bioRxiv Science⌕ Search

Biology subjects

Morgan, E. R.

Publications and source records attributed to Morgan, E. R..

12 recordsLinked to original sources

Spatio-temporal machine learning for multi-horizon prediction of bluetongue outbreaks

Reliable early warning of infectious disease outbreaks remains a major challenge for surveillance systems, particularly for vector-borne pathogens whose transmission depends on interactions among hosts, vectors, and climate-sensitive environmental conditions. Data-driven forecasting offers a promising approach for predicting outbreak risk using surveillance and environmental data. This study develops a logit-weighted ensemble (LWE), a machine-learning framework that predicts outbreak occurrence 1-6 months ahead at the administrative unit-month scale using routinely available outbreak notifications and gridded climate data. Bluetongue virus (BTV), an arbovirus of ruminants transmitted by Culicoides biting midges, provides a well-characterised system in which transmission is strongly shaped by climate, making it a useful system for applying and testing this approach. The framework is evaluated using surveillance data collected between 2005 and 2024 from France, Greece, and Italy, selected for their long-running and high-quality outbreak surveillance records. Across all three countries, the LWE achieved the strongest and most stable predictive performance under a recall-focused evaluation that prioritises correctly identifying outbreak months. It outperformed or matched 14 benchmark models, with differences becoming more pronounced at longer lead times (month +3 onward), when predictions are more uncertain and outbreaks are relatively rare. Predictability varied across countries, with the highest performance in Greece, strong performance in France, and lower, more variable performance in Italy, reflecting differences in how consistently outbreaks occur and spread across regions. Overall, the results demonstrate that horizon-aware, climate-informed forecasting can reliably identify months and locations at elevated risk of outbreak occurrence up to six months in advance, supporting surveillance planning and preparedness across heterogeneous European settings. The ensemble framework provides a robust and portable strategy for outbreak prediction using routinely collected surveillance and environmental data. Author SummaryPredicting infectious disease outbreaks before they occur remains a major challenge, particularly for diseases influenced by environmental conditions. In this study, we focus on bluetongue, a viral disease of livestock transmitted by biting midges, where transmission is strongly affected by climate and seasonal patterns. We develop a method that uses routinely collected outbreak reports and climate data to estimate where and when outbreaks are more likely to occur, up to six months in advance. We apply this approach across three European countries with a history of bluetongue outbreaks. We find that combining climate information with recent outbreak patterns can provide useful early signals of increased risk. Predictions are most accurate at shorter timeframes, but longer-range forecasts can still support planning and preparedness. Because our approach uses widely available data, it could be applied in other regions or to similar environmentally driven diseases. However, it does not include factors such as vaccination, animal movement, or detailed information on vector populations, which may also influence how outbreaks develop. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=98 SRC="FIGDIR/small/726753v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@45e41borg.highwire.dtl.DTLVardef@82c787org.highwire.dtl.DTLVardef@1f97888org.highwire.dtl.DTLVardef@1586747_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

Development and validation of a multilocus sequence typing scheme for Fasciola hepatica using next-generation deep amplicon sequencing

Fasciolosis caused by Fasciola hepatica is an economically important disease in sheep and cattle. Knowledge of the population genetic structure of F. hepatica is important for understanding gene flow and informing disease control. In the present study, we designed, developed, and validated a multilocus sequence typing (MLST) scheme based on six markers. These markers were selected by aligning newly sequenced whole-genome sequence (WGS) data with available reference genomes and selecting variable regions with five or more single-nucleotide polymorphisms SNPs from different scaffolds of the F. hepatica reference genome Fasciola 10x pilon (GCA_900302435.1). Twenty markers were initially identified, of which 12 were multiplexed for deep amplicon sequencing after validation on worm and faecal eggs DNA; six markers were ultimately retained for downstream population genetics analysis. These markers were used to investigate population genetic structure in 15 cattle- and 27 sheep-derived F. hepatica populations in UK. A total of 53 unique alleles from six MLST markers were identified from 30 faecal (cattle = 13, sheep = 17) and 12 adult worm (cattle = 2, sheep = 10) populations. Shared alleles were observed in sheep- and cattle-derived populations. The highest allelic variation was observed in the Scottish Borders, Southern Scotland, and South-West England, and the lowest in North-West England. Minimal genetic differentiation was observed between cattle- and sheep-derived populations, with most genetic structuring within rather than between populations. Five markers showed high allelic polymorphism, whereas one marker showed low levels of allelic polymorphism, highlighting the importance of multilocus approaches. Overall, this six MLST-marker panel provides a tool for population genetic studies, revealing high gene flow and clonal expansion of F. hepatica across hosts and regions in the UK.

genetics↗

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↗

Limited genetic structure and high gene flow in Fasciola hepatica populations infecting ruminants in different geographic areas in the UK

The liver fluke, Fasciola hepatica, is a major parasitic threat to ruminant health and productivity worldwide, with important implications for food security, animal welfare, and zoonotic risk. This study developed and validated a multiplex deep amplicon sequencing assay targeting the mitochondrial NADH dehydrogenase 1 (mt-ND1) and cytochrome c oxidase subunit 1 (mt-COX1) loci for high-throughput genotyping of F. hepatica. DNA was extracted from eggs sedimented from sheep and cattle faeces (n = 78) received from farms and from adult worm pools (n = 12) isolated at abattoirs from diverse regions across the UK. Following high-throughput sequencing, bioinformatics analysis was performed to demultiplex Illumina sequence reads and extract amplicon sequence variants (ASVs). A total of 11 ASVs were identified at each locus (mt-ND1: 264-279 bp; mt-COX1: 312-319 bp), with two or three predominant ASVs per locus, along with rare variants. Network and PCA analyses revealed two distinct clusters at the mt-ND1 locus: one primarily associated with sheep and another shared between sheep and cattle. In contrast, mt-COX1 sequence reads formed a single dominant cluster. Population analyses revealed extensive ASV sharing across regions, indicating high gene flow, likely facilitated by livestock movement and parasite adaptation.

evolutionary biology↗

Substantial cold tolerance in all life stages of the biting midge Culicoides nubeculosus (Diptera: Ceratopogonidae)

In temperate regions, vector-borne disease risk is mediated by cold winter conditions, however, the cold tolerance of key vector taxa remains poorly understood. Culicoides biting midges are the primary vectors of several pathogens of medical and veterinary importance including bluetongue virus, where seasonal cold weather in temperate regions limits midge activity and pathogen transmission. Here, we provide the first comprehensive assessment of cold tolerance across all developmental stages of Culicoides nubeculosus, a widely used laboratory species that is endemic to northern Europe. Eggs, first-instar larvae, fourth-instar larvae, pupae, and adults were exposed to acute (1 h) and extended (6 and 24 h) cold treatments spanning -1 to -18 {degrees}C, with survival, development, emergence, and adult wing size quantified. Culicoides nubeculosus showed substantial but stage-specific cold tolerance, with survival limits of [≤] -18 {degrees}C for eggs, -14 {degrees}C for pupae, -10 {degrees}C for L1 larvae and adults, and -7 {degrees}C for L4 larvae. While the effect of cold exposure duration varied across temperatures and life stages, extended exposure generally reduced survival at lower temperatures. Cold stress caused sublethal effects, including reduced adult emergence when eggs or larvae were exposed and reductions in adult wing size of up to [~]10%, depending on the life stage. These results reveal substantial cold tolerance across the full life history of C. nubeculosus, suggesting that factors beyond temperature influence population phenology. Our findings provide new insights into Culicoides ecology, with implications for seasonal vector population dynamics and arbovirus transmission risk in temperate regions. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/692099v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@199de25org.highwire.dtl.DTLVardef@c75202org.highwire.dtl.DTLVardef@1d91e6dorg.highwire.dtl.DTLVardef@15c9984_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

Development of a qPCR assay and tremabiome deep amplicon sequencing method for differentiation of fluke species in livestock

BackgroundTrematode parasites, or flukes, are a significant economic threat to ruminant production worldwide. Traditional diagnostic methods rely on egg sedimentation from faeces, a time-consuming methodology lacking sensitivity and specificity. This study aimed to develop and validate two diagnostic methods: firstly, qPCR for accurate identification of Fasciola spp, and secondly, tremabiome, deep amplicon sequencing technique for identifying fluke species using faecal egg DNA. MethodologyTo detect fluke infection primers targeting mitochondrial DNA were repurposed to develop a SYBR Green qPCR diagnostic. For the identification of fluke species, a tremabiome approach was developed. A reference sequence library and taxonomy file were generated for 21 fluke species, enabling species sequence read separation and extracting amplicon sequence variants (ASVs). To validate the qPCR and tremabiome approach, 402 faecal samples were collected from cattle and sheep across the UK. Fluke eggs were isolated by sedimentation, detected by microscopy and qPCR, and tremabiome used to identify fluke eggs to species level. ResultsqPCR demonstrated high analytical sensitivity, detecting Fasciola hepatica DNA down to 19.2fg and F. gigantica down to 6.4fg, with no cross-amplification of other flukes. Tremabiome was able to detect as few as five F. hepatica and Calicophoron daubneyi eggs and identify mixed infections. High levels of co-infection (14.4%) of F. hepatica and C. daubneyi were observed in faecal samples, followed by single infections with C. daubneyi (12.6%) and F. hepatica (3.2%). Notably, tremabiome detected F. hepatica in 20 samples missed by qPCR. Data analysis identified 55 and 32 ASVs for F. hepatica and C. daubneyi, respectively, with phylogenetic clustering within their respective clades. ConclusionThis study developed qPCR assay for Fasciola detection and validated a tremabiome deep amplicon sequencing for fluke species differentiation. These approaches have improved capacity to identify fluke species compared to microscopy and are valuable tools for enhancing fasciolosis surveillance and control. Author SummaryFlukes are flatworm parasites that cause disease domestic and wild animals and humans. The main species infecting cattle and sheep globally are the liver flukes F. hepatica and F. gigantica, with other species including the rumen fluke Calicophoron daubneyi locally important or emerging. Infections result in serious economic losses. The traditional method of diagnosing fluke infection involves observation of eggs in faecal samples under the microscope, but this can be time-consuming and error prone, since the eggs of different species often look similar. In this study, we developed and validated two methods to improve detection: qPCR, a sensitive DNA-based test to identify Fasciola infections, and tremabiome, a DNA sequencing technique that can accurately differentiate between different fluke species. We tested these methods using faecal samples collected from cattle and sheep across the UK. The qPCR could detect small amounts of Fasciola DNA, while tremabiome was more sensitive, identifying different fluke species from as few as five eggs. Our study found that co-infections of F. hepatica and C. daubneyi are common in the UK. The approaches we have developed could be valuable tools for to improve fluke diagnosis and enable better control of this important parasitic disease.

molecular biology↗

GLOWORM-META: Modelling gastrointestinal nematode metapopulation dynamics to inform cattle biosecurity research

Gastrointestinal nematode (GIN) parasite infections in grazing livestock cause significant disease, and are responsible for estimated annual losses of over {euro}1.8 billion in Europe alone. The management of GINs in cattle is threatened by anthelmintic drug resistance (AR). Immediate action is needed to slow the progression of AR in cattle GINs and avoid the increasingly common scenario of multiple drug resistance seen in sheep. Although AR can arise independently on multiple farms, it may also be spread between holdings via purchased cattle. Therefore, effective biosecurity measures on cattle enterprises could help to reduce the risk of establishment of AR populations. A metapopulation model was developed and validated for two GIN species infecting cattle, Ostertagia ostertagi and Cooperia oncophora, incorporating the full parasite life cycle, weather- and immunity-dependent parasite life history traits and multiple pasture sub-populations. This allowed for complex grazing management strategies and weather influences to be simulated. The models successfully replicated the seasonal patterns and intensity of infections reported in multiple published longitudinal datasets. Global sensitivity analysis against four Quantities of Interest (QoIs) related to factors affecting the safety of the resident herd and of the purchased animals was used to quantify the influence of candidate biosecurity measures. The duration of quarantine, the date of purchase (weather/seasonal influences) and the intensity of infection on the day of purchase strongly influenced the QoIs. The outcomes for the UK were not significantly influenced by the geographic location of the purchasing farm, suggesting that the influence of weather patterns on GIN populations outweighs that of regional climate differences, and thus regional variations to GIN biosecurity recommendations are not warranted without alternative evidence to support this. The model presented here is the first full lifecycle GIN metapopulation model for O. ostertagi and C. oncophora, validated against longitudinal field data, and can be broadly used to evaluate the relative efficacy of a range of cattle GIN management strategies, as demonstrated here. These findings offer valuable insights to focus initial biosecurity recommendations for cattle enterprises, and are being used to direct qualitative and quantitative research to refine recommendations. HighlightsO_LIA metapopulation model for cattle GINs was developed C_LIO_LIThe model includes weather-dependence and complex grazing C_LIO_LIThe model replicated seasonal infection patterns from multiple datasets C_LIO_LISensitivity analysis explored influential biosecurity measures C_LIO_LIThe influence of weather outweighed that of geographic location (climate) C_LIO_LIInitial recommendations for biosecurity and further research are made C_LI

ecology↗

Chromosomal genome assembly resolves drug resistance loci in the parasitic nematode Teladorsagia circumcincta

The parasitic nematode Teladorsagia circumcincta is one of the most important pathogens of sheep and goat farming in temperate climates worldwide and can rapidly evolve resistance to drugs used to control it. To understand the genetics of drug resistance, we have generated a highly contiguous genome assembly for the UK T. circumcincta isolate, MTci2. Assembly using PacBio long-reads and Hi-C long-molecule scaffolding together with manual curation resulted in a 573 Mb assembly (N50 = 84 Mb, n = 1,286) with five autosomal and one sex-linked chromosomal-scale scaffolds consistent with its karyotype. The genome resource was further improved via annotation of 22,948 genes, with manual curation of over 3,200 of these, resulting in a robust and near complete resource (96.3% complete protein BUSCOs) to support basic and applied research on this important veterinary pathogen. Genome-wide analyses of drug resistance, combining evidence from three distinct experiments, identified selection around known candidate genes for benzimidazole, levamisole and ivermectin resistance, as well as novel regions associated with ivermectin and moxidectin resistance. These insights into contemporary and historic genetic selection further emphasise the importance of contiguous genome assemblies in interpreting genome-wide genetic variation associated with drug resistance and identified key loci to prioritise in developing diagnostic markers of anthelmintic resistance to support parasite control. AUTHOR SUMMARYUnderstanding the genetics of anthelmintic resistance is a critical part of the sustainable control of parasitic worms. Here, we have generated a chromosome-scale genome assembly for the gastrointestinal nematode, Teladorsagia circumcincta, one of the most important pathogens of sheep in temperate climates worldwide. This genome and its annotation offers a substantial improvement over existing genetic resources, and will enable new insight into the biology for this parasite and new opportunities to characterise therapeutic targets such as drug and vaccine candidates. We used this resource to map genetic variation associated with resistance to multiple anthelmintic drug classes used as the primary means of parasite control, confirming known candidate genes and variants (i.e., beta-tubulin isotypes 1 and 2 associated with benzimidazole resistance, and acr-8 associated with levamisole resistance, and pgp-9 copy number variation, of which overexpression is associated broadly with anthelmintic resistance) and revealing new regions of the genome associated with drug treatment responses (i.e. 34-38 Mb on chromosome 5 associated with ivermectin resistance). Our results highlight the importance of a contiguous genome assembly and the use of complementary experimental approaches to reveal the impact of drug-mediated selection, both historically and directly in response to treatment, on genome-wide genetic variation.

genomics↗

Nutritional characterisation and seasonal variation of goat forages in Central Malawi

Goat ownership is prevalent across rural Malawi and provides a vital source of income, nutrition, and food security. However, goat performance is poor, and this presents a risk to individuals and communities who depend on them. Whilst mitigating this through supplementation of persevered forages may be possible, this is a challenge due to limitations of resources and the fact that goats typically free-roam during the dry season. Nutrition is fundamental to health and productivity of any livestock enterprise, it is required to be able to deal with stresses, such as disease, and to enable growth and production. The aim of this study was to characterise the nutritional profile of naturally available forages in Malawi, including the seasonal variation in nutrition. Samples of herbaceous forages and browse were collected over a 17-month period, across four villages (30 farms/smallholders) in Central Malawi. Forages underwent nutritional analysis for crude protein, fibre fractions, and ash/organic matter and NDVI obtained from satellite imagery was used as a measure of forage availability. Forage nutrition and availability were most adequate in the wet season, with higher concentrations of crude protein and a greater availability of herbaceous plants. There were significant differences in low-digestibility fibre fractions between locations, likely due to local factors such as soil and hydrology. The fall in crude protein concentrations from the wet season to the dry season represent a seasonal nutrition-gap which may result in risks to goat health and productivity.

zoology↗

Opportunities to improve goat production and food security in Botswana through forage nutrition and the use of supplemental feeds

Goats fulfil a central role in food security across Africa with over half of households owning or rearing goats in rural areas. However, goat performance is poor and mortality high. This study assessed the nutritional quality of commonly used feeds and proposes feed-baskets to enhance goat nutrition and health. Feeds were collected from 11 areas within the Central District of Botswana, and macronutrient analyses were conducted, including crude protein, fibre fractions, ash, and metabolizable energy (ME). Forage nutrition was compared across seasons and soil types. Additionally, seasonal supplementation trials were conducted to evaluate consumption rates of various supplements, including crop residues, pellets, Lablab purpureus, and Dichrostachys cinerea. Each supplement was provided ad libitum for a 24-hour period, and consumption rates determined. Findings revealed significant differences in nutrition among various feed sources, across seasons, and in relation to soil types (p < 0.001). Consumption rates of supplements were higher during the dry season, possibly due to reduced forage availability. Supplement consumption rates varied across supplements, with crop residues accounting for approximately 1% of dry matter intake, compared to up to 45% for pellets, 13% for L. purpureus, and 15% for D. cinerea. While wet season feed baskets exhibited higher ME values compared to dry-season feed-baskets, the relative impact of supplementation was more pronounced during the dry season. These results highlight the potential for optimizing goat diets through improved grazing and browsing management, especially during the reduced nutritional availability in the dry season.

zoology↗

Novel epidemiological model of gastrointestinal-nematode infection to assess grazing cattle resilience by integrating host growth, parasite, grass and environmental dynamics

Gastrointestinal nematode (GIN) infections are ubiquitous and often cause morbidity and reduced performance in livestock. Emerging anthelmintic resistance and increasing change in climate patterns require evaluation of alternatives to traditional treatment and management practices. Mathematical models of parasite transmission between hosts and the environment have contributed towards the design of appropriate control strategies in ruminants, but have yet to account for relationships between climate, infection pressure, immunity, resources, and growth. Here, we develop a new epidemiological model of GIN transmission in a herd of grazing cattle, including host tolerance (body weight and feed intake), parasite burden and acquisition of immunity, together with weather-dependent development of parasite free-living stages, and the influence of grass availability on parasite transmission. Dynamic host, parasite and environmental factors drive a variable rate of transmission. Using literature sources, the model was parametrised for Ostertagia ostertagi, the prevailing pathogenic GIN in grazing cattle populations in temperate climates. Model outputs were validated on published empirical studies from first season grazing cattle in Northern Europe. These results show satisfactory qualitative and quantitative performance of the model; they also indicate the model may approximate the dynamics of grazing systems under co-infection by O. ostertagi and Cooperia oncophora, a second GIN species common in cattle. In addition, model behaviour was explored under illustrative anthelmintic treatment strategies, considering impacts on parasitological and performance variables. The model has potential for extension to explore altered infection dynamics as a result of management and climate change, and to optimise treatment strategies accordingly. As the first mechanistic model to combine parasitic and free-living stages of GIN with host feed-intake and growth, it is well suited to predict complex system responses under non-stationary conditions. We discuss the implications, limitations and extensions of the model, and its potential to assist in the development of sustainable parasite control strategies. HIGHLIGHTSO_LINematode control in cattle is complicated by drug resistance and climate change C_LIO_LIA model was developed to predict GIN epidemiology under varying conditions C_LIO_LIThe model incorporates cattle growth, infection and immunity, grass availability, weather C_LIO_LIPredictions were validated against empirical studies of GIN in N Europe C_LIO_LIThe model applies to Ostertagia ostertagi, and possibly to co-infecting Cooperia C_LI O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY https://www.lmcni.com/ C_FIG_DISPLAY

ecology↗

Accurate and interpretable prediction of poor health in small ruminants with accelerometers and machine learning

Assessment of the health status of individual animals is a key step in the timely and targeted treatment of infections, which is critical in the fight against anthelmintic and antimicrobial resistance. The FAMACHA scoring system has been used successfully to detect anaemia caused by infection with the parasitic nematode Haemonchus contortus in small ruminants and is an effective way to identify individuals in need of treatment. However, assessing FAMACHA is labour-intensive and costly as individuals must be manually examined at frequent intervals. Here, we used accelerometers to measure the individual activity of extensively grazing small ruminants (sheep and goats) exposed to natural Haemonchus contortus worm infection in southern Africa over long time scales (13+ months). When combined with machine learning, this activity data can predict poorer health (increases in FAMACHA score), as well as those individuals that respond to treatment, all with precision up to 83%. We demonstrate that these classifiers remain robust over time. Interpretation of trained classifiers reveals that poorer health significantly affects the night-time activity levels in the sheep. Our study thus reveals behavioural patterns across two small ruminant species, which lowcost biologgers can exploit to detect subtle changes in animal health and enable timely and targeted intervention. This has real potential to improve economic outcomes and animal welfare as well as limit the use of anthelmintic drugs and diminish pressures on anthelmintic resistance in both commercial and resource-poor communal farming.

animal behavior and cognition↗