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Lamberton, P. H. L.

Publications and source records attributed to Lamberton, P. H. L..

3 recordsLinked to original sources

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↗

Extensive transmission and variation in a functional receptor for praziquantel resistance in endemic Schistosoma mansoni

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 Schistosoma mansoni samples (and the closely related outgroup species, S. rodhaini) 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. We characterised variation across the transient receptor potential melastatin ion channel, TRPMPZQ, a target of praziquantel, which has recently been found to influence praziquantel susceptibility. Functional profiling of TRPMPZQ variants found in endemic populations identified four mutations that reduced channel sensitivity to praziquantel, indicating standing variation for resistance. Analysis of parasite infrapopulations sampled from individuals pre- and post-treatment identified instances of treatment failure, further indicative of potential praziquantel resistance. As schistosomiasis is targeted for elimination as a public health problem by 2030 in all currently endemic countries, and even interruption of transmission in selected African regions, we provide an in-depth genomic characterisation of endemic populations and an approach to identify emerging praziquantel resistance alleles. One Sentence SummaryPopulation genomics and functional genetics of praziquantel resistance in Schistosoma mansoni

genomics↗

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↗