Scrapie infectivity is quickly cleared in tissues of orally-infected farmed fish

BACKGROUND: Scrapie and bovine spongiform encephalopathy (BSE) belongs to the group of animal transmissible spongiform encephalopathy (TSE). BSE epidemic in the UK and elsewhere in Europe has been linked to the use of bovine meat and bone meals (MBM) in the feeding of cattle. There is concern that pigs, poultry and fish bred for human consumption and fed with infected MBM would eventually develop BSE or carry residual infectivity without disease. Although there has been no evidence of infection in these species, experimental data on the susceptibility to the BSE agent of farm animals other than sheep and cow are limited only to pigs and domestic chicken. In the framework of a EU-granted project we have challenged two species of fish largely used in human food consumption, rainbow trout (Oncorhynchus mykiss) and turbot (Scophthalmus maximus), with a mouse-adapted TSE strain (scrapie 139A), to assess the risk related to oral consumption of TSE contaminated food. In trout, we also checked the "in vitro" ability of the pathological isoform of the mouse prion protein (PrP(Sc)) to cross the intestinal epithelium when added to the mucosal side of everted intestine. RESULTS: Fish challenged with a large amount of scrapie mouse brain homogenate by either oral or parenteral routes, showed the ability to clear the majority of infectivity load. None of the fish tissues taken at different time points after oral or parenteral inoculation was able to provoke scrapie disease after intracerebral inoculation in recipient mice. However, a few recipient mice were positive for PrP(Sc )and spongiform lesions in the brain. We also showed a specific binding of PrP(Sc )to the mucosal side of fish intestine in the absence of an active uptake of the prion protein through the intestinal wall. CONCLUSION: These results indicate that scrapie 139A, and possibly BSE, is quickly removed from fish tissues despite evidence of a prion like protein in fish and of a specific binding of PrP(Sc )to the mucosal side of fish intestine

Mosquito vectors, malaria and other vector-borne diseases

Vector-borne diseases (VBDs) pose a major threat to the health of societies around the world. According to the World Health Organization (WHO), VBDs account for around 17% of the estimated global burden of communicable diseases (before the COVID-19 pandemics) and claim >700.000 lives every year and huge public health and economic costs. The burden is highest in tropical and subtropical areas, where > 240 million yearly cases are reported. More than 80% of the global population live in areas at risk from at least one major vector-borne disease, with more than half at risk from two or more. The dynamic and complex nature of vector-borne pathogens complicates predictions of the impact of existing, re-emerging or new VBDs on human health. Despite this unpredictability and global efforts to fight against vector-borne pathogens and their vectors, WHO expects both intensification of some VBDs and emergence of others (particularly mosquito-borne arboviruses) also in temperate regions, including Europe. Research on vector-borne pathogens, vectors and human and non-human hosts and on their reciprocal interactions in relation to social and climatic changes has been and must continue to be a foundation upon which VBD control programs are built. Research on topics related to VBDs is one of the core interest of the parasitology units at DSPMI, starting from pivotal studies on Afrotropical malaria vector bionomics and evolution and on human genetics and malaria and extending in the last couple of decades to studies on pathogen-mosquito interactions, arbovirus mosquito vectors bionomics and epidemiology, vectors of zoonotic or animal diseases (e.g. sandflies and Drosophilids), as well as to studies on genetic, metabolic and behavioral insecticide resistance mechanisms and on the development and validation of novel diagnostic, monitoring and control tools. These research activities are carried out in collaboration with extensive network of collaborators in Italy (e.g., Università degli Studi di Bari, Camerino, Trento, Piemonte Orientale, Napoli Federico II, Istituto Superiore di Sanità; IZS Venezie; Fondazione Edmund Mach, Fondazione Bruno Kessler, Fondazione Policlinico Militare Celio, MUSE di Trento), Europe (e.g., Universities of Glasgow, Imperial College London, Liverpool Schools of Tropical Medicine, Institut Pasteur Paris, IRD Montpellier), US and America (e.g., National Institute of Health, Yale University, Notre-Dame University, Universidad de Los Andes, Colombia) and Africa (e.g., Centre National de Recherche et de Formation sur le Paludisme in Burkina Faso, University of Ouagadougou, Institut Pasteur de Côte d’Ivoire, Institut Pasteur of Dakar Senegal). The researchers are involved in large international networks (e.g. MalariaGEN coordinated by Oxford University), play leading roles at the European level (e.g. coordination of the Aedes Invasive Mosquito AIM-COST Action funded by EC Horizon Europe) and are funded by several agencies as EC, NIH-USA, Italian Ministry of Research (including MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases, Project no. PE00000007, INF-ACT), Italian Ministry of Defense, Institut Pasteur Paris, Institut Pasteur - Fondazione Cenci-Bolognetti, Università Sapienza research grants

Abstracts from the 23rd Italian congress of Cystic Fibrosis and the 13th National congress of Cystic Fibrosis Italian Society

Cystic Fibrosis (CF) occurs most frequently in caucasian populations. Although less common, this disorder have been reported in all the ethnicities. Currently, there are more than 2000 described sequence variations in CFTR gene, uniformly distributed and including variants pathogenic and benign (CFTR1:www.genet.sickkids.on.ca/). To date,only a subset have been firmily established as variants annotated as disease-causing (CFTR2: www.cftr2.org). The spectrum and the frequency of individual CFTR variants, however, vary among specific ethnic groups and geographic areas. Genetic screening for CF with standard panels of CFTR mutations is widely used for the diagnosis of CF in newborns and symptomatic patients, and to diagnose CF carrier status. These screening panels have an high diagnostic sensitivity (around 85%) for CFTR mutations in caucasians populations but very low for non caucasians. Developed in the last decade, Next-Generation Sequencing (NGS) has been the last breakthrough technology in genetic studies with a substantial reduction in cost per sequenced base and a considerable enhancement of the sequence generation capabilities. Extended CFTR gene sequencing in NGS includes all the coding regions, the splicing sites and their flankig intronic regions, deep intronic regions where are localized known mutations,the promoter and the 5'-3' UTR regions. NGS allows the analysis of many samples concurrently in a shorter period of time compared to Sanger method . Moreover, NGS platforms are able to identify CFTR copy number variation (CNVs), not detected by Sanger sequencing. This technology has provided new and reliable approaches to molecular diagnosis of CF and CFTR-Related Disorders. It also allows to improve the diagnostic sensitivity of newborn and carrier screeningmolecular tests. In fact, bioinformatics tools suitable for all the NGS platforms can filter data generated from the gene sequencing, and analyze only mutations with well-established disease liability. This approach allows the development of targeted mutations panels with a higher number of frequent CF mutations for the target populationcompared to the standard panels and a consequent enhancement of the diagnostic sensitivity. Moreover, in the emerging challenge of diagnosing CF in non caucasians patients, the possibility of customize a NGS targeted mutations panel should increase the diagnostic sensitivity when the target population has different ethnicities