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Detecting nested clusters of human alveolar echinococcosis

  • ZEINABA SAID-ALI (a1) (a2), FRÉDÉRIC GRENOUILLET (a1) (a2) (a3), JENNY KNAPP (a1) (a2) (a3), SOLANGE BRESSON-HADNI (a1) (a2) (a3), DOMINIQUE ANGÈLE VUITTON (a2), FRANCIS RAOUL (a1) (a2), CARINE RICHOU (a2) (a3), LAURENCE MILLON (a1) (a2) and PATRICK GIRAUDOUX (a1) (a2) (a3) (a4)...


Recent changes in the epidemiology of alveolar echinococcosis (AE) in Eurasia have led to increasing concerns about the risk of human AE and the need for a thorough evaluation of the epidemiological situation. The aim of this study was to explore the use of a National Register to detect complex distribution patterns on several scales. The data were human AE cases from the FrancEchino register, diagnosed in France from 1982 to 2011. We used the Kulldorff spatial scan analysis to detect non-random locations of cases. We proposed an exploratory method that was based on the successive detection of nested clusters inside each of the statistically significant larger clusters. This method revealed at least 4 levels of disease clusters during the study period. The spatial variations of cluster location over time were also shown. We conclude that National Human AE registers, although not exempted from epidemiological biases, are currently the best way to achieve an accurate representation of human AE distribution on various scales. Finally, we confirm the multi-scale clustered distribution of human AE, and we hypothesize that our study may be a reasonable starting point from which to conduct additional research and explore the processes that underlie such distributions.


Corresponding author

*Corresponding author: Chrono-environment, University of Franche-Comté-CNRS, Place Leclerc, F-25030 Besançon, France. Tel: +33 381 665 745. Fax: +33 381 665 797. E-mail:


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Allen, T. E. and Star, T. B. (1982). Hierarchy Perspectives for Ecological Complexity. University of Chicago Press, Chicago.
Atkinson, J. A. M., Gray, D. J., Clements, A. C. A., Barnes, T. S., McManus, D. P. and Yang, Y. R. (2013). Environmental changes impacting Echinococcus transmission: research to support predictive surveillance and control. Global Change Biology 19, 677688.
Bivand, R. S., Pebesma, E. J. and Gomes-Rubio, V. (2008). Applied Spatial Data Analysis with R. Springer, Dortrecht.
Boscoe, F. P., McLaughlin, C., Schymura, M. J. and Kielb, C. L. (2003). Visualization of the spatial scan statistic using nested circles. Health and Place 9, 273277.
Bresson-Hadni, S., Laplante, J. J., Lenys, D., Rohmer, P., Gottstein, B., Jacquier, P., Mercet, P., Meyer, J. P., Miguet, J. P. and Vuitton, D. A. (1994). Seroepidemiological screening of Echinococcus multilocularis infection in a European area endemic for Alveolar echinococcosis. American Journal of Tropical Medicine and Hygiene 51, 837846.
Brunetti, E., Kern, P., Vuitton, D. A. and Writing Panel, W.-I. (2010). Expert consensus for the diagnosis and treatment of cystic and alveolar echinococcosis in humans. Acta Tropica 114, 116.
Chen, J., Roth, R. E., Naito, A. T., Lengerich, E. J. and MacEachren, A. M. (2008). Geovisual analytics to enhancve spatial scan statistic interpretation: an analysis of U.S. cervical cancer mortality. International Journal of Health Geographics 7, 118.
Combes, B., Comte, S., Raton, V., Raoul, F., Boué, F., Umhang, G., Favier, S., Dunoyer, C., Woronoff, N. and Giraudoux, P. (2012). Westward spread of Echinococcus multilocularis in foxes, France, 2005–2010. Emerging Infectious Diseases 18, 20592062.
Craig, P. S. and Echinococcosis Working Group in China (2006). Epidemiology of human alveolar echinococcosis in China. Parasitology International 55, S221S225. doi: 10.1016/j.parint.2005.11.034.
Danson, F. M., Craig, P. S., Man, W., Shi, D. and Giraudoux, P. (2004). Landscape dynamics and risk modeling of human alveolar echinococcosis. Photogrammetric Engineering and Remote Sensing 70, 359366.
Danson, F. M., Graham, A. J., Pleydell, D. R. J., Campos-Ponce, M., Giraudoux, P. and Craig, P. S. (2003). Multi-scale spatial analysis of human alveolar echinococcosis risk in China. Parasitology 127, 133141.
Davidson, R. K., Romig, T., Jenkins, E., Tryland, M. and Robertson, L. J. (2012). The impact of globalisation on the distribution of Echinococcus multilocularis. Trends in Parasitology 28, 239247. doi: 10.1016/
Eckert, J., Conraths, F. J. and Tackmann, K. (2000). Echinococcosis: an emerging or re-emerging zoonosis? International Journal for Parasitology 30, 12831294.
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, France.
Giraudoux, P., Craig, P. S., Delattre, P., Bartholomot, B., Bao, G., Barnish, G., Harraga, S., Quéré, J. P., Raoul, F., Wang, Y. H., Shi, D. and Vuitton, D. (2003). Interactions between landscape changes and host communities can regulate Echinococcus multilocularis transmission. Parasitology 127, 121131.
Giraudoux, P., Delattre, P., Takahashi, K., Raoul, F., Quere, J. P., Craig, P. and Vuitton, D. (2002). Transmission ecology of Echinococcus multilocularis in wildlife: what can be learned from comparative studies and multiscale approaches? In Cestode Zoonoses: Echinococcosis and Cysticercosis: an Emergent and Global Problem (ed. Craig, P. and Pawlowski, Z.), pp. 251266. IOS Press, Amsterdam.
Giraudoux, P., Raoul, F., Afonso, E., Ziadinov, I., Yang, Y., Li, L., Quere, J. P., Feng, X. H., Wang, Q., Wen, H., Ito, A. and Craig, P. S. (2013 a). Transmission ecosystems of Echinococcus multilocularis in China and Central Asia. Parasitology 140, in press.
Giraudoux, P., Raoul, F., Pleydell, D., Li, T. Y., Han, X. M., Qiu, J. M., Xie, Y., Wang, H., Ito, A. and Craig, P. S. (2013 b). Drivers of Echinococcus multilocularis transmission in China: host biodiversity, landscape or climate? PLoS Neglected Tropical Diseases 7, e2045.
Grenouillet, F., Knapp, J., Millon, L., Raton, V., Richou, C., Piarroux, M., Piarroux, R., Manition, G., Vuitton, D. A. and Bresson-Hadni, S. (2010). L’échinococcose alvéolaire humaine en France en 2010. Bulletin Epidemiologique Hebdomadaire, Hors-Série, 2425.
Jenkins, D. J., Romig, T. and Thompson, R. C. A. (2005). Emergence/re-emergence of Echinococcus spp.- a global update. International Journal for Parasitology 35, 12051219. doi: 10.1016/j.ijpara.2005.07.014.
Jorgensen, P., an der Heiden, M., Kern, P., Schoneberg, I., Krause, G. and Alpers, K. (2008). Underreporting of human alveolar echinococcosis, Germany. Emerging Infectious Diseases 14, 935937.
Kern, P., Bardonnet, K., Renner, E., Auer, H., Pawlowski, Z., Ammann, R. W., Vuitton, D. A., Kern, P. and European Echinococcsis, R. (2003). European echinococcosis registry: human alveolar echinococcosis, Europe, 1982–2000. Emerging Infectious Diseases 9, 343349.
Kulldorff, M. and Nagarwalla, N. (1995). Spatial disease clusters: detection and inference. Statistics in Medicine 14, 799810.
Li, T. Y., Chen, X. W., Zhen, R., Qiu, J. M., Qiu, D. C., Xiao, N., Ito, A., Wang, H., Giraudoux, P., Sako, Y., Nakao, M. and Craig, P. S. (2010). Widespread co-endemicity of human cystic and alveolar echinococcosis on the eastern Tibetan Plateau, northwest Sichuan/southeast Qinghai, China. Acta Tropica 113, 248256.
Moro, P. and Schantz, P. M. (2009). Echinococcosis: a review. International Journal of Infectious Diseases 13, 125133.
Naing, N. N. (2000). Easy way to learn standardization: direct and indirect methods. Malaysian Journal of Medical Sciences 7, 1015.
Ozouf-Marignier, M. V. and Verdier, N. (2009). Le canton d'hier à aujourd'hui: étude cartographique d'un maillage. In Le canton, un territoire du quotidien (ed. Lagadec, Y., Le Bihan, J. and Tanguy, J. F.), pp. 281295. Presses Universitaires de Rennes, Rennes, France.
Piarroux, M., Piarroux, R., Giorgi, R., Knapp, J., Bardonnet, K., Sudre, B., Watelet, J., Dumortier, J., Gerard, A., Beytout, J., Abergel, A., Mantion, G., Vuitton, D. A., Bresson-Hadni, S. and FrancEchino, N. (2011). Clinical features and evolution of alveolar echinococcosis in France from 1982 to 2007: results of a survey in 387 patients. Journal of Hepatology 55, 10251033.
Piarroux, M., Piarroux, R., Knapp, J., Bardonnet, K., Dumortier, J., Watelet, J., Gerard, A., Beytout, J., Abergel, A., Bresson-Hadni, S. and Gaudart, J. (2013). Population at risk for alveolar echinoccocosis, France. Emerging Infectious Diseases 19, 721728.
R Development Core Team (2012). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria.
Schweiger, A., Ammann, R. W., Candinas, D., Clavien, P. A., Eckert, J., Gottstein, B., Halkic, N., Muellhaupt, B., Prinz, B. M., Reichen, J., Tarr, P. E., Torgerson, P. R. and Deplazes, P. (2007). Human alveolar echinococcosis after fox population increase, Switzerland. Emerging Infectious Diseases 13, 878882.
Torgerson, P. R., Keller, K., Magnotta, M. and Ragland, N. (2010). The Global Burden of Alveolar Echinococcosis. PLOS Neglected Tropical Diseases 4, e722.
Viel, J. F., Giraudoux, P., Abrial, V. and Bresson-Hadni, S. (1999). Water vole (Arvicola terrestris scherman) density as risk factor for human alveolar echinococcosis. American Journal of Tropical Medicine and Hygiene 61, 559565.
Vuitton, D., Bresson-Hadni, S., Liance, M., Meyer, J. P., Giraudoux, P. and Lenys, D. (1990). L'échinococcose alvéolaire humaine : hasard épidémiologique ou fatalité immunologique? Gastroentérologie clinique et biologique 14, 124130.
Vuitton, D. A., Wang, Q., Zhou, H. X., Raoul, F., Knapp, J., Bresson-Hadni, S., Wen, H. and Giraudoux, P. (2011). A historical view of alveolar echinococcosis, 160 years after the discovery of the first case in humans: part 1. What have we learnt on the distribution of the disease and on its parasitic agent? Chinese Medical Journal 124, 29432953.
Vuitton, D. A., Zhou, H., Bresson-Hadni, S., Wang, Q., Piarroux, M., Raoul, F. and Giraudoux, P. (2003). Epidemiology of alveolar echinococcosis with particular reference to China and Europe. Parasitology 127, S87S107.
Whittemore, A. S., Friend, N., Brown, B. W. and Holly, E. A. (1987). A test to detect clusters of disease. Biometrika 74, 631635. doi: 10.1093/biomet/74.3.631.
Yamasaki, H., Nakao, M., Nakaya, K., Schantz, P. M. and Ito, A. (2008). Short report: Genetic analysis of Echinococcus multilocularis originating from a patient with alveolar echinococcosis occurring in Minnesota in 1977. American Journal of Tropical Medicine and Hygiene 79, 245247.
Zhou, H. X., Chai, S. X., Craig, P. S., Delattre, P., Quere, J. P., Raoul, F., Vuitton, D. A., Wen, H. and Giraudoux, P. (2000). Epidemiology of alveolar echinococcosis in Xinjiang Uygur autonomous region, China: a preliminary analysis. Annals of Tropical Medicine and Parasitology 94, 715729.



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