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The serial interval distribution is used to approximate the generation time distribution, an essential parameter to infer the transmissibility (${R}_t$) of an epidemic. However, serial interval distributions may change as an epidemic progresses. We examined detailed contact tracing data on laboratory-confirmed cases of COVID-19 in Hong Kong during the five waves from January 2020 to July 2022. We reconstructed the transmission pairs and estimated time-varying effective serial interval distributions and factors associated with longer or shorter intervals. Finally, we assessed the biases in estimating transmissibility using constant serial interval distributions. We found clear temporal changes in mean serial interval estimates within each epidemic wave studied and across waves, with mean serial intervals ranged from 5.5 days (95% CrI: 4.4, 6.6) to 2.7 (95% CrI: 2.2, 3.2) days. The mean serial intervals shortened or lengthened over time, which were found to be closely associated with the temporal variation in COVID-19 case profiles and public health and social measures and could lead to the biases in predicting ${R}_t$. Accounting for the impact of these factors, the time-varying quantification of serial interval distributions could lead to improved estimation of ${R}_t$, and provide additional insights into the impact of public health measures on transmission.
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We described the frequency of residential case clusters and the efficiency of compulsory testing in identifying cases using buildings targeted in compulsory testing and locally infected coronavirus disease 2019 (COVID-19) cases matched by residence in Hong Kong. Most of the buildings (4246 of 7688, 55.2%) with COVID-19 cases identified had only 1 reported case, and 13% of the daily reported cases were detected through compulsory testing. Compulsory testing notices could be essential in attempting to eliminate infections ("zero COVID") and have an impact early in an epidemic, but they appear to be relatively inefficient in response to sustained community transmission.
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COVID-19 , Epidemias , Humanos , COVID-19/epidemiologia , Hong Kong/epidemiologia , SARS-CoV-2RESUMO
BACKGROUND: The time-varying reproduction number, Rt, is commonly used to monitor the transmissibility of an infectious disease during an epidemic, but standard methods for estimating Rt seldom account for the impact of overdispersion on transmission. METHODS: We developed a negative binomial framework to estimate Rt and a time-varying dispersion parameter (kt). We applied the framework to COVID-19 incidence data in Hong Kong in 2020 and 2021. We conducted a simulation study to compare the performance of our model with the conventional Poisson-based approach. RESULTS: Our framework estimated an Rt peaking around 4 (95% credible interval = 3.13, 4.30), similar to that from the Poisson approach but with a better model fit. Our approach further estimated kt <0.5 at the start of both waves, indicating appreciable heterogeneity in transmission. We also found that kt decreased sharply to around 0.4 when a large cluster of infections occurred. CONCLUSIONS: Our proposed approach can contribute to the estimation of Rt and monitoring of the time-varying dispersion parameters to quantify the role of superspreading.
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COVID-19 , Epidemias , Humanos , COVID-19/epidemiologia , Simulação por Computador , Hong Kong/epidemiologia , ReproduçãoRESUMO
BACKGROUND: Testing of an entire community has been used as an approach to control coronavirus disease 2019 (COVID-19). In Hong Kong, a universal community testing program (UCTP) was implemented at the fadeout phase of a community epidemic in July to September 2020. We described the utility of the UCTP in finding unrecognized infections and analyzed data from the UCTP and other sources to characterize transmission dynamics. METHODS: We described the characteristics of people participating in the UCTP and compared the clinical and epidemiological characteristics of COVID-19 cases detected by the UCTP versus those detected by clinical diagnosis and public health surveillance (CDPHS). We developed a Bayesian model to estimate the age-specific incidence of infection and the proportion of cases detected by CDPHS. RESULTS: In total, 1.77 million people, 24% of the Hong Kong population, participated in the UCTP from 1 to 14 September 2020. The UCTP identified 32 new infections (1.8 per 100000 samples tested), consisting of 29% of all local cases reported during the two-week UCTP period. Compared with the CDPHS, the UCTP detected a higher proportion of sporadic cases (62% vs 27%, P<.01) and identified 6 (out of 18) additional clusters during that period. We estimated that 27% (95% credible interval: 22%, 34%) of all infections were detected by the CDPHS in the third wave. CONCLUSIONS: We reported empirical evidence of the utility of population-wide COVID-19 testing in detecting unrecognized infections and clusters. Around three quarters of infections have not been identified through existing surveillance approaches including contact tracing.
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COVID-19 , Ácidos Nucleicos , Teorema de Bayes , COVID-19/diagnóstico , COVID-19/epidemiologia , Teste para COVID-19 , Estudos Transversais , Hong Kong/epidemiologia , Humanos , SARS-CoV-2RESUMO
BACKGROUND: Disparities were marked in previous pandemics, usually with higher attack rates reported for those in lower socioeconomic positions and for ethnic minorities. METHODS: We examined characteristics of laboratory-confirmed coronavirus disease 2019 (COVID-19) cases in Hong Kong, assessed associations between incidence and population-level characteristics at the level of small geographic areas, and evaluated relations between socioeconomics and work-from-home (WFH) arrangements. RESULTS: The largest source of COVID-19 importations switched from students studying overseas in the second wave to foreign domestic helpers in the third. The local cases were mostly individuals not in formal employment (retirees and homemakers) and production workers who were unable to WFH. For every 10% increase in the proportion of population employed as executives or professionals in a given geographic region, there was an 84% (95% confidence interval [CI], 1-97%) reduction in the incidence of COVID-19 during the third wave. In contrast, in the first 2 waves, the same was associated with 3.69 times (95% CI, 1.02-13.33) higher incidence. Executives and professionals were more likely to implement WFH and experienced frequent changes in WFH practice compared with production workers. CONCLUSIONS: Consistent findings on the reversed socioeconomic patterning of COVID-19 burden between infection waves in Hong Kong in both individual- and population-level analyses indicated that risks of infections may be related to occupations involving high exposure frequency and WFH flexibility. Contextual determinants should be taken into account in policy planning aiming at mitigating such disparities.
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COVID-19 , Minorias Étnicas e Raciais , Hong Kong/epidemiologia , Humanos , Pandemias , SARS-CoV-2RESUMO
AIM: To compare the clinical features of Middle East respiratory syndrome coronavirus (MERS-CoV) infection between paediatric and adult cases. METHODS: Using multiple public data sources, we created an enhanced open-source surveillance dataset of all MERS-CoV cases between 20 September 2012 and 31 December 2018 in Saudi Arabia including available risk factor data. RESULTS: Of the 1791 cases of MERS-CoV identified, 30 cases (1.7%) were aged under 18 years and 1725 cases (96.3%) were aged 18 years and over. Three paediatric cases were fatal, aged 0, 2 and 15 years. The odds of asymptomatic MERS-CoV infection among cases under 18 years (n = 10/23; 44%) was significantly higher (odds ratio (OR) = 4.98; 95% confidence interval (CI): 2.15-11.51; P = 0.001) compared to adults (n = 199/1487; 13%). The odds of hospitalisation were significantly lower (OR = 0.17; 95% CI: 0.08-0.39; P < 0.001) among cases under 18 years (n = 12/24; 50%) compared to adults (n = 1231/1443; 85%). Children were more likely to have a known source of exposure compared to adults (OR = 2.68; 95% CI: 1.29-5.56; P = 0.008). CONCLUSIONS: Clinically severe illness is less common in children, although death can occur, and the proportion of paediatric cases (1.7%) is similar to that reported for COVID-19. Age-specific differences in the clinical presentation of MERS-CoV cases could have implications for transmission for other betacoronaviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Children may be at risk within the household with an infected adult. More studies are required on the role of children in transmission of betacoronaviruses.
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Infecções por Coronavirus/epidemiologia , Coronavírus da Síndrome Respiratória do Oriente Médio , Adolescente , Adulto , Distribuição por Idade , Infecções Assintomáticas/epidemiologia , COVID-19 , Criança , Pré-Escolar , Doenças Transmissíveis Emergentes/epidemiologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/prevenção & controle , Feminino , Humanos , Lactente , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Arábia Saudita/epidemiologiaRESUMO
Variola virus is at risk of re-emergence either through accidental release, bioterrorism, or synthetic biology. The use of phylogenetics and phylogeography to support epidemic field response is expected to grow as sequencing technology becomes miniaturized, cheap, and ubiquitous. In this study, we aimed to explore the use of common VARV diagnostic targets hemagglutinin (HA), cytokine response modifier B (CrmB), and A-type inclusion protein (ATI) for phylogenetic characterization as well as the representativeness of modelling strategies in phylogeography to support epidemic response should smallpox re-emerge. We used Bayesian discrete-trait phylogeography using the most complete data set currently available of whole genome (n = 51) and partially sequenced (n = 20) VARV isolates. We show that multilocus models combining HA, ATI, and CrmB genes may represent a useful heuristic to differentiate between VARV Major and subclades of VARV Minor which have been associated with variable case-fatality rates. Where whole genome sequencing is unavailable, phylogeography models of HA, ATI, and CrmB may provide preliminary but uncertain estimates of transmission, while supplementing whole genome models with additional isolates sequenced only for HA can improve sample representativeness, maintaining similar support for transmission relative to whole genome models. We have also provided empirical evidence delineating historic international VARV transmission using phylogeography. Due to the persistent threat of re-emergence, our results provide important research for smallpox epidemic preparedness in the posteradication era as recommended by the World Health Organisation.
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Hemaglutininas Virais/genética , Filogenia , Serpinas/genética , Vírus da Varíola/genética , Proteínas Virais/genética , Teorema de Bayes , Filogeografia , Vírus da Varíola/patogenicidadeRESUMO
Background: Hong Kong enforced stringent travel restrictions during the COVID-19 pandemic. Understanding the characteristics of imported COVID-19 cases is important for establishing evidence-based control measures. Methods: Retrospective cohort study summarising the characteristics of imported cases detected in Hong Kong between 13 November 2020 and 31 January 2022, when compulsory quarantine was implemented. Findings: A total of 2269 imported COVID-19 cases aged 0-85 years were identified, of which 48.6 % detected on arrival. A shorter median delay from arrival to isolation was observed in Delta and Omicron cases (3 days) than in ancestral strain and other variants cases (12 days; p < 0.001). Lower Ct values at isolation were observed in Omicron cases than in ancestral strain or other variants cases. No Omicron cases were detected beyond 14 days after arrival. Cases detected after 14 days of quarantine (n=58, 2.6 %) were more likely asymptomatic at isolation and had higher Ct value during isolation, some of them indicating re-positivity or post-arrival infections. Conclusions: Testing inbound travellers at arrival and during quarantine can detect imported cases early, but may not prevent all COVID-19 introductions into the community. Public health measures should be adapted in response to the emergence of SARS-CoV-2 variants based on evidence from ongoing surveillance.
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Background: On-arrival quarantine has been one of the primary measures to prevent the introduction of SARS-CoV-2 into Hong Kong since the start of the pandemic. Most on-arrival quarantines have been done in hotels, with the duration of quarantine and testing frequency during quarantine modified over time along with other pandemic control measures. However, hotels are not designed with infection control in mind. We aimed to systematically study the potential risk of acquisition of SARS-CoV-2 infection among individuals undergoing hotel quarantine. Methods: We examined data on each laboratory-confirmed COVID-19 case identified in on-arrival quarantine in a hotel in Hong Kong between 1 May 2020 and 31 January 2022. We sequenced the whole genomes of viruses from cases that overlapped with other confirmed cases in terms of the hotel of stay, date of arrival and date of testing positive. By combining multiple sources of evidence, we identify probable and plausible transmission events and calculate the overall risk of transmission. Findings: Among 221 imported cases that overlapped with other cases detected during hotel quarantine with available sequence data, phylogenomic analyses identified five probable and two plausible clusters of within-hotel transmission. Only two of these clusters were recognised at the time. Including other clusters reported in Hong Kong, we estimate that 8-11 per 1000 cases identified in hotel quarantine may be infected by another unlinked case during quarantine, or 2-3 per 100,000 overseas arrivals. Interpretation: We have identified additional undetected occurrences of COVID-19 transmission within hotel quarantine in Hong Kong. Although hotels provide suboptimal infection control as improvised quarantine facilities, the risk of contracting infection whilst in quarantine is low. However, these unlikely events could have high consequences by allowing the virus to spread into immunologically naïve communities. Additional vigilance should be taken in the absence of improved controls to identify such events. If on-arrival quarantine is expected to be used for a long time, quarantine facilities could be purpose-built to minimise the risk of transmission. Funding: Health and Medical Research Fund, Hong Kong.
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Hong Kong experienced a surge of Omicron BA.2 infections in early 2022, resulting in one of the highest per-capita death rates of COVID-19. The outbreak occurred in a dense population with low immunity towards natural SARS-CoV-2 infection, high vaccine hesitancy in vulnerable populations, comprehensive disease surveillance and the capacity for stringent public health and social measures (PHSMs). By analyzing genome sequences and epidemiological data, we reconstructed the epidemic trajectory of BA.2 wave and found that the initial BA.2 community transmission emerged from cross-infection within hotel quarantine. The rapid implementation of PHSMs suppressed early epidemic growth but the effective reproduction number (Re) increased again during the Spring festival in early February and remained around 1 until early April. Independent estimates of point prevalence and incidence using phylodynamics also showed extensive superspreading at this time, which likely contributed to the rapid expansion of the epidemic. Discordant inferences based on genomic and epidemiological data underscore the need for research to improve near real-time epidemic growth estimates by combining multiple disparate data sources to better inform outbreak response policy.
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COVID-19 , Humanos , COVID-19/epidemiologia , Hong Kong/epidemiologia , SARS-CoV-2/genética , Surtos de Doenças , Número Básico de ReproduçãoRESUMO
China experienced a resurgence of seasonal influenza activity throughout 2021 despite intermittent control measures and prolonged international border closure. We show genomic evidence for multiple A(H3N2), A(H1N1), and B/Victoria transmission lineages circulating over 3 years, with the 2021 resurgence mainly driven by two B/Victoria clades. Phylodynamic analysis revealed unsampled ancestry prior to widespread outbreaks in December 2020, showing that influenza lineages can circulate cryptically under non-pharmaceutical interventions enacted against COVID-19. Novel haemagglutinin gene mutations and altered age profiles of infected individuals were observed, and Jiangxi province was identified as a major source for nationwide outbreaks. Following major holiday periods, fluctuations in the effective reproduction number were observed, underscoring the importance of influenza vaccination prior to holiday periods or travel. Extensive heterogeneity in seasonal influenza circulation patterns in China determined by historical strain circulation indicates that a better understanding of demographic patterns is needed for improving effective controls.
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Superspreading, or overdispersion in transmission, is a feature of SARS-CoV-2 transmission which results in surging epidemics and large clusters of infection. The dispersion parameter is a statistical parameter used to characterize and quantify heterogeneity. In the context of measuring transmissibility, it is analogous to measures of superspreading potential among populations by assuming that collective offspring distribution follows a negative-binomial distribution. We conducted a systematic review and meta-analysis on globally reported dispersion parameters of SARS-CoV-2 infection. All searches were carried out on 10 September 2021 in PubMed for articles published from 1 January 2020 to 10 September 2021. Multiple estimates of the dispersion parameter have been published for 17 studies, which could be related to where and when the data were obtained, in 8 countries (e.g. China, the United States, India, Indonesia, Israel, Japan, New Zealand and Singapore). High heterogeneity was reported among the included studies. The mean estimates of dispersion parameters range from 0.06 to 2.97 over eight countries, the pooled estimate was 0.55 (95% CI: 0.30, 0.79), with changing means over countries and decreasing slightly with the increasing reproduction number. The expected proportion of cases accounting for 80% of all transmissions is 19% (95% CrI: 7, 34) globally. The study location and method were found to be important drivers for diversity in estimates of dispersion parameters. While under high potential of superspreading, larger outbreaks could still occur with the import of the COVID-19 virus by traveling even when an epidemic seems to be under control.
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COVID-19 , Epidemias , Animais , COVID-19/epidemiologia , COVID-19/veterinária , China/epidemiologia , Índia , SARS-CoV-2RESUMO
COVID-19 remains a persistent threat, especially with the predominant Omicron variant emerging in early 2022, presenting with high transmissibility, immune escape, and waning. There is a need to rapidly ramp up global vaccine coverage while enhancing public health and social measures. Timely and reliable estimation of the reproduction number throughout a pandemic is critical for assessing the impact of mitigation efforts and the potential need to adjust for control measures. We conducted a systematic review on the reproduction numbers of the Omicron variant and gave the pooled estimates. We identified six studies by searching PubMed, Embase, Web of Science, and Google Scholar for articles published between 1 January 2020 and 6 March 2022. We estimate that the effective reproduction number ranges from 2.43 to 5.11, with a pooled estimate of 4.20 (95% CI: 2.05, 6.35). The Omicron variant has an effective reproduction number which is triple (2.71 (95% CI: 1.86, 3.56)) that of the Delta variant.
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COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , Humanos , Saúde Pública , Reprodução , SARS-CoV-2/genéticaRESUMO
Many locations around the world have used real-time estimates of the time-varying effective reproductive number ([Formula: see text]) of COVID-19 to provide evidence of transmission intensity to inform control strategies. Estimates of [Formula: see text] are typically based on statistical models applied to case counts and typically suffer lags of more than a week because of the latent period and reporting delays. Noting that viral loads tend to decline over time since illness onset, analysis of the distribution of viral loads among confirmed cases can provide insights into epidemic trajectory. Here, we analyzed viral load data on confirmed cases during two local epidemics in Hong Kong, identifying a strong correlation between temporal changes in the distribution of viral loads (measured by RT-qPCR cycle threshold values) and estimates of [Formula: see text] based on case counts. We demonstrate that cycle threshold values could be used to improve real-time [Formula: see text] estimation, enabling more timely tracking of epidemic dynamics.
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COVID-19/transmissão , Modelos Epidemiológicos , SARS-CoV-2 , Carga Viral , Número Básico de Reprodução/estatística & dados numéricos , COVID-19/epidemiologia , COVID-19/virologia , Simulação por Computador , Sistemas Computacionais , Epidemias , Hong Kong/epidemiologia , Humanos , Modelos Estatísticos , Pandemias , Carga Viral/estatística & dados numéricosRESUMO
Hong Kong employed a strategy of intermittent public health and social measures alongside increasingly stringent travel regulations to eliminate domestic SARS-CoV-2 transmission. By analyzing 1899 genome sequences (>18% of confirmed cases) from 23-January-2020 to 26-January-2021, we reveal the effects of fluctuating control measures on the evolution and epidemiology of SARS-CoV-2 lineages in Hong Kong. Despite numerous importations, only three introductions were responsible for 90% of locally-acquired cases. Community outbreaks were caused by novel introductions rather than a resurgence of circulating strains. Thus, local outbreak prevention requires strong border control and community surveillance, especially during periods of less stringent social restriction. Non-adherence to prolonged preventative measures may explain sustained local transmission observed during wave four in late 2020 and early 2021. We also found that, due to a tight transmission bottleneck, transmission of low-frequency single nucleotide variants between hosts is rare.
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COVID-19/epidemiologia , SARS-CoV-2/genética , COVID-19/transmissão , COVID-19/virologia , Genômica , Hong Kong/epidemiologia , Humanos , Saúde Pública , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/fisiologia , ViagemRESUMO
OBJECTIVES: mask-wearing outside the home has been almost universal in Hong Kong since late January 2020 with very high compliance. Nevertheless, community spread of COVID-19 has still occurred. We aimed to assess the settings where COVID-19 transmission occurred and determine the fraction of transmission events that occurred in settings where masks are not usually worn. METHODS: we reviewed detailed information provided by the Hong Kong Department of Health on local COVID-19 cases diagnosed up to 30 September 2020 to determine the most likely settings in which transmission occurred. We classified them in probably mask-on or mask-of and compared the prevalence of asymptomatic infections in these settings. RESULTS: among the 2425 cases (65.3%, 2425/3711) with information on transmission setting, 77.6% of the transmission occurred in household and social settings where face masks are not usually worn. Infections that occurred in mask-on settings were more likely to be asymptomatic (adjusted odds ratio 1.33; 95% confidence interval: 1.04, 1.68). CONCLUSIONS: we conclude that universal mask-wearing can reduce transmission, but transmission can continue to occur in settings where face masks are not usually worn. The higher proportion of asymptomatic cases in mask-on settings could be related to a milder disease presentation or earlier case detection.
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COVID-19 , Hong Kong/epidemiologia , Humanos , Máscaras , SARS-CoV-2RESUMO
BACKGROUND: A large cluster of 59 cases were linked to a single flight with 146 passengers from New Delhi to Hong Kong in April 2021. This outbreak coincided with early reports of exponential pandemic growth in New Delhi, which reached a peak of > 400 000 newly confirmed cases on 7 May 2021. METHODS: Epidemiological information including date of symptom onset, date of positive-sample detection and travel and contact history for individual cases from this flight were collected. Whole genome sequencing was performed, and sequences were classified based on the dynamic Pango nomenclature system. Maximum-likelihood phylogenetic analysis compared sequences from this flight alongside other cases imported from India to Hong Kong on 26 flights between June 2020 and April 2021, as well as sequences from India or associated with India-related travel from February to April 2021 and 1217 reference sequences. RESULTS: Sequence analysis identified six lineages of SARS-CoV-2 belonging to two variants of concern (Alpha and Delta) and one variant of public health interest (Kappa) involved in this outbreak. Phylogenetic analysis confirmed at least three independent sub-lineages of Alpha with limited onward transmission, a superspreading event comprising 37 cases of Kappa and transmission of Delta to only one passenger. Additional analysis of another 26 flights from India to Hong Kong confirmed widespread circulation of all three variants in India since early March 2021. CONCLUSIONS: The broad spectrum of disease severity and long incubation period of SARS-CoV-2 pose a challenge for surveillance and control. As illustrated by this particular outbreak, opportunistic infections of SARS-CoV-2 can occur irrespective of variant lineage, and requiring a nucleic acid test within 72 hours of departure may be insufficient to prevent importation or in-flight transmission.
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Viagem Aérea , COVID-19 , Doença Relacionada a Viagens , COVID-19/epidemiologia , COVID-19/transmissão , Surtos de Doenças , Hong Kong , Humanos , Índia , FilogeniaRESUMO
Hong Kong utilized an elimination strategy with intermittent use of public health and social measures and increasingly stringent travel regulations to control SARS-CoV-2 transmission. By analyzing >1700 genome sequences representing 17% of confirmed cases from 23-January-2020 to 26-January-2021, we reveal the effects of fluctuating control measures on the evolution and epidemiology of SARS-CoV-2 lineages in Hong Kong. Despite numerous importations, only three introductions were responsible for 90% of locally-acquired cases, two of which circulated cryptically for weeks while less stringent measures were in place. We found that SARS-CoV-2 within-host diversity was most similar among transmission pairs and epidemiological clusters due to a strong transmission bottleneck through which similar genetic background generates similar within-host diversity. ONE SENTENCE SUMMARY: Out of the 170 detected introductions of SARS-CoV-2 in Hong Kong during 2020, three introductions caused 90% of community cases.
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Epidemics are influenced by both disease and societal factors and can grow exponentially over short time periods. Epidemic risk analysis can help in rapidly predicting potentially serious outcomes and flagging the need for rapid response. We developed a multifactorial risk analysis tool 'EpiRisk' to provide rapid insight into the potential severity of emerging epidemics by combining disease-related parameters and country-related risk parameters. An initial set of 18 disease and country-related risk parameters was reduced to 14 following qualitative discussions and the removal of highly correlated parameters by a correlation and clustering analysis. Of the remaining parameters, three risk levels were assigned ranging from low (1) moderate (2) and high (3). The total risk score for an outbreak of a given disease in a particular country is calculated by summing these 14 risk scores, and this sum is subsequently classified into one of four risk categories: low risk (<21), moderate risk (21-29), high risk (30-37) and extreme risk (>37). Total risk scores were calculated for nine retrospective outbreaks demonstrating an association with the actual impact of those outbreaks. We also evaluated to what extent the risk scores correlate with the number of cases and deaths in 61 additional outbreaks between 2002 and 2018, demonstrating positive associations with outbreak severity as measured by the number of deaths. Using EpiRisk, timely intervention can be implemented by predicting the risk of emerging outbreaks in real time, which may help government and public health professionals prevent catastrophic epidemic outcomes.
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Surtos de Doenças , Saúde Pública , Humanos , Estudos Retrospectivos , Medição de RiscoRESUMO
BACKGROUND: Over the last two decades, Australia has experienced four severe influenza seasons caused by a predominance of influenza A (A/H3N2): 2003, 2007, 2012, and 2017. METHODS: We compared the epidemiology, genetics, and transmission dynamics of severe A/H3N2 seasons in Australia from 2003 to 2017. RESULTS: Since 2003, the proportion of notifications in 0-4 years old has decreased, while it has increased in the age group >80 years old (P < .001). The genetic diversity of circulating influenza A/H3N2 viruses has also increased over time with the number of single nucleotide polymorphisms significantly (P < .05) increasing. We also identified five residue positions within or near the receptor binding site of HA (144, 145, 159, 189, and 225) undergoing frequent mutations that are likely involved in significant antigenic drift and possibly severity. The Australian state of Victoria was identified as a frequent location for transmission either to or from other states and territories over the study years. The states of New South Wales and Queensland were also frequently implicated as locations of transmission to other states and territories but less so over the years. This indicates a stable but also changing dynamic of A/H3N2 circulation in Australia. CONCLUSION: These results have important implications for future influenza surveillance and control policy in the country. Reasons for the change in age-specific infection and increased genetic diversity of A/H3N2 viruses in recent years should be explored.