Anaplasma phagocytophilum causes human granulocytic anaplasmosis. However, despite its ubiquitous presence in animals and ticks, human cases are rarely reported in Europe. We generated genetic data from A. phagocytophilum from patients and compared them with sequences from wild and domestic animals to assess the zoonotic potential of the respective genotypes. The genomic sequence of an A. phagocytophilum isolate obtained from a Slovenian patient was determined. We also sequenced a groEL-gene fragment of eight isolates from human patients from France and Poland. The A. phagocytophilum genome from the Slovenian patient was more closely related to isolates from dogs than from sheep. Using groEL-based typing, isolates from humans were found within a distinct subcluster of A. phagocytophilum Ecotype I. This subcluster was defined as zoonotic. Strains from dogs, horses, cats, foxes, wolves, and wild boar were significantly overrepresented in this branch. Variants outside this subcluster were more abundant and found in a wider variety of domestic and wild animals, most notably ruminants. A similar pattern was observed for the MLST analyses targeting seven housekeeping genes. Human anaplasmosis in Europe is associated with a specific subcluster of A. phagocytophilum Ecotype I, which is not primarily associated with ruminants, but rather with dogs, horses, cats, carnivores, wild boar and hedgehogs. Our findings provide a reasonable explanation for the discrepancy between the omnipresence of A. phagocytophilum in the environment and the limited number of reported human cases. We recommend taking this genetic sub-clustering into account for future risk assessments.

Centre for Infectious Diseases Research National Institute for Public Health and the Environment Bilthoven 3720 BA the Netherlands

Centre for Monitoring of Vectors Netherlands Institute for Vectors Invasive Plants and Plant Health Netherlands Food and Consumer Product Safety Authority 6706 EA Wageningen the Netherlands

CNR des Borrelia Hôpitaux Universitaires de Strasbourg F 67000 Strasbourg France

Department of Infection and Immunity Luxembourg Institute of Health Esch sur Alzette Luxembourg

Department of Infectious Diseases and Neuroinfections Medical University of Bialystok Zurawia 14 15 540 Bialystok Poland

Department of Infectious Diseases University Medical Centre Ljubljana Japljeva 2 1525 Ljubljana Slovenia

Department of Veterinary Sciences Faculty of Agrobiology Food and Natural Resources Czech University of Life Sciences Prague Czech Republic

Future Genomics Technologies BV 2333 BE Leiden the Netherlands

Institute of Microbiology and Immunology Faculty of Medicine University of Ljubljana Zaloška 4 1000 Ljubljana Slovenia

Institute of Virology University of Mainz Mainz Germany

Université de Strasbourg UR3073 PHAVI CHRU de Strasbourg Instituts de Bactériologie et de Parasitologie 3 rue Koeberlé F 67000 Strasbourg France

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