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High-resolution phylogeography of zoonotic tapeworm Echinococcus granulosus sensu stricto genotype G1 with an emphasis on its distribution in Turkey, Italy and Spain

  • LIINA KINKAR (a1), TEIVI LAURIMÄE (a1), SAMI SIMSEK (a2), IBRAHIM BALKAYA (a3), ADRIANO CASULLI (a4), MARIA TERESA MANFREDI (a5), FRANCISCO PONCE-GORDO (a6), ANTONIO VARCASIA (a7), ANTTI LAVIKAINEN (a8), LUIS MIGUEL GONZÁLEZ (a9), STEFFEN REHBEIN (a10), JOKE VAN DER GIESSEN (a11), HEIN SPRONG (a11) and URMAS SAARMA (a1)...

Summary

Echinococcus granulosus is the causative agent of cystic echinococcosis. The disease is a significant global public health concern and human infections are most commonly associated with E. granulosus sensu stricto (s. s.) genotype G1. The objectives of this study were to: (i) analyse the genetic variation and phylogeography of E. granulosus s. s. G1 in part of its main distribution range in Europe using 8274 bp of mtDNA; (ii) compare the results with those derived from previously used shorter mtDNA sequences and highlight the major differences. We sequenced a total of 91 E. granulosus s. s. G1 isolates from six different intermediate host species, including humans. The isolates originated from seven countries representing primarily Turkey, Italy and Spain. Few samples were also from Albania, Greece, Romania and from a patient originating from Algeria, but diagnosed in Finland. The analysed 91 sequences were divided into 83 haplotypes, revealing complex phylogeography and high genetic variation of E. granulosus s. s. G1 in Europe, particularly in the high-diversity domestication centre of western Asia. Comparisons with shorter mtDNA datasets revealed that 8274 bp sequences provided significantly higher phylogenetic resolution and thus more power to reveal the genetic relations between different haplotypes.

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Corresponding author

*Corresponding author: Department of Zoology, Institute of Ecology and Earth Sciences, University of Tartu, Vanemuise 46, 51014 Tartu, Estonia. E-mail: Urmas.Saarma@ut.ee

References

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Altintas, N. (2003). Past to present: echinococcosis in Turkey. Acta Tropica 85, 105112.
Alvarez Rojas, C. A., Romig, T. and Lightowlers, M. W. (2014). Echinococcus granulosus sensu lato genotypes infecting humans – review of current knowledge. International Journal for Parasitology 44, 918.
Andresiuk, M. V., Gordo, F. P., Saarma, M., Elissondo, M. C., Taraborelli, A., Casalongue, C., Denegri, G. and Saarma, U. (2013). Echinococcus granulosus genotype G1 dominated in cattle and sheep during 2003–2006 in Buenos Aires province, an endemic area for cystic echinococcosis in Argentina. Acta Tropica 127, 136142.
Avise, J. C. (2000). Phylogeography: The History and Formation of Species. Harvard University Press, Cambridge, Massachusetts.
Badaraco, J. L., Ayala, F. J., Bart, J. M., Gottstein, B. and Haag, K. L. (2008). Using mitochondrial and nuclear markers to evaluate the degree of genetic cohesion among Echinococcus populations. Experimental Parasitology 119, 453459.
Bandelt, H. J., Forster, P. and Rohl, A. (1999). Median-joining networks for inferring intraspecific phylogenies. Molecular Biology and Evolution 16, 3748.
Bart, J. M., Morariu, S., Knapp, J., Ilie, M. S., Pitulescu, M., Anghel, A., Cosoroaba, I. and Piarroux, R. (2006). Genetic typing of Echinococcus granulosus in Romania. Parasitology Research 98, 130137.
Beato, S., Parreira, R., Calado, M. and Crácio, M. A. A. (2010). Apparent dominance of the G1–G3 genetic cluster of Echinococcus granulosus strains in the central inland region of Portugal. Parasitology International 59, 638642.
Boufana, B., Lahmar, S., Rebaï, W., Safta, Z. B., Jebabli, L., Ammar, A., Kachti, M., Aouadi, S. and Craig, P. S. (2014). Genetic variability and haplotypes of Echinococcus isolates from Tunisia. Transactions of the Royal Society of Tropical Medicine and Hygiene 108, 706714.
Boufana, B., Lett, W. S., Lahmar, S., Buishi, I., Bodell, A. J., Varcasia, A., Casulli, A., Beeching, N. J., Campbell, F., Terlizzo, M., McManus, D. P. and Craig, P. S. (2015). Echinococcus equinus and Echinococcus granulosus sensu stricto from the United Kingdom: genetic diversity and haplotypic variation. International Journal for Parasitology 45, 161166.
Bowles, J., Blair, D. and McManus, D. P. (1992). Genetic variants within the genus Echinococcus identified by mitochondrial DNA sequencing. Molecular and Biochemical Parasitology 54, 165173.
Bowles, J., Blair, D. and McManus, D. (1994). Molecular genetic characterization of the cervid strain (‘northern form’) of Echinococcus granulosus . Parasitology 109, 215221.
Breyer, I., Georgieva, D., Kudrova, R. and Gottstein, B. (2004). Echinococcus granulosus strain typing in Bulgaria: the G1 genotype is predominant in intermediate and definitive wild hosts. Parasitology Research 93, 127130.
Busi, M., Šnábel, V., Varcasia, A., Garippa, G., Perrone, V., De Liberato, C. and D'Amelio, S. (2007). Genetic variation within and between G1 and G3 genotypes of Echinococcus granulosus in Italy revealed by multilocus DNA sequencing. Veterinary Parasitology 150, 7583.
Cardona, G. A. and Carmena, D. (2013). A review of the global prevalence, molecular epidemiology and economics of cystic echinococcosis in production animals. Veterinary Parasitology 192, 1032.
Carmena, D., Sánchez-Serrano, L. and Barbero-Martínez, I. (2008). Echinococcus granulosus infection in Spain. Zoonoses and Public Health 55, 156165.
Casulli, A., Manfredi, M. T., La Rosa, G., Di Cerbo, A. R., Genchi, C. and Pozio, E. (2008). Echinococcus ortleppi and E. granulosus G1, G2 and G3 genotypes in Italian bovines. Veterinary Parasitology 155, 168172.
Casulli, A., Interisano, M., Sreter, T., Chitimia, L., Kirkova, Z., La Rosa, G. and Pozio, E. (2012). Genetic variability of Echinococcus granulosus sensu stricto in Europe inferred by mitochondrial DNA sequences. Infection Genetics and Evolution 12, 377383.
Chaligiannis, I., Maillard, S., Boubaker, G., Spiliotis, M., Saratsis, A., Gottstein, B. and Sotiraki, S. (2015). Echinococcus granulosus infection dynamics in livestock of Greece. Acta Tropica 150, 6470.
Chessa, B., Pereira, F., Arnaud, F., Amorim, A., Goyache, F., Mainland, I., Kao, R., Pemberton, J., Beraldi, D., Stear, M., Alberti, A., Pittau, M., Iannuzzi, L., Banabazi, M., Kazwala, R., Zhang, Y., Arranz, J. J., Ali, B., Wang, Z., Uzun, M., Dione, M., Olsaker, I., Holm, L.-E., Saarma, U., Ahmad, S., Marzanov, N., Eythorsdottir, E., Holland, M., Ajmone-Marsan, P., Bruford, M., Kantanen, J., Spencer, T. and Palmarini, M. (2009). Revealing the history of sheep domestication using retrovirus integrations. Science 324, 532536.
Dakkak, A. (2010). Echinococcosis/hydatidosis: a severe threat in Mediterranean countries. Veterinary Parasitology 174, 211.
Daniel-Mwambete, K., Ponce-Gordo, F. and Cuesta-Bandera, C. (2004). Genetic identification and host range of the Spanish strains of Echinococcus granulosus . Acta Tropica 91, 8793.
Daumerie, D., Savioli, L., Crompton, D. W. T. and Peters, P. (2010). Working to Overcome the Global Impact of Neglected Tropical Diseases: First WHO Report on Neglected Tropical Diseases. World Health Organization, France.
Deplazes, P., van Knapen, F., Schweiger, A. and Overgaauw, P. A. (2011). Role of pet dogs and cats in the transmission of helminthic zoonoses in Europe, with a focus on echinococcosis and toxocarosis. Veterinary Parasitology 182, 4153.
Dore, F., Varcasia, A., Pipia, A. P., Sanna, G., Pinna Parpaglia, M. L., Corda, A., Romig, T. and Scala, A. (2014). Ultrasound as a monitoring tool for cystic echinococcosis in sheep. Veterinary Parasitology 203, 5964.
Eckert, J., Gemmell, M. A., Meslin, F.-X. and Pawlowski, Z. S. (eds.) (2001). WHO/OIE Manual on Echinococcosis in Humans and Animals: A Public Health Problem of Global Concern. WHO/OIE, Paris.
Excoffier, L., Laval, G. and Schneider, S. (2005). Arlequin ver. 3.0: an integrated software package for population genetics data analysis. Evolutionary Bioinformatics Online 1, 4750.
FAO/WHO [Food and Agriculture Organization of the United Nations/World Health Organization]. (2014). Multicriteria-based ranking for risk management of food-borne parasites. Microbiological Risk Assessment Series No. 23. Rome. 302 pp.
Fu, Y. X. (1997). Statistical tests of neutrality of mutations against population growth, hitchhiking and background selection. Genetics 147, 915925.
Garippa, G. and Manfredi, M. T. (2009). Cystic echinococcosis in Europe and in Italy. Veterinary Research Communications 33, 3539.
Giannetto, S., Poglayen, G., Brianti, E., Sorgi, C., Gaglio, G., Canu, S. and Virga, A. N. (2004). An epidemiological updating on cystic echinococcosis in cattle and sheep in Sicily, Italy. Parassitologia 46, 423424.
González, L. M., Daniel-Mwambete, K., Montero, E., Rosenzvit, M. C., McManus, D. P., Gárate, T. and Cuesta-Bandera, C. (2002). Further molecular discrimination of Spanish strains of Echinococcus granulosus . Experimental Parasitology 102, 4656.
Haag, K. L., Araujo, A. M., Gottstein, B., Siles-Lucas, M., Thompson, R. and Zaha, A. (1999). Breeding systems in Echinococcus granulosus (Cestoda; Taeniidae): selfing or outcrossing? Parasitology 118, 6371.
Kedra, A. H., Swiderski, Z., Tkach, V., Dubinsky, P., Pawlowski, Z., Stefaniak, J. and Pawlowski, J. (1999). Genetic analysis of Echinococcus granulosus from humans and pigs in Poland, Slovakia and Ukraine. A multicenter study. Acta Parasitologica 44, 248254.
Keis, M., Remm, J., Ho, S. Y. W., Davison, J., Tammeleht, E., Tumanov, I. L., Saveljev, A. P., Männil, P., Kojola, I., Abramov, A. V., Margus, T. and Saarma, U. (2013). Complete mitochondrial genomes and a novel spatial genetic method reveal cryptic phylogeographic structure and migration patterns among brown bears in north-western Eurasia. Journal of Biogeography 40, 915927.
Knapp, J., Nakao, M., Yanagida, T., Okamoto, M., Saarma, U., Lavikainen, A. and Ito, A. (2011). Phylogenetic relationships within Echinococcus and Taenia tapeworms (Cestoda: Taeniidae): an inference from nuclear protein-coding genes. Molecular Phylogenetics and Evolution 61, 628638.
Knapp, J., Gottstein, B., Saarma, U. and Millon, L. (2015). Taxonomy, phylogeny and molecular epidemiology of Echinococcus multilocularis: from fundamental knowledge to health ecology. Veterinary Parasitology 213, 8591.
Konyaev, S. V., Yanagida, T., Ivanov, M. V., Ruppel, V. V., Sako, Y., Nakao, M. and Ito, A. (2012). The first report on cystic echinococcosis in a cat caused by Echinococcus granulosus sensu stricto (G1). Journal of Helminthology 86, 391394.
Korsten, M., Ho, S. Y. W., Davison, J., Pähn, B., Vulla, E., Roht, M., Tumanov, I. L., Kojola, I., Andersone-Lilley, Z., Ozolins, J., Pilot, M., Mertzanis, Y., Giannakopoulos, A., Vorobiev, A. A., Markov, N. I., Saveljev, A. P., Lyapunova, E. A., Abramov, A. V., Männil, P., Valdmann, H., Pazetnov, S. V., Pazetnov, V. S., Rõkov, A. and Saarma, U. (2009). Sudden expansion of a single brown bear lineage in northern continental Eurasia: a general model for mammals after the last ice age? Molecular Ecology 18, 19631979.
Laurimaa, L., Davison, J., Süld, K., Plumer, L., Oja, R., Moks, E., Keis, M., Hindrikson, M., Kinkar, L., Laurimäe, T., Abner, J., Remm, J., Anijalg, P. and Saarma, U. (2015). First report of highly pathogenic Echinococcus granulosus genotype G1 in European Union urban environment. Parasites & Vectors 8, 182.
Lavikainen, A., Lehtinen, M., Meri, T., Hirvelä-Koski, V. and Meri, S. (2003). Molecular genetic characterization of the Fennoscandian cervid strain, a new genotypic group (G10) of Echinococcus granulosus . Parasitology 127, 207215.
Lavikainen, A., Lehtinen, A., Laaksonen, S., Agren, E., Oksanen, A. and Meri, S. (2006). Molecular characterization of Echinococcus isolates of cervid origin from Finland and Sweden. Parasitology 133, 565570.
Librado, P. and Rozas, J. (2009). DnaSP v5: a software for comprehensive analysis of DNA polymorphism data. Bioinformatics 25, 14511452.
Marcinkute, A., Šarkunas, M., Moks, E., Saarma, U., Jokelainen, P., Bagrade, G., Laivacuma, S., Strupas, K., Sokolovas, V. and Deplazes, P. (2015). Echinococcus infections in the Baltic region. Veterinary Parasitology 213, 121131.
Martin-Hernando, M. P., González, L. M., Ruiz-Fons, F., Garate, T. and Gortazar, C. (2008). Massive presence of Echinococcus granulosus (Cestoda, Taeniidae) cysts in a wild boar (Sus scrofa) from Spain. Parasitology Research 103, 705707.
Mitrea, I. L., Ionita, M., Costin, I. I., Predoi, G., Avram, E., Rinaldi, L., Maurelli, M. P., Cringoli, G. and Genchi, C. (2014). Occurrence and genetic characterization of Echinococcus granulosus in naturally infected adult sheep and cattle in Romania. Veterinary Parasitology 206, 159166.
Moks, E., Jõgisalu, I., Saarma, U., Talvik, H., Järvis, T. and Valdmann, H. (2006). Helminthologic survey of the wolf (Canis lupus) in Estonia, with an emphasis on Echinococcus granulosus . Journal of Wildlife Diseases 42, 359365.
Moks, E., Jõgisalu, I., Valdmann, H. and Saarma, U. (2008). First report of Echinococcus granulosus G8 in Eurasia and a reappraisal of the phylogenetic relationships of ‘genotypes’ G5-G10. Parasitology 135, 647654.
Morgan, E., Clare, E., Jefferies, R. and Stevens, J. (2012). Parasite epidemiology in a changing world: can molecular phylogeography help us tell the wood from the trees? Parasitology 139, 19241938.
Nakao, M., McManus, D., Schantz, P., Craig, P. and Ito, A. (2007). A molecular phylogeny of the genus Echinococcus inferred from complete mitochondrial genomes. Parasitology 134, 713722.
Nakao, M., Li, T., Han, X., Ma, X., Xiao, N., Qiu, J., Wang, H., Yanagida, T., Mamuti, W. and Wen, H. (2010). Genetic polymorphisms of Echinococcus tapeworms in China as determined by mitochondrial and nuclear DNA sequences. International Journal for Parasitology 40, 379385.
Nakao, M., Yanagida, T., Konyaev, S., Lavikainen, A., Odnokurtsev, V. A., Zaikov, V. A. and Ito, A. (2013). Mitochondrial phylogeny of the genus Echinococcus (Cestoda: Taeniidae) with emphasis on relationships among Echinococcus canadensis genotypes. Parasitology 140, 16251636.
Nakao, M., Lavikainen, A. and Hoberg, E. (2015). Is Echinococcus intermedius a valid species? Trends in Parasitology 31, 342343.
Oksanen, A. and Lavikainen, A. (2015). Echinococcus canadensis transmission in the North. Veterinary Parasitology 213, 182186.
Onac, D., Győrke, A., Oltean, M., Gavrea, R. and Cozma, V. (2013). First detection of Echinococcus granulosus G1 and G7 in wild boars (Sus scrofa) and red deer (Cervus elaphus) in Romania using PCR and PCR-RFLP techniques. Veterinary Parasitology 193, 289291.
Rannamäe, E., Lõugas, L., Niemi, M., Kantanen, J., Maldre, L., Kadõrova, N. and Saarma, U. (2016). Maternal and paternal genetic diversity of ancient sheep in Estonia from the late bronze age to the post-medieval period, and comparison with other regions in Eurasia. Animal Genetics 47, 208218.
Romig, T., Dinkel, A. and Mackenstedt, U. (2006). The present situation of echinococcosis in Europe. Parasitology International 55, S187S191.
Romig, T., Ebi, D. and Wassermann, M. (2015). Taxonomy and molecular epidemiology of Echinococcus granulosus sensu lato. Veterinary Parasitology 213, 7684.
Saarma, U., Jõgisalu, I., Moks, E., Varcasia, A., Lavikainen, A., Oksanen, A., Simsek, S., Andresiuk, V., Denegri, G. and González, L. M. (2009). A novel phylogeny for the genus Echinococcus, based on nuclear data, challenges relationships based on mitochondrial evidence. Parasitology 136, 317328.
Scala, A., Garippa, G., Varcasia, A., Tranquillo, V. M. and Genchi, C. (2006). Cystic echinococcosis in slaughtered sheep in Sardinia (Italy). Veterinary Parasitology 135, 3338.
Schneider, R., Gollackner, B., Schindl, M., Tucek, G. and Auer, H. (2010). Echinococcus canadensis G7 (pig strain): an underestimated cause of cystic echinococcosis in Austria. American Journal of Tropical Medicine and Hygiene 82, 871874.
Sherifi, K., Rexhepi, A., Hamidi, A., Behluli, B., Zessin, K. H., Mathis, A. and Deplazes, P. (2011). Detection of patent infections of Echinococcus granulosus (“sheep-strain”, G1) in naturally infected dogs in Kosovo. Berliner und Munchener Tierarztliche Wochenschrift 124, 518521.
Simsek, S. and Cevik, A. (2014). First detection and molecular characterization of Echinococcus equinus in a mule in Turkey. Acta Parasitologica 59, 773777.
Simsek, S., Roinioti, E. and Eroksuz, H. (2015). First report of Echinococcus equinus in a donkey in Turkey. Korean Journal of Parasitology 53, 731735.
Sobrino, R., González, L. M., Vicente, J., Fernández de Luco, D., Garate, T. and Gortázar, C. (2006). Echinococcus granulosus (Cestoda, Taeniidae) in the Iberian wolf. Parasitology Research 99, 753756.
Tajima, F. (1989). Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123, 585595.
Thompson, R. (2008). The taxonomy, phylogeny and transmission of Echinococcus . Experimental Parasitology 119, 439446.
Thompson, R. A. and McManus, D. P. (2002). Towards a taxonomic revision of the genus Echinococcus . Trends in Parasitology 18, 452457.
Utuk, A. E. and Simsek, S. (2013). Molecular characterization of the horse isolate of Echinococcus granulosus in Turkey. Journal of Helminthology 87, 305308.
Varcasia, A., Canu, S., Lightowlers, M. W., Scala, A. and Garippa, G. (2006). Molecular characterization of Echinococcus granulosus strains in Sardinia. Parasitology Research 98, 273277.
Varcasia, A., Canu, S., Kogkos, A., Pipia, A. P., Scala, A., Garippa, G. and Seimenis, A. (2007). Molecular characterization of Echinococcus granulosus in sheep and goats of Peloponnesus, Greece. Parasitology Research 101, 11351139.
Varcasia, A., Garippa, G., Pipia, A. P., Scala, A., Brianti, E., Giannetto, S., Battelli, G., Poglayen, G. and Micagni, G. (2008). Cystic echinococcosis in equids in Italy. Parasitology Research 102, 815818.
Varcasia, A., Tanda, B., Giobbe, M., Solinas, C., Pipia, A. P., Malgor, R., Carmona, C., Garippa, G. and Scala, A. (2011). Cystic echinococcosis in Sardinia: farmers’ knowledge and dog infection in sheep farms. Veterinary Parasitology 181, 335340.
Vural, G., Baca, A. U., Gauci, C. G., Bagci, O., Gicik, Y. and Lightowlers, M. W. (2008). Variability in the Echinococcus granulosus cytochrome C oxidase 1 mitochondrial gene sequence from livestock in Turkey and a re-appraisal of the G1-3 genotype cluster. Veterinary Parasitology 154, 347350.
Xhaxhiu, D., Kusi, I., Rapti, D., Kondi, E., Postoli, R., Rinaldi, L., Dimitrova, Z. M., Visser, M., Knaus, M. and Rehbein, S. (2011). Principal intestinal parasites of dogs in Tirana, Albania. Parasitology Research 108, 341353.
Yan, N., Nie, H.-M., Jiang, Z.-R., Yang, A.-G., Deng, S.-J., Guo, L., Yu, H., Yan, Y.-B., Tsering, D. and Kong, W.-S. (2013). Genetic variability of Echinococcus granulosus from the Tibetan plateau inferred by mitochondrial DNA sequences. Veterinary Parasitology 196, 179183.
Yanagida, T., Mohammadzadeh, T., Kamhawi, S., Nakao, M., Sadjjadi, S. M., Hijjawi, N., Abdel-Hafez, S. K., Sako, Y., Okamoto, M. and Ito, A. (2012). Genetic polymorphisms of Echinococcus granulosus sensu stricto in the Middle East. Parasitology International 61, 599603.
Yang, Y. R., Rosenzvit, M. C., Zhang, L. H., Zhang, J. Z. and McManus, D. P. (2005). Molecular study of Echinococcus in west-central China. Parasitology 131, 547555.
Zeder, M. A. (2008). Domestication and early agriculture in the Mediterranean Basin: origins, diffusion, and impact. Proceedings of the National Academy of Sciences of the United States of America 105, 1159711604.

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