Biology subjects

Dennis, T. P. W.

Publications and source records attributed to Dennis, T. P. W..

13 recordsLinked to original sources

bioRxiv2025

A genomic toolkit for surveillance and elimination of the principal malaria vectors in Southeast Asia.

While substantial progress has been made toward malaria elimination in Southeast Asia, major challenges remain. The principal mosquito vectors, Anopheles dirus and Anopheles minimus, inhabit diverse ecological niches and exhibit a wide range of behavioural and physiological insecticide resistance phenotypes, complicating vector control efforts. In Africa, genomic surveillance has transformed our understanding of vector evolution and resistance, supported by open-access tools and data. Comparable resources for Southeast Asian vectors remain limited. Here, we release Adir1.0, a curated, analysis-ready catalog of 540 An. dirus whole-genome sequences, accessible for interactive cloud-based analysis via the malariagen-data-python application programming interface (API). Alongside, we provide an updated Amin1.0 API to enhance functionality and usability, enabling integrated analyses across historical and new datasets. We demonstrate these resources by performing the first exploratory population genomic analysis of An. dirus from Bangladesh, Thailand, and Cambodia, revealing population structure, candidate regions of physiological resistance, and genomic structural variation. Together, these resources provide a foundation for genomic surveillance studies to inform vector control and malaria elimination strategies in Southeast Asia.

genetics↗

bioRxiv2025

Prevalence of zoonotic hepatic nematode varies with small mammal community diversity across a heterogenous landscape in Eastern Uganda

Identifying key drivers of pathogen infection prevalence and intensity in wildlife is essential to understand disease dispersal and transmission. Calodium hepatica (syn. Capillaria hepatica) is a generalist nematode that infects liver parenchyma of mammals worldwide and is capable of human infections. Prevalence ranges from 0-100% in wildlife, often varying across small geographic areas, making it an ideal parasite for understanding ecological drivers of variation. Here, we quantify prevalence of Calodium hepatica and present initial surveys of synanthropic small mammals in four villages representing differing land cover. Cross-sectional rodent trapping was conducted within and around households over consecutive dry seasons in Eastern Uganda. 18s rRNA gene of C. hepatica was amplified and a sub-set of PCR products sequenced to confirm presence of C. hepatica. Landscape structural diversity was classified by tree crown density and mean canopy height derived from 30m LiDAR data within a 0.5km buffer. Multivariable binomial generalised linear models were fit to C. hepatica prevalence. C. hepatica infection was common (overall 34.5%, CI95% 27.9-41.0) and found in rodent and shrew species inside and outside residences. We observe village-level differences in prevalence (18.2%-75.0%), with higher C. hepatica prevalence associated with higher relative proportion of Rattus rattus to other species (aOR=2.22 CI95% 1.30-3.85). Host diversity appears to be protective against parasite prevalence. Differences in molecular and macroscopy identification highlight challenges in diagnosis and a need for more specialized molecular tools. Further investigation is required to understand individual host and community variation in pathogen infection intensity and implications for zoonotic risk. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=127 SRC="FIGDIR/small/674808v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@e9cfdaorg.highwire.dtl.DTLVardef@4d0f6dorg.highwire.dtl.DTLVardef@12fe43dorg.highwire.dtl.DTLVardef@1318d83_HPS_FORMAT_FIGEXP M_FIG C_FIG Key FindingsO_LIZoonotic reservoirs, including Rattus rattus, Mastomys erythroleucus and Crocidura olivieri, are abundant in human-modified habitats and show elevated levels of household incursion C_LIO_LIHigh prevalence of Calodium hepatica, a nematode endoparasite, was identified in a range of small mammal species C_LIO_LIHigher proportion of native small mammal species relative to Rattus rattus appears protective against zoonotic pathogen load, with higher village-level C. hepatica prevalence in ecologically depleted sites C_LIO_LISmall-holder agriculture may provide a dilution effect through secondary wildlife support and small mammal competition, while dense village settings potentiate C. hepatica prevalence C_LI

ecology↗

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↗

bioRxiv2025

The origin, invasion history and resistance architecture of Anopheles stephensi in Africa.

The invasion of Africa by the Asian urban malaria vector, Anopheles stephensi, endangers 126 million people across a rapidly urbanising continent where malaria is primarily a rural disease. Control of An. stephensi requires greater understanding of its origin, invasion dynamics, and mechanisms of widespread resistance to vector control insecticides. We present a genomic surveillance study of 551 An. stephensi sampled across the invasive and native ranges in Africa and Asia. Our findings support a hypothesis that an initial invasion from Asia to Djibouti seeded separate incursions to Sudan, Ethiopia, and Yemen before spreading inland, aided by favourable temperature, vegetation cover, and human transit conditions. Insecticide resistance in invasive An. stephensi is conferred by detoxification genes introduced from Asia. These findings, and a companion genomic data catalogue, will form the foundation of an evidence base for surveillance and management strategies for An. stephensi.

genomics↗

bioRxiv2025

Distinct Genetic Populations and Resistance Backgrounds of the Malaria Vector Anopheles funestus in Tanzania

Population genetic analysis of mosquitoes is becoming increasingly important for understanding the distribution of insecticide resistance alleles, devising sustainable insecticide-based vector control approaches, and how malaria vector populations are structured in space. Anopheles funestus is the dominant malaria vector in Tanzania and most parts of East and Southern Africa. To better understand its population genomic structure in Tanzania, we sequenced the genomes of 334 individual An. funestus mosquitoes from 11 administrative regions. We found two genetically differentiated populations; one inland and at high altitude (found in Katavi, Kagera, Kigoma, and Mwanza) and a second coastal, at low altitude (found in Pwani, Morogoro, Tanga, Ruvuma, Mtwara, Dodoma, and Lindi), with differences in genetic diversity and inbreeding. We found asynchronous selective sweeps, associated with insecticide resistance phenotypes, at the Cyp9k1 gene, and Cyp6p gene cluster, with distinct copy number-variant profiles between the coastal and inland populations. These results suggest that inland and coastal An. funestus populations have divergent histories, with the arid, central region of Tanzania, which also contains the Rift Valley being a possible barrier to gene flow. Such population disconnectedness should be considered for insecticide deployment, resistance management, and the rollout of novel genetic- based vector control approaches. These findings provide the most detailed study of Tanzanian An. funestus population structure and resistance genetics to date. Future research should examine the epidemiological relevance of this discontinuity in gene flow and whether these populations have different malaria transmission abilities.

genetics↗

bioRxiv2024

Cryptic population structure and insecticide resistance in Anopheles gambiae from the southern Democratic Republic of Congo

The Democratic Republic of Congo (DRC) suffers from one of the highest malaria burdens worldwide, but information on its Anopheles vector populations is relatively limited. Preventative malaria control in DRC is reliant on pyrethroid-treated nets, raising concerns over the potential impacts of insecticide resistance. We sampled Anopheles gambiae from three geographically distinct populations (Kimpese, Kapolowe and Mikalayi) in southern DRC, collecting from three sub-sites per population and characterising mosquito collections from each for resistance to pyrethroids using WHO tube bioassays. Resistance to each of three different pyrethroids was generally high in An. gambiae with <92% mortality in all tests, but varied between collections, with mosquitoes from Kimpese being the most resistant. Whole genome sequencing of 165 An. gambiae revealed evidence for genetic differentiation between Kimpese and Kapolowe / Mikalayi, but not between the latter two sample sites despite separation of approximately 800km. Surprisingly, there was evidence of population structure at a small spatial scale between collection subsites in Kimpese, despite separation of just tens of kilometres. Intra-population (H12) and inter-population (FST) genome scans identified multiple peaks corresponding to genes associated with insecticide resistance such as the voltage gated sodium channel (Vgsc) target site on chromosome 2L, a Cyp6 cytochrome P450 cluster on chromosome arm 2R, and the Cyp9k1 P450 gene on chromosome X. In addition, in the Kimpese subsites, the P450 redox partner gene Cpr showed evidence for contemporary selection (H12) and population differentiation (FST) meriting further exploration as a potential resistance associated marker.

evolutionary biology↗

bioRxiv2024

Signatures of adaptation at key insecticide resistance loci in Anopheles gambiae in Southern Ghana revealed by low-coverage WGS.

Resistance to insecticides and adaptation to a diverse range of environments present challenges to Anopheles gambiae s.l. mosquito control efforts in sub-Saharan Africa. Whole-genome-sequencing is often employed for identifying the genomic basis underlying adaptation in Anopheles, but remains expensive for large-scale surveys. Low-coverage whole-genome-sequencing (lcWGS) can identify regions of the genome involved in adaptation at a lower cost, but is currently untested in Anopheles mosquitoes. Here, we use lcWGS to investigate population genetic structure and identify signatures of local adaptation in Anopheles mosquitoes across southern Ghana. In contrast to previous analyses, we find no structuring by ecoregion, with Anopheles coluzzii and Anopheles gambiae populations largely displaying the hallmarks of large, unstructured populations. However, we find signatures of selection at insecticide resistance (IR) loci that appear ubiquitous across ecoregions in An. coluzzii, and strongest in forest ecoregions in An. gambiae. In the IR gene Cyp9k1, we find species-specific alleles under selection, suggesting interspecific variation in the precise mechanism of resistance conferred by Cyp9k1. Our study highlights resistance candidate genes in this region, and validates lcWGS, potentially to very low coverage levels, for population genomics and exploratory surveys for adaptation in Anopheles taxa.

evolutionary biology↗

bioRxiv2023

Estimating the number of breeders from helminth larvae with genomic data.

Effective control of helminth infections requires the application of mathematical models to inform control efforts and policy, the development of product profiles for new drugs, and the monitoring of existing drugs for resistance. Key to the success of these approaches is accurately estimating the number of worms within a host, as well as distinguishing, in drug efficacy trials and monitoring, between adults surviving treatment and adults who have reinfected a host following drug treatment. In practice, observing adult worms is often extremely challenging in a patient, as many adult helminths are embedded deep in host tissues. Genetic approaches to infer kinship between larvae or eggs offer a solution to establish adult worm burdens, and to distinguish between treatment failure or treatment success followed by reinfection. Here, we use low-coverage whole-genome, and mitochondrial sequencing, of Onchocerca volvulus larvae to estimate the number of adults contributing to pools of offspring of known and unknown parentage. lcWGS reconstructs full-sibling relationships, resolving the number of unique adult worms contributing to a pool of offspring. Mitochondrial genotyping reconstructs maternal sib-ship, thus estimating the minimum number of adult females within a patient. Further development will improve these techniques for evaluating adult worm burden and trial outcome.

genomics↗

bioRxiv2022

Target-enrichment sequencing yields valuable genomic data for difficult-to-culture bacteria of public health importance

Genomic data contribute invaluable information to the epidemiological investigation of pathogens of public health importance. However, whole genome sequencing (WGS) of bacteria typically relies on culture, which represents a major hurdle for generating such data for a wide range of species for which culture is challenging. In this study, we assessed the use of culture-free target-enrichment sequencing as a method for generating genomic data for two bacterial species: 1) Bacillus anthracis, which causes anthrax in both people and animals and whose culture requires high level containment facilities; and 2) Mycoplasma amphoriforme, a fastidious emerging human respiratory pathogen. We obtained high quality genomic data for both species directly from clinical samples, with sufficient coverage (>15X) for confident variant calling over at least 80% of the baited genomes for over two thirds of the samples tested. Higher qPCR cycle threshold (Ct) values (indicative of lower pathogen concentrations in the samples), pooling libraries prior to capture, and lower captured library concentration were all statistically associated with lower capture efficiency. The Ct value had the highest predictive value, explaining 52% of the variation in capture efficiency. Samples with Ct values [≤] 30 were over 6 times more likely to achieve the threshold coverage than those with a Ct > 30. We conclude that target-enrichment sequencing provides a valuable alternative to standard WGS following bacterial culture and creates opportunities for an improved understanding of the epidemiology and evolution of many clinically important pathogens for which culture is challenging. Data summaryThe authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files. Scripts used in this study can be accessed on GitHub at https://github.com/tristanpwdennis/bactocap. All sequence data generated during this study have been deposited in the European Nucleotide Archive (ENA) Sequence Read Archive (SRA) under project accession numbers PRJEB46822 (B. anthracis) and PRJEB50216 (M. amphoriforme). Accession numbers for individual samples, along with metadata, laboratory parameters and sequence quality metrics, are available at the University of Glasgows data repository, Enlighten, at http://dx.doi.org/10.5525/gla.researchdata.1249.

molecular biology↗

bioRxiv2021

Population genomics of Bacillus anthracis from an anthrax hyperendemic area reveals transmission processes across spatial scales and unexpected within-host diversity

Genomic sequencing has revolutionized our understanding of bacterial disease epidemiology, but remains underutilized for zoonotic pathogens in remote endemic settings. Anthrax, caused by the spore-forming bacterium Bacillus anthracis, remains a threat to human and animal health and rural livelihoods in low- and middle-income countries. While the global genomic diversity of B. anthracis has been well-characterized, there is limited information on how its populations are genetically structured at the scale at which transmission occurs, critical for understanding the pathogens evolution and transmission dynamics. Using a uniquely rich dataset, we quantified genome-wide single nucleotide polymorphisms (SNPs) among 73 B. anthracis isolates derived from 33 livestock carcasses sampled over one year throughout the Ngorongoro Conservation Area, Tanzania, an area hyperendemic for anthrax. Genome-wide SNPs distinguished 22 unique B. anthracis genotypes within the study area. However, phylogeographic structure was lacking, as identical SNP profiles were found throughout the study area, likely the result of the long and variable periods of spore dormancy and long-distance livestock movements. Significantly, divergent genotypes were obtained from spatio-temporally linked cases and even individual carcasses. The high number of SNPs distinguishing isolates from the same host is unlikely to have arisen during infection, as supported by our simulation models. This points to an unexpectedly wide transmission bottleneck for B. anthracis, with an inoculum comprising multiple variants being the norm. Our work highlights that inferring transmission patterns of B. anthracis from genomic data will require analytical approaches that account for extended and variable environmental persistence as well as co-infection. ImportancePathogens transmitted between animals and people affect the health and livelihoods of farmers, particularly in developing countries dependent on livestock. Understanding over what distances these pathogens are transmitted and how they evolve is important to inform control strategies towards reducing disease impacts. Information on the circulation of Bacillus anthracis, which causes the often-lethal disease anthrax, is lacking for settings where the disease is commonplace. Consequently, we examined its genetic variability in an area in Tanzania where anthrax is widespread. We found no clear link between how closely cases were sampled and their genetic similarity. We suspect this lack of congruence is primarily driven by large-scale livestock movements, which control efforts should take into consideration. Another significant finding was the co-occurrence of multiple B. anthracis types within individual hosts, suggesting animals are commonly infected with a mixture of variants. This needs to be accounted for when investigating possible connections between cases.

genomics↗

bioRxiv2018

Insights into circovirus host range from the genomic fossil record.

A diverse range of DNA sequences derived from circoviruses (family Circoviridae) have been identified in samples obtained from humans and domestic animals, often in association with pathological conditions. In the majority of cases, however, little is known about the natural biology of the viruses from which these sequences are derived. Endogenous circoviral elements (CVe) are DNA sequences derived from circoviruses that occur in animal genomes and provide a useful source of information about circovirus-host relationships. In this study we screened genome assemblies of 675 animal species and identified numerous circovirus-related sequences, including the first examples of CVe derived from cycloviruses. We confirmed the presence of these CVe in the germline of the elongate twig ant (Pseudomyrmex gracilis), thereby establishing that cycloviruses infect insects. We examined the evolutionary relationships between CVe and contemporary circoviruses, showing that CVe from ants and mites group relatively closely with cycloviruses in phylogenies. Furthermore, the relatively random interspersal of CVe from insect genomes with cyclovirus sequences recovered from vertebrate samples, suggested that contamination might be an important consideration in studies reporting these viruses. Our study demonstrates how endogenous viral sequences can inform metagenomics-based virus discovery. In addition, it raises doubts about the role of cycloviruses as pathogens of humans and other vertebrates.

microbiology↗

bioRxiv2018

Whole-genome sequencing of parvoviruses from wild and domestic animals in Brazil provides new insights into parvovirus distribution and diversity

AbstractParvoviruses (family Parvoviridae) are small, single-stranded DNA viruses. Many parvoviral pathogens of medical, veterinary and ecological importance have been identified. In this study, we used high-throughput sequencing (HTS) to investigate the diversity of parvoviruses infecting wild and domestic animals in Brazil. We identified 21 parvovirus sequences (including twelve nearly complete genomes and nine partial genomes) in samples derived from rodents, bats, opossums, birds and cattle in Pernambuco, Sao Paulo, Parana and Rio Grande do Sul states. These sequences were investigated using phylogenetic and distance-based approaches, and were thereby classified into eight parvovirus species (six of which have not been described previously), representing six distinct genera in the subfamily Parvovirinae. Our findings extend the known biogeographic range of previously characterized parvovirus species, and the known host range of three parvovirus genera (Dependovirus, Aveparvovirus, and Tetraparvovirus). Moreover, our investigation provides a window into the ecological dynamics of parvovirus infections in vertebrates, revealing that many parvovirus genera contain well-defined sub-lineages that circulate widely throughout the world within particular taxonomic groups of hosts.

microbiology↗

bioRxiv2018

The evolution, distribution and diversity of endogenous circoviral elements

Circoviruses (family Circoviridae) are small, non-enveloped viruses that have short, single-stranded DNA genomes. Circovirus sequences are frequently recovered in metagenomic investigations, indicating that these viruses are widespread, yet they remain relatively poorly understood. Endogenous circoviral elements (CVe) are DNA sequences derived from circoviruses that occur in vertebrate genomes. CVe can provide unique, retrospective information about the biology and evolution of circoviruses. In this study, we screened 362 vertebrate genome assemblies in silico to generate a catalog of CVe loci. We identified a total of 179 CVe sequences, most of which have not been reported previously. We show that these CVe loci reflect at least 19 distinct germline integration events. We determine the structure of CVe loci, identifying some that show evidence of potential functionalization. We also identify orthologous copies of CVe in snakes, fish, birds, and mammals, allowing us to add new calibrations to the timeline of circovirus evolution. Finally, we observed that some ancient CVe group robustly with contemporary circoviruses in phylogenies, with all sequences within these groups being derived from the same host class or order, implying a hitherto underappreciated stability in circovirus-host relationships. The openly available dataset constructed in this investigation provides new insights into circovirus evolution, and can be used to facilitate further studies of circoviruses and CVe.\n\nAbbreviations

evolutionary biology↗