Fasciola hepatica demonstrates high levels of genetic diversity, a lack of population structure and high gene flow: possible implications for drug resistance

Fasciola hepatica, the liver fluke, is a trematode parasite of considerable economic importance to the livestock industry and is a re-emerging zoonosis that poses a risk to human health in F. hepatica-endemic areas worldwide. Drug resistance is a substantial threat to the current and future control of F. hepatica, yet little is known about how the biology of the parasite influences the development and spread of resistance. Given that F. hepatica can self-fertilise and therefore inbreed, there is the potential for greater population differentiation and an increased likelihood of recessive alleles, such as drug resistance genes, coming together. This could be compounded by clonal expansion within the snail intermediate host and aggregation of parasites of the same genotype on pasture. Alternatively, widespread movement of animals that typically occurs in the UK could promote high levels of gene flow and prevent population differentiation. We identified clonal parasites with identical multilocus genotypes in 61% of hosts. Despite this, 84% of 1579 adult parasites had unique multilocus genotypes, which supports high levels of genotypic diversity within F. hepatica populations. Our analyses indicate a selfing rate no greater than 2%, suggesting that this diversity is in part due to the propensity for F. hepatica to cross-fertilise. Finally, although we identified high genetic diversity within a given host, there was little evidence for differentiation between populations from different hosts, indicating a single panmictic population. This implies that, once those emerge, anthelmintic resistance genes have the potential to spread rapidly through liver fluke populations

Fasciola and fasciolosis in ruminants in Europe: Identifying research needs

18 páginas, 1 figura, 2 tablas.Fasciola hepatica is a trematode parasite with a global distribution, which is responsible for considerable disease and production losses in a range of food producing species. It is also identified by WHO as a re-emerging neglected tropical disease associated with endemic and epidemic outbreaks of disease in human populations. In Europe, F. hepatica is mostly associated with disease in sheep, cattle and goats. This study reviews the most recent advances in our understanding of the transmission, diagnosis, epidemiology and the economic impact of fasciolosis. We also focus on the impact of the spread of resistance to anthelmintics used to control F. hepatica and consider how vaccines might be developed and applied in the context of the immune-modulation driven by the parasite. Several major research gaps are identified which, when addressed, will contribute to providing focussed and where possible, bespoke, advice for farmers on how to integrate stock management and diagnosis with vaccination and/or targeted treatment to more effectively control the parasite in the face of increasing the prevalence of infection and spread of anthelmintic resistance that are likely to be exacerbated by climate change.All authors are members of the Livestock Helminth Research Alliance (LiHRA), whose vision is to improve the health, wealth and productivity of European livestock by providing sustainable helminth control options. This review was commissioned by DISCONTOOLS (www.discontools.eu) as part of the process of identifying research gaps which impinge on effective and sustainable control of fasciolosis in food producing animals in Europe. DJLW, JC, LR, CC, JPA, AMM all received funding from the European Union through the following awards: FPVI‐FOOD‐CT‐200X‐023025‐DELIVER; FPVII‐KBBE‐2011‐5‐288975‐GLOWORM; FPVII‐KBBE‐2010‐4‐265862‐PARAVAC; H2020‐635408‐PARAGONE. DJLW, JEH, NJB received funding from the Biotechnology and Biological Sciences Research Council (BBSRC) through awards: BB/K015591/1 and BBI002480/1, and RJF was supported by BBSRC award BB/M018520/1. MMV was funded by the Spanish “Ramón y Cajal” Programme of the Ministry of Economy and Competitiveness (RYC‐2015‐18368). CC was funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections at the University of Liverpool in partnership with Public Health England (PHE) and Liverpool School of Tropical Medicine (LSTM). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health or PHE.Peer reviewe

Cardiac abnormalities in adults with the attenuated form of mucopolysaccharidosis type I

Background: Cardiac involvement in mucopolysaccharidosis type I (MPS I) has been studied primarily in its most severe forms. Cardiac involvement, particularly left ventricular (LV) systolic and diastolic function, in the attenuated form of MPS I is less well known. Methods: Cardiac function was prospectively investigated in 9 adult patients with the attenuated form of MPS I. All patients underwent 12-lead electrocardiography, 24 h Holter monitoring and two-dimensional echocardiography including tissue Doppler imaging (TDI). Eighteen age- and sex-matched healthy volunteers served as a control group. Results: Aortic, mitral and tricuspid valve thickening was seen in, respectively, 5 (56%), 4 (44%) and 2 (22%) patients. Moderate mitral valve stenosis was seen in 1 patient and moderate aortic stenosis in 2 patients. All patients had mild-to-moderate aortic and mitral valve regurgitation and 6 patients (67%) had mild-to-moderate tricuspid valve regurgitation. Despite normal LV dimensions, ejection fraction and mass index, MPS patients had lower mean systolic mitral annular velocities (6.1±0.6 vs 9.1±1.4 cm/s, p<0.01) compared to normal control subjects. Similarly, mean early diastolic mitral annular velocities were lower in MPS patients (7.8±0.9 vs 13.3±3.3 cm/s, p<0.01). Conclusion: MPS I patients with the attenuated phenotype have not only valvular abnormalities but also LV diastolic and systolic abnormalities

Marine Biodiversity in the Australian Region

The entire Australian marine jurisdictional area, including offshore and sub-Antarctic islands, is considered in this paper. Most records, however, come from the Exclusive Economic Zone (EEZ) around the continent of Australia itself. The counts of species have been obtained from four primary databases (the Australian Faunal Directory, Codes for Australian Aquatic Biota, Online Zoological Collections of Australian Museums, and the Australian node of the Ocean Biogeographic Information System), but even these are an underestimate of described species. In addition, some partially completed databases for particular taxonomic groups, and specialized databases (for introduced and threatened species) have been used. Experts also provided estimates of the number of known species not yet in the major databases. For only some groups could we obtain an (expert opinion) estimate of undiscovered species. The databases provide patchy information about endemism, levels of threat, and introductions. We conclude that there are about 33,000 marine species (mainly animals) in the major databases, of which 130 are introduced, 58 listed as threatened and an unknown percentage endemic. An estimated 17,000 more named species are either known from the Australian EEZ but not in the present databases, or potentially occur there. It is crudely estimated that there may be as many as 250,000 species (known and yet to be discovered) in the Australian EEZ. For 17 higher taxa, there is sufficient detail for subdivision by Large Marine Domains, for comparison with other National and Regional Implementation Committees of the Census of Marine Life. Taxonomic expertise in Australia is unevenly distributed across taxa, and declining. Comments are given briefly on biodiversity management measures in Australia, including but not limited to marine protected areas

The Knowledge Argument and Howard Robinson’s 2016 case for Dualism and Mental Substance

Standard physicalist responses to Frank Jackson’s Knowledge Argument (1982) are argued to be unsatisfactory. Related arguments are then considered for Mind Body Dualism from Howard Robinson (2016), covering topics of scientific reduction and supervenience. I object to Robinson’s arguments for the mind dependence of various entities

Evidence-based pragmatic guidelines for the follow-up of testicular cancer: optimising the detection of relapse

Testicular germ cell tumours (TGCTs) are the most common cause of cancer in men between the ages of 15 and 40 years, and, overall, the majority of patients should expect to be cured. The European Germ Cell Cancer Consensus Group has provided clear guidelines for the primary treatment of both seminoma and nonseminomatous germ cell tumours. There is, however, no international consensus on how best to follow patients after their initial management. This must promptly and reliably identify relapses without causing further harm. The standardising of follow-up would result in optimising risk-benefit ratios for individual patients, while ensuring economic use of resources. We have identified the seven common scenarios in managing seminomas and nonseminomas of the various stages and discuss the pertinent issues around relapse and follow-up. We review the available literature and present our comprehensive TGCT follow-up guidelines. Our protocols provide a pragmatic, easily accessible user-friendly basis for other centres to use or to adapt to suit their needs. Furthermore, this should enable future trials to address specific issues around follow-up giving meaningful and useful results