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Understanding the sentiments of social media posts can help health authorities respond to disease outbreaks, through a proxy measure of fear, confidence, and community compliance. Sentiment analysis identifies a pattern of emotion through the written word and assigns a positive, neutral, or negative value to it. As of February 2023, there were 677.7 million confirmed cases of coronavirus disease (COVID-19) and more than 6.7 million confirmed deaths. In this paper, around 170,000 COVID-19-related tweets were collected between September 2020 and January 2021 in the contiguous United States. Data preprocessing and exploratory investigation were completed for analysis of the collected dataset. Further, a novel and unified architecture called attention-based one-dimensional convolution with bidirectional long short-term memory layers (CNN-BiLSTM-ATT) is proposed to classify people’s sentiments as positive, neutral, and negative based on COVID-19-related tweets. In the CNN-BiLSTM-ATT model, the CNN layer can extract the low-level semantic features from textual data, and the BiLSTM layer can extract both the previous and future contextual representations. The attention module can improve the information focus from the outputted layer of the BiLSTM. The proposed method can extract both the local phrase representations and the global feature of sentences. Numerical experiments were conducted on COVID-19-related tweets using the proposed method and other baseline models to compare their performances. Our experimental results demonstrate that the CNN-BiLSTM-ATT model achieves an average accuracy of 95.16% and a macro-average F1-score of 95.12%, which outperforms the baseline models.

Background The cause of acute paediatric hepatitis of unknown aetiology (2022) has not been established despite extensive investigation.Objective To summarise the evidence for and against a causal role for human adenovirus (HAdv), adeno-associated virus 2 (AAV-2) and SARS-CoV-2 in outbreaks of paediatric hepatitis in 2022.Methods We appraised and summarised relevant evidence for each of the Bradford Hill criteria for causality using quantitative (statistical modelling) and qualitative (narrative coherence) approaches. Each team member scored the evidence base for each criterion separately for HAdv, AAV-2 and SARS-CoV-2; differences were resolved by discussion. We additionally examined criteria of strength and temporality by examining the lagged association between SARS-CoV-2 positivity, respiratory HAdv positivity, positive faecal HAdv specimens and excess A&E attendances in 1–4 years for liver conditions in England.Results Assessing criteria using the published literature and our modelling: for HAdv three Bradford Hill criteria (strength, consistency and temporality) were partially met; and five criteria (consistency, coherence, experimental manipulation, analogy and temporality) were minimally met. For AAV-2, the strength of association criterion was fully met, five criteria (consistency, temporality, specificity, biological gradient and plausibility) were partially met and three (coherence, analogy and experimental manipulation) were minimally met. For SARS-CoV-2, five criteria (strength of association, plausibility, temporality, coherence and analogy) were fully met; one (consistency) was partially met and three (specificity, biological gradient and experimental manipulation) were minimally met.Conclusion Based on the Bradford Hill criteria and modelling, HAdv alone is unlikely to be the cause of the recent increase in hepatitis in children. The causal link between SARS-CoV-2, and to a lesser degree AAV-2, appears substantially stronger but remains unproven. Hepatitis is a known complication of multisystem inflammatory syndrome in children following COVID-19, and SARS-CoV-2 has been linked to increased susceptibility to infection post-COVID-19, which may suggest complex causal pathways including a possible interaction with AAV-2 infection/reactivation in hosts that are genetically susceptible or sensitised to infection.

Abstract Background Residential aged-care facilities in Australia emerged as the high-risk setting the COVID-19 outbreaks due to community transmission. The vulnerable aged-care residents of these facilities suffered due to low hospital transfers and high mortality and morbidity rates. This study aimed to monitor and report the burden of COVID-19 in residential aged-care facilities across Australia and the impact of hospital transfer policies on resident hospitalisation during the first year of the pandemic. Methods We conducted a retrospective cohort study by collecting data from weekly aged-care outbreak reports published by open sources and official government sources between 1st March and 20th November 2020. A comprehensive line list of outbreaks was created using open-source data. The line list included the name of the facility, location, COVID-19 cases among residents, & staff, resident hospitalisations, mode of transmission, number of resident deaths, and state policies involving resident hospitalisation. We also searched the websites of these facilities to collect data on their COVID-19 policies for the residents, staff, and visitors. Statistical analyses were performed on the data obtained. Results 126 aged-care COVID-19 outbreaks were identified in Australia during the study period. The incidence rate of COVID-19 infections among aged-care residents in Australia was (1118.5 per 100,000 resident population) which is 10 times higher than the general population (107.6 per 100,000 population). The hospitalisation rate for aged-care residents in Australia was 0.93 per 100,000 population. The hospitalisation rate of aged-care residents in Victoria was 3.14 per 100,000 population despite having the highest COVID-19 cases. Excluding South Australia, all states followed ad-hoc case-by-case hospital transfer policies for aged-care residents. Conclusion This study documented a higher risk of COVID-19 infection for aged-care residents and workers but found low hospitalisation rates among residents across Australia. The hospitalisation rates in Victoria were higher than the national average but low when considering the COVID-19 infection rates in the state. The hospitalisation rates could have been impacted due to the state hospital transfer policies at that time. Immediate transfer of infected residents to hospitals may improve their survival and reduce the risk of infection to the other residents, as healthcare settings have more advanced infection control measures and are well-equipped with trained staff and resources.

Abstract Background Rotavirus is a leading cause of hospitalized diarrhea cases in Indonesia. Despite the rotavirus vaccine being recommended by the Indonesian Pediatric Society since 2011, it has yet to be been included in the Indonesian national immunization program (NIP) schedule. Objective To explore maternal knowledge of and attitudes towards rotavirus diarrhea, as well as barriers to vaccine acceptance in Yogyakarta, Indonesia. Methods We conducted 26 in-depth interviews in two districts (rural and urban areas) of Yogyakarta Province, Indonesia. Participants included women in their third trimester of pregnancy and mothers of infants younger than 14 weeks. We then proceeded with thematic analysis. Results Participants did not perceive diarrhea as being a priority health problem. Very few had heard of rotavirus diarrhea or were aware of vaccine availability. While participants would accept vaccinating their children against rotavirus, some key barriers impacted vaccine use. As the rotavirus vaccine is not included in the Indonesian NIP, parents perceived it as not essential. Parents were concerned about the safety and benefit of the vaccine due to its perceived newness. Other concerns were cost and halal status. Participants expressed a need for more information on the vaccine's effectiveness and safety, with their primary healthcare providers (HCPs) considered to play the most important role in vaccine acceptance. Conclusions In Yogyakarta, Indonesia, awareness of the seriousness of rotavirus disease and the availability of the rotavirus vaccine is low. Its newness, safety, efficacy, and cost, and doubts about its halal status, were barriers to vaccine acceptance. Information and recommendations from HCPs play an essential role in vaccine acceptance.

Abstract Background COVID-19 mass vaccination programs place an additional burden on healthcare services. We aim to model the queueing process at vaccination sites to inform service delivery. Methods We use stochastic queue network models to simulate queue dynamics in larger mass vaccination hubs and smaller general practice (GP) clinics. We estimate waiting times and daily capacity based on a range of assumptions about appointment schedules, service times and staffing and stress-test these models to assess the impact of increased demand and staff shortages. We also provide an interactive applet, allowing users to explore vaccine administration under their own assumptions. Results Based on our assumed service times, the daily throughput for an eight-hour clinic at a mass vaccination hub ranged from 500 doses for a small hub to 1400 doses for a large hub. For GP clinics, the estimated daily throughput ranged from about 100 doses for a small practice to almost 300 doses for a large practice. What-if scenario analysis showed that sites with higher staff numbers were more robust to system pressures and mass vaccination sites were more robust than GP clinics. Conclusions With the requirement for ongoing COVID-19 booster shots, mass vaccination is likely to be a continuing feature of healthcare delivery. Different vaccine sites are useful for reaching different populations and maximising coverage. Stochastic queue networks offer a flexible and computationally efficient approach to simulate vaccination queues and estimate waiting times and daily throughput to inform service delivery.

The use of artificial intelligence (AI) to generate automated early warnings in epidemic surveillance by harnessing vast open-source data with minimal human intervention has the potential to be both revolutionary and highly sustainable. AI can overcome the challenges faced by weak health systems by detecting epidemic signals much earlier than traditional surveillance. AI-based digital surveillance is an adjunct to—not a replacement of—traditional surveillance and can trigger early investigation, diagnostics and responses at the regional level. This narrative review focuses on the role of AI in epidemic surveillance and summarises several current epidemic intelligence systems including ProMED-mail, HealthMap, Epidemic Intelligence from Open Sources, BlueDot, Metabiota, the Global Biosurveillance Portal, Epitweetr and EPIWATCH. Not all of these systems are AI-based, and some are only accessible to paid users. Most systems have large volumes of unfiltered data; only a few can sort and filter data to provide users with curated intelligence. However, uptake of these systems by public health authorities, who have been slower to embrace AI than their clinical counterparts, is low. The widespread adoption of digital open-source surveillance and AI technology is needed for the prevention of serious epidemics.

Objectives: Rhinoviruses (RV) represent the most common aetiological agent of all acute respiratory tract infections across all age groups and a significant burden of disease among children. Recent studies have shown that RV-A and RV-C species are associated with increased disease severity. In order to better understand the potential associations between RV species and clinical features among paediatric cases, this study aimed to integrate genetic and epidemiological data using Bayesian phylogenetic methods. Methods: Potential associations between RV species and subtypes, and clinical disease severity using a matched dataset of 52 RV isolates sampled from children (< 18 years) in Sydney, Australia, between 2006 and 2009 were uncovered using epidemiological and phylogenetic methods. Results: It was found that RV-C was significantly more likely to be isolated from paediatric cases aged < 2 years compared with RV-A, although no significant differences in recorded symptoms were observed. Significant phylogenetic-trait associations between age and the VP4/VP2 capsid protein phylogeny suggest that age-specific variations in infectivity among subtypes may may be possible. Conclusion: This study adds to the growing body of epidemiological evidence concerning RV. Improving surveillance and testing for RV, including routine whole genome sequencing, may improve understanding of the varied disease outcomes of RV species and subtypes. Future studies could aim to identify specific genetic markers associated with age-specific infectivity of RV, which could inform treatment practices and public health surveillance of RV.

Objectives: To determine patterns of mask wearing and other infection prevention behaviours, over two time periods of the COVID-19 pandemic, in cities where mask wearing was not a cultural norm. Methods: A cross-sectional survey of masks and other preventive behaviours in adults aged ≥18 years was conducted in five cities: Sydney and Melbourne, Australia; London, UK; and Phoenix and New York, USA. Data were analysed according to the epidemiology of COVID-19, mask mandates and a range of predictors of mask wearing. Results: The most common measures used were avoiding public areas (80.4%), hand hygiene (76.4%), wearing masks (71.8%) and distancing (67.6%). Over 40% of people avoided medical facilities. These measures decreased from March–July 2020. Pandemic fatigue was associated with younger age, low perceived severity of COVID-19 and declining COVID-19 prevalence. Predictors of mask wearing were location (US, UK), mandates, age

The reemergence of smallpox as a bioterrorism attack is now an increasing and legitimate concern. Advances in synthetic biology have now made it possible for the virus to be synthesized in a laboratory, with methods publicly available. Smallpox introduction into a susceptible population, with increased immunosuppression and an aging population, raises questions of how vaccination should be used in an epidemic situation when supply may be limited. We constructed three modified susceptible-latent-infectious-recovered (SEIR) models to simulate targeted, ring and mass vaccination in response to a smallpox outbreak in Sydney, Australia. We used age-specific distributions of susceptibility, infectivity, contact rates, and tested outputs under different assumptions. The number of doses needed of second- and third-generation vaccines are estimated, along with the total number of deaths at the end of the epidemic. We found a faster response is the key and ring vaccination of traced contacts is the most effective strategy and requires a smaller number of doses. However if public health authorities are unable to trace a high proportion of contacts, mass vaccination with at least 125,000 doses delivered per day is required. This study informs a better preparedness and response planning for vaccination in a case of a smallpox outbreak in a setting such as Sydney.

Summary: Background: Vaccine derived poliovirus (VDPV) remains a major barrier to polio eradication, and recent growing emergences are concerning. This paper presents the global epidemiology of circulating VDPV (cVDPV) by exploring associations between demographic and socioeconomic factors with its recent rise. Methods: Data on reported cVDPV cases and isolates between January 1 2016 and June 30 2021 were compiled from EPIWATCH, an open-source observatory for outbreak scanning and analysis, the World Health Organisation (WHO) and ProMed, and analysed descriptively. Reports containing cVDPV case information were included while duplicates and defective links were excluded. Data collection occurred from April 5 2021 to July 16 2021. To identify factors associated with cVDPV, a retrospective case-control study comparing socioeconomic profiles of countries which reported cVDPV with those that did not was undertaken with weighted logistic regression analysis. Findings: cVDPV caused by serotype 2 poliovirus was the predominant strain (95%) of 1818 total human cVDPV cases reported. Of 40 countries reporting cVDPV cases or isolates, 22 (55%) had polio vaccination coverages below 80%. Low vaccination coverage (Adjusted OR = 83·41, 95% CI: [5·01, 1387·71], p = 0·0020) was found to be associated with increased odds of reporting cVDPV after adjusting for confounding effects of GDP per capita, female adult literacy rates, maternal mortality rate, and Global Peace Index. Interpretation: Our findings reinforce the importance of maintaining high levels of vaccination, as risk of re-emergence rises when immunity wanes. Interventions to increase vaccination and standards of living in developing countries, coupled with robust surveillance are required if humanity hopes to eradicate polio in the near future. Funding: This research was supported by the MRFF 2021 Frontier Health and Medical Research Grant (ID RFRHPI000280), Department of Health, the Australian Government.

Abstract Background The pandemic of COVID-19 has occurred close on the heels of a global resurgence of measles. In 2019, an unprecedented epidemic of measles affected Samoa, requiring a state of emergency to be declared. Measles causes an immune amnesia which can persist for over 2 years after acute infection and increases the risk of a range of other infections. Methods We modelled the potential impact of measles-induced immune amnesia on a COVID-19 epidemic in Samoa using data on measles incidence in 2018–2019, population data and a hypothetical COVID-19 epidemic. Results The young population structure and contact matrix in Samoa results in the most transmission occurring in young people

The frequency of serious epidemics has continued to increase in the last decade. The ability to predict the risk of outbreaks can improve prevention and control. There are few prediction models available, and of these most are manually constructed by human experts. These manual models are affected by the lack of automation and have limitations in data processing. They can be enhanced with modern machine-learning techniques. Machine learning (ML) based prediction models, however, have higher requirement for professional knowledge and are not broadly accessible to researchers who do not have ML expertise. We proposed automated machine learning (AutoML) as an advanced solution. It automates the entire ML design process for users without requiring ML knowledge, therefore allows non-ML experts to individually build ML models. To demonstrate the functionality of AutoML to develop reliable systems, we expanded an existing manually developed risk analysis model, EPIRISK, that uses economic, social and medical risk factors to predict epidemic risk. Using the AutoML platform BrewAI, we obtained an automatically generated ML model to predict epidemic risk. This was compared with six traditionally built machine learning models. The AutoML tool generated a model of 77% accuracy in predicting risk. It had similar accuracy to the six traditional built ML models. Such tools are easy to use and could make ML models more accessible to non-ML experts.

A review on the use of non-pharmaceutical interventions (NPI) was conducted in long-term care facilities. The use of personal protective equipment, isolation and re-testing of COVID-19 were protective against the infection. Facilities which implemented NPIs prior to the outbreak had fewer COVID-19 outbreaks, odds ratio=0.70. Re-testing of asymptomatic people during outbreaks is crucial.

Objective(s): To estimate the impact of universal community face mask use in Victoria, Australia along with other routine disease control measures in place.Methods: A mathematical modeling study using an age structured deterministic model for Victoria, was simulated for 123 days between 1 June 2020 and 1 October 2020, incorporating lockdown, contact tracing, and case findings with and without mask use in varied scenarios. The model tested the impact of differing scenarios of the universal use of face masks in Victoria, by timing, varying mask effectiveness, and uptake.Results: A six-week lockdown with standard control measures, but no masks, would have resulted in a large resurgence by September, following the lifting of restrictions. Mask use can substantially reduce the epidemic size, with a greater impact if at least 50% of people wear a mask which has an effectiveness of at least 40%. Early mask use averts more cases than mask usage that is only implemented closer to the peak. No mask use, with a 6-week lockdown, results in 67,636 cases and 120 deaths by 1 October 2020 if no further lockdowns are used. If mask use at 70% uptake commences on 23 July 2020, this is reduced to 7,961 cases and 42 deaths. We estimated community mask effectiveness to be 11%.Conclusion(s): Lockdown and standard control measures may not have controlled the epidemic in Victoria. Mask use can substantially improve epidemic control if its uptake is higher than 50% and if moderately effective masks are used. Early mask use should be considered in other states if community transmission is present, as this has a greater effect than later mask wearing mandates.

Hepatitis A (Hep A) can cause sporadic or epidemic disease and has been frequently linked to contamination of the global food chain. Global surveillance data on Hep A are unavailable, and in some countries, reporting is incomplete or not timely, either because of lack of human resources or sensitivities around reporting. The use of vast open-source data such as news-feeds and social media however can overcome barriers to surveillance and provide timely data on global epidemics. In this study we use EpiWATCH, semi-automated outbreak scanning service to review the global epidemiology of Hep A reports from 2016-2018. We reviewed the EpiWATCH Outbreak Alerts database for reports on the Hep A dated between August 1, 2016, to April 31, 2018 which was the analysed by outbreak clusters, location, and time. Of 5098 total entries in the database a total of 169 non-duplicate Hep A outbreak reports were found and included for descriptive analysis. The majority of outbreak reports (68.6%%; N=116/169) originated from the United States of America (USA). The largest Hep A outbreaks were multi-country outbreaks in the European region, and multistate outbreaks in the USA and Australia. Homelessness (mainly in US outbreaks) was the predominant risk factor (40.2%), followed by foodborne outbreaks (26.6%) and outbreaks in men who have sex with men (6.5%). Using EpiWATCH we found that the emergence of outbreaks in homeless people has dominated the epidemiology of Hep A in the U.S and this appears a relatively new phenomenon. Epidemic intelligence systems such as EpiWATCH are a useful proxy for global surveillance of Hep A outbreaks and using open-source data can provide epidemic intelligence and outbreak alerts where global data is unavailable.

Aims: The aim of this study was to examine the association of influenza infection and vaccination with extent of cardiac damage during acute myocardial infarctions (AMIs) as measured by serum biomarkers and left ventricular ejection function (LVEF) in patients. Methods: Post-hoc analysis was performed on data from a prospective case-control study of influenza and AMI, conducted in a tertiary care hospital in Sydney, Australia. We included 275 cases of AMI, aged ≥ 40 years admitted to the cardiology during the study period. Results: Mean and median CK-MB levels were significantly higher among unvaccinated group compared to vaccinated group (p value

Objective This study comprehensively estimated the excess cardiovascular disease (CVD) mortality attributable to influenza in an older (age ≥65 years) population.Design Ecological study.Setting Aggregated data from administrative systems on CVD mortality, influenza surveillance and meteorological data in Beijing, China.Main outcome measure Excess overall CVD, and separately for ischaemic heart disease (IHD), ischaemic stroke, haemorrhagic stroke mortality attributable to influenza, adjusting for influenza activity, time trend, seasonality and ambient temperature.Results CVD (risk ratio (RR) 1.02, 95% CI 1.01, 1.02), IHD (RR 1.01, 95% CI 1.01, 1.02), ischaemic stroke (RR=1.03, 95% CI 1.02, 1.04), but not haemorrhagic stroke (RR=1.00, 95% CI 0.99, 1.01) mortality, were significantly associated with every 10% increase in influenza activity. An increase in circulating A(H1N1)09pdm, A(H3N2) and B type virus were all significantly associated with CVD and ischaemic stroke mortality, but only A(H3N2) and B type virus with IHD mortality. The strongest increase in disease mortality was in the same week as the increase in influenza activity. Annual excess CVD mortality rate attributable to influenza ranged from 54 to 96 per 100 000 population. The 3%–6% CVD mortality attributable to influenza activity was related to an annual excess of 916–1640 CVD deaths in Beijing, China.Conclusions Influenza activity has moderate to strong associations with CVD, IHD and ischaemic stroke mortality in older adults in China. Promoting influenza vaccination could have major health benefit in this population.Background Influenza may trigger serious CVD events. An estimation of excess CVD mortality attributable to influenza has particular relevance in China where vaccination is low and CVD burden is high.Methods This study analysed data at the population level (age ≥65 years) using linked aggregated data from administrative systems on CVD mortality, influenza surveillance and meteorological data during 2011 to 2018. Quasi-Poisson regression models were used to estimate the excess overall CVD, and separately for IHD, ischaemic stroke, haemorrhagic stroke mortality attributable to influenza, adjusting for influenza activity, time trend, seasonality and ambient temperature. Analyses were also undertaken for influenza subtypes (A(H1N1)09pdm, A(H3N2) and B viruses), and mortality risk with time lags of 1–5 weeks following influenza activity in the current week.

Background In a previous randomised controlled trial (RCT) in hospital healthcare workers (HCWs), cloth masks resulted in a higher risk of respiratory infections compared with medical masks. This was the only published RCT of cloth masks at the time of the COVID-19 pandemic.Objective To do a post hoc analysis of unpublished data on mask washing and mask contamination from the original RCT to further understand poor performance of the two-layered cotton cloth mask used by HCWs in that RCT.Setting 14 secondary-level/tertiary-level hospitals in Hanoi, Vietnam.Participants A subgroup of 607 HCWs aged ≥18 years working full time in selected high-risk wards, who used a two-layered cloth mask and were part of a randomised controlled clinical trial comparing medical masks and cloth masks.Intervention Washing method for cloth masks (self-washing or hospital laundry). A substudy of contamination of a sample of 15 cloth and medical masks was also conducted.Outcome measure Infection rate over 4 weeks of follow up and viral contamination of masks tested by multiplex PCR.Results Viral contamination with rhinovirus was identified on both used medical and cloth masks. Most HCW (77% of daily washing) self-washed their masks by hand. The risk of infection was more than double among HCW self-washing their masks compared with the hospital laundry (HR 2.04 (95% CI 1.03 to 4.00); p=0.04). There was no significant difference in infection between HCW who wore cloth masks washed in the hospital laundry compared with medical masks (p=0.5).Conclusions Using self-reported method of washing, we showed double the risk of infection with seasonal respiratory viruses if masks were self-washed by hand by HCWs. The majority of HCWs in the study reported hand-washing their mask themselves. This could explain the poor performance of two layered cloth masks, if the self-washing was inadequate. Cloth masks washed in the hospital laundry were as protective as medical masks. Both cloth and medical masks were contaminated, but only cloth masks were reused in the study, reiterating the importance of daily washing of reusable cloth masks using proper method. A well-washed cloth mask can be as protective as a medical mask.Trial resgistration number ACTRN12610000887077.

Anti-Microbial Resistance (AMR) is a significant public health threat in many countries around the world, endangering the control of infections and infectious disease. AMR related illness has been responsible for annual global mortality of 700,000. Besides health outcomes, they bear an adverse impact on economic development. However, the lack of comprehensive global AMR surveillance data and an over-reliance on indicator-based surveillance system has limited the early detection of emerging AMR threats and trends. Methods; EpiWATCH outbreak database has been used to retrieve AMR outbreak reports between August 2016-March 2020 using keywords such as resistance, resistant, superbug, bugs, MRSA and VRE. Cases were grouped according to geolocation and time to conduct a descriptive epidemiologic analysis of the outbreak. Results; A total of 60 reports on AMR outbreak were detected. Majority of the infections were caused by gram-negative bacteria. Drug-resistant Klebsiella. Acinetobacter and New Delhi Metallo-β-lactamase-1 (NDM-1) Carbapenemase-producing Enterobacteriaceae acquired in hospitals were strongly associated with mortality. As dense places, schools and universities were at-risk locations in the community for Methicillin-resistant Staphylococcus Aureus (MRSA) outbreaks and in hospital settings, the Neonatal units were at risk. Conclusion; EpiWATCH detected AMR outbreaks quickly and timely compared to an indicator-based surveillance system. It detected outbreaks by pathogens not monitored by the World Health Organisation. Also, it presented information on both colonised and infected cases from the population. Thus, EpiWATCH could be complemented with an indicator-based surveillance system for strengthening surveillance and identifying action areas.

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 (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.

Smallpox was declared eradicated in 1980, with known seed stock retained in two high security Biosafety Level 4 laboratories in the United States and Russia. Experts agree the likelihood of theft from these laboratories is low, and that synthetic creation of smallpox is a theoretical possibility. Until 2017 it was believed that synthetic smallpox was technically too complex a task to be a serious threat. However, in 2017, Canadian scientists synthesised a closely related orthopoxvirus, horsepox, using mail order DNA and $100,000. Simultaneously, terrorist groups have declared intent to conduct biological attacks. In this context an exercise was held on August 16th 2018, with international and cross-sectoral stakeholders to review preparedness for a bioterrorism attack in the Asia-Pacific region and globally. The exercise was conducted by The National Health and Medical Research Council (NHMRC) Centre for Research Excellence, Integrated Systems for Epidemic Response, with contextual input from the Ministry of Health and Medical Services Fiji. The scenario involved a deliberate release in Fiji, followed by a larger release in a more populous Asian country. Mathematical modelling was used to underpin epidemic projections under different conditions. The exercise alternated between clinical, public health, emergency and societal responses, with participants making real-time decisions on cross-sectoral response across the region and the world. Key weak points which are influential in determining the final size and impact of the epidemic were identified (based on mathematical modelling of transmission in Fiji and globally). We identified potential gaps in preparedness for smallpox and factors which influence the severity of a smallpox epidemic. This included identifying which determinants of epidemic size are potentially within our control, and which are not. Influential factors within our control include: preventing an attack through intelligence, law enforcement and legislation; speed of diagnosis; speed and completeness of case finding and case isolation; speed and security of vaccination response, including stockpiling; speed and completeness of contact tracing; protecting critical infrastructure and business continuity; non-pharmaceutical interventions (social distancing, PPE, border control); protecting first responders; operational support and logistics; social mobilisation and risk communication. Based on discussion at the workshop between diverse stakeholders, recommendations were made to guide improved prevention, mitigation and rapid response, thus providing a holistic, cross-sectoral framework for prevention of a worst-case scenario smallpox pandemic.

The promise of genetic engineering to reduce the burden of disease on the human population, alleviate suffering and provide new avenues for mastering disease has recently been overshadowed by the announcement by He Jiankui of successful germ line modification of two human embryos, and their subsequent successful birth. The use of gene editing technologies enabled by CRISPR-Cas9 and related systems to successfully modify the germ line of humans has now been proven. The ramifications of this event are significant for both medicine but also in diverse other areas of human society. Such technologies can now be considered as a possible route to achieve military, economic and social advantage compared to rivals. In this article the possible emergence of a genetic warfare escalation is highlighted, and some simple avenues for military use of gene editing to enhance and augment friendly forces, or target enemy forces, are identified. We suggest that He’s work, conducted clandestinely and apparently outside of regulatory frameworks, possibly represents the Trinity Test of genetic warfare, and momentum driving an emerging genetic warfare arms race may be beginning to gather.

On August 16th, 2018, we held Exercise Mataika to test preparedness for a worst-case scenario of a smallpox attack which begins in the Pacific and is followed by a larger scale attack in a highly populous Asian country. The exercise was underpinned by mathematical modelling which aimed to determine the duration and magnitude of the epidemic under different scenarios, the critical threshold for epidemic control, and scenarios where the current stockpile of vaccine is adequate. We constructed a modified SEIR model for smallpox transmission. We found that time to commencing the response, rates of contact tracing and ring vaccination, and rates of case isolation are all influential factors on epidemic size and duration. Ideally, the response should commence in 20 days after the attack, corresponding to 8 days after the first symptoms appear, given an average incubation period of 12 days. Every day of delay worsens the epidemic. The WHO stockpile of vaccine of 34 million doses is adequate if rates of case isolation and ring vaccination are maintained above 60%. If rates of contact tracing, ring vaccination and case isolation fall below 53%, epidemic control is lost. In such a scenario, the epidemic persists for longer than 10 years and over a billion doses of vaccine are needed for epidemic control. There are modifiable factors which can prevent a catastrophic scenario following smallpox re-emergence. These include very rapid response time and high rates of isolation and ring vaccination. Training and capacity building, as well as pre-vaccinated teams, can also assist with rapid response. In low income countries, a smallpox epidemic could overwhelm the health system and far exceed human resource capacity, so low rates of case isolation and contact tracing is a realistic possibility. The consequences of poor epidemic control are catastrophic if rates of case isolation and ring vaccination fall below 53%, the threshold for epidemic control. Global cooperation is also critical, to ensure that vaccine and other resources are directed quickly to affected areas.

Objective: To understand the global outbreak surveillance needs of stakeholders involved in epidemic response in selected countries and areas in the Asia–Pacific region in order to inform development of an epidemic observatory, Epi-watch. Methods: We designed an online, semi-structured stakeholder questionnaire to collect information on global outbreak surveillance sources and limitations from participants who use epidemic intelligence and outbreak alert services in their work in government and nongovernment organizations in the Asia–Pacific region. Results: All respondents agreed that it was important to remain up to date with global outbreaks. The main reason cited for following global outbreak news was as an early warning for serious epidemics. Mainstream media and specialist Internet sources such as the World Health Organization (n = 54/91; 59%), the Program for Monitoring Emerging Diseases (ProMED)-mail (n = 45/91; 49%) and the United States Centers for Disease Control and Prevention (n = 31/91; 34%) were the most common sources for global outbreak news; rapid intelligence services such as HealthMap were less common (n = 9/91; 10%). Only 51% (n = 46/91) of respondents thought that their sources of outbreak news were timely and sufficient for their needs. Conclusion: For those who work in epidemic response, epidemic intelligence is important and widely used. Stakeholders are less aware of and less frequently use rapid sources such as HealthMap and rely more on validated but less timely traditional sources of disease surveillance. Users identified a need for more timely and reliable epidemic intelligence.

Abstract Background The aim of this study was to estimate the prevalence of pneumonia and secondary bacterial infections during the pandemic of influenza A(H1N1)pdm09. Methods A systematic review was conducted to identify relevant literature in which clinical outcomes of pandemic influenza A(H1N1)pdm09 infection were described. Published studies (between 01/01/2009 and 05/07/2012) describing cases of fatal or hospitalised A(H1N1)pdm09 and including data on bacterial testing or co-infection. Results Seventy five studies met the inclusion criteria. Fatal cases with autopsy specimen testing were reported in 11 studies, in which any co-infection was identified in 23% of cases (Streptococcus pneumoniae 29%). Eleven studies reported bacterial co-infection among hospitalised cases of A(H1N1)2009pdm with confirmed pneumonia, with a mean of 19% positive for bacteria (Streptococcus pneumoniae 54%). Of 16 studies of intensive care unit (ICU) patients, bacterial co-infection identified in a mean of 19% of cases (Streptococcus pneumoniae 26%). The mean prevalence of bacterial co-infection was 12% in studies of hospitalised patients not requiring ICU (Streptococcus pneumoniae 33%) and 16% in studies of paediatric patients hospitalised in general or pediatric intensive care unit (PICU) wards (Streptococcus pneumoniae 16%). Conclusion We found that few studies of the 2009 influenza pandemic reported on bacterial complications and testing. Of studies which did report on this, secondary bacterial infection was identified in almost one in four patients, with Streptococcus pneumoniae the most common bacteria identified. Bacterial complications were associated with serious outcomes such as death and admission to intensive care. Prevention and treatment of bacterial secondary infection should be an integral part of pandemic planning, and improved uptake of routine pneumococcal vaccination in adults with an indication may reduce the impact of a pandemic.

Abstract Background Rotavirus is a leading cause of severe diarrheal disease, and one of the common causes of death in children aged under five years old. The dominant epidemic strains may change in different years in the same area. In order to provide evidence for rotavirus epidemic control and inform vaccine development, we analyzed epidemiological patterns and genetic characteristics of rotavirus in Beijing during 2011–2016. Methods Stool specimens of outpatient children under five years old were collected from three children’s hospitals on a weekly basis. Group A rotavirus antigens were detected using enzyme-linked immunosorbent assay (ELISA) kit. The partial VP4 genes and VP7 genes of rotavirus were both amplified and sequenced. Genotyping and phylogenetic analyses were performed. Logistic regression and Chi-square tests were performed to determine differences across age groups, districts and years in rotavirus prevalence and genotype distribution. Results A total of 3668 stool specimens from children with acute diarrhea identified through hospital-based surveillance were collected from 2011 to 2016 in Beijing. A total of 762 (20.8%) specimens tested positive for rotavirus. The rotavirus-positive rate was highest among the 1–2 years old age group (29.0%, 310/1070). November, December and January were the highest rotavirus-positive rate months each year. G9 was the most common G genotype (64.4%, 461/716), and P [8] was the most common P genotype (87.0%, 623/716) among the 716 rotavirus-positive specimens. G9P [8], G3P [8] and G2P [4] were the most common strains. The rotavirus-positive rates of samples in 2012 and 2013 were higher than that in 2011, and the dominant genotype changed from G3P [8] to G9P [8] in 2012 and 2013. VP7 gene sequences of G9 strains in this study clustered into two main lineages. Most of the G9 strains exhibited the highest nucleotide similarity (99.1%~ 100.0%) to the strain found in Japan (MI1128). VP4 gene sequences of P [8] strains were almost P[8]b. Conclusions Rotavirus accounted for more than one fifth of childhood diarrhea in Beijing during the study period. Targeted measures such as immunization with effective rotavirus vaccines should be carried out to reduce the morbidity and mortality due to rotavirus.

Abstract Objective Compare the adoption and adherence to health protection behaviours prior to and during travel among international Australian travellers who return to Australia with notified chikungunya or malaria infection. This information could inform targeted health promotion and intervention strategies to limit the establishment of these diseases within Australia. Results Seeking travel advice prior to departure was moderate (46%, N = 21/46) yet compliance with a range of recommended anti-vectorial prevention measures was low among both chikungunya and malaria infected groups (16%, N = 7/45). Reasons for not seeking advice between groups was similar and included ‘previous overseas travel with no problems’ (45%, N = 9/20) and ‘no perceived risk of disease’ (20%, N = 4/20). Most chikungunya cases (65%, N = 13/20) travelled to Indonesia and a further 25% (N = 5/20) visited India, however most malaria cases (62%, N = 16/26) travelled to continental Africa with only 12% (N = 3/26) travelling to India. The majority (50%, N = 10/20) of chikungunya cases reported ‘holiday’ as their primary purpose of travel, compared to malaria cases who most frequently reported travel to visit friends and family (VFR; 42%, N = 11/26). These results provide import data that may be used to support distinct public health promotion and intervention strategies of two important vector-borne infectious diseases of concern for Australia.

Objectives In this study, we aimed to measure the awareness, acceptability and perceptions of current issues in biosecurity posed by infectious diseases dual-use research of concern (DURC) in the community. DURC is conducted today in many locations around the world for the benefit of humanity but may also cause harm through either a laboratory accident or deliberate misuse. Most DURC is approved by animal ethics committees, which do not typically consider harm to humans. Given the unique characteristics of contagion and the potential for epidemics and pandemics, the community is an important stakeholder in DURC.Design Self-administered web-based cross-sectional survey.Participants Participants over the age of 18 in Australia and 21 in the USA were included in the survey. A total of 604 participants completed the study. The results of 52 participants were excluded due to potential biases about DURC stemming from their employment as medical researchers, infectious diseases researchers or law enforcement professionals, leaving 552 participants. Of those, 274 respondents resided in Australia and 278 in the USA.Outcomes Baseline awareness, acceptability and perceptions of current issues surrounding DURC. Changes in perception from baseline were measured after provision of information about DURC.Results Presurvey, 77% of respondents were unaware of DURC and 64% found it unacceptable or were unsure. Two-thirds of respondents did not change their views. The baseline perception of high risk for laboratory accidents (29%) and deliberate bioterrorism (34%) was low but increased with increasing provision of information (42% and 44% respectively, p

Background: Internet-based surveillance systems have become invaluable tools to complement traditional surveillance in the early detection of infectious disease outbreaks. Search results limited to only English-language sources may lead to missed opportunities in global outbreak monitoring efforts. The Malay language has 290 million native speakers across the Southeast Asian region (Indonesia, Malaysia, Brunei, Singapore and the southern parts of Thailand and the Philippines), which is an important region for outbreaks. The aim of this research is to determine the completeness of reports of Malay language outbreak detection by commonly used open source surveillance platforms. Methods: We searched ProMED-mail, HealthMap, and Google News to investigate outbreak events in Malaysia and Indonesia between 1st August 2016 and 31st August 2017. We also cross-checked published epidemic reports in Medline to determine the proportion of outbreaks that are published. Results: A total of 371 entries from ProMED-mail and HealthMap were included. A Google News search query using Malay language keywords resulted in 453 news outbreak reports, 98 of which were missed by either or both ProMED-mail and HealthMap. During the study time frame, only 40 published epidemic reports were found in MEDLINE, showing the importance of informal data sources to identify outbreaks. Some diseases such as mumps, dengue and avian influenza had different local terminology in Indonesia and Malaysia. Conclusions: Search results limited to only English-language sources may lead to reduced outbreak detection. The inclusion of keywords in the Malay language improves epidemic intelligence in the region, but needs to be nuanced for local terminology, which may differ between countries. Informal Internet-based surveillance can improve compliance with International Health Regulations (IHR) for low income countries, because it is less resource-intensive than formal surveillance. However, there is a need to include local language search terms to improve outbreak detection, especially in regions at high risk of emerging infectious diseases.

Bioterrorism and pandemics pose great risk to the health and safety of our modern world. Pandemic scenario exercises commonly use diseases that are most likely to cause moderate harm in an epidemic scenario such as influenza. Despite the generalisable nature of most pandemic responses, exercises often fail to take account of the broader impacts of a pandemic scenario. In August 2018, The Exercise Mataika pandemic workshop was conducted by the NHMRC Centre for Research Excellence Integrated Systems for Epidemic Response at the University of New South Wales, Australia. By utilising a high risk, worst case scenario – the deliberate release of Smallpox in Fiji and a much larger Asian country – impacts not often considered in pandemic planning, such as the resiliency of the health system, absenteeism, social cohesion, and broader impacts on society were considered, and compared, across geographic and social groupings. This study aimed to collect and analyse participant perceptions and evaluation of Exercise Mataika. A mixed methods study collecting participants ratings of experience, value and utility aspects of the scenario coupled with a thematic analysis of qualitative responses was conducted. Quantitative ratings for the activity were overwhelmingly positive, with respondents highlighting that the activity was useful, different in format, identified issues not often explored in pandemic exercises, and was a valuable educational and networking opportunity. Qualitative analysis and combined mixed-methods analysis revealed more nuanced findings. While respondents remained positive about the exercise format, subgroups highlighted potential missed opportunities and areas within the scenario where greater focus could have been directed. Overall the findings highlighted the value of including a wide range of exercise attendees both across sectors and nationalities, and addressing a far broader set of considerations across multiple domains. These findings will guide future development of pandemic response exercises and education.

MERS-CoV infection emerged in the Kingdom of Saudi Arabia (KSA) in 2012 and has spread to 26 countries. However, 80% of all cases have occurred in KSA. The largest outbreak outside KSA occurred in South Korea (SK) in 2015. In this report, we describe an epidemiological comparison of the two outbreaks. Data from 1299 cases in KSA (2012–2015) and 186 cases in SK (2015) were collected from publicly available resources, including FluTrackers, the World Health Organization (WHO) outbreak news and the Saudi MOH (MOH). Descriptive analysis, t-tests, Chi-square tests and binary logistic regression were conducted to compare demographic and other characteristics (comorbidity, contact history) of cases by nationality. Epidemic curves of the outbreaks were generated. The mean age of cases was 51 years in KSA and 54 years in SK. Older males (⩾70 years) were more likely to be infected or to die from MERS-CoV infection, and males exhibited increased rates of comorbidity in both countries. The epidemic pattern in KSA was more complex, with animal-to-human, human-to-human, nosocomial and unknown exposure, whereas the outbreak in SK was more clearly nosocomial. Of the 1186 MERS cases in KSA with reported risk factors, 158 (13.3%) cases were hospital associated compared with 175 (94.1%) in SK, and an increased proportion of cases with unknown exposure risk was found in KSA (710, 59.9%). In a globally connected world, travel is a risk factor for emerging infections, and health systems in all countries should implement better triage systems for potential imported cases of MERS-CoV to prevent large epidemics.Emerging Microbes & Infections (2017) 6, e51; doi:10.1038/emi.2017.40; published online 7 June 2017

This study compared the phylogeography of MERS-CoV between hospital outbreak-associated cases and sporadic cases in Saudi Arabia. We collected complete genome sequences from human samples in Saudi Arabia and data on the multiple risk factors of human MERS-CoV in Saudi Arabia reported from 2012 to 2018. By matching each sequence to human cases, we identified isolates as hospital outbreak-associated cases or sporadic cases. We used Bayesian phylogenetic methods including temporal, discrete trait analysis and phylogeography to uncover transmission routes of MERS-CoV isolates between hospital outbreaks and sporadic cases. Of the 120 sequences collected between 19 June 2012 and 23 January 2017, there were 64 isolates from hospital outbreak-associated cases and 56 from sporadic cases. Overall, MERS-CoV is fast evolving at 7.43 × 10−4 substitutions per site per year. Isolates from hospital outbreaks showed unusually fast evolutionary speed in a shorter time-frame than sporadic cases. Multiple introductions of different MERS-CoV strains occurred in three separate hospital outbreaks. MERS-CoV appears to be mutating in humans. The impact of mutations on viruses transmissibility in humans is unknown.

Planning for a re-emergent epidemic of smallpox requires surge capacity of space, resources and personnel within health systems. There are many uncertainties in such a scenario, including likelihood and size of an attack, speed of response and health system capacity. We used a model for smallpox transmission to determine requirements for hospital beds, contact tracing and health workers (HCWs) in Sydney, Australia, during a modelled epidemic of smallpox. Sensitivity analysis was done on attack size, speed of response and proportion of case isolation and contact tracing. We estimated 100638 clinical HCWs and 14595 public hospital beds in Sydney. Rapid response, case isolation and contact tracing are influential on epidemic size, with case isolation more influential than contact tracing. With 95% of cases isolated, outbreak control can be achieved within 100 days even with only 50% of contacts traced. However, if case isolation and contact tracing both fall to 50%, epidemic control is lost. With a smaller initial attack and a response commencing 20 days after the attack, health system impacts are modest. The requirement for hospital beds will vary from up to 4% to 100% of all available beds in best and worst case scenarios. If the response is delayed, or if the attack infects 10000 people, all available beds will be exceeded within 40 days, with corresponding surge requirements for clinical health care workers (HCWs). We estimated there are 330 public health workers in Sydney with up to 940,350 contacts to be traced. At least 3 million respirators will be needed for the first 100 days. To ensure adequate health system capacity, rapid response, high rates of case isolation, excellent contact tracing and vaccination, and protection of HCWs should be a priority. Surge capacity must be planned. Failures in any of these could cause health system failure, with inadequate beds, quarantine spaces, personnel, PPE and inability to manage other acute health conditions.

Two distinct phenomena of airborne transmission of variola virus (smallpox) were described in the pre-eradication era—direct respiratory transmission, and a unique phenomenon of transmission over greater distances, referred to as “aerial convection”. We conducted an analysis of data obtained from a systematic review following the PRISMA criteria, on the long-distance transmission of smallpox. Of 8179 studies screened, 22 studies of 17 outbreaks were identified—12 had conclusive evidence of aerial convection and five had partially conclusive evidence. Aerial convection was first documented in 1881 in England, when smallpox incidence had waned substantially following mass vaccination, making unusual transmissions noticeable. National policy at the time stipulated spatial separation of smallpox hospitals from other buildings and communities. The evidence supports the transmission of smallpox through aerial convection at distances ranging from 0.5 to 1 mile, and one instance of 15 km related to bioweapons testing. Other explanations are also possible, such as missed chains of transmission, fomites or secondary aerosolization from contaminated material such as bedding. The window of observation of aerial convection was within the 100 years prior to eradication. Aerial convection appears unique to the variola virus and is not considered in current hospital infection control protocols. Understanding potential aerial convection of variola should be an important consideration in planning for smallpox treatment facilities and protecting potential contacts and surrounding communities.