on may 2 , 2003 , a 47-year - old - woman , who lived in northwestern slovenia , was admitted to the department of infectious diseases , university medical centre ljubljana , slovenia , with a 7-day history of fever < 40.0c , severe headache , nausea , dry cough , malaise , intense myalgia , and arthralgia . the last bite occurred 14 days before onset of her illness while she was walking in the woods near her home ; no skin lesions appeared at the site of the bites . she had not been vaccinated against tbe , nor had she traveled outside slovenia during the last few years . when she sought treatment , her body temperature was 38.5c , pulse rate was 90 beats / min , and blood pressure was 110/70 mm hg . with the exception of fever , the physical examination did not show any notable abnormality ; rash and meningeal signs were not present . routine laboratory tests showed leukopenia , thrombocytopenia , abnormal liver function test results , elevated concentration of serum c - reactive protein , and elevated procalcitonin levels ( table 1 ) . the fever subsided in 3 days ( on day 10 after the onset of her illness ) , and the patient was discharged from the hospital . her condition improved , but the headache persisted and intensified . on may 13 , she was reexamined in our department , and lumbar puncture was performed . cerebrospinal fluid examination showed normal protein and glucose concentrations but a mildly elevated number of leukocytes ( 7 x 10/l ) . at subsequent evaluations , the patient reported feeling better . on day 20 after onset , the control laboratory test results , including liver function test results , were within the normal range . several microbiologic procedures , including those for determining infections with a. phagocytophilum , ehrlichia chaffeensis , b. burgdorferi s.l . , and tbe virus , were performed to elucidate the cause of the illness . giemsa - stained peripheral blood smear examination by light microscopy for the presence of ehrlichial morulae within leukocytes was negative . serum samples were tested by an indirect immunofluorescence assay for the presence of specific igg antibodies to a. phagocytophilum ( strain usg3 propagated in hl60 promyelocyte cells ) , igm and igg antibodies to e. chaffeensis antigens ( mrl diagnostics , cypress , california , usa ) , and igm and igg antibodies to b. burgdorferi s.l ( whole cells of a local isolate of b. afzelii were used as an antigen ) . the presence of serum tbe virus igm and igg antibodies was assessed by enzyme - linked immunosorbent assay ( elisa ) ( dade behring marburg gmbh , marburg , germany ) . the results of serologic tests indicating recent infection with a. phagocytophilum and tbe virus are depicted in table 2 . primers ehr521 and ehr790 , which amplified the 16s rrna gene of a. phagocytophilum , produced a fragment of the expected size ( 293 bp ) in the acute - phase blood specimen ( figure ) ( 12 ) . no nucleic acids were amplified with primers specific for e. chaffeensis he1 and he3 ( table 2 ) ( 13 ) . * pcr , polymerase chain reaction ; elisa , enzyme - linked immunosorbent assay ; ifa , indirect immunofluorescence assay ; ig , immunoglobulin ; neg , negative ; pos , positive ; tbev , tickborne encephalitis virus . primers ehr521 and ehr790 specific to a. phagocytophilum and primers he1 and he3 specific to e. chaffeensis . cut - off value for tbev igm is 0.2720.372 and for igg is 7.5 u / ml , according to the manufacturer 's procedure polymerase chain reaction amplification of anaplasma phagocytophilum dna from the patient 's acute - phase blood sample . amplified dna was separated by electrophoresis through the 2% agarose gel stained with ethidium bromide . lane 1 , patient sample ( note the presence of the band at 293 bp ) ; lane 2 , negative sample ; lane 3 , negative control ( no - dna template control ) ; lane 4 positive control ( dna extracted from the cultured isolate of a. phagocytophilum ) . few reports have been published on serologic evidence of coinfection with tbe virus and a. phagocytophilum in europe . the results on groups of persons representing different risk categories for tick exposure in switzerland provided serologic evidence of coinfection with a. phagocytophilum and tbe virus ( 9 ) . weber et al . , who retrospectively tested serum specimens of patients with lyme borreliosis or tbe for antibodies to a. phagocytophilum , reported similar findings ( 10 ) . although serologic data suggested coinfection with a. phagocytophilum and tbe virus , no confirmation of acute hge was obtained among the residents of switzerland . in the czech republic , where tbe is endemic , among 67 patients hospitalized for tbe , 6 ( 9% ) were seropositive to a. phagocytophilum ( 11 ) . in slovenia , the background seroprevalence of hge in children and young adults ( 15% ) was found to be similar to that of lyme borreliosis ( 15% ) and tbe ( 13% ) ( 14 ) . in addition , a prospective study was performed to establish the etiologic agents of acute febrile illnesses that occurred within 6 weeks after a tick bite in residents of slovenia , by using a combination of microbiologic and clinical criteria . out of 130 adult patients , 36 ( 28% ) had laboratory evidence of tbe virus infection ( all had clinically confirmed disease ) , whereas 4 of 22 ( 17% ) patients with the evidence of a. phagocytophilum infection , had confirmed hge . infection by multiple organisms ( > 1 ) was found in 19 ( 15% ) of 130 patients . four of them had confirmed tbe and also met the study criteria for probable hge but not for confirmed hge ( 7 ) . the clinical signs and symptoms of hge are unspecific and usually consist of fever , headache , chills , malaise , myalgia , or arthralgia , which often occur after a tick bite . laboratory analysis shows leukopenia , thrombocytopenia , lymphopenia , elevated activity of hepatic enzymes , and an elevated concentration of c - reactive protein ( 7 ) . however , leukopenia and thrombocytopenia are common not only in hge patients but also during the initial phase of tbe , in which they were found in 67% and 71% of patients , respectively ( 15 ) . for most patients in whom tbe develops our patient , however , had a monophasic course of febrile illness , which was observed in 27% of patients with tbe in slovenia ( 16 ) . in our report , the diagnosis of tbe was established by the presence of a febrile illness after a tick bite with headache , mild lymphocytic pleocytosis , and demonstration of serum igm and igg antibodies to tbe virus by elisa , the serologic method of choice with the specificity 99.9% for igm and 99.5% for igg and the sensitivity 99.8% and 96.8% for igm and igg , respectively ( 17 ) . the presence of tbe igm antibodies 144 days after the onset of illness in our patient ( table 2 ) is not surprising because the igm antibodies as a rule persist for several months after acute infection ( 17 ) . however , changes in antibody titers as demonstrated in our patient attest for recent infection . the febrile illness associated with leukopenia , thrombocytopenia , an elevated concentration of serum c - reactive protein , and the demonstration of a. phagocytophilum infection by seroconversion as well as a positive pcr result also met the criteria for confirmed hge . to our knowledge , the patient reported herein represents the first case of concurrent confirmed tbe and confirmed hge . some reports suggest that coinfection with more than 1 tickborne pathogen may influence the natural history of each of the corresponding diseases , making the clinical course more severe and the outcome less favorable ( 1 ) . in spite of proven coinfection and fulfillment of criteria for confirmed tbe and hge ( and the absence of treatment with doxycycline , which could have influenced the natural course of hge ) , however , the information obtained from a single patient does not allow for a reliable conclusion on the potential influence of tbe virus and a. phagocytophilum coinfection on the clinical features and course of the combined illness .