Publications by authors named "Stephen R Doyle"

Reconciling organism-scale biology at cellular-scale resolution has been a monumental challenge. Recently, Gramberg et al. uncovered the spatial organisation of gene expression in the common liver fluke, Fasciola hepatica.

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Concerns about the emergence of benzimidazole resistance in soil-transmitted helminths (STH) infections, particularly against Trichuris trichiura, have arisen. Previous studies of veterinary nematodes have linked benzimidazole resistance to single-nucleotide polymorphisms (SNPs) at three specific codons in the beta-tubulin gene, but similar associations in STH have not been consistently observed. In this work, we screened the complete beta-tubulin gene previously linked to benzimidazole resistance in T.

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Mass-drug administration (MDA) of human populations using praziquantel monotherapy has become the primary strategy for controlling and potentially eliminating the major neglected tropical disease schistosomiasis. To understand how long-term MDA impacts schistosome populations, we analysed whole-genome sequence data of 570 samples (and the closely related outgroup species, from eight countries incorporating both publicly-available sequence data and new parasite material. This revealed broad-scale genetic structure across countries but with extensive transmission over hundreds of kilometres.

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  • The text discusses a parasitic flatworm's life cycle, focusing on the miracidium stage which infects freshwater snails to eventually cause schistosomiasis in humans.
  • Researchers created a detailed cellular atlas revealing the 365 cells in the miracidium and identified 19 distinct cell clusters through single-cell RNA sequencing.
  • The study found that most of the larva's cells are somatic, with a small percentage being stem cells, and the stem cells display distinct characteristics potentially related to sex.
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  • Dirofilaria immitis is a significant veterinary parasite, and the rise of drug-resistant strains in the USA highlights the need to investigate resistance in other regions through global population genetic studies and genome sequencing.
  • Researchers focused on immature life stages of D. immitis, which are easier to sample from dog blood than adult worms, conducting whole-genome amplification and sequencing on nine microfilaria samples.
  • The study found that less than 1% of sequenced reads matched D. immitis genomes due to a high prevalence of dog DNA in the samples, showcasing the difficulties of genome-wide studies on parasitic life stages amid host DNA contamination.
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Recently, a S168T variant in the acetylcholine receptor subunit ACR-8 was associated with levamisole resistance in the parasitic helminth Haemonchus contortus. Here, we used the Xenopus laevis oocyte expression system and two-electrode voltage-clamp electrophysiology to measure the functional impact of this S168T variant on the H. contortus levamisole-sensitive acetylcholine receptor, L-AChR-1.

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Haemonchus contortus is a parasitic haematophagous nematode that primarily affects small ruminants and causes significant economic loss to the global livestock industry. Treatment of haemonchosis typically relies on broad-spectrum anthelmintics, resistance to which is an important cause of treatment failure. Resistance to levamisole remains less widespread than to other major anthelmintic classes, prompting the need for more effective and accurate surveillance to maintain its efficacy.

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  • National programs in Africa are shifting from controlling river blindness (onchocerciasis) to completely eliminating the parasite that causes it, O. volvulus, due to the success of mass drug administration (MDA) of ivermectin.
  • To effectively eliminate the disease, it's crucial to identify geographic transmission zones to assess the risk of reintroducing the parasite through migration or vector movement.
  • Research analyzing the genetic structure of O. volvulus in Ghana, Mali, and Côte d'Ivoire reveals that river basins do not necessarily represent separate transmission zones, suggesting a need for more precise boundaries to improve control strategies.
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The flatworm Schistosoma mansoni is an important but neglected pathogen that causes the disease schistosomiasis in millions of people worldwide. The parasite has a complex life cycle, undergoing sexual reproduction in a mammalian host and asexual replication in a snail host. Understanding the molecular mechanisms that the parasite uses to transition between hosts and develop into dimorphic reproductively competent adults may reveal new strategies for control.

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The heartworm, Dirofilaria immitis, is a filarial parasitic nematode responsible for significant morbidity and mortality in wild and domesticated canids. Resistance to macrocyclic lactone drug prevention represents a significant threat to parasite control and has prompted investigations to understand the genetic determinants of resistance. This study aimed to improve the genomic resources of D.

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Our knowledge of the diet of wild octopus paralarvae, Octopus vulgaris, is restricted to the first 2 weeks of its planktonic phase when they are selective hunters found near the coastline. These small paralarvae, bearing only three suckers per arm, are transported by oceanic currents from the coast towards offshore waters, where they complete the planktonic phase over 2 months. Here, we have investigated the trophic ecology of O.

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The identification of gastrointestinal helminth infections of humans and livestock almost exclusively relies on the detection of eggs or larvae in faeces, followed by manual counting and morphological characterisation to differentiate species using microscopy-based techniques. However, molecular approaches based on the detection and quantification of parasite DNA are becoming more prevalent, increasing the sensitivity, specificity and throughput of diagnostic assays. High-throughput sequencing, from single PCR targets through to the analysis of whole genomes, offers significant promise towards providing information-rich data that may add value beyond traditional and conventional molecular approaches; however, thus far, its utility has not been fully explored to detect helminths in faecal samples.

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Soil-transmitted helminths (STH) are targeted for control through mass drug-administration campaigns to prevent morbidity affecting at-risk groups in endemic regions. Although broadly successful, the use of albendazole and mebendazole achieved variable progress, with deficiencies against and a predictable low efficacy against . Novel drug combinations offer a potential solution, providing they can be delivered safely and maintain efficacy against all STH species.

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Article Synopsis
  • Parasitic helminths, like other pathogens, can quickly develop resistance to drugs, making it crucial to understand the genetics behind this resistance, especially in nematodes.
  • This study used genetic crosses in natural hosts to map resistance genes for major classes of anthelmintics, identifying new alleles linked to resistance against benzimidazoles, levamisole, and ivermectin.
  • The findings pinpoint the gene cky-1 as significant for ivermectin survival, providing a pathway for developing molecular diagnostics to address drug resistance in parasitic infections.
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Understanding the composition of gastrointestinal nematode communities may help to mitigate or exploit parasite adaptations within their host. We have used nemabiome deep amplicon sequencing of internal transcribed spacer-2 (ITS-2) ribosomal DNA to describe the temporal and host species composition of gastrointestinal nematode communities following sampling of six Scottish ponies across 57 months. In the absence of parasite control, each horse showed seasonal trends of increases and decreases in faecal egg counts, consistent with the epidemiology of equine strongylid parasites, however, the composition of parasites within individuals changed over time.

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  • In schistosomiasis control areas in Africa, regular mass drug administration (MDA) with praziquantel (PZQ) is crucial for disease management, but the genetic impact of this treatment on schistosomes is not well understood.
  • A study collected whole-genome sequence data from 174 miracidia in Uganda, revealing that the parasite populations in fishing communities have greater genetic diversity than those in nearby villages, with variations observed before and after PZQ treatment.
  • The research indicated that post-treatment parasite populations show signs of natural selection, potentially leading to reduced susceptibility to PZQ, highlighting concerns about the effectiveness of the drug over time.
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  • Haemonchus contortus is a blood-sucking parasitic worm that affects small ruminants, causing health and economic issues globally, with resistance to common treatments becoming a major problem.
  • Levamisole (LEV) is a key treatment option, as it has lower resistance rates; it works by binding to acetylcholine receptors in the worms, leading to paralysis.
  • Recent studies have identified a specific genetic change (S168T) in the acr-8 gene associated with LEV resistance; an optimized PCR test was developed to detect this variant, showing its prevalence in resistant populations and its potential use for diagnosing LEV resistance in the field.
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In 2020, WHO recognised the importance of strongyloidiasis alongside soil-transmitted helminths (STH) in their 2021-30 roadmap, which aspires to target Strongyloides stercoralis with preventive chemotherapy by use of ivermectin. Combination treatment with both albendazole, the primary drug used to treat STH, and ivermectin, would improve the efficiency of mass drug administration targeting both STH and S stercoralis. In this Personal View, we discuss the challenges and opportunities towards the development of an efficient control programme for strongyloidiasis, particularly if it is to run concurrently with STH control.

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Rapid advancement in high-throughput sequencing and analytical approaches has seen a steady increase in the generation of genomic resources for helminth parasites. Now, helminth genomes and their annotations are a cornerstone of numerous efforts to compare genetic and transcriptomic variation, from single cells to populations of globally distributed parasites, to genome modifications to understand gene function. Our understanding of helminths is increasingly reliant on these genomic resources, which are primarily static once published and vary widely in quality and completeness between species.

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  • Trichuriasis, caused by the whipworm Trichuris trichiura, is a neglected tropical disease that affects around 500 million people, mainly in areas with poor sanitation where fecal-oral transmission is common.
  • Researchers conducted a population genomics study using whole-genome sequencing of whipworm samples from various locations, including ancient samples dating back up to 1,000 years.
  • The findings indicate a genetic structure among whipworm populations, with the highest genetic variation in Uganda, suggesting an African origin and highlighting potential zoonotic reservoirs, which could help improve genomic epidemiology efforts against this disease.*
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  • Ivermectin is crucial for global health in humans and animals, but resistance to the drug is widespread in parasites, raising concerns about treatment effectiveness.
  • Despite extensive research, the genetic basis for this resistance in parasitic helminths remains poorly understood due to their complex genomes and evolutionary factors.
  • A genetic study of Haemonchus contortus revealed that resistant populations exhibit specific gene expression changes linked to ivermectin resistance, including upregulation of key genes involved in neuronal function and cellular processes.
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Gastrointestinal (GI) helminth infections cause significant morbidity in both humans and animals worldwide. Specific and sensitive diagnosis is central to the surveillance of such infections and to determine the effectiveness of treatment strategies used to control them. In this article, we: (i) assess the strengths and limitations of existing methods applied to the diagnosis of GI helminth infections of humans and livestock; (ii) examine high-throughput sequencing approaches, such as targeted molecular barcoding and shotgun sequencing, as tools to define the taxonomic composition of helminth infections; and (iii) discuss the current understanding of the interactions between helminths and microbiota in the host gut.

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The anthelmintic praziquantel (PZQ) is an essential tool in controlling schistosomiasis, so reports of reduced PZQ efficacy are of great public health concern. Le Clec'h et al. recently identified a gene responsible for PZQ resistance in experimentally selected resistant Schistosoma mansoni.

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Haemonchus contortus is a pathogenic gastrointestinal nematode of small ruminants and, in part due to its capacity to develop resistance to drugs, contributes to significant losses in the animal production sector worldwide. Despite decades of research, comparatively little is known about the specific mechanism(s) driving resistance to drugs such as ivermectin in this species. Here we describe a genome-wide approach to detect evidence of selection by ivermectin treatment in a field population of H.

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We present a genome assembly and annotation of an individual female , a parasitic filarial nematode that is transmitted by hard ticks (Ixodidae) to infect a broad range of native Australian murid and marsupial hosts. The genome sequence is 76.9 Mbp in length, and although in draft form (N50 = 99 kbp, N50[n] = 232), is largely complete based on universally conserved orthologs (BUSCOs; genome = 94.

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