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bioRxiv2023

Clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus (HPAIV) from the 2021/22 epizootic is highly duck adapted and poorly adapted to chickens

The 2021/2022 epizootic of high pathogenicity avian influenza (HPAIV) remains one of the largest ever in the UK, being caused by a clade 2.3.4.4b H5N1 HPAIV. This epizootic affected more than 145 poultry premises, most likely through independent incursion from infected wild birds, supported by more than 1700 individual detections of H5N1 from wild bird mortalities. Here an H5N1 HPAIV, representative of this epizootic (H5N1-21), was used to investigate its virulence, pathogenesis and transmission in layer chickens and pekin ducks, two species of epidemiological importance. We inoculated both avian species with decreasing H5N1-21 doses. The virus was highly infectious in ducks, with high infection levels and accompanying shedding of viral RNA, even in ducks inoculated with the lowest dose, reflecting the strong waterfowl adaptation of the clade 2.3.4.4 HPAIVs. Duck-to-duck transmission was very efficient, coupled with high environmental contamination. H5N1-21 was frequently detected in water sources, serving as likely sources of infection for ducks, but inhalable dust and aerosols represented low transmission risks. In contrast, chickens inoculated with the highest dose exhibited lower rates of infection compared to ducks. There was no evidence for experimental H5N1-21 transmission to any naive chickens, in two stocking density scenarios, coupled with minimal and infrequent contamination being detected in the chicken environment. Systemic viral dissemination to multiple organs reflected the pathogenesis and high mortalities in both species. In summary, the H5N1-21 virus is highly infectious and transmissible in anseriformes, yet comparatively poorly adapted to galliformes, supporting strong host preferences for wild waterfowl. Key environmental matrices were also identified as being important in the epidemiological spread of this virus during the continuing epizootic.

microbiology↗
bioRxiv2023

A Bayesian inference method to estimate transmission trees with multiple introductions; applied to SARS-CoV-2 in Dutch mink farms.

Knowledge of who infected whom during an outbreak of an infectious disease is important to determine risk factors for transmission and to design effective control measures. Both whole-genome sequencing of pathogens and epidemiological data provide useful information about the transmission events and underlying processes. Existing models to infer transmission trees usually assume that the pathogen is introduced only once from outside into the population of interest. However, this is not always true. For instance, SARS-CoV-2 is suggested to be introduced multiple times in mink farms in the Netherlands from the SARS-CoV-2 pandemic among humans. Here, we developed a Bayesian inference method combining whole-genome sequencing data and epidemiological data, allowing for multiple introductions of the pathogen in the population. Our method does not a priori split the outbreak into multiple phylogenetic clusters, nor does it break the dependency between the processes of mutation, within-host dynamics, transmission, and observation. We implemented our method as an additional feature in the R-package phybreak. On simulated data, our method identifies the number of introductions with high accuracy. Moreover, when a single introduction was simulated, our method produces similar estimates of parameters and transmission trees as the existing package. When applied to data from a SARS-CoV-2 outbreak in Dutch mink farms, the method provides strong evidence for 13 introductions, which is 20 percent of all infected farms. Using the new feature of the phybreak package, transmission routes of a more complex class of infectious disease outbreaks can be inferred which will aid infection control in future outbreaks.

evolutionary biology↗
bioRxiv2023

Deep learning approaches to viral phylogeography are fast and as robust as likelihood methods to model misspecification

Analysis of phylogenetic trees has become an essential tool in epidemiology. Likelihood-based methods fit models to phylogenies to draw inferences about the phylodynamics and history of viral transmission. However, these methods are computationally expensive, which limits the complexity and realism of phylodynamic models and makes them ill-suited for informing policy decisions in real-time during rapidly developing outbreaks. Likelihood-free methods using deep learning are pushing the boundaries of inference beyond these constraints. In this paper, we extend, compare and contrast a recently developed deep learning method for likelihood-free inference from trees. We trained multiple deep neural networks using phylogenies from simulated outbreaks that spread among five locations and found they achieve close to the same levels of accuracy as Bayesian inference under the true simulation model. We compared robustness to model misspecification of a trained neural network to that of a Bayesian method. We found that both models had comparable performance, converging on similar biases. We also implemented a method of uncertainty quantification called conformalized quantile regression which we demonstrate has similar patterns of sensitivity to model misspecification as Bayesian highest posterior intervals (HPI) and greatly overlap with HPIs, but have lower precision (more conservative). Finally, we trained and tested a neural network against phylogeographic data from a recent study of the SARS-Cov-2 pandemic in Europe and obtained similar estimates of region-specific epidemiological parameters and the location of the common ancestor in Europe. Along with being as accurate and robust as likelihood-based methods, our trained neural networks are on average over 3 orders of magnitude faster. Our results support the notion that neural networks can be trained with simulated data to accurately mimic the good and bad statistical properties of the likelihood functions of generative phylogenetic models.

evolutionary biology↗
bioRxiv2023

Systematic review and meta-analysis of transcriptomic studies on different brain regions reveals different sex-based profiles in schizophrenic patients

BackgroundSchizophrenia is a severe neuropsychiatric disorder characterized by altered perception, mood, and behavior that profoundly impacts patients and society despite its relatively low prevalence. Previous studies have suggested that the dopamine D2 receptor gene and genes involved in glutamatergic neurotransmission, synaptic plasticity, and immune function as genetic risk factors. Sex-based differences also exist in schizophrenia epidemiology, symptomatology and outcomes; however, we lack a transcriptomic profile that considers sex and differentiates specific cerebral regions. MethodsWe performed a systematic review on bulk RNA-sequencing studies of post-mortem brain samples. Then, we fulfilled differential expression analysis on each study and summarized their results with regions-specific meta-analyses (prefrontal cortex and hippocampus) and a global all-studies meta-analysis. Finally, we used the consensus transcriptomic profiles to functionally characterize the impact of schizophrenia in males and females by protein-protein interaction networks, enriched biological processes and dysregulated transcription factors. ResultsWe discovered the sex-based dysregulation of 265 genes in the prefrontal, 1.414 genes in the hippocampus and 66 genes in the all-studies meta-analyses. The functional characterization of these gene sets unveiled increased processes related to immune response functions in the prefrontal cortex in male and the hippocampus in female schizophrenia patients and the overexpression of genes related to neurotransmission and synapses in the prefrontal cortex of female schizophrenia patients. Considering a meta-analysis of all brain regions available, we encountered the relative overexpression of genes related to synaptic plasticity and transmission in female and the overexpression of genes involved in organizing genetic information and protein folding in male schizophrenia patients. The protein-protein interaction networks and transcription factors activity analyses supported these sex-based profiles. ConclusionsOur results report multiple sex-based transcriptomic alterations in specific brain regions of schizophrenia patients, which provides new insight into the role of sex in schizophrenia. Moreover, we unveil a partial overlapping of inflammatory processes in the prefrontal cortex of males and the hippocampus of females. Plain language summarySchizophrenia is a severe neuropsychiatric disorder characterized by altered perception, mood, and behavior that profoundly impacts patients and society. Previous studies have suggested dopamine and glutamate neurotransmission genes, as well as immune function alteration as genetic risk factors. Schizophrenia epidemiology, symptomatology and outcomes are different for women and men, but the biological reason is not understood. Therefore, we reviewed all RNA-sequencing studies of post-mortem brain samples of women and men affected by schizophrenia available. Then, we compared the gene expression on each study for males and females and integrated the results of studies on different regions meta-analyses: prefrontal cortex, hippocampus and all-studies. Finally, we functionally characterize the impact of schizophrenia in males and females by protein-protein interaction networks, enriched biological processes and dysregulated transcription factors. We discovered the sex-based dysregulation of 265 genes in the prefrontal cortex, 1.414 genes in the hippocampus and 66 genes in the all-studies meta-analyses. The functional characterization of these genes unveiled increased immune response functions in the prefrontal cortex in men and the hippocampus in women schizophrenia patients, as well as increased neurotransmission and synapses in the prefrontal cortex of female schizophrenia patients. The protein-protein interaction networks and transcription factors activity analyses supported these sex-based profiles. Our results report multiple transcriptomic alterations in specific brain regions of schizophrenia patients, which provides new insight into the role of sex in schizophrenia. Moreover, we unveil a partial overlapping of inflammatory processes in the prefrontal cortex of males and the hippocampus of females. HighlightsO_LIThe expression of 265 genes is altered in the prefrontal cortex of schizophrenic patients, being overexpressed in females those related to synaptic transmission. C_LIO_LIIn the prefrontal cortex of males, overexpressed genes and overactivated transcription factors are linked to immune response and inflammation. C_LIO_LIConversely, genes and transcription factors more activated in the hippocampus of females are related to immune response, whereas those genes more expressed in males are linked to protein processing. C_LIO_LIThe global meta-analysis unveils groups of long non-coding genes and pseudogenes differentially expressed in males and females. C_LIO_LIThe effects of schizophrenia are closely related in the prefrontal cortex of males and the hippocampus of females. C_LI

molecular biology↗
bioRxiv2023

Identification of further variation at the lipooligosaccharide outer core locus in Acinetobacter baumannii genomes and extension of the OCL reference sequence database for Kaptive

The outer core locus (OCL) that includes genes for the synthesis of the variable outer core region of the lipooligosaccharide (LOS) is one of the key epidemiological markers used for tracing the spread of Acinetobacter baumannii, a bacterial pathogen of global concern. In this study, we screened 12476 publicly available A. baumannii genome assemblies for novel OCL sequences, detecting six new OCL types that were designated OCL17-OCL22. These were compiled with previously characterised OCL to create an updated version of the A. baumannii OCL reference database, providing a total of 22 OCL reference sequences for use with the bioinformatics tool, Kaptive. Use of this database against the 12476 downloaded assemblies found OCL1 to be the most common locus, present in 73.6% of sequenced genomes assigned by Kaptive with a match confidence score of Good or above. OCL1 was most common amongst isolates belonging to sequence types, ST1, ST2, ST3 and ST78, all of which are over-represented clonal lineages associated with extensive antibiotic resistance. The highest level of diversity in OCL types was found in ST2, with eight different OCL identified. The updated OCL reference database is available for download from GitHub (https://github.com/katholt/Kaptive; under version v 2.0.5), and has been integrated for use on Kaptive-Web (https://kaptive-web.erc.monash.edu/) and PathogenWatch (https://pathogen.watch/), enhancing current methods for A. baumannii strain identification, classification and surveillance. IMPACT STATEMENTIn the absence of effective treatment options for multi-drug resistant Acinetobacter baumannii, the highest-ranking critical priority bacterial pathogen of global concern, national and global surveillance is necessary to detect, track and subsequently curb the spread of isolates that resist current therapies. Several epidemiological markers are used to characterise A. baumannii strains by detecting genetic differences in specific regions of the genome. One of these is the chromosomal OC locus (OCL) responsible for the synthesis of the outer core (OC) component of the lipooligosaccharide (LOS). Here, we provide an update to the international A. baumannii OCL reference sequence database, extending the number of known OCL types to assist with clinical surveillance of important strains or clonal lineages. Data summaryO_LIThe updated A. baumannii OCL reference sequence database including 22 annotated OCL sequences is available for download under Kaptive v. 2.0.5 at https://github.com/katholt/Kaptive. C_LIO_LIGenome assemblies or GenBank records used as representative reference sequences are listed in Table 1 and acknowledged in each record in the database. C_LI O_TBL View this table: org.highwire.dtl.DTLVardef@1d32ff1org.highwire.dtl.DTLVardef@1f0af8borg.highwire.dtl.DTLVardef@94f185org.highwire.dtl.DTLVardef@7c8b7aorg.highwire.dtl.DTLVardef@a93255_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 1.C_FLOATNO O_TABLECAPTIONInformation on A. baumannii OCL reference sequences used to populate the updated OCL database for Kaptive v 2.0.5 C_TABLECAPTION C_TBL

microbiology↗
bioRxiv2023

A systematic review on leptospirosis in cattle: a European perspective

BackgroundLeptospirosis is a zoonotic disease which is globally distributed. Bovine leptospirosis often results in economic losses through its severe impact on reproduction performance. However, a clear overview of the disease characteristics in European cattle is lacking. The objective of this review was to summarise the current knowledge and state of the research on the epidemiology of bovine leptospirosis in Europe. MethodologyWe conducted a systematic literature review following the PRISMA guidelines. We screened four electronic databases (Pubmed, Web of Science, Scopus, CABI) and included studies published between 2001 and 2021, in English, German, and French. Identified papers were filtered according to predefined inclusion and exclusion criteria. ResultsSixty-two studies were included. Reported seroprevalences were remarkably variable among studies, probably reflecting local variations but also heterogeneity in the study designs, laboratory methods, and sample sizes. The five most reported circulating serogroups in European cattle were Sejroe, Australis, Grippotyphosa, Icterohaemorrhagiae, and Pomona. Abortion and fertility disorders were the most frequently reported signs of leptospirosis in European cattle and were generally associated with chronic infections. The acute form primarily affected juveniles and foetuses. Risk factors positively associated with leptospirosis in cattle were diverse, related to environmental (e.g. geographic location), climatic (e.g. flooding), and medical (e.g. presence of other diseases) parameters, as well as farming practices (e.g. purchase policy, herd size) and individual factors (e.g. animal age and breed). ConclusionsClinical features of bovine leptospirosis in Europe cover a large range of signs and confirmation of infection requires laboratory tests. The epidemiology of the disease is very local, most probably influenced by context-specific factors. This work highlights several research gaps, including a lack of research data from several countries, a lack of methodological harmonisation, a lack of large-scale studies, an underrepresentation of beef herds in the studies, and a lack of molecular investigations. Author SummaryLeptospirosis is a zoonotic disease that has been reported in cattle worldwide. This review systematically evaluated the available literature (2001-2021) on (i) the methods of diagnostics, (ii) (sero)prevalence, (iii) circulating serogroups/serovars, (iv) clinical signs, (v) and risk factors associated with leptospirosis in European cattle. We found that the prevalence of the disease was very variable among studies. Similarly, a wide range of clinical signs were described, but the most frequently reported ones were abortion and fertility disorders. Risk factors of infection in cattle included herd size, purchase of animals, access to pasture and natural water sources, contact with other animal species, presence of other diseases on farm, animal age, and occurrence of extreme weather events. This review highlights that leptospirosis should be considered as a differential diagnosis in case of abortion or reproductive failure in European cattle and emphasises the need for integrated disease prevention and control measures at farm or regional level. We identified several research gaps, particularly a lack of research data from several countries, a lack of large-scale studies, an underrepresentation of beef herds, and a limited use of molecular tools in the studies.

microbiology↗
bioRxiv2023

Uncovering the Environmental Conditions Required for Phyllachora maydis Infection and Tar Spot Development on Corn in the United States for Use as Predictive Models for Future Epidemics

Phyllachora maydis is a fungal pathogen causing tar spot of corn (Zea mays L.), a new and emerging, yield-limiting disease in the United States. Since being first reported in Illinois and Indiana in 2015, P. maydis can now be found across much of the corn growing of the United States. Knowledge of the epidemiology of P. maydis is limited but could be useful in developing tar spot prediction tools. The research presented here aims to elucidate the environmental conditions necessary for the development of tar spot in the field and the creation of predictive models to anticipate future tar spot epidemics. Extended periods (30-day windowpanes) of moderate ambient temperature were most significant for explaining the development of tar spot. Shorter periods (14- to 21-day windowpanes) of moisture (relative humidity, dew point, number of hours with predicted leaf wetness) were negatively correlated with tar spot development. These weather variables were used to develop multiple logistic regression models, an ensembled model, and two machine learning models for the prediction of tar spot development. This work has improved the understanding of P. maydis epidemiology and provided the foundation for the development of a predictive tool for anticipating future tar spot epidemics.

plant biology↗
bioRxiv2023

Inoviridae prophage dynamics during diversification, succession and Atlantic invasion of Pacific-native Vibrio parahaemolyticus.

The epidemiology of Vibrio parahaemolyticus, the leading cause of seafood-borne bacterial gastroenteritis of humans world-wide, dramatically changed in the United States following the establishment of a Pacific native lineage called sequence type (ST) 36 in the Atlantic. In this study we used phylogeography based on traceback to environmental source locations and comparative genomics to identify features that promoted evolution, dispersal, and competitive dominance of ST36. The major genomic differentiation and competitive success of ST36 was associated with a striking succession of filamentous prophage in the family Inoviridae (inoviruses), including loss of an inovirus prophage that had been maintained for decades in the endemic north Pacific population. Subsequently, at least five distinct progenitors arising from this diversification translocated from the Pacific into the Atlantic and established four geographically defined clonal subpopulations with remarkably low migration or mixing. Founders of two prevailing Atlantic subpopulations each acquired new stable and diagnostic inoviruses while other subpopulations that apparently declined did not. Broader surveys indicate inoviruses are common and active among the global population of V. parahaemolyticus and though inovirus replacements, such as in ST36, appear to be infrequent, they are notable in pathogenic lineages that dispersed. ImportanceAn understanding of the processes that contribute to emergence of pathogens from environmental reservoirs is critical as changing climate precipitates pathogen evolution and population expansion. Phylogeographic analysis of Vibrio parahaemolyticus hosts combined with analysis of their Inoviridae phage resolved ambiguities of diversification dynamics which preceded successful Atlantic invasion by the epidemiologically predominant ST36 lineage. It has been established experimentally that filamentous phage can limit host recombination, but here we show that phage loss is linked to rapid bacterial host diversification during epidemic spread in natural ecosystems alluding to a potential role for ubiquitous inoviruses in the adaptability of pathogens. This work paves the way for functional analyses to define the contribution of inoviruses in the evolutionary dynamics of environmentally transmitted pathogens.

microbiology↗
bioRxiv2023

Comparative genomics of carbapenemase-producing Morganella spp.

BackgroundMorganella are opportunistic pathogens involved in various infections. In Morganella, intrinsic resistance to multiple antibiotics including colistin combined with the emergence of carbapenemase-producers (CP) strongly limits the antimicrobial armamentarium. MethodsFrom 2013 to 2021, 172 highly drug-resistant (XDR) Morganella isolates from 8 European countries and Canada, two reference strains from the Pasteur Institute collection and two susceptible isolates were characterized by WGS, antimicrobial susceptibility testing and biochemical tests. Complete genomes from Genbank (n=103) were included for genomic analysis. Intrinsic resistance mechanism to polymyxins was deciphered by combining genetic analysis with mass spectrometry on the lipid A. FindingsMorganella could be separated into 4 species named M. psychrotolerans, M. sibonii, M. morganii and a new species represented by a unique strain. Morganella morganii included two subspecies: M. morganii subsp. morganii (the most prevalent) and M. morganii subsp. intermedius. Intrinsic resistance to tetracycline and conservation of metabolic pathways correlated this refined taxonomy. CP were mostly identified among five high-risk clones of M. morganii subsp. morganii. A single nucleotide polymorphism (SNP) cut-off of 100 was used to decipher outbreaks involving this species. Cefepime-zidebactam and ceftazidime-avibactam were the most potent antimicrobials towards the 172 XDR Morganella spp. isolates of our collection (including 145 CP) except for metallo-{beta}-lactamase-producers. The intrinsic resistance to polymyxins corresponds to the addition of L-Ara4N on the lipid A. InterpretationThis global characterization of the widest collection of XDR Morganella spp. highlighted the need to clarify the taxonomy, deciphered intrinsic resistance mechanisms and paved the way for further genomic comparisons. FundingNone RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSOn January 28th 2022, we have searched for the terms "Morganella" and "carbapenemase" in all published reports available in PubMed with no language restriction. We identified a total of 43 articles and most of them (41/43) corresponded to a report of a single isolate of carbapenemase-producing Morganella morganii. Only one article aimed to decipher the antimicrobial susceptibility on a collection of Proteus, Providencia and Morganella isolated from global hospitalized patients with intra-abdominal and urinary tract infections. However, this collection only included 7 M. morganii isolates. On March 2021, when we finished the inclusions in our collection, only 104 genomes of Morganella spp. were available in the NCBI database. Since September 2021, very few reports were published on carbapenemase-producing Morganella with the exception of a study from Xiang G et al. reported 40 multi-drug resistant M. morganii isolates recovered from three hospitals in China from 2014 to 2020. Unfortunately, this collection included only two carbapenemase-producing M. morganii isolates (one OXA-48 and one IMP-1). A report of KPC-producing M. morganii in Japan and a longitudinal study of carbapemase-producing Enterobactrales in Taiwan that did not focused on Morganella. We also searched in PubMed for the terms Morganella sibonii" or "Morganella psychrotolerans" in all published reports with no language restrictions. Our search identified a total of 20 articles. None of them was related to antimicrobial resistance and no study deciphered the Morganella spp. epidemiology on clinical isolates. Added values of this studyThis global characterization involved the widest collection of Morganella spp. isolates ever reported (barely doubling the number of Morganella spp. genomes in Genbank). In addition, 145 isolates of this worldwide collection made of 172 multidrug resistant Morganella spp. were carbapenemase producers for which therapeutic alternatives are scarce due to intrinsic resistance to last resort molecules, such as polymyxin. First, we found that cefepime-zidebactam and ceftazidime-avibactam were the most potent antimicrobials towards XDR Morganella spp. isolates except for metallo-{beta}-lactamase-producers. Then, we observed that carbapenemase-encoding genes were present in different Morganella species highlighting necessary changes in the taxonomy. Morganella genus could be divided into 4 species named M. psychrotolerans, M. sibonii, M. morganii and a new species represented by a unique strain. Morganella morganii includes two subspecies: M. morganii subsp. morganii (the most prevalent) and M. morganii subsp. intermedius. We demonstrated that this refined taxonomy correlated with the intrinsic resistance to tetracycline, which was found only in M. sibonii, as well as several metabolic pathways (e.g. trehalose assimilation, type III (T3SS) and type IV secretion system (T6SS), etc....). In addition, we highlighted five "high-risk" clones of carbapenemase-producing M. morganii subsp. morganii that have already disseminated worldwide. Combining whole genome sequencing (WGS) data with epidemiological investigations, we demonstrated that a cut-off of 100 single nucleotide polymorphisms (SNPs) could be used to discriminate clonally-related from sporadic independent isolates. This information is of the utmost importance since WGS is now considered as the reference method to identify and follow outbreaks. The intrinsic resistance of Morganella spp. to polymyxins was well-known but the underlying mechanism was unclear. Here, we demonstrated that the addition of L-Ara4N on the lipid A of Morganella is involved. Implications of all the available evidenceThe identification of "high-risk" clones among highly-drug resistant Morganella spp. paves the way of future investigations to better understand and hopefully limit the spread of these bugs. Additionally, our results identified new components and virulence factors of some Morganella species (e.g. T6SS and T3SS in M. sibonii) that deserve further investigation since they might be implicated in the bacterial lifestyle of this genus.

microbiology↗
bioRxiv2023

Stray cats and dogs carrying zoonotic Enterocytozoon bieneusi genotype D in China: a public health concern

Enterocytozoon bieneusi is reported to be a common microsporidian of humans and animals in various countries. However, scarce information on E. bieneusi has been recorded in cats (Felis catus) and dogs (Canis familiaris) in China. As such, we undertook molecular epidemiological investigation of E. bieneusi in cats and dogs in Shanghai, China. A total of 359 genomic DNAs were extracted from individual faecal samples from cats (n = 59) and dogs (n = 300), and then tested using a nested PCR-based sequencing approach employing internal transcribed spacer (ITS) of nuclear ribosomal DNA as the genetic marker. Enterocytozoon bieneusi was detected in 34 of all 359 (9.5%) faecal samples from cats (32.2%; 19/59) and dogs (5.0%; 15/300), including 24 stray cats and dogs (22.6%; 24/106), as well as ten household/raised cats and dogs (4.0%; 10/253). Correlation analyses revealed that E. bieneusi positive rates were significantly associated with stray cats and dogs (P < 0.05). The analysis of ITS sequence data revealed the presentation of five known genotypes CD7, CHN-HD2, D, PtEb IX and Type IV and two novel genotypes D-like1 and PtEb IX-like1. Zoonotic genotype D was the predominant type with percentage of 61.8 (21/34). Phylogenetic analysis of ITS sequence data sets showed that genotypes D, D-like1 and Type IV clustered within Group 1, showing zoonotic potential. The others were assigned into Group 10 with host specificity. These findings suggested that cats and dogs in Shanghai harbor zoonotic genotype D of E. bieneusi and may have a significant risk for zoonotic transmission. Further insight into the epidemiology of E. bieneusi in animals, water and the environment from other areas in China will be important to have an informed position on the public health significance of microsporidiosis caused by this microbe.

genetics↗
bioRxiv2023

Detection and Molecular Characterization of Animal Adenovirus and Astrovirus from Western Maharashtra, India

BackgroundAstroviruses (AstV) and adenoviruses (AdV) are associated with diarrhoea in young ones of animals. However, the epidemiology and genetic diversity of AstVs and AdVs in animals are not well studied. Hence the present study was conducted to detect and characterize AstVs and AdVs in calves, piglets and puppies in India. FindingsOut of the processed porcine (48), canine (80), and bovine (65) faecal samples from Western Maharashtra, India, the porcine AstV (PAstV), bovine AstV (BAstV), canine AstV (CAstV), and porcine AdV (PAdV) were detected in 12.5%, 7.69%, 3.75% and 4.1% of samples, respectively. In the RNA-dependent RNA polymerase region-based phylogenetic analysis the detected BAstV strains grouped with MAstV-28, MAstV-33, and MAstV-35, CAstV strains belonged to MAstV-5, PAstV strains belonged to MAstV-24, MAstV-26, and MAstV-31. Both the detected PAdV were of genotype 3, exhibiting 91.9-92.5% nucleotide identity with Ivoirian and Chinese strains. The study reports first-time BAstVs from calves and PAdV-3 from piglets in India. ConclusionThe study revealed diversity in the circulation of AstVs and AdVs in young ones of dogs, pigs and calves. Therefore, extensive epidemiological investigations of AstV and AdV are necessary to confirm their association with diarrhoea and to develop diagnostic tools and control measures.

microbiology↗
bioRxiv2023

Curbing zoonotic disease spread in multi-host-species systems will require integrating novel data streams and analytical approaches: evidence from a scoping review of bovine tuberculosis

BackgroundZoonotic diseases represent a significant societal challenge in terms of their health and economic impacts. One Health approaches to managing zoonotic diseases are becoming more prevalent, but require novel thinking, tools and cross-disciplinary collaboration. Bovine tuberculosis (bTB) is one example of a costly One Health challenge with a complex epidemiology involving human, domestic animal, wildlife and environmental factors, which require sophisticated collaborative approaches. ObjectiveWe undertook a scoping review of multi-host bTB epidemiology to identify recent trends in species publication focus, methodologies, scales and One Health approaches. We aimed to identify research gaps where novel research could provide insights to inform control policy, for bTB and other zoonoses. ResultsThe review included 167 articles. We found different levels of research attention across episystems, with a significant proportion of the literature focusing on the badger-cattle-TB episystem, with far less attention given to the multi-host episystems of southern Africa. We found a limited number of studies focusing on management solutions and their efficacy, with very few studies looking at modelling exit strategies. Surprisingly, only a small number of studies looked at the effect of human disturbances on the spread of bTB involving wildlife hosts. Most of the studies we reviewed focused on the effect of badger vaccination and culling on bTB dynamics with few looking at how roads, human perturbations and habitat change may affect wildlife movement and disease spread. Finally, we observed a lack of studies considering the effect of weather variables on bTB spread, which is particularly relevant when studying zoonoses under climate change scenarios. ConclusionsSignificant technological and methodological advances have been applied to bTB episystems, providing explicit insights into its spread and maintenance across populations. We identified a prominent bias towards certain species and locations. Generating more high-quality empirical data on wildlife host distribution and abundance, high-resolution individual behaviours and greater use of mathematical models and simulations are key areas for future research. Integrating data sources across disciplines, and a "virtuous cycle" of well-designed empirical data collection linked with mathematical and simulation modelling could provide additional gains for policy-makers and managers, enabling optimised bTB management with broader insights for other zoonoses.

ecology↗
bioRxiv2023

A systemic approach allows to identify the pedoclimatic conditions most critical in the susceptibility of a grapevine cultivar to esca/Botryosphaeria dieback

Esca and/or Botryosphaeria dieback (esca-BD) are two of the most destructive grapevine trunk diseases in the world, disease complex which remains poorly understood. As some vine cultivars show highly variable susceptibility to esca-BD, we designed a four-year experiment to identify which environmental factors influence the expression of the disease. We collected epidemiological and physiological data once a year for four consecutive years in 19 vineyard plots located in four wine-growing regions of Western Switzerland. We compared these data with climatic data obtained from weather stations for these same plots for four years and over the long term. We also estimated the soil water holding capacity of each plot. Confounding factors were minimal because all vineyards were planted in 2003 with the same cultivar and all plants grafted in the same nursery with genetically homogeneous grafting material. Principal component and regression analyses of combined epidemiological, biotic and pedoclimatic data identified a positive correlation between soil water retention capacity and plant mortality due to esca-BD. These analyses also showed that leaf disease symptoms and apoplexy are more frequent when cold, wet periods are followed - or alternate with - hot, dry periods, and that apoplexy occurs more frequently when weather conditions change abruptly (cold, wet May followed by a hot June) and deviate significantly from long-term climatic conditions. Regression analyses show that the soil water holding capacity impacts less the disease expression when the climate is warm and dry, both at the regional and at year-specific levels. Having identified the most important environmental factors towards expression of esca-BD, this study allows recommendations to be given to the winegrowers for the cultivar studied but can also be used as a model to identify the environmental factors that influence the expression of fungal diseases in other grapevine cultivars, other grapevine trunk diseases and even in other woody plants.

plant biology↗
bioRxiv2023

A laboratory framework for ongoing optimisation of amplification based genomic surveillance programs

Constantly evolving viral populations affect the specificity of primers and quality of genomic surveillance. This study presents a framework for continuous optimisation of sequencing efficiency for public health surveillance based on the ongoing evolution of the COVID-19 pandemic. SARS-CoV-2 genomic clustering capacity based on three amplification based whole genome sequencing schemes was assessed using decreasing thresholds of genome coverage and measured against epidemiologically linked cases. Overall genome coverage depth and individual amplicon depth were used to calculate an amplification efficiency metric. Significant loss of genome coverage over time was documented which was recovered by optimisation of primer pooling or implementation of new primer sets. A minimum of 95% genome coverage was required to cluster 94% of epidemiologically defined SARS-CoV-2 transmission events. Clustering resolution fell to 70% when only 85% of genome coverage was achieved. The framework presented in this study can provide public health genomic surveillance programs a systematic process to ensure an agile and effective laboratory response during rapidly evolving viral outbreaks.

genomics↗
bioRxiv2023

Genomic Characterisation of Multidrug-Resistant Pathogenic Enteric Bacteria from healthy children in Osun State, Nigeria

Antimicrobial resistance (AMR) has been established to be a significant driver for the persistence and spread of bacterial infections. It is, therefore, essential to conduct epidemiological surveillance of AMR in healthy individuals to understand the actual dynamics of AMR in Nigeria. Multi-drug resistant Klebsiella quasivariicola (n=1), Enterobacter hormaechei (n=1), and Escherichia coli (n=3) from stool samples of healthy children were subjected to whole genome sequencing using Illumina Nextseq1000/2000 and Oxford nanopore. Bioinformatics analysis reveals antimicrobial resistance, virulence genes, and plasmids. This pathogenic enteric bacteria harbored more than three plasmid replicons of either Col and/or Inc type associated with outbreaks and AMR resistant gene pmrB responsible for colistin resistance. Plasmid reconstruction revealed an integrated tetA gene responsible for tetracycline resistance, and caa gene responsible for toxin production in two of the E.coli isolates, and a cusC gene known to induce neonatal meningitis in the K. quasivariicola ST3879. The global spread of MDR pathogenic enteric bacteria is a worrying phenomenon, and close surveillance of healthy individuals, especially children, is strongly recommended to prevent the continuous spread and achieve the elimination and eradication of these infections. Molecular epidemiological surveillance using whole genome sequencing (WGS) will improve the detection of MDR pathogens in Nigeria.

microbiology↗
bioRxiv2023

High performance enrichment-based genome sequencing to support the investigation of hepatitis A virus outbreaks

Hepatitis A virus (HAV) infections are an increasing public health concern in low-endemicity regions due to outbreaks from foodborne infections and sustained transmission among vulnerable groups, including persons experiencing homelessness, those who inject drugs, and men who have sex with men (MSM), which is further compounded by aging, unvaccinated populations. DNA sequence characterisation of HAV for source tracking is performed by comparing small subgenomic regions of the virus. While this approach has been successful when robust epidemiological data are available, poor genetic resolution can lead to conflation of outbreaks with sporadic cases. HAV outbreak investigations would greatly benefit from the additional phylogenetic resolution obtained by whole virus genome sequence comparisons. However, HAV genomic approaches can be difficult because of challenges in isolating the virus, low sensitivity of direct metagenomic sequencing in complex sample matrices like various foods such as fruits, vegetables and molluscs, and difficulty designing highly multiplexed PCR primers across diverse HAV genotypes. Here, we introduce a proof-of-concept pan-HAV oligonucleotide hybrid capture enrichment assay from serum and frozen berry specimens that yields complete and near-complete HAV genomes from as few as four input HAV genome copies. We used this method to recover HAV genomes from human serum specimens with high C{tau} values (34{middle dot}7--42{middle dot}7), with high assay performance for all six human HAV sub-genotypes, both contemporary and historical. Our approach provides a highly sensitive and streamlined workflow for HAV WGS from diverse sample types, that can be the basis for harmonised and high-resolution molecular epidemiology during HAV outbreak surveillance. ImportanceThis proof-of-concept study introduces a hybrid capture oligo panel for whole genome sequencing (WGS) of all six human pathogenic hepatitis A virus (HAV) subgenotypes, exhibiting a higher sensitivity than some conventional genotyping assays. The ability of hybrid capture to enrich multiple targets allows for a single, streamlined workflow, thus facilitating the potential harmonization of molecular surveillance of HAV with other enteric viruses. Even challenging sample matrices can be accommodated, making it suitable for broad implementation in clinical and public health laboratories. The ability to capture small amounts of virus from complex samples is promising for passive surveillance application to environmental substrates, such as wastewater. This innovative approach has significant implications for enhancing multijurisdictional outbreak investigations, as well as our understanding of the global diversity and transmission dynamics of HAV.

genomics↗
bioRxiv2023

Biophysical principles predict fitness of SARS-CoV-2 variants

SARS-CoV-2 employs its spike proteins receptor binding domain (RBD) to enter host cells. The RBD is constantly subjected to immune responses, while requiring efficient binding to host cell receptors for successful infection. However, our understanding of how RBDs biophysical properties contribute to SARS-CoV-2s epidemiological fitness remains largely incomplete. Through a comprehensive approach, comprising large-scale sequence analysis of SARS-CoV-2 variants and the discovery of a fitness function based on binding thermodynamics, we unravel the relationship between the biophysical properties of RBD variants and their contribution to viral fitness. We developed a biophysical model that uses statistical mechanics to map the molecular phenotype space, characterized by binding constants of RBD to ACE2, LY-CoV016, LY-CoV555, REGN10987, and S309, onto a epistatic fitness landscape. We validate our findings through experimentally measured and machine learning (ML) estimated binding affinities, coupled with infectivity data derived from population-level sequencing. Our analysis reveals that this model effectively predicts the fitness of novel RBD variants and can account for the epistatic interactions among mutations, including explaining the later reversal of Q493R. Our study sheds light on the impact of specific mutations on viral fitness and delivers a tool for predicting the future epidemiological trajectory of previously unseen or emerging low frequency variants. These insights offer not only greater understanding of viral evolution but also potentially aid in guiding public health decisions in the battle against COVID-19 and future pandemics. Significance StatementThis research presents a biophysical model that maps the molecular properties of SARS-CoV-2s receptor binding domain into an epistatic fitness landscape. By linking the binding affinities of the virus to its epidemic fitness, we offer a powerful tool for understanding and predicting the emergence and success of new viral variants. Our model, validated with real-world data and informed by theoretical insights, provides a foundation for interpreting the evolutionary trajectory of past pandemics and predicting those of the future. The adaptability of this biophysical model extends to the key proteins of other viruses as well, signifying its potential in guiding public health interventions, and advancing our understanding of viral evolution.

biophysics↗
bioRxiv2023

EPINEST, an agent-based model to simulate epidemic dynamics in large-scale poultry production and distribution networks

The rapid intensification of poultry production raises important concerns about the associated risks of zoonotic infections. Here, we introduce EPINEST (EPI-demic NEtwork Simulation in poultry Transportation systems): an agent-based modelling designed to simulate pathogen transmission within realistic poultry production and distribution networks. The modular structure of the model allows for easy parameterization to suit specific countries and system configurations. Moreover, the framework enables the replication of a wide range of eco-epidemiological scenarios by incorporating diverse pathogen life-history traits, modes of transmission and interactions between multiple strains and/or pathogens. EPINEST was developed in the context of an interdisciplinary multicentre study conducted in Bangladesh, India, Vietnam and Sri Lanka, and will facilitate the investigation of the spreading patterns of various health hazards such as avian influenza, Campylobacter, Salmonella and antimicrobial resistance in these countries. Furthermore, this modelling framework holds potential for broader application in veterinary epidemiology and One Health research, extending its relevance beyond poultry to encompass other livestock species and disease systems.

bioinformatics↗