The patient was a previously healthy man >50 years of age from Bourbon County, Kansas, USA. While working outdoors on his property in late spring 2014, the patient had several tick bites and found an engorged tick on his shoulder several days before he became ill with nausea, weakness, and diarrhea. The following day, a fever, anorexia, chills, headache, myalgia, and arthralgia developed. On the third day of illness, the patient went to his primary care physician, who empirically prescribed doxycycline for a presumed tickborne illness because of his history of tick bites, symptoms, and no reported travel outside the immediate area. The following morning, the patient’s wife found him obtunded (experiencing reduced consciousness) but arousable. He was taken by ambulance to a local hospital.

At the hospital, he had a temperature of 37.3°C, a pulse rate of 84 beats/min, and an increased blood pressure of 151/65 mm Hg. The patient had a papular rash on his trunk, but otherwise results of his physical examination were unremarkable. Initial laboratory findings showed leukopenia (2,200 cells/μL), lymphopenia (absolute lymphocyte count 550 cells/μL), thrombocytopenia (72,000 cells/μL), mild hyponatremia (sodium 133 mmol/L), hypokalemia (potassium 3.0 mmol/L), a creatinine level (0.8 mg/dL) within the reference range (0.6 mg/dL–1.2 mg/dL), a slightly increased level of blood urea nitrogen (25 μg/dL), and increased levels of aspartate aminotransferase (138 U/L) and alanine aminotransferase (86 U/L). He was admitted because of the principal problems of dehydration, syncope, and possible tickborne illness. He was given an intravenous (IV) fluid bolus, then maintenance fluids, and doxycycline (200 mg IV every 12 h for the first 24 h, then 100 mg IV every 12 h).

Despite doxycycline therapy, the patient continued to report malaise and anorexia, and periodic fevers (maximum temperature 38.8°C) developed. At day 8 postillness onset, the patient was transferred to a tertiary care center for further evaluation and management. Patient samples collected before transfer showed no serologic evidence of Rocky Mountain spotted fever, Lyme disease, or ehrlichiosis.

At initial assessment at the tertiary care center, the patient was febrile (temperature 39.4°C) and had a nontender left axillary lymphadenopathy; a diffuse maculopapular rash on his chest, abdomen, and back; petechiae on his soft palate and lower extremities; and bibasilar crackles in the lung fields. Laboratory testing continued to show mild leukopenia (3,600 cells/μL) but also showed worsening thrombocytopenia (34,000 cells/μL). His renal function was normal, but his aspartate aminotransferase level had increased to 119 U/L. Doxycycline treatment (100 mg IV every 12 h) was continued, and the patient was evaluated further for a potential etiology of his illness.

Hematologic results suggested that his persistent thrombocytopenia and leukopenia were secondary to acute bone marrow suppression. A chest, abdomen, and pelvis computed tomography scan with contrast showed trace pleural effusions, bibasilar atelectasis, and multiple prominent abdominal lymph nodes. At day 9 postillness onset, he remained lucid and interactive, but he continued to have episodic high fever (temperature >39°C) and progressive dyspnea developed, which resulted in a need for supplemental oxygen. A chest radiograph showed new findings of pulmonary venous congestion and interstitial edema, suggestive of progressive heart failure or fluid overload, and an echocardiogram showed global hypokinesis.

Because of increasing supplemental oxygen needs and progressive lactic acidosis, he was transferred to the intensive care unit and given broad-spectrum antimicrobial drugs on day 10 of his illness. His renal function began to deteriorate and his aminotransferase levels continued to increase. The patient was intubated because of acute respiratory distress syndrome and was given 3 vasopressor medications because of shock. The patient subsequently had sustained ventricular tachycardia with persistent hypotension and eventual pulseless electrical activity with refractory shock. After multiple resuscitations, the decision was made to withdraw further care, and he died shortly after being extubated, 11 days after first becoming ill. An autopsy was not performed.

Results of comprehensive evaluations for tickborne diseases, including serologic testing for Rocky Mountain spotted fever, tularemia, brucella, babesiosis, and Q fever; molecular testing for Ehrlichia spp. and Anaplasma phagocytophilum; and blood thin smears for Babesia spp. were negative. Results of evaluations for fungal pathogens (Aspergillus spp. galactomannan, antibodies against Histoplasma spp., and Histoplasma spp. antigen in serum and urine) were negative. Evaluations for cytomegalovirus, Epstein-Barr virus, and parvovirus showed past infection. Test results for hepatitis B and C viruses, West Nile virus, and HIV were also negative. Blood, sputum, and urine bacterial cultures were negative. A whole blood specimen collected 9 days after illness onset was sent to the Centers for Disease Control and Prevention (CDC) (Fort Collins, CO, USA) for Heartland virus testing as part of an active institutional review board-approved protocol.

Using traditional techniques (i.e., PRNT and culturing on animal cells) in combination with NGS, we isolated a novel virus from a blood sample collected 9 days after illness onset from a previously healthy man. It is likely that this novel Thogotovirus, which we are proposing to call Bourbon virus after the county of residence of the patient, was the cause of his illness. Although it is unclear what role the virus played in the death of the patient, the high level of viremia, as shown by multiple isolations from the blood of the patient 2 days before his death, suggests that this might have contributed to the death of the patient.

The patient had a history of tick exposure, as well as symptoms and laboratory findings (i.e., leukopenia and thrombocytopenia) consistent with a tickborne illness. Several tickborne pathogens, such as Ehrlichia chaffensis, Rickettsia, and Heartland virus, are present in eastern Kansas and adjacent areas (17–19). However, the patient did not respond to doxycycline therapy initiated 3 days after illness onset and had negative results for these and other tickborne pathogens.

Of the 7 symptomatic human infections that have been associated with viruses in the genus Thogotovirus, most case-patients have had neurologic findings (e.g., meningitis, encephalitis) without any described abnormalities in blood counts (9,11). Although cerebrospinal fluid was not tested for the patient reported, his clinical signs and symptoms were not suggestive of neurologic infection. Furthermore, the patient did not have any respiratory symptoms that would be expected with other viruses that are known human pathogens in the large family of Orthomyxoviridae, such as influenza virus (1).

Phylogenetic analyses indicated that Bourbon virus is most closely related to Dhori and Batken viruses. However, the branch lengths suggest a relatively distant evolutionary distinction of Bourbon virus from Dhori and Batken viruses, which have only been described in the Eastern Hemisphere. Dhori, Batken, and Thogoto viruses have been identified in various hard tick species (1). However, Batken virus also has been identified in mosquitoes (1). It is currently unknown how Bourbon virus is transmitted to humans. However, illness onset of the patient in late spring and a history of finding an embedded tick before becoming ill support the notion that Bourbon virus might be transmitted by ticks. Therefore, to potentially prevent Bourbon virus disease, as well as other tickborne diseases, persons should be advised to avoid tick bites by using an insect repellent registered with the US Environmental Protection Agency to be effective against ticks, wearing long sleeves and pants, avoiding bushy and wooded areas, and performing tick checks after spending time outdoors.

The discovery of Bourbon virus, in addition to recent discoveries of tick-associated Heartland and severe fever with thrombocytopenia syndrome viruses (19,20), suggests that the public health burden of these pathogens has been underestimated. As nonselective molecular methods of pathogen identification (i.e., NGS sequencing) become more widely used, ideally in combination with classical microbiologic techniques, it is anticipated that similar discoveries will be made in the future.

It is currently not known how many human infections and disease cases might be attributable to this novel pathogen. On the basis of limited information for our case-patient, health care providers might consider Bourbon virus as a potential infectious etiology in patients in whom fever, leukopenia, and thrombocytopenia develop without a more likely explanation and who have shown negative results for other tickborne diseases (e.g., ehrlichiosis, anaplasmosis, or Heartland virus disease) or have not responded to doxycycline therapy. Work is planned to identify additional human infections with this novel virus, as well as to explore its potential geographic distribution. Also, more comprehensive virologic characterizations and field work are ongoing to better understand the biology of, and to identify potential vectors and reservoirs for, Bourbon virus. These data will be critical to further characterize the epidemiology and illness caused by Bourbon virus and to implement potential prevention and control measures.