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Bayesian estimation of Lassa virus epidemiological parameters: implications for spillover prevention using wildlife vaccination

Lassa virus is a significant burden on human health throughout its endemic region in West Africa, with most human infections the result of spillover from the primary rodent reservoir of the virus, the natal multimammate mouse, M. natalensis. Here we develop a Bayesian methodology for estimating epidemiological parameters of Lassa virus within its rodent reservoir and for generating probabilistic predictions for the efficacy of rodent vaccination programs. Our approach uses Approximate Bayesian Computation (ABC) to integrate mechanistic mathematical models, remotely-sensed precipitation data, and Lassa virus surveillance data from rodent populations. Using simulated data, we show that our method accurately estimates key model parameters, even when surveillance data are available from only a relatively small number of points in space and time. Applying our method to previously published data from two villages in Guinea estimates the time-averaged R0 of Lassa virus to be 1.658 and 1.453 for rodent populations in the villages of Bantou and Tanganya, respectively. Using the posterior distribution for model parameters derived from these Guinean populations, we evaluate the likely efficacy of vaccination programs relying on distribution of vaccine-laced baits. Our results demonstrate that effective and durable reductions in the risk of Lassa virus spillover into the human population will require repeated distribution of large quantities of vaccine. Author SummaryLassa virus is a chronic source of illness throughout West Africa, and is considered to be a threat for widespread emergence. Because most human infections result from contact with infected rodents, interventions that reduce the number of rodents infected with Lassa virus represent promising opportunities for reducing the public health burden of this disease. Evaluating how well alternative interventions are likely to perform is complicated by our relatively poor understanding of viral epidemiology within the reservoir population. Here we develop a novel statistical approach that couples mathematical models and viral surveillance data from rodent populations to robustly estimate key epidemiological parameters. Applying our method to existing data from Guinea yields well-resolved parameter estimates and allows us to simulate a variety of rodent vaccination programs. Together, our results demonstrate that rodent vaccination alone is unlikely to be an effective tool for reducing that public health burden of Lassa fever within West Africa.

ecology↗

Multilevel HierCC typing scheme for global genomic epidemiology and antimicrobial resistance surveillance of Campylobacter jejuni

Campylobacter jejuni is the most common bacterial cause of human gastroenteritis around the world. The disease burden and financial cost associated with C. jejuni pose significant challenges to the global public health system. A stable, scalable and standardised typing scheme is essential for epidemiological and AMR surveillance for prevention and control of C. jejuni infections. We curated and assembled a C. jejuni global whole genome sequencing (WGS) dataset of 63,012 publicly available Illumina short-read genomes. A C. jejuni global cgMLST scheme with 1161 core loci was developed using a representative subset of 2,587 genomes. HierCC clustering of the cgMLST profiles was performed for all levels and suitable HierCC levels were selected to enable epidemiological analysis. Antimicrobial resistance (AMR) prediction was performed using AbritAMR. A HierCC cluster was classified as a resistant cluster if [≥]80% of the isolates were resistant to at least one antibiotic.We selected 9 HierCC levels (HC2, HC4, HC6, HC12, HC19, HC55, HC100, HC167 and HC264) to form the multilevel HierCC scheme. The multilevel design allowed natural and genetically discrete clusters to be described consistently at both global and local scale. We showcased the utility of the scheme with identification of country and continent specific clusters at HC264 to HC19 levels and differentiation of animal host specific (specialist) from human infection (generalist) clusters at HC264 to HC55 levels. In the USA dataset from 2016 to 2022, a total of 276 resistant clusters were identified with 22 resistant clusters increasing in frequence in recent years. An increased prevalence of C. jejuni carrying 50S_L22 mutations in the USA was observed from 2016 to 2022, suggesting continuing selection pressure from macrolide use in the farm animals. We developed a novel multilevel HierCC typing scheme to standardise AMR surveillance and provide flexible typing resolution for both short- and long-term epidemiological investigations of C. jejuni at global and local levels.

microbiology↗

Reference-free clustering as an epidemiological tool for Mycobacterium tuberculosis lineage typing

Whole-genome sequencing (WGS) of Mycobacterium tuberculosis (Mtb) is widely used in the epidemiological investigation of recent transmission events, resulting in high-resolution strain typing. Accurate and rapid strain typing is essential for informing outbreak investigations and guiding tuberculosis control strategies. However, the gold-standard reference-guided SNP-calling pipeline currently used for strain typing relies on computationally intensive reference-mapping approaches, making it challenging to perform in many high-burden, resource-limited settings, where simplified and scalable genomic tools are urgently needed. To address these limitations, we explored reference-free methods for medium resolution epidemiology, namely Mtb strain (lineage) typing, using a dataset of 535 complete genomes spanning the human- and animal-adapted lineages. Illumina paired-end reads were simulated from each complete genome, assembled, and analysed using three reference-free, k-mer-based tools: MASH, PopPUNK, and SKA2 (Split K-mer Analysis). Genetic distances were generated for each method and compared with a ground truth lineage assignment from with TB Profiler. Our results demonstrated that reference-free methods can effectively distinguish Mtb lineages, with SKA2 showing the most promising performance across all datasets. SKA2 consistently recovered lineage and sub-lineage structure with high accuracy, demonstrating strong potential as an alternative to traditional WGS workflows. These findings highlight the utility of reference-free methods, particularly SKA2, for enabling accessible, scalable, and rapid Mtb strain typing, while supporting genomic epidemiology with low computational resources.

bioinformatics↗

Integrated epidemiological and genomic analysis of some respiratory Bovine Coronavirus isolates reveals circulation of GIIb strains and ongoing viral evolution in U.S. Cattle (2020-2025)

Bovine coronavirus (BCoV) is an important contributor to the respiratory disease complex in cattle; however, integrated genomic and epidemiological data describing currently circulating respiratory BCoV strains in the United States remain limited. The objective of this study was to monitor respiratory BCoV at the genomic level and analyze its epidemiological patterns over a five-year period. A total of 4,505 respiratory samples submitted to a diagnostic laboratory between January 2020 and November 2025 were analyzed, of which 693 (15.38%) tested positive for BCoV. Positivity was highest in young calves (0-40 days; 20.0%) and declined significantly with increasing age based on logistic regression analysis. Temporal trend analysis using LOESS smoothing and the Mann-Kendall test showed no significant monotonic change in BCoV detection during the study period. Co-infection analysis indicated that BCoV was commonly detected with other viral respiratory pathogens, while bacterial pathogens predominated in many samples. Lung tissues from infected cattle were screened by RT-PCR, and selected samples with high viral loads were subjected to next-generation sequencing. Complete genome sequencing identified four respiratory BCoV isolates ([~]31 kb), all clustering within genotype GIIb with recent U.S. strains. Comparative genomic analysis revealed several amino acid substitutions in structural and non-structural proteins that may influence viral attachment, replication, and tissue tropism. These findings provide updated epidemiological and genomic insights into respiratory BCoV circulating in U.S. cattle.

microbiology↗

Evolutionary and epidemiological considerations for anthelmintic treatments in ruminant livestock

Anthelmintic drug resistance is a concern for the sustained control of gastrointestinal nematodes (GINs) in ruminant livestock globally. Evolutionary-epidemiological modelling, which considers both parasite dynamics and resistance dynamics in response to interventions, can be useful in determining which anthelmintic resistance management (ARM) strategies may be effective without compromising parasite control. We address two key questions in ARM. First, how to improve the measurement of AR in populations. Second, identifying effective ARM strategies to slow the spread of AR while maintaining effective parasite control. We developed a simulation framework which tracks the weather-dependent epidemiology of GINs and AR evolution, providing a highly flexible methodology to evaluate multiple ARM strategy options in a single modelling framework, allowing for novel insights due to direct comparisons between strategies. Simulations to refine our understanding of anthelmintic resistance management evaluated the impact of key areas of uncertainty, including transmission intensity, resistance intensity, resistance frequency, drug decay and linking faecal egg count reduction tests (FECRT) to resistance allele frequency. Large-scale simulations present a methodologically thorough evaluation of how treatment choices simultaneously impact epidemiological and evolutionary outcomes. Phenotypic classifications of resistance status using FECRT failed to capture fine scale changes in resistance allele frequency. The pharmacokinetics of drug decay strongly influenced ARM outcomes, and trade-offs between ARM and effective parasite control depends on genetic factors underpinning resistance. Combination therapies appear to be the most effective resistance management strategy evaluated. Our findings suggest practical implementations to manage anthelmintic resistance must simultaneously consider parasite transmission, pharmacology and parasite genetics to be robust and sustainable. We provide a rigorous simulation framework to enable such discussions allowing for a refinement into our understanding of parasite control in the presence of resistance evolution.

evolutionary biology↗

Genomic infectious disease epidemiology in partially sampled and ongoing outbreaks

Genomic data is increasingly being used to understand infectious disease epidemiology. Isolates from a given outbreak are sequenced, and the patterns of shared variation are used to infer which isolates within the outbreak are most closely related to each other. Unfortunately, the phylogenetic trees typically used to represent this variation are not directly informative about who infected whom - a phylogenetic tree is not a transmission tree. However, a transmission tree can be inferred from a phylogeny while accounting for within-host genetic diversity by colouring the branches of a phylogeny according to which host those branches were in. Here we extend this approach and show that it can be applied to partially sampled and ongoing outbreaks. This requires computing the correct probability of an observed transmission tree and we herein demonstrate how to do this for a large class of epidemiological models. We also demonstrate how the branch colouring approach can incorporate a variable number of unique colours to represent unsampled intermediates in transmission chains. The resulting algorithm is a reversible jump Monte-Carlo Markov Chain, which we apply to both simulated data and real data from an outbreak of tuberculosis. By accounting for unsampled cases and an outbreak which may not have reached its end, our method is uniquely suited to use in a public health environment during real-time outbreak investigations. We implemented our technique in an R package called TransPhylo, which is freely available from https://github.com/xavierdidelot/TransPhylo.

Epidemiology↗

Combining Ensemble Learning Techniques and G-Computation to Investigate Chemical Mixtures in Environmental Epidemiology Studies

BackgroundAlthough biomonitoring studies demonstrate that the general population experiences exposure to multiple chemicals, most environmental epidemiology studies consider each chemical separately when assessing adverse effects of environmental exposures. Hence, the critical need for novel approaches to handle multiple correlated exposures.\n\nMethodsWe propose a novel approach using the G-formula, a maximum likelihood-based substitution estimator, combined with an ensemble learning technique (i.e. SuperLearner) to infer causal effect estimates for a multi-pollutant mixture. We simulated four continuous outcomes from real data on 5 correlated exposures under four exposure-response relationships with increasing complexity and 500 replications. The first simulated exposure-response was generated as a linear function depending on two exposures; the second was based on a univariate nonlinear exposure-response relationship; the third was generated as a linear exposure-response relationship depending on two exposures and their interaction; the fourth simulation was based on a non-linear exposure-response relationship with an effect modification by sex and a linear relationship with a second exposure. We assessed the method based on its predictive performance (Minimum Square error [MSE]), its ability to detect the true predictors and interactions (i.e. false discovery proportion, sensitivity), and its bias. We compared the method with generalized linear and additive models, elastic net, random forests, and Extreme gradient boosting. Finally, we reconstructed the exposure-response relationships and developed a toolbox for interactions visualization using individual conditional expectations.\n\nResultsThe proposed method yielded the best average MSE across all the scenarios, and was therefore able to adapt to the true underlying structure of the data. The method succeeded to detect the true predictors and interactions, and was less biased in all the scenarios. Finally, we could correctly reconstruct the exposure-response relationships in all the simulations.\n\nConclusionsThis is the first approach combining ensemble learning techniques and causal inference to unravel the effects of chemical mixtures and their interactions in epidemiological studies. Additional developments including high dimensional exposure data, and testing for detection of low to moderate associations will be carried out in future developments.

epidemiology↗

Zika virus outbreak in Cabo Verde Islands, West Africa: early epidemiological findings

IntroductionThe Zika virus (ZIKV) outbreak in the island nation of Cabo Verde was of unprecedented magnitude in Africa and the first to be associated with microcephaly in the continent.\n\nMethodsUsing a simple mathematical framework we present a first epidemiological assessment of attack and observation rates from 7,580 ZIKV notified cases and 18 microcephaly reports between July 2015 and May 2016.\n\nResultsIn line with observations from the Americas and elsewhere, the single-wave Cabo Verdean ZIKV epidemic was characterized by a basic reproductive number of 1.85 (95% CI, 1.5 -2.2), with overall the attack rate of 51.1% (range 42.1 - 61.1) and observation rate of 2.7% (range 2.29 - 3.33).\n\nConclusionCurrent herd-immunity may not be sufficient to prevent future small-to-medium epidemics in Cabo Verde. Together with a small observation rate, these results highlight the need for rapid and integrated epidemiological, molecular and genomic surveillance to tackle forthcoming outbreaks of ZIKV and other arboviruses.

epidemiology↗

Causal inference in cancer epidemiology: what is the role of Mendelian randomization?

Observational epidemiological studies are prone to confounding, measurement error, and reverse causation, undermining their ability to generate reliable causal estimates of the effect of risk factors to inform cancer prevention and treatment strategies. Mendelian randomization (MR) is an analytical approach that uses genetic variants to proxy potentially modifiable exposures (e.g. environmental factors, biological traits, and druggable pathways) to permit robust causal inference of the effects of these exposures on diseases and their outcomes. MR has seen widespread adoption within population health research in cardio-metabolic disease, but also holds much promise for identifying possible interventions (e.g., dietary, behavioural, or pharmacological) for cancer prevention and treatment. However, some methodological and conceptual challenges in the implementation of MR are particularly pertinent when applying this method to cancer aetiology and prognosis, including reverse causation arising from disease latency and selection bias in studies of cancer progression. These issues must be carefully considered to ensure appropriate design, analysis, and interpretation of such studies.\n\nIn this review, we provide an overview of the key principles and assumptions of MR focusing on applications of this method to the study of cancer aetiology and prognosis. We summarize recent studies in the cancer literature that have adopted a MR framework to highlight strengths of this approach compared to conventional epidemiological studies. Lastly, limitations of MR and recent methodological developments to address them are discussed, along with the translational opportunities they present to inform public health and clinical interventions in cancer.

epidemiology↗

Can we use routinely collected hospital and GP data for epidemiological study of common hand conditions? A UK Biobank based validation project

ObjectiveRoutine health records can be of great value in epidemiological and genetic studies if they are able to reliably identify true disease cases, especially when linked to large cohort studies. Little research has been undertaken into whether coding within UK electronic health records (EHR) is able to accurately identify clinical disease cases of common hand conditions. There is therefore a relative paucity of hand surgical research using EHRs due to concerns that cases cannot be accurately identified.\n\nThe aim of this study was to investigate the accuracy of hospital and primary care coding of routine EHRs for carpal tunnel syndrome (CTS) and base of thumb osteoarthritis (BTOA). Self-reported disease state as recorded in UK Biobank, a large prospective cohort study was also investigated.\n\nMethodsCode lists for each condition were generated by a team of clinicians, clinical coders and epidemiologists. All patients recruited to UK Biobank in one geographical region (Lothian, Scotland) where linked primary and secondary care coded datasets available were included. A decision- making algorithm was designed to define an administratively-confirmed or a clinically confirmed disease case. Patient electronic medical records (EMRs) were independently interrogated by two clinicians and inter-observer reliability calculated.\n\nResultsOf the 17,201 Biobank participants in NHS Lothian, 268 had at least one code for CTS and 82 for BTOA. For CTS, 159 cases were confirmed, 100 cases had insufficient information and 9 cases were refuted. Excluding missing data, the positive predictive value (PPV) for true clinical disease cases was 96% for incident disease (90% for prevalent disease; overall 94%).\n\nFor BTOA, 27 cases were confirmed, 46 cases had insufficient information, and 9 cases were refuted. Excluding missing data, PPV for incident disease was 81% (prevalent disease 56%, overall PPV 75%). Interrogation of the disease cases with insufficient information noted a large proportion arising from primary care and self-report coding systems.\n\nAnalyzing code combinations revealed that secondary care codes had the highest PPV for CTS and BTOA, emphasizing a more robust evaluation of PPV for patients requiring hospital based care. Overall, inter-observer reliability was good, with agreement in 90% of cases (Cohens kappa of 0.79) for clinical disease cases in CTS and agreement of 98%, (kappa 0.96) for BTOA.\n\nConclusionsWe have demonstrated that coding within UK Biobank is of sufficient quality to enable use of the resource for epidemiological and genetic research into common hand conditions, and that EMRs can be used for manual validation of UK health coding systems. Further work is needed to consider potential regional and interdisciplinary differences in coding practice, in strategies for dealing with missing data in EHRs, and to validate coding of common hand conditions in primary care.

epidemiology↗

Mapping malaria by combining parasite genomic and epidemiologic data

Recent global progress in scaling up malaria control interventions has revived the goal of complete elimination in many countries. Decreasing transmission intensity generally leads to increasingly patchy spatial patterns of malaria transmission, however, and control programs must accurately identify remaining foci in order to target interventions efficiently. In particular, mosquito control interventions like bed nets and insecticide spraying are best targeted to transmission hotspots, and the role of connectivity between different pockets of local transmission becomes increasingly important since humans are able to move parasites beyond the limits of mosquito dispersal and re-introduce parasites to previously malaria-free regions. Quantifying the connectivity between regions due to human travel, measuring malaria transmission intensity in different areas, and monitoring parasite spatial spread are therefore key issues for policy-makers because they underpin the feasibility of elimination and inform the path to its attainment. To this end, recent efforts have been made to develop new approaches to incorporating human mobility into spatial epidemiological models, for example using mobile phone data, and there has been a surge of interest in collecting spatially informative parasite samples to measure the genomic signatures of parasite connectivity. Due to their complicated life-cycles, Plasmodium parasites pose unique challenges to researchers in this respect and new methods that move beyond traditional phylogenetic and population genetic tools must be developed to harness genetic information effectively. Here, we discuss the spatial epidemiology of malaria in the context of transmission-reduction interventions, and the challenges and promising directions for the development of integrated mapping, modeling, and genomic approaches that leverage disparate data sets to measure both connectivity and transmission.

epidemiology↗

Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: an overview of the data from the epidemiological studies within the IMI DIRECT Consortium

Abstract/SummaryO_ST_ABSBackground and aimsC_ST_ABSUnderstanding the aetiology, clinical presentation and prognosis of type 2 diabetes (T2D) and optimizing its treatment might be facilitated by biomarkers that help predict a persons susceptibility to the risk factors that cause diabetes or its complications, or response to treatment. The IMI DIRECT (Diabetes Research on Patient Stratification) Study is a European Union (EU) Innovative Medicines Initiative (IMI) project that seeks to test these hypotheses in two recently established epidemiological cohorts. Here, we describe the characteristics of these cohorts at baseline and at the first main follow-up examination (18-months).\n\nMaterials and methodsFrom a sampling-frame of 24,682 European-ancestry adults in whom detailed health information was available, participants at varying risk of glycaemic deterioration were identified using a risk prediction algorithm and enrolled into a prospective cohort study (n=2127) undertaken at four study centres across Europe (Cohort 1: prediabetes). We also recruited people from clinical registries with recently diagnosed T2D (n=789) into a second cohort study (Cohort 2: diabetes). The two cohorts were studied in parallel with matched protocols. Endogenous insulin secretion and insulin sensitivity were modelled from frequently sampled 75g oral glucose tolerance (OGTT) in Cohort 1 and with mixed-meal tolerance tests (MMTT) in Cohort 2. Additional metabolic biochemistry was determined using blood samples taken when fasted and during the tolerance tests. Body composition was assessed using MRI and lifestyle measures through self-report and objective methods.\n\nResultsUsing ADA-2011 glycaemic categories, 33% (n=693) of Cohort 1 (prediabetes) had normal glucose regulation (NGR), and 67% (n=1419) had impaired glucose regulation (IGR). 76% of the cohort was male, age=62(6.2) years; BMI=27.9(4.0) kg/m2; fasting glucose=5.7(0.6) mmol/l; 2-hr glucose=5.9(1.6) mmol/l [mean(SD)]. At follow-up, 18.6(1.4) months after baseline, fasting glucose=5.8(0.6) mmol/l; 2-hr OGTT glucose=6.1(1.7) mmol/l [mean(SD)]. In Cohort 2 (diabetes): 65% (n=508) were lifestyle treated (LS) and 35% (n=271) were lifestyle + metformin treated (LS+MET). 58% of the cohort was male, age=62(8.1) years; BMI=30.5(5.0) kg/m2; fasting glucose=7.2(1.4)mmol/l; 2-hr glucose=8.6(2.8) mmol/l [mean(SD)]. At follow-up, 18.2(0.6) months after baseline, fasting glucose=7.8(1.8) mmol/l; 2-hr MMTT glucose=9.5(3.3) mmol/l [mean(SD)].\n\nConclusionThe epidemiological IMI DIRECT cohorts are the most intensely characterised prospective studies of glycaemic deterioration to date. Data from these cohorts help illustrate the heterogeneous characteristics of people at risk of or with T2D, highlighting the rationale for biomarker stratification of the disease - the primary objective of the IMI DIRECT consortium.\n\nAbbreviations

epidemiology↗

A mechanistic hydro-epidemiological model of liver fluke risk

The majority of existing models for predicting disease risk in response to climate change are empirical. These models exploit correlations between historical data, rather than explicitly describing relationships between cause and response variables. Therefore, they are unsuitable for capturing impacts beyond historically observed variability and cannot be employed to assess interventions. In this study, we integrate environmental and epidemiological processes into a new mechanistic model, taking the widespread parasitic disease of fasciolosis as an example. The model simulates environmental suitability for disease transmission, explicitly linking the parasite life-cycle to key weather-water-environment conditions. First, using epidemiological data, we show that the model can reproduce observed infection levels in time and space over two case studies in the UK. Second, to overcome data limitations, we propose a calibration approach based on Monte Carlo sampling and expert opinion, which allows constraint of the model in a process-based way, including a quantification of uncertainty. Finally, comparison with information from the literature and a widely-used empirical risk index shows that the simulated disease dynamics agree with what has been traditionally observed, and that the new model gives better insight into the time-space patterns of infection, which will be valuable for decision support.

epidemiology↗

A Generative Bayesian Approach for Incorporating Biosurveillance Sources into Epidemiological Models

Biosurveillance \"systematically collects and analyzes data for the purpose of detecting cases of disease, [and] outbreaks of disease.\" (Wagner, Moore and Aryel, 2006) This typically involves using a set of known sources of epidemiological data, instead of opportunistically using the data sources which become available over time. This work attempts to partially remedy that limitation by using an easily adapted generative Bayesian econometric model to allow incorporation of novel data sources. This is done by building a generative model of the information sources, then using Bayesian Markov-chain Monte-Carlo to find the relationships between data and actual caseloads to use in an epidemiological model 1. While the application presented is limited to three data sources for a single disease (influenza), the methodology is potentially widely applicable, and enables rapid incorporation of a variety of sources and source types.

epidemiology↗

Epidemiology of a bubonic plague outbreak in Glasgow, Scotland in 1900

On August 3, 1900, bubonic plague (Yersinia pestis) broke out in Glasgow for the first time during the Third Pandemic. The local sanitary authorities rigorously tracked the spread of the disease and they found that nearly all of the 35 cases could be linked by contact with a previous case. Despite trapping hundreds of rats in the area, there was no evidence of a rat epizootic and the investigators speculated that the outbreak could be due to human-to-human transmission of bubonic plague. Here we use a likelihood-based method to reconstruct transmission trees for the outbreak. From the description of the outbreak and the reconstructed trees, we infer several epidemiological parameters. We found that the estimated mean serial interval was 7.4 days and the mean effective reproduction number dropped below 1 after implementation of control measures. We also found that there was a high rate of secondary transmissions within households and observations of transmissions from individuals who were not terminally septicemic. Our results provide important insights into the epidemiology of plague that are useful for modeling current and historic plague epidemics.

epidemiology↗

The Clinical and Molecular Epidemiology of CTX-M-9 Group Producing Enterobacteriaceae infections in children

BackgroundThe pandemic of extended-spectrum-beta-lactamase (ESBL)-producing-Enterobacteriaceae (Ent) is strongly linked to the dissemination of CTX-M-type-ESBL-Ent. We sought to define the epidemiology of infections in children due to an emerging resistance type, CTX-M-9-group-producing-Ent (CTX-M-9-grp-Ent).\n\nMethodsA multi-centered case-control analysis of Chicago children with CTX-M-9-grp-Ent infections was performed. Cases were defined as children possessing extended-spectrum-cephalosporin-resistant (ESC-R) infections. PCR and DNA analysis assessed beta-lactamase (bla) genes, multi-locus sequence types (MLST) and phylogenetic grouping of E. coli. Controls were children with ESC-susceptible (ESC-S)-Ent infections matched 3:1 by age, source, and hospital. The clinical-epidemiologic predictors of CTX-M-9-grp-Ent infection were assessed.\n\nResultsOf 356 ESC-R-Ent isolates from children (median age 4.1 years), CTX-M-9-group was the solely detected bla gene in 44(12.4%). The predominant species was E. coli (91%) of virulent phylogroups D(60%) and B2(40%). MLST revealed multiple strain types. On multivariable analysis, CTX-M-9-grp-Ent occurred more often in E. coli (OR 7.0), children of non-black-white-Hispanic race (OR 6.5), and outpatients (OR 4.5) which was a very unexpected finding for infections due to antibiotic-resistant bacteria. Residents of South Chicago were 6.7 times more likely to have CTX-M-9-grp-Ent infections than those in the reference region (West), while residence in Northwestern Chicago was associated with an 81% decreased risk. Other demographic, comorbidity, invasive-device, and antibiotic use differences were not found.\n\nConclusionsCTX-M-9-grp-Ent infection is strikingly associated with patient residence and is occurring in children without traditional in-patient exposure risk factors. This suggests that among children, the community environment may be a key contributor in the spread of these resistant pathogens.

epidemiology↗

Asthma-Neoplasms Relationships: New Insights Using Machine Inference, Epidemiological Reasoning, And Big Data

BackgroundA relationship between asthma and the risk of having cancer has been identified in several studies. However, these studies have used different methodologies, been primarily cross-sectional in nature, and the results have been contradictory. Population-level analyses are required to determine if a relationship truly exists. MethodsWe developed a novel machine learning tool to infer associations, Causal Inference using the Composition of Transactions (CICT). Two all payers claim datasets of over two hundred million hospitalization encounters from the US-based Healthcare Cost and Utilization Project (HCUP) were used for discovery and validation. Associations between asthma and neoplasms were discovered in data from the State of Florida. Validation was conducted on eight cohorts of patients with asthma, and seven subtypes of asthma and COPD using datasets from the State of California. Control groups were matched by gender, age, race, and history of tobacco use. Odds ratio analysis with Bonferroni-Holm correction measured the association of asthma and COPD with 26 different benign and malignant neoplasms. ICD9CM codes were used to identify exposures and outcomes. FindingsCICT identified 17 associations between asthma and the risk of neoplasia in the discovery dataset. In the validation studies, 208 case-control analyses were conducted between subtypes of Asthma (N= 999,370, male= 33%, age= 50) and COPD (N=715,971, male = 50%, age=69) with the corresponding matched control groups (N=8,400,004, male= 42%, age= 47). Allergic asthma was associated with benign neoplasms of the meninges, salivary, pituitary, parathyroid, and thyroid glands (OR:1.52 to 2.52), and malignant neoplasms of the breast, intrahepatic biliary system, hematopoietic, and lymphatic system (OR: 1.45 to 2.05). COPD was associated with malignant neoplasms in the lung, bladder, and hematopoietic systems. InterpretationThe combined use of machine learning methods for knowledge discovery and epidemiological methods shows that allergic asthma is associated with the development of neoplasia, including in glandular organs, ductal tissues, and hematopoietic systems. Also, our findings differentiate the pattern of neoplasms between allergic asthma and obstructive asthma. This suggests that inflammatory pathways that are active in asthma also contribute to neoplastic transformation in specific organ systems such as secretory organs. FundingNone At a Glance CommentaryOver the past three decades, studies have suggested that asthma could increase the risk of developing cancer, but a consensus has not been reached. The debate persists because the current evidence has been derived using cross-sectional statistical designs, limited datasets, and small cohorts and conflicting results. In addition, the mechanism by which allergic airway inflammation contributes to neoplastic transformation is postulated but not proven. Here, we present the largest study to date on this association in patients with asthma or COPD. A knowledge discovery method was used for hypothesis generation that, when combined with epidemiological reasoning tools, identified associations between airway disease and neoplasia. The results reveal novel relationships between allergic asthma and benign glandular tumors and confirm the well-known connections between COPD and lung cancer. Further, we identified a novel association between COPD and asthma with hematological malignancies. These findings rectify contradictory results from other studies and demonstrate more specifically that the types of neoplasms associated with asthma compared to COPD that infers mechanistic plausibility.

epidemiology↗

SimpactCyan 1.0: An Open-source Simulator for Individual-Based Models in HIV Epidemiology with R and Python Interfaces

SimpactCyan is an open-source simulator for individual-based models in HIV epidemiology. Its core algorithm is written in C++ for computational efficiency, while the R and Python interfaces aim to make the tool accessible to the fast-growing community of R and Python users. Transmission, treatment and prevention of HIV infections in dynamic sexual networks are simulated by discrete events. A generic "intervention" event allows model parameters to be changed over time, and can be used to model medical and behavioural HIV prevention programmes. First, we describe a more efficient variant of the modified Next Reaction Method that drives our continuous-time simulator. Next, we outline key built-in features and assumptions of individual-based models formulated in SimpactCyan, and provide code snippets for how to formulate, execute and analyse models in SimpactCyan through its R and Python interfaces. Lastly, we give two examples of applications in HIV epidemiology: the first demonstrates how the software can be used to estimate the impact of progressive changes to the eligibility criteria for HIV treatment on HIV incidence. The second example illustrates the use of SimpactCyan as a data-generating tool for assessing the performance of a phylodynamic inference framework.

epidemiology↗