods: We reviewed respiratory virus laboratory data, Google mobility data and PHSMs in five geographically diverse regions in Australia and New Zealand. We also described respiratory virus activity from January 2017 to August 2021. Results: We observed a change in the prevalence of circulating respiratory viruses following the emergence of SARS-CoV-2 in early 2020. Influenza activity levels were very low in all regions, lower than those recorded in 2017-2019, with less than 1% of laboratory samples testing positive for influenza virus. In contrast, rates of human rhinovirus infection were increased. Respiratory syncytial virus (RSV) activity was delayed; however, once it returned, most regions experienced activity levels well above those seen in 2017-2019. The timing of the resurgence in the circulation of both rhinovirus and RSV differed within and between the two countries. Discussion: The findings of this study suggest that as domestic and international borders are opened up and other COVID-19 PHSMs are lifted, clinicians and public health professionals should be prepared for resurgences in influenza and other respiratory viruses. Recent patterns in RSV activity suggest that these resurgences in non-COVID-19 viruses have the potential to occur out of season and with increased impact.