Our objective is to determine the agent(s) associated with acute non-respiratory fevers of unknown origins in horses in specific geographical regions of the United States which include the Northeast, Mid-Atlantic, and Great Lakes areas.  These areas are recognized as having the highest recorded cases of human tick borne disease in the United States. We speculate that horses living in these areas are also exposed to these ticks, and can become infected and develop fevers ( >/= 101.5 degrees) that as of this time are undiagnosed and recognized as fevers of unknown origins.(FUOs)  We also speculate that  bacteria like agents such as Leptospira sp., Bartonella sp. and Neorickettsia sp. may be implicated in these fevers.  Some of these undiagnosed fevers may be due to co-infections of any of these agents.

Our aims are to:  1) Identify the presence of potential tick-transmitted (Anaplasma sp., Babesia sp., Borrelia sp., Ehrlichia sp., Rickettsia sp.), or other non-respiratory bacterial infection (Leptospira sp., Bartonella sp. Neorickettsia sp.) in horses with FUO and on premise controls in clinical practice in the targeted geographic areas. 2) Determine the correlation between the presence of identified agents with fever in the study subjects;

3) Identify ticks found on/in the environment of horses in the study areas and determine the prevalence of the tick-associated pathogens noted above in this population.  Blood samples from horses meeting a case definition of an acute onset fever without respiratory signs, and no previous antibiotic therapy within 7 days prior to the fever will be submitted by participating practitioners in the targeted geographic areas.  6 locales ecologically similar for tick habitat and possible Leptospirosis exposure will be sampled using a sample kit supplied by the Animal Health Diagnostic Center.  One control blood sample will be submitted for each animal meeting case definition from a horse residing on the same premise, free from fever or other signs of infectious disease. Horse-associated ticks and ticks found in the same environment as the horses will also be solicited for identification and testing.  Samples from the blood and from tick homogenates will be analyzed for the presence of Anaplasma sp. and Ehrlichia sp., Babesia sp., Borrelia burgdorferi, Neorickettsia sp., Rickettsia sp., Bartonella sp. and Leptospira sp. all of which are known to be present in the target geographic region Samples will be analyzed by polymerase chain reaction (PCR) using group-specific 16 S ribosomal RNA gene (Ehrlichia,  Anaplasma, Rickettsia sp.), 18S ribosomal RNA gene (Babesiasp.) flagellar DNA (Borrelia), and 16s-23S ribosomal RNA gene intergenic region after growth  in enrichment (Bartonella sp.) as target sequences. Samples positive by PCR on any group-specific assay will be further characterized by species-specific secondary PCR assays or by sequence and phylogenetic analysis.  This will be the first study determining the presence of the selected agents we have chosen in horses with FUOs. These agents are also recognized as newly emerging diseases in humans in these geographic areas.