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As infected and vaccinated population increases, some countries decided not to impose non-pharmaceutical intervention measures anymore and to coexist with COVID-19. However, we do not have a comprehensive understanding of its consequence, especially for China where most population has not been infected and most Omicron transmissions are silent. This paper aims to reveal the complete silent transmission dynamics of COVID-19 by agent-based simulations overlaying a big data of more than 0.7 million real individual mobility tracks without any intervention measures throughout a week in a Chinese city, with an extent of completeness and realism not attained in existing studies. Together with the empirically inferred transmission rate of COVID-19, we find surprisingly that with only 70 citizens to be infected initially, 0.33 million becomes infected silently at last. We also reveal a characteristic daily periodic pattern of the transmission dynamics, with peaks in mornings and afternoons. In addition, by inferring individual professions, visited locations and age group, we found that retailing, catering and hotel staff are more likely to get infected than other professions, and elderly and retirees are more likely to get infected at home than outside home. Author summary: Since 2019, we have witnessed the worldwide battle against COVID-19. As infected and vaccinated population increases, some countries chose not to impose any non-pharmaceutical measures and to live with COVID-19. In the literature, an extensive effort has been made to understand the effectiveness of intervention measures against COVID-19 and to predict its prevalence, but much less is known about the risk of choosing to coexist with COVID-19. Here, we conduct agent-based simulations overlaying a high-frequency mobility big data which records individual mobility tracks up to every second in a large-scale city in northern China, revealing the comprehensive transmission dynamics from a few initial infected individuals to city-wise infections. Such comprehensive understanding will provide useful insights into our battle against COVID-19. [ABSTRACT FROM AUTHOR]

Developing new methods for modelling infectious diseases outbreaks is important for monitoring transmission and developing policy. In this paper we propose using semi-mechanistic Hawkes Processes for modelling malaria transmission in near-elimination settings. Hawkes Processes are well founded mathematical methods that enable us to combine the benefits of both statistical and mechanistic models to recreate and forecast disease transmission beyond just malaria outbreak scenarios. These methods have been successfully used in numerous applications such as social media and earthquake modelling, but are not yet widespread in epidemiology. By using domain-specific knowledge, we can both recreate transmission curves for malaria in China and Eswatini and disentangle the proportion of cases which are imported from those that are community based. Author summary: This paper introduces a mathematically well-founded method for infectious disease outbreaks known as Hawkes Processes. These semi-mechanistic models are relatively new to the infectious diseases toolkit and enable us to combine disease specific information such as the infectious profile with statistical rigour to recreate temporal disease transmission. We show that these methods are very suited to modelling malaria in communities close to eliminating malaria—in particular China and Eswatini—where we are able to disentangle the contribution of exogenous (external) transmission and endogenous (person-to-person) transmission. This is particularly important for developing policies when counties are approaching elimination. [ABSTRACT FROM AUTHOR]

Clusters of genetically similar infections suggest rapid transmission and may indicate priorities for public health action or reveal underlying epidemiological processes. However, clusters often require user-defined thresholds and are sensitive to non-epidemiological factors, such as non-random sampling. Consequently the ideal threshold for public health applications varies substantially across settings. Here, we show a method which selects optimal thresholds for phylogenetic (subset tree) clustering based on population. We evaluated this method on HIV-1 pol datasets (n = 14, 221 sequences) from four sites in USA (Tennessee, Washington), Canada (Northern Alberta) and China (Beijing). Clusters were defined by tips descending from an ancestral node (with a minimum bootstrap support of 95%) through a series of branches, each with a length below a given threshold. Next, we used pplacer to graft new cases to the fixed tree by maximum likelihood. We evaluated the effect of varying branch-length thresholds on cluster growth as a count outcome by fitting two Poisson regression models: a null model that predicts growth from cluster size, and an alternative model that includes mean collection date as an additional covariate. The alternative model was favoured by AIC across most thresholds, with optimal (greatest difference in AIC) thresholds ranging 0.007–0.013 across sites. The range of optimal thresholds was more variable when re-sampling 80% of the data by location (IQR 0.008 − 0.016, n = 100 replicates). Our results use prospective phylogenetic cluster growth and suggest that there is more variation in effective thresholds for public health than those typically used in clustering studies. Author summary: A genetic cluster of virus infections is a group of DNA or RNA sequences that are much more similar to each other than they are to other infections from the same population of hosts. These clusters can reveal where virus transmission has been occurring the most rapidly, which can provide useful information for a public health response. Genetic clusters are often built by reconstructing a phylogeny—a tree-based model of how the sequences are related by common ancestors—and locating distinct parts of the tree with short branches. However, there are no objective, general-purpose criteria for deciding which parts of a tree constitute clusters, and there are an unlimited number of ways to partition a tree into clusters. In this study, we develop a computational method to determine the best clustering criteria based on our ability to predict where the next infections will occur. We apply this method to anonymized HIV-1 sequence data sets from Canada, the United States, and China, to characterize the sensitivity of clustering criteria to different risk populations and sampling contexts. Our results indicate that the clustering criteria typically used for phylogenetic studies of HIV-1 are not optimal for public health applications. [ABSTRACT FROM AUTHOR]

Anthropogenic environments such as those created by intensive farming of livestock, have been proposed to provide ideal selection pressure for the emergence of antimicrobial-resistant Escherichia coli bacteria and antimicrobial resistance genes (ARGs) and spread to humans. Here, we performed a longitudinal study in a large-scale commercial poultry farm in China, collecting E. coli isolates from both farm and slaughterhouse; targeting animals, carcasses, workers and their households and environment. By using whole-genome phylogenetic analysis and network analysis based on single nucleotide polymorphisms (SNPs), we found highly interrelated non-pathogenic and pathogenic E. coli strains with phylogenetic intermixing, and a high prevalence of shared multidrug resistance profiles amongst livestock, human and environment. Through an original data processing pipeline which combines omics, machine learning, gene sharing network and mobile genetic elements analysis, we investigated the resistance to 26 different antimicrobials and identified 361 genes associated to AR phenotypes; 58 of these were known AMR-associated genes and 35 were associated to multidrug resistance. We uncovered an extensive network of genes, correlated to AMR phenotypes, shared among livestock, humans, farm and slaughterhouse environments. We also found several human, livestock and environmental isolates sharing closely related mobile genetic elements carrying AR genes across host species and environments. In a scenario where no consensus exists on how antibiotic use in the livestock may affect antibiotic resistance in the human population, our findings provide novel insights into the broader epidemiology of antimicrobial resistance in livestock farming. Moreover, our original data analysis method has the potential to uncover AR transmission pathways when applied to the study of other pathogens active in other anthropogenic environments characterised by complex interconnections between host species. Author summary: Livestock have been suggested as an important source of antimicrobial-resistant (AMR) Escherichia coli, capable of infecting humans and carrying resistance to drugs used in human medicine. China has a large intensive livestock farming industry, poultry being the second most important source of meat in the country, and is the largest user of antibiotics for food production in the world. Here we studied antimicrobial resistance gene overlap between E. coli isolates collected from humans, livestock and their shared environments in a large-scale Chinese poultry farm and associated slaughterhouse. By using a computational approach that integrates machine learning, whole-genome sequencing, gene sharing network and mobile genetic elements analysis we characterized the E. coli community structure, antimicrobial resistance phenotypes and the genetic relatedness of non-pathogenic and pathogenic E. coli strains. We uncovered the network of genes, associated with AMR, shared across host species (animals and workers) and environments (farm and slaughterhouse). Our approach opens up new avenues for the development of a fast, affordable and effective computational solutions that provide novel insights into the broader epidemiology of antimicrobial resistance in livestock farming. [ABSTRACT FROM AUTHOR]

Infectious diseases attack humans from time to time and threaten the lives and survival of people all around the world. An important strategy to prevent the spatial spread of infectious diseases is to restrict population travel. With the reduction of the epidemic situation, when and where travel restrictions can be lifted, and how to organize orderly movement patterns become critical and fall within the scope of this study. We define a novel diffusion distance derived from the estimated mobility network, based on which we provide a general model to describe the spatiotemporal spread of infectious diseases with a random diffusion process and a deterministic drift process of the population. We consequently develop a multi-source data fusion method to determine the population flow in epidemic areas. In this method, we first select available subregions in epidemic areas, and then provide solutions to initiate new travel flux among these subregions. To verify our model and method, we analyze the multi-source data from mainland China and obtain a new travel flux triggering scheme in the selected 29 cities with the most active population movements in mainland China. The testable predictions in these selected cities show that reopening the borders in accordance with our proposed travel flux will not cause a second outbreak of COVID-19 in these cities. The finding provides a methodology of re-triggering travel flux during the weakening spread stage of the epidemic. Author summary: Human infectious diseases spread from their origins to other places with population movements. In order to curb the spatial spread of infectious diseases, many countries and regions may introduce some travel restrictions when the epidemic is severe, and reopen the borders as the epidemic eases. This process involves some important issues such as the start and end time of travel restrictions, the geographical scope of the implementation of the exit strategy, and the allowable passenger flow on traffic lines. Here, we integrate multi-source data with a mathematical model, and consequently develop a new method to determine the travel flux in epidemic areas. As an application, we use this method to calculate when and where the travel restrictions targeting COVID-19 in China in early 2020 could be lifted, and how to optimize passenger flow along the traffic lines among the reopened cities. The testable predictions indicate that the population flow in accordance with our proposed movement pattern will not cause a resurgent outbreak of COVID-19 in the cities studied. [ABSTRACT FROM AUTHOR]

In January 2020, a COVID-19 outbreak was detected in Sichuan Province of China. Six weeks later, the outbreak was successfully contained. The aim of this work is to characterize the epidemiology of the Sichuan outbreak and estimate the impact of interventions in limiting SARS-CoV-2 transmission. We analyzed patient records for all laboratory-confirmed cases reported in the province for the period of January 21 to March 16, 2020. To estimate the basic and daily reproduction numbers, we used a Bayesian framework. In addition, we estimate the number of cases averted by the implemented control strategies. The outbreak resulted in 539 confirmed cases, lasted less than two months, and no further local transmission was detected after February 27. The median age of local cases was 8 years older than that of imported cases. We estimated R0 at 2.4 (95% CI: 1.6–3.7). The epidemic was self-sustained for about 3 weeks before going below the epidemic threshold 3 days after the declaration of a public health emergency by Sichuan authorities. Our findings indicate that, were the control measures be adopted four weeks later, the epidemic could have lasted 49 days longer (95% CI: 31–68 days), causing 9,216 more cases (95% CI: 1,317–25,545). Author summary: Since its emergence in Wuhan, SARS-CoV-2 rapidly started its spread across China. On January 21, 2020 the first COVID-19 case was detected in the Sichuan Province of China and led to an outbreak of local transmission. Less than two months later, the outbreak was over with the last reported case on March 4, 2020. In this study, we analyzed patient records for all laboratory-confirmed cases reported in the Sichuan to provide an epidemiological characterization of the outbreak, to estimate SARS-CoV-2 transmission potential, and to assess the impact of the adopted interventions. We estimated that, during the initial exponential growth phase of the outbreak, each COVID-19 case has generated a mean of 2.4 secondary cases (95% CI: 1.6–3.7). Moreover, we estimated that, were the Sichuan strict containment measures implemented four weeks later, the outbreak would have caused 9,216 more cases (95% CI: 1,317–25,545). Our findings suggest the key role of a quick response to COVID-19 outbreaks and the importance of an adequate surveillance and monitoring system. [ABSTRACT FROM AUTHOR]

Recent advances in mathematical modeling and inference methodologies have enabled development of systems capable of forecasting seasonal influenza epidemics in temperate regions in real-time. However, in subtropical and tropical regions, influenza epidemics can occur throughout the year, making routine forecast of influenza more challenging. Here we develop and report forecast systems that are able to predict irregular non-seasonal influenza epidemics, using either the ensemble adjustment Kalman filter or a modified particle filter in conjunction with a susceptible-infected-recovered (SIR) model. We applied these model-filter systems to retrospectively forecast influenza epidemics in Hong Kong from January 1998 to December 2013, including the 2009 pandemic. The forecast systems were able to forecast both the peak timing and peak magnitude for 44 epidemics in 16 years caused by individual influenza strains (i.e., seasonal influenza A(H1N1), pandemic A(H1N1), A(H3N2), and B), as well as 19 aggregate epidemics caused by one or more of these influenza strains. Average forecast accuracies were 37% (for both peak timing and magnitude) at 1-3 week leads, and 51% (peak timing) and 50% (peak magnitude) at 0 lead. Forecast accuracy increased as the spread of a given forecast ensemble decreased; the forecast accuracy for peak timing (peak magnitude) increased up to 43% (45%) for H1N1, 93% (89%) for H3N2, and 53% (68%) for influenza B at 1-3 week leads. These findings suggest that accurate forecasts can be made at least 3 weeks in advance for subtropical and tropical regions. [ABSTRACT FROM AUTHOR]