Search bioRxiv⌕ Search

SEARCH · Search bioRxiv

Results for “Epidemiology”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
bioRxiv2023

Large-scale epidemiological study on feline autosomal dominant polycystic kidney disease and identification of novel PKD1 gene variants

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease in cats. In most cases, the responsible abnormality is a nonsense single nucleotide polymorphism in exon 29 of the PKD1 gene (chrE3:g.42858112C>A, the conventional PKD1 variant). Epidemiological studies on feline ADPKD caused by the conventional PKD1 variant have been conducted in several countries, including Japan. However, they were limited to Persian cats or cats already suspected of ADPKD. There are no data on the prevalence of the conventional PKD1 variant among a wider cat population in Japan that is not limited to certain breeds or clinical backgrounds. This large-scale epidemiological study involving 1,281 cats aimed to establish a new genotyping assay to detect the conventional PKD1 variant rapidly. Among the cats examined in this study, 1.8% (23/1,281) harbored the conventional PKD1 variant. The odds of having the conventional PKD1 variant were significantly higher in Persian cats, Scottish Folds, and Exotic Shorthairs than in the other breeds. Furthermore, targeted resequencing of PKD1 was performed in cats with ADPKD and healthy cats to search for new variants that may be involved in ADPKD. We identified four variants unique to ADPKD cats that were not found in healthy cats, all of which were in exon 15. This indicates that variants in exon 15 of PKD1, in addition to the conventional variant in exon 29, are key factors in the pathogenesis of ADPKD in cats.

molecular biology↗
bioRxiv2023

Genomic epidemiology of Treponema pallidum and circulation of strains with diminished tprK antigen variation capability in Seattle, 2021-2022

BackgroundSyphilis incidence continues to increase dramatically in the United States and yet little is known about Treponema pallidum (TP) genomic epidemiology within American metropolitan areas. MethodsWe performed whole genome sequencing and tprK deep sequencing of 28 TP-containing specimens collected mostly from remnant Aptima swabs from 24 individuals from Seattle Sexual Health Clinic during 2021-2022. ResultsAll 12 individuals infected with Nichols lineage strains were MSM, while a specific SS14 cluster (average 0.33 SNPs) included 1 MSW and five women. All TP strains sequenced were azithromycin resistant via 23S rRNA A2058G mutation. Identical TP genomic sequences were found in pharyngeal and rectal swab specimens taken from the same individuals concurrently. tprK sequences were less variable between patient-matched specimens and between epidemiologically-linked clusters. We detected a 528 bp deletion in the tprK donor site locus, eliminating nine tprK donor sites, in TP genomes of three individuals with secondary syphilis, associated with diminution of overall tprK sequence diversity. ConclusionsWe developed an end-to-end workflow for public health genomic surveillance of TP from remnant Aptima swab specimens. With its high rate of gene conversion, tprK sequencing may assist in linking cases beyond routine TP genome sequencing. TP strains with deletions in tprK donor sites currently circulate and are associated with diminished antigenic diversity of the TprK putative outer membrane protein.

genomics↗
bioRxiv2023

Epidemiological modeling of SARS-CoV-2 in white-tailed deer (Odocoileus virginianus) reveals conditions for introduction and widespread transmission

Emerging infectious diseases with zoonotic potential often have complex socioecological dynamics and limited ecological data, requiring integration of epidemiological modeling with surveillance. Although our understanding of SARS-CoV-2 has advanced considerably since its detection in late 2019, the factors influencing its introduction and transmission in wildlife hosts, particularly white-tailed deer (Odocoileus virginianus), remain poorly understood. We use a Susceptible-Infected-Recovered-Susceptible epidemiological model to investigate the spillover risk and transmission dynamics of SARS-CoV-2 in wild and captive white-tailed deer populations across various simulated scenarios. We found that captive scenarios pose a higher risk of SARS-CoV-2 introduction from humans into deer herds and subsequent transmission among deer, compared to wild herds. However, even in wild herds, the transmission risk is often substantial enough to sustain infections. Furthermore, we demonstrate that the strength of introduction from humans influences outbreak characteristics only to a certain extent. Transmission among deer was frequently sufficient for widespread outbreaks in deer populations, regardless of the initial level of introduction. We also explore the potential for fence line interactions between captive and wild deer to elevate outbreak metrics in wild herds that have the lowest risk of introduction and sustained transmission. Our results indicate that SARS-CoV-2 could be introduced and maintained in deer herds across a range of circumstances based on testing a range of introduction and transmission risks in various captive and wild scenarios. Our approach and findings will aid One Health strategies that mitigate persistent SARS-CoV-2 outbreaks in white-tailed deer populations and potential spillback to humans.

ecology↗
bioRxiv2023

An Immuno-Epidemiological Model of Foot-and-Mouth Disease (FMD) in the African Buffalo Population with Carrier Transmission

Foot-and-mouth disease (FMD) is a highly contagious disease that spreads among cloven-hoofed animals. Although not deadly, FMD can cause major delays in meat and dairy production. One major concern is that the foot-and-mouth disease virus (FMDV) can persist in African buffalo hosts as natural reservoirs for long periods of time, causing the pathogens to reemerge in susceptible populations. In this paper, we present a novel immuno-epidemiological model of FMD in the African buffalo host populations. Upon infection, the hosts can undergo two phases, namely the acute and the carrier stages. In our model, we divide the infectious population based upon these two stages so that we can dynamically capture the immunological characteristics of both phases of the disease to better understand the carriers role in disease transmission. We first define the within-host viral-immune kinetics dependent epidemiological basic reproduction number[R] 0 and show that it is a threshold condition for the local stability of the disease-free equilibrium and existence of the endemic equilibrium. We also analytically show that the system always displays forward bifurcation with respect to between-host epidemic parameters. Later, by using a sensitivity analysis (SA) approach developed for multi-scale models, we assess the impact of the acute infection and carrier phase immunological parameters on[R] 0. Interestingly, our numerical results show that the within-carrier infected host immune kinetics parameters and the susceptible individual recruitment rates play significant roles in disease persistence, which are consistent with experimental and field studies.

systems biology↗
bioRxiv2023

Adolescent chronic sleep restriction promotes alcohol drinking in adulthood: evidence from epidemiological and preclinical data.

Epidemiological investigations have indicated that insufficient sleep is prevalent among adolescents, posing a globally underestimated health risk. Sleep fragmentation and sleep loss during adolescence have been linked to concurrent emotional dysregulation and an increase in impulsive, risk-taking behaviors, including a higher likelihood of substance abuse. Among the most widely used substances, alcohol stands as the primary risk factor for deaths and disability among individuals aged 15-49 worldwide. While the association between sleep loss and alcohol consumption during adolescence is well documented, the extent to which prior exposure to sleep loss in adolescence contributes to heightened alcohol use later in adulthood remains less clearly delineated. Here, we analyzed longitudinal epidemiological data spanning 9 years, from adolescence to adulthood, including 5497 participants of the Avon Longitudinal Study of Parents And Children cohort. Sleep and alcohol measures collected from interviews and questionnaires at 15 and 24 years of age were analyzed with multivariable linear regression and a cross-lagged autoregressive path model. Additionally, we employed a controlled preclinical experimental setting to investigate the causal relationship underlying the associations found in the human study and to assess comorbid behavioral alterations. Preclinical data were collected by sleep restricting Marchigian Sardinian alcohol preferring rats (msP, n=40) during adolescence and measuring voluntary alcohol drinking concurrently and in adulthood. Polysomnography was used to validate the efficacy of the sleep restriction procedure. Behavioral tests were used to assess anxiety, risky behavior, and despair. In humans, after adjusting for covariates, we found a cross-sectional association between all sleep parameters and alcohol consumption at 15 years of age but not at 24 years. Notably, alcohol consumption (Alcohol Use Disorder Identification Test for Consumption) at 24 years was predicted by insufficient sleep at 15 years whilst alcohol drinking at 15 years could not predict sleep problems at 24. In msP rats, adolescent chronic sleep restriction escalated alcohol consumption and led to increased propensity for risk-taking behavior in adolescence and adulthood. Our findings demonstrate that adolescent insufficient sleep causally contributes to higher adult alcohol consumption, potentially by promoting risky behavior.

neuroscience↗
bioRxiv2023

Molecular epidemiology of Cercospora leaf spot on resistant and susceptible sugar beet hybrids

Cercospora leaf spot (CLS), caused by Cercospora beticola, is a major foliar disease impacting sugar beet production worldwide. The development of new resistant sugar beet hybrids is a powerful tool to better manage the disease, but it is unclear how these hybrids affect CLS epidemiology. We used a molecular epidemiology approach to study natural epidemics of CLS affecting two susceptible and two resistant sugar beet hybrids at two field sites. Infected plants were geotagged on a weekly basis. Isolations of C. beticola were made from infected leaves and genotyped using six simple sequence repeat loci to identify clones. We determined that CLS epidemics had a later onset in plots planted to resistant hybrids, but once the pathogen established an infection, there was little difference between resistant and susceptible hybrids in the probability of localized spread and dispersal. We found that different clones often infected the same leaf and that clusters of infected plants were often colonized by a mixture of clones. There was little overall difference in genetic diversity between resistant and susceptible hybrids, however genotypic evenness differed at one site. In this site we found one genotype restricted to the resistant cultivars at a high frequency. At the end of the epidemic infections were not randomly distributed across the fields and we found that a single clone could spread over a distance of 100 m during a growing season.

pathology↗
bioRxiv2023

An unusual two-strain cholera outbreak in Lebanon, 2022-2023: a genomic epidemiology study

BackgroundCholera is a bacterial infection caused by the ingestion of contaminated water or food. It principally affects the gastrointestinal system and spreads easily, causing outbreaks. The first case of cholera in this outbreak was detected in Lebanon in October 2022. The outbreak lasted three months, with 8,007 suspected cases (671 laboratory-confirmed) and 23 deaths. We characterised the Vibrio cholerae strain responsible for this cholera outbreak. MethodsIn total, 34 Vibrio cholerae isolates collected by random sampling of stools, water and plant samples throughout the outbreak and over the affected regions were studied by phenotypic methods and microbial genomics. FindingsAll isolates were V. cholerae O1, serotype Ogawa strains from wave 3 of the seventh pandemic El Tor (7PET) lineage. Phylogenomic analysis unexpectedly revealed the presence of two different 7PET strains, a highly unusual finding outside the Bay of Bengal, where several sublineages circulate together. The dominant strain had a narrow antibiotic resistance profile and was phylogenetically related to South Asian V. cholerae isolates. The second strain, which was found exclusively in South Lebanon and Beqaa, was resistant to multiple antibiotics, including macrolides, third-generation cephalosporins and cotrimoxazole. It belonged to the AFR13 sublineage and clustered with V. cholerae isolates collected in Yemen from 2016 to 2019. This second Lebanese strain also harboured the same multidrug-resistance (MDR) IncC-type plasmid found in Yemeni isolates from 2018. InterpretationThe 2022-2023 Lebanese cholera outbreak was caused by the simultaneous introduction of two different 7PET strains. The MDR strain was geographically limited, but the spread of this clone or the horizontal transfer of the MDR plasmid to more susceptible clones could affect epidemic cholera case management. Genomic surveillance is crucial to prevent further spread, and to ensure a prompt and effective response to outbreaks. FundingThe study was funded by the Centers for Disease Control (CDC) award number BAA 75D301-21-C-12132, a grant awarded to the American University of Beirut, WHO country office Lebanon, the Lebanese University, and Institut Pasteur. RESEARCH IN CONTEXT PANELO_ST_ABSEvidence before this studyC_ST_ABSWhole-genome sequencing (WGS) has greatly advanced our understanding and the characterisation of Vibrio cholerae outbreaks. However, few studies in the Middle East and North Africa (MENA) region have used this powerful technology. We searched PubMed for studies investigating the molecular epidemiology of V. cholerae by WGS in the MENA region, including Lebanon, with the terms "cholera*" AND "a country name of MENA countries" with no restrictions on language or date. The very small number of studies identified concerned Yemen and Algeria. All the outbreaks in the MENA region investigated to date and many others worldwide were caused by a single strain introduced once, contrasting with the endemic setting (the Bay of Bengal) in which several lineages circulate together. One manuscript addressing the history of cholera in Africa from a genomic perspective assigned three Lebanese strains from past outbreaks in 1970 and 1993 as O1 Ogawa isolates from waves 1 and 2 of the seventh pandemic lineage (7PET). Added value of the studyWe provide the first comprehensive overview of the molecular epidemiology of the V. cholerae strains responsible for the 2022-2023 Lebanese cholera outbreak. The use of WGS made it possible to distinguish clearly between two phylogenetically distant strains from genomic wave 3 of the 7PET lineage responsible for the Lebanese outbreak and to assign their putative origins to South Asia and Yemen. Based on their different susceptibility patterns (a predominant strain with a narrow resistance profile and a minor strain with an extended resistance profile), WGS excluded the hypothesis of the multidrug-resistant (MDR) minor strain emerging from the susceptible dominant strain through the acquisition of the MDR plasmid, instead clearly demonstrating the seeding of the outbreak by two different introductions. Implications of all available evidenceThis study demonstrates the importance of WGS associated with national surveillance for obtaining new insights and perspectives, modifying our perception of V. cholerae outbreak. This unexpected occurrence of a two-strain outbreak in a setting considered non-endemic for V. cholerae requires tight control by the local health authorities to prevent the sporadic introduction and spread of additional strains. Our findings raise the question of the extent to which the strains identified, particularly those from South Asia, spread in Iraq and Syria, neighbouring countries that declared cholera outbreaks before Lebanon. It is difficult to answer this question due to the lack of strains collected from these countries. Regional surveillance of the causal agent of cholera is therefore essential, to unravel transmission events and monitor the emergence of antimicrobial drug-resistant strains observed in many countries around the world.

microbiology↗
bioRxiv2023

Molecular Epidemiology of multidrug-resistant Klebsiella pneumoniae, Enterobacter cloacae, and Escherichia coli outbreak among neonates in Tembisa Hospital, South Africa

BackgroundAn outbreak of multidrug-resistant Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae infections in a neonatal ward within a tertiary hospital in South Africa resulted in the mortality of 10 patients within six months. In this work, the genomic epidemiology of and the molecular factors mediating this outbreak were investigated. MethodsBacterial cultures obtained from clinical samples collected from the infected neonates underwent phenotypic and molecular analyses to determine their species, sensitivity to antibiotics, production of carbapenemases, complete resistance genes profile, clonality, epidemiology, and evolutionary relationships. Mobile genetic elements flanking the resistance genes and facilitating their spread were also characterized. ResultsThe outbreak was centered in two major wards and affected mainly neonates between September 2019 and March 2020. Most isolates (n = 27 isolates) were K. pneumoniae while both E. coli and E. cloacae had three isolates each. Notably, 33/34 isolates were multidrug resistant (MDR), with 30 being resistant to at least four drug classes. All the isolates were carbapenemase-positive, but four blaOXA-48 isolates were susceptible to carbapenems. BlaNDM-1 (n = 13) and blaOXA-48/181 (n = 15) were respectively found on IS91 and IS6-like IS26 composite transposons in the isolates alongside several other resistance genes. The repertoire of resistance and virulence genes, insertion sequences, and plasmid replicon types in the strains explains their virulence, resistance, and quick dissemination among the neonates. ConclusionsThe outbreak of fatal MDR infections in the neonatal wards were mediated by clonal (vertical) and horizontal (plasmid-mediated) spread of resistant and virulent strains (and genes) that have been also circulating locally and globally.

microbiology↗
bioRxiv2024

Controlling for polygenic genetic confounding in epidemiologic association studies

Epidemiologic associations estimated from observational data are often confounded by genetics due to pervasive pleiotropy among complex traits. Many studies either neglect genetic confounding altogether or rely on adjusting for polygenic scores (PGS) in regression analysis. In this study, we unveil that the commonly employed PGS approach is inadequate for removing genetic confounding due to measurement error and model misspecification. To tackle this challenge, we introduce PENGUIN, a principled framework for polygenic genetic confounding control based on variance component estimation. In addition, we present extensions of this approach that can estimate genetically-unconfounded associations using GWAS summary statistics alone as input and between multiple generations of study samples. Through simulations, we demonstrate superior statistical properties of PENGUIN compared to the existing approaches. Applying our method to multiple population cohorts, we reveal and remove substantial genetic confounding in the associations of educational attainment with various complex traits and between parental and offspring education. Our results show that PENGUIN is an effective solution for genetic confounding control in observational data analysis with broad applications in future epidemiologic association studies.

genetics↗
bioRxiv2024

Antimicrobial resistance, virulence genes profiles and molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae strains from captive giant pandas (Ailuropoda melanoleuca)

This study aimed to investigate the antibiotic susceptibility, antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), virulence genes, and molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains isolated from giant pandas. The screening of 178 nonduplicated Klebsiella pneumoniae strains identified eight CRKP strains, with the most abundant ARGs observed in ampC/blaDHA, blaSHV-01, blaSHV-02, tetB-01, tetB-02, tetC-01, and tetC-02. MGE analysis revealed the presence of intI1 in all strains, while other MGEs exhibited varying detection rates. Strain 24 exhibited the highest diversity in terms of MGE species. Seven virulence genes including wabG, uge, ycf, entB, kpn, alls, and wcaG, showed positive results with different proportions across the strains. Molecular epidemiology analysis using pulsed-field gel electrophoresis (PFGE) patterns indicated a high level of genetic diversity among the CRKP strains. Multi-locus sequence typing (MLST) analysis classified the strains into different sequence types (STs). In conclusion, this study highlighted the diverse nature of CRKP strains found in giant pandas, which exhibited varying levels of antibiotic resistance along with multiple ARGs and virulence genes present. These findings emphasized the importance of monitoring and researching antibiotic resistance within wildlife populations to safeguard the health status of these endangered animals.

zoology↗
bioRxiv2024

Developing epidemiological preparedness for a plant disease invasion: modelling citrus huanglongbingin the European Union

Huanglongbing (HLB; citrus greening) is the most damaging disease of citrus worldwide. While citrus production in the USA and Brazil have been affected for decades, HLB has not been detected in the European Union (EU). However, psyllid vectors have already invaded and spread in Portugal and Spain, and in 2023 the psyllid species known to vector HLB in the Americas was first reported within the EU. We develop a landscape-scale, epidemiological model, accounting for heterogeneous citrus cultivation and vector dispersal, as well as climate and disease management. We use our model to predict HLB dynamics following introduction into high-density citrus areas in Spain, assessing detection and control strategies. Even with significant visual surveillance, we predict any epidemic will be widespread on first detection, with eradication unlikely. Introducing increased inspection and roguing following first detection, particularly if coupled with intensive insecticide use, could potentially sustain citrus production for some time. However, this may require chemical application rates that are not permissible in the EU. Disease management strategies targeting asymptomatic infection will likely lead to more successful outcomes. Our work highlights modelling as a key component of developing epidemiological preparedness for a pathogen invasion that is, at least somewhat, predictable in advance.

ecology↗
bioRxiv2024

Comprehensive Molecular Epidemiology of Influenza Viruses in Brazil: Insights from a Nationwide Analysis

Influenza A and B viruses pose significant global health threats, with substantial impacts on morbidity and mortality. Understanding their molecular epidemiology in Brazil, a key hub for the circulation and dissemination of these viruses in South America, remains limited. This study, part of the Center for Viral Surveillance and Serological Assessment (CeVIVAS) project, addresses this by analyzing data and samples from all Brazilian macroregions, along with publicly available sequences from 2021-2023. Phylogenetic analysis of the Hemagglutinin (HA) segment of Influenza A/H1N1pdm09, A/H3N2, and Influenza B/Victoria-lineage revealed the predominance of A/H3N2 2a.3 strain in 2021 and early 2022. This was succeeded by A/H3N2 2b until October 2022, after which A/H1N1pdm09 5a.2a and 5a.2a.1 lineages became prevalent, maintaining this status throughout 2023. B/Victoria circulated at low levels between December 2021 and September 2022, becoming co-prevalent with A/H1N1pdm09 5a.2a and 5a.2a.1 lineages. Comparing the vaccine strain A/Darwin/9/2021 with circulating A/H3N2 viruses from 2021-2023 revealed shared mutations to aspartic acid at residues 186 and 225, altering the RBD domains charge. For A/H1N1pdm09, the 2022 consensus of 5a.2a.1 and the vaccine strain A/Victoria/2570/2019 had 14 amino acid substitutions. Key residues such as H180, D187, K219, R223, E224, and T133 are involved in hydrogen interactions with sialic acids, while N130, K142, and D222 may influence distance interactions based on docking analyses. Distinct Influenza A lineage frequency patterns across Brazils macroregions underscore regional variations in virus circulation. This study characterizes the dynamics of Influenza A and B viruses in Brazil, offering valuable insights into their circulation patterns. These findings have significant public health implications, informing strategies to mitigate transmission risks, optimize vaccination efforts, and enhance outbreak control measures. Author summaryThis study investigates the molecular epidemiology of Influenza A and B viruses in Brazil from 2021 to 2023. Utilizing data from the Center for Viral Surveillance and Serological Assessment (CeVIVAS) and public databases, we performed a comprehensive phylogenetic analysis of the Hemagglutinin segments of Influenza A/H1N1pdm09, A/H3N2, and B/Victoria-lineage viruses across all Brazilian macroregions. Key findings reveal that the A/H3N2 2a.3 strain was predominant in 2021 and early 2022, followed by A/H3N2 2b, and later by A/H1N1pdm09 5a.2a and 5a.2a.1 lineages in late 2022 and throughout 2023. The B/Victoria strain circulated at low levels initially and later co-prevailed with A/H1N1pdm09 lineages. Comparing the vaccine strain A/Darwin/9/2021 with circulating A/H3N2 viruses from 2021-2023 and A/Victoria/2570/2019 with 5a.2a.1 of A/H1N1pdm09 circulating in 2022 revealed significant mutations which could affect the interaction of the viruses with sialic acids and potentially impact vaccine efficacy. Notably, we identified a substitution pattern among the predominant Influenza subtypes and observed distinct regional variations in Influenza A lineage frequencies across Brazil. These findings are critical for optimizing vaccination strategies and provide valuable data to inform public health policy and improve health outcomes.

evolutionary biology↗
bioRxiv2024

Genomic epidemiology and phenotypic characterisation of Salmonella entericaserovar Panama in Victoria, Australia

Salmonella enterica serovar Panama, a causative agent of non-typhoidal salmonellosis (NTS), is one of several serovars that causes invasive NTS disease (iNTS) in humans. S. Panama is an understudied pathogen, with its pathobiology poorly understood. It is a predominant iNTS serovar in Australia, a high-income country with high rates of salmonellosis, where S. Panama has been documented to have a high odds ratio for causing iNTS. This study investigates the genomic epidemiology and antimicrobial resistance profiles of all S. Panama isolates recovered in Victoria, Australia, between 2000 and 2020. We examined the infection dynamics of S. Panama in seven isolates, representing the genetic diversity of the study population. Two sub-lineages, encompassed within a previously described Asian lineage, were identified. Multi-drug resistance (resistance to [≥]3 drug classes) was detected in 46 (51.7%) Australian isolates. The plasmid-mediated colistin resistance gene, mcr1.1, was detected in one Australian S. Panama isolate, carried by an IncI plasmid previously reported in Salmonella and Escherichia coli isolates collected from poultry in South-East Asia. Examination of the intracellular replication dynamics of S. Panama isolates demonstrated diverse phenotypes. In THP-1 derived macrophages, despite low host cell uptake, S. Panama showed higher replication rates over time compared to S. enterica serovar Typhimurium. However, a causative genotype could not be identified to explain this observed phenotype. This study provides insights into the S. Panama isolates imported into Australia over two-decades, showing MDR was common in this iNTS serovar, and colistin resistance reported for the first time. It provides the first data on the host-pathogen interactions of S. Panama in Australia, which will aid our collective understanding of the pathobiology of S. Panama and iNTS serovars more broadly. Author SummaryIn Australia, non-typhoidal Salmonella (NTS) cases have been on the rise since the 1970s; characterised by self-limiting enteritis, some NTS infections can result in systemic infections called invasive NTS disease. Salmonella enterica serovar Panama is a leading iNTS serovar in Australia. This study characterised the genomic epidemiology of S. Panama, identifying two lineages circulating in Australia over two decades and placing them within a global context. It also investigated the antimicrobial resistance (AMR) mechanisms of S. Panama, with multi-drug resistance commonly observed. Further, it identified the first plasmid-mediated colistin-resistant S. Panama in Australia. We additionally examined the characteristics of S. Panama-mediated host-pathogen interactions in both epithelial and macrophage cells lines, providing the first insight into the infection dynamics of this understudied pathogen. Thus, this study combines genomics and in vitro infection experiments to understand the pathogenic behaviour of the neglected iNTS S. Panama.

microbiology↗
bioRxiv2024

Genomic Epidemiology of Monkeypox Virus During the 2022 Outbreak in New York City

New York City (NYC) was one of the hotspots of monkeypox virus (MPXV) infections in the United States during the multi-country mpox outbreak in 2022. This study used the most comprehensive dataset to date to investigate the genomic characteristics of MPXV in NYC. We performed Nextclade lineage assignment, phylogenetic and mutational analyses on 1,138 specimens from 748 individuals at the NYC Public Health Lab in the context of 2,968 MPXV sequences sampled globally. Nextclade lineage assignment showed B.1.12 as a NYC specific lineage and phylogenetic analysis showed NYC and North America specific clades. The majority of mutations showed signatures of APOBEC3 activity. When looking at the intra-host genomic diversity for MPXV, distinct MPXV genomic profiles were observed in 6.4% of individuals with multiple sampled specimens, with at least 4.2% of NYC cases due to multiple MPXV infections from distinct viral strains. Further, 13% of the sequences in infected patients had a lack of concordance between epidemiologic and genetic linkages. This study identified NYC-specific MPXV genomic profiles and provided a conservative estimate of simultaneous infections with multiple MPXV variants, likely due to behavioral risk factors during the peak of the outbreak in July 2022. Improving concordance between genomic and epidemiological clusters for mpox investigations may require expanding partnerships with testing labs, clinics, and community groups to enhance the representativeness of MPXV samples that are available for sequencing.

genomics↗
bioRxiv2024

PGSFusion streamlines polygenic score construction and epidemiological applications in biobank-scale cohorts

BackgroundThe polygenic score (PGS) is an estimate of an individuals genetic susceptibility to a specific complex trait and has been instrumental to the development of precision medicine. Clinically, the simplest form of PGS, which is calculated as a weighted sum of variant counts, has been widely applied to conduct disease risk classification. Unfortunately, despite the critical importance of PGS, there are few online resources available to biologists and epidemiologists to calculate PGS in a user-friendly manner. ResultsTo address this need, we have developed a web server, PGSFusion, that streamlines the construction of PGS using a large variety of methods targeting different epidemiological requirements. PGSFusion included 16 PGS methods in four categories, which are single-trait, annotation-based, multiple-trait, and cross-ancestry. In addition, PGSFusion also utilizes UK Biobank data to provide two kinds of in-depth analyses: i) prediction performance evaluation to display the consistency between PGS and specific traits and the effect size of PGS in different genetic risk groups; ii) joint effect analysis to investigate the interaction between PGS and covariates, as well as the genetic effect size in different subgroups of covariates. PGSFusion automatically identifies the required information in uploaded summary statistics files, provides a selection of suitable methods, and outputs calculated PGSs and their corresponding epidemiological results, all without requiring prior programming knowledge. To demonstrate the function of PGSFusion, we showcase three case studies in different application scenario, highlighting its versatility and values to researchers. ConclusionsOverall, PGSFusion presents an easy-to-use, effective, and extensible platform for PGS construction, promoting the accessibility and utility of PGS for researchers in the field of precision medicine.

bioinformatics↗
bioRxiv2024

Genomic Epidemiology and Microevolution of the Zoonotic Pathogen Corynebacterium ulcerans

Corynebacterium ulcerans is an emerging zoonotic pathogen that belongs to the Corynebacterium diphtheriae (Cd) species complex (CdSC), and that causes diphtheria-like infections in humans. Our understanding of the transmission, phylogeography and evolution of C. ulcerans remains limited, in part due to the lack of a standardized genomic epidemiology toolkit. The aim of this work was to develop a core genome multi-locus sequence typing (cgMLST) scheme for high-resolution genotyping and classification of C. ulcerans strains, and to explore transmission, spatial spread and genomic evolution among 582 C. ulcerans isolates from sporadic clinical cases and reported case clusters. The cgMLST scheme combines 1,628 loci with highly reproducible allele calls and shows high strain subtyping resolution. We demonstrate its utility for capturing population structure by defining sublineages (SL, maximum 940 allele differences) and clonal groups (CG, 194 allele differences, AD) and for epidemiological surveillance by defining genetic clusters, i.e., previously undetected chains of transmission (25 AD). Genetic clusters correspond to cryptic and case clusters that were associated with specific geographical regions within France. Major C. ulcerans sublineages (SL325, SL331, SL339) and clonal groups (CG325, CG331, CG583) showed strong associations with diphtheria toxin variants and tox-carrying prophages or other genetic elements. The evolutionary dynamics of tox gene presence or absence varied sharply among clonal groups. The cgMLST scheme is publicly available (https://bigsdb.pasteur.fr/diphtheria) and provides a common framework for investigating the ecology, evolution and variations in virulence among C. ulcerans strains. The implementation of a standardized high-resolution genotyping method will also facilitate the tracing of C. ulcerans transmission and spread across hosts and from local to global spatial scales.

microbiology↗
bioRxiv2024

Genomic Epidemiology of SARS-CoV-2 in Norfolk, UK, March 2020 - December 2022

BackgroundIn the UK, the COVID-19 Genomics UK Consortium (COG-UK) established a real time national genomic surveillance system during the COVID-19 pandemic, producing centralised data for monitoring SARS-CoV-2. As a COG-UK partner, Quadram Institute Bioscience (QIB) in Norfolk sequenced over 87,000 SARS-CoV-2 genomes, contributing to the region becoming densely sequenced. Retrospective analysis of SARS-CoV-2 lineage dynamics in this region may contribute to preparedness for future pandemics. Methods29,406 SARS-CoV-2 whole genome sequences and corresponding metadata from Norfolk were extracted from the COG-UK dataset, sampled between March 2020 and December 2022, representing 9.9% of regional COVID-19 cases. Sequences were lineage typed using Pangolin, and subsequent lineage analysis carried out in R using RStudio and related packages, including graphical analysis using ggplot2. Results401 global lineages were identified, with 69.8% appearing more than once and 31.2% over ten times. Temporal clustering identified six lineage communities based on first lineage emergence. Alpha, Delta, and Omicron variants of concern (VOC) accounted for 8.6%, 34.9% and 48.5% of sequences respectively. These formed four regional epidemic waves alongside the remaining lineages which appeared in the early pandemic prior to VOC designation and were termed pre-VOC lineages. Regional comparison highlighted variability in VOC epidemic wave dates dependent on location. ConclusionThis study is the first to assess SARS-CoV-2 diversity in Norfolk across a large timescale within the COVID-19 pandemic. SARS-CoV-2 was both highly diverse and dynamic throughout the Norfolk region between March 2020 - December 2022, with a strong VOC presence within the latter two thirds of the study period. The study also displays the utility of incorporating genomic epidemiological methods into pandemic response. Data summaryThe COG-UK collection of SARS-CoV-2 sequences and metadata are available for public download on their archive website under the Latest sequence data heading . Sequence names for all sequences used from this dataset alongside GISAID accession numbers where present are available in Supplementary Table 1. Impact statementWe extracted 29,406 regional Norfolk based SARS-CoV-2 sequences from the COG-UK SARS-CoV-2 dataset and revealed significant regional diversity and dynamic emergence of variant of concern (VOC) epidemic waves - spanning Alpha, Delta and Omicron lineages. We also applied statistical modelling to complement genomic methodology, with temporal clustering of significant first lineage emergences chronologically matching VOC waves and subwaves. The study highlights the importance of integration of genomic epidemiology into public health strategies for pandemic response, and the utility of using this data for retrospective research.

genomics↗
bioRxiv2025

Do epidemiologically impactful vector control interventions disrupt mosquito population structure?

Large epidemiological impacts resulting from disease vector control interventions are typically associated with significant disruption of vector populations. While vector density is a frequently measured response, impacts on demography and connectivity are suspected but rarely quantified. We analysed low-coverage whole-genome sequence data of 893 Anopheles gambiae mosquitoes collected between 2014-2015 during a cluster-randomized control trial (cRCT) in Burkina Faso to compare a pyrethroid-only net (ITN) with a pyrethroid-pyriproxyfen (ITN-PPF) net. Despite reductions of clinical malaria by 12%, and vector density by 22% in the ITN-PPF arm, we found no significant changes in An. gambiae population genetic structure or diversity. We found remarkably low population differentiation, and a lack of discernible clustering by treatment, time, or space. Nucleotide diversity and inbreeding coefficient remained stable between treatments, and genome-wide scans showed no putative signatures of selection between trial arms. These results show that ITN-PPF did not alter An. gambiae genetic structure, possibly due to large, vagile populations in West Africa. More widely, this is first evidence that epidemiologically meaningful reductions in vector density may not impact genetic diversity or connectivity, and challenges what constitutes adequate vector control in large populations.

ecology↗