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      Epidemiological distribution of Echinococcus granulosus s. l. infection in human and domestic animal hosts in European Mediterranean and Balkan countries: A systematic review

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          Abstract

          Cystic echinococcosis (CE) is a neglected zoonosis caused by infection with the cestode Echinococcus granulosus sensu lato. We carried out a systematic literature review on E. granulosus s. l. human and animal (cattle, sheep, dog) infection in European Mediterranean and Balkan countries in 2000–2019, to provide a picture of its recent epidemiology in this endemic area. MEDLINE, EMBASE, Scopus, Google Scholar and Open Grey databases were searched. Included cases were: i) for humans, data from hospital records and imaging studies; ii) for dogs, data from necropsy and coprological studies; iii) for ruminants, cases based on slaughter inspection. The NUTS (Nomenclature of Territorial Units for Statistics) classification was used to categorize extracted data in epidemiological units, defined as data referred to one NUTS2 (basic region) in one year time. Data were then aggregated to NUTS1 level (major regions), calculating the average incidence value of included epidemiological units. For prevalence studies covering different epidemiological units, the pooled prevalence was estimated. Data were extracted from 79 publications, 25 on human infection (covering 437 epidemiological units), and 54 on animal infection (52 epidemiological units for cattle, 35 for sheep and 25 for dogs). At NUTS1 level, average annual incidence rates of human CE ranged from 0.10–7.74/100,000; pooled prevalence values ranged from 0.003–64.09% in cattle, 0.004–68.73% in sheep, and 0–31.86% in dogs. Southern and insular Italy, central Spain, Romania and Bulgaria reported the highest values. Bovine data showed a more similar pattern to human data compared to sheep and dogs. Limitation of evidence included the paucity of human prevalence studies, data heterogeneity, and the patchy geographical coverage, with lack of data especially for the Balkans. Our results confirm Italy, Spain, and Eastern Europe being the most affected areas, but data are extremely heterogeneous, geographical coverage very patchy, and human prevalence studies extremely scant. Results also highlight the notorious problem of underreporting of E. granulosus s. l. infection in both humans and animals.

          Author summary

          Cystic echinococcosis (CE) is a neglected zoonosis caused by infection with the parasite Echinococcus granulosus sensu lato, naturally transmitted between canids and livestock; CE in humans can be a serious condition. In endemic areas, CE is responsible for significant health and economic losses, but its real burden is difficult to estimate. E. granulosus s. l. is especially present in areas where livestock breeding is practiced, including European Mediterranean and Balkan countries. We carried out a systematic literature review on the epidemiology of E. granulosus s. l. human and animal infection in this area in 2000–2019. Data were extracted from 79 publications, and referred to Nomenclature of Territorial Units for Statistics (NUTS) levels per year. Average annual incidence rates of human CE ranged from 0.10–7.74/100,000; pooled prevalences ranged from 0.003–64.09% in cattle, 0.004–68.73% in sheep, and 0–31.86% in dogs. Bovine data showed a more similar pattern to human data compared to sheep and dogs. Our results confirm that Italy, Spain, and Eastern Europe are the most affected areas, but data are extremely heterogeneous, geographical coverage very patchy, and human prevalence studies extremely scant. Results also highlight the well-known problem of underreporting of E. granulosus s. l. infection in both humans and animals.

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          Most cited references89

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          The European Union summary report on trends and sources of zoonoses, zoonotic agents and food‐borne outbreaks in 2015

          (2016)
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            Ecology and Life Cycle Patterns of Echinococcus Species.

            The genus Echinococcus is composed of eight generally recognized species and one genotypic cluster (Echinococcus canadensis cluster) that may in future be resolved into one to three species. For each species, we review existing information on transmission routes and life cycles in different geographical contexts and - where available - include basic biological information of parasites and hosts (e.g., susceptibility of host species). While some Echinococcus spp. are transmitted in life cycles that involve predominantly domestic animals (e.g., dog - livestock cycles), others are wildlife parasites that do or do not interact with domestic transmission. In many cases, life cycle patterns of the same parasite species differ according to geography. Simple life cycles contrast with transmission patterns that are highly complex, involving multihost systems that may include both domestic and wild mammals. Wildlife transmission may be primary or secondary, i.e., resulting from spillovers from domestic animals. For most of the species and regions, existing information does not yet permit a conclusive description of transmission systems. Such data, however, would be highly relevant, e.g., for anticipation of geographical changes of the presence and frequency of these parasites in a warming world, or for initiating evidence-based control strategies.
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              Echinococcus granulosus sensu lato genotypes infecting humans--review of current knowledge.

              Genetic variability in the species group Echinococcus granulosus sensu lato is well recognised as affecting intermediate host susceptibility and other biological features of the parasites. Molecular methods have allowed discrimination of different genotypes (G1-10 and the 'lion strain'), some of which are now considered separate species. An accumulation of genotypic analyses undertaken on parasite isolates from human cases of cystic echinococcosis provides the basis upon which an assessment is made here of the relative contribution of the different genotypes to human disease. The allocation of samples to G-numbers becomes increasingly difficult, because much more variability than previously recognised exists in the genotypic clusters G1-3 (=E. granulosus sensu stricto) and G6-10 (Echinococcus canadensis). To accommodate the heterogeneous criteria used for genotyping in the literature, we restrict ourselves to differentiate between E. granulosus sensu stricto (G1-3), Echinococcus equinus (G4), Echinococcus ortleppi (G5) and E. canadensis (G6-7, G8, G10). The genotype G1 is responsible for the great majority of human cystic echinococcosis worldwide (88.44%), has the most cosmopolitan distribution and is often associated with transmission via sheep as intermediate hosts. The closely related genotypes G6 and G7 cause a significant number of human infections (11.07%). The genotype G6 was found to be responsible for 7.34% of infections worldwide. This strain is known from Africa and Asia, where it is transmitted mainly by camels (and goats), and South America, where it appears to be mainly transmitted by goats. The G7 genotype has been responsible for 3.73% of human cases of cystic echinococcosis in eastern European countries, where the parasite is transmitted by pigs. Some of the samples (11) could not be identified with a single specific genotype belonging to E. canadensis (G6/10). Rare cases of human cystic echinococcosis have been identified as having been caused by the G5, G8 and G10 genotypes. No cases of human infection with G4 have been described. Biological differences between the species and genotypes have potential to affect the transmission dynamics of the parasite, requiring modification of methods used in disease control initiatives. Recent investigations have revealed that the protective vaccine antigen (EG95), developed for the G1 genotype, is immunologically different in the G6 genotype. Further research will be required to determine whether the current EG95 vaccine would be effective against the G6 or G7 genotypes, or whether it will be necessary, and possible, to develop genotype-specific vaccines. Copyright © 2013 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: VisualizationRole: Writing – review & editing
                Role: Data curationRole: ResourcesRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                10 August 2020
                August 2020
                : 14
                : 8
                : e0008519
                Affiliations
                [1 ] Department of Infectious-Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar (Verona), Italy
                [2 ] Department of Animal Medicine, Production and Health, University of Padova, Legnaro (Padova), Italy
                University of Zurich, SWITZERLAND
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-2882-3343
                http://orcid.org/0000-0001-5529-2854
                Article
                PNTD-D-20-00593
                10.1371/journal.pntd.0008519
                7440662
                32776936
                f3d7b917-ad34-4c0f-91c5-bc5dec475bb5
                © 2020 Tamarozzi et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 11 April 2020
                : 25 June 2020
                Page count
                Figures: 5, Tables: 5, Pages: 23
                Funding
                RC received a grant (BIRD174940), by the Department of Animal Medicine, Production and Health of the University of Padova ( https://www.maps.unipd.it/). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Epidemiology
                Medicine and Health Sciences
                Medical Conditions
                Parasitic Diseases
                Helminth Infections
                Echinococcosis
                Medicine and Health Sciences
                Medical Conditions
                Tropical Diseases
                Neglected Tropical Diseases
                Echinococcosis
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Vertebrates
                Amniotes
                Mammals
                Dogs
                Biology and Life Sciences
                Zoology
                Animals
                Vertebrates
                Amniotes
                Mammals
                Dogs
                People and Places
                Geographical Locations
                Europe
                Biology and Life Sciences
                Agriculture
                Animal Management
                Livestock
                Biology and Life Sciences
                Veterinary Science
                Veterinary Epidemiology
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Vertebrates
                Amniotes
                Mammals
                Ruminants
                Sheep
                Biology and Life Sciences
                Zoology
                Animals
                Vertebrates
                Amniotes
                Mammals
                Ruminants
                Sheep
                People and places
                Geographical locations
                Europe
                European Union
                Italy
                Custom metadata
                vor-update-to-uncorrected-proof
                2020-08-20
                All relevant data are within the manuscript and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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