Late last year, the Kansas Department of Health and Environment announced the discovery of a previously unknown virus that has been linked to the death of a Kansas man in late spring 2014. Now researchers have published the details of the man’s illness and describe the so-called Bourbon virus.

Olga I Kosoy, MS, from the Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, and colleagues report their findings online February 20 and in the May issue of Emerging Infectious Diseases.
The Bourbon virus, named after the county in which the man lived, belongs to a group of viruses called thogotoviruses, which have not been known to cause illness in the United States until now. Worldwide, thogotoviruses are known to have caused illness in only eight patients, including the Kansas man.

A Tick Bite Preceded Illness

The Kansas man had been working outside when he noticed several tick bites. He removed an engorged tick from his shoulder several days before becoming ill with nausea, weakness, and diarrhea. The following day, he developed a fever, anorexia, chills, headache, myalgia, and arthralgia. He went to his primary care physician on the third day of illness, who empirically prescribed doxycycline for a presumed tickborne illness because of patient’s history and the fact that he had not traveled outside his immediate area. The man’s wife found him obtunded but able to be aroused the following day.

He was admitted to the hospital, where he developed thrombocytopenia and leukopenia. He was given intravenous fluids for dehydration and placed on intravenous doxycycline.

He continued to complain of malaise and anorexia and developed periodic fevers to a maximum temperature of 38.8°C. On the eighth day after illness onset, he was transferred to a tertiary care center. Blood samples taken before his transfer showed no serologic evidence of Rocky Mountain spotted fever, Lyme disease, or ehrlichiosis.
The patient developed a temperature of 39.4°C and 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. He continued to have mild leukopenia (3600 cells/μL), as well as worsening thrombocytopenia (34,000 cells/μL).

He had a chest, abdomen, and pelvis computed tomography scan, which showed trace pleural effusions, bibasilar atelectasis, and multiple prominent abdominal lymph nodes. He developed progressive dyspnea, for which he required oxygen, pulmonary venous congestion, and interstitial edema, and an echocardiogram revealed global hypokinesis.

His condition continued to worsen, and on the tenth day of illness, he was transferred to the intensive care unit and intubated for acute respiratory distress syndrome. He continued to deteriorate, developed refractory shock, and then died from cardiopulmonary arrest on the eleventh day.

Virus Discovery

Serologic and molecular tests were negative for Rocky Mountain spotted fever, tularemia, brucella, babesiosis, Q fever, Ehrlichia species, Anaplasma phagocytophilum, and Babesia species. Fungal pathogen tests (Aspergillus spp. galactomannan, antibodies against Histoplasma species, and Histoplasma species antigen in serum and urine) were also negative.

Testing showed he had previously been infected with cytomegalovirus, Epstein-Barr virus, and parvovirus. Test results for hepatitis B and C viruses, West Nile virus, and HIV were negative, as were blood, sputum, and urine bacterial cultures.

Using a whole-blood specimen that was collected 9 days after the patient became ill, scientists at the Centers for Disease Control and Prevention in Fort Collins, Colorado, conducted testing for Heartland virus antibodies using plaque reduction neutralization. This test was negative for Heartland virus but showed the presence of another virus, and next-generation sequencing and phylogenetic analysis showed that the virus was a novel virus of the genus Thogotovirus.

High levels of viremia in blood taken 2 days before the patient died suggest the virus may have contributed to the man’s death.

Phylogenetic analyses showed that the virus is most closely related to the Dhori and Batken viruses, which have only been seen in the Eastern Hemisphere. Dhori, Batken, and Thogoto viruses have been seen in various hard tick species, but Batken virus has also been seen in mosquitos; therefore, the current mode of transmission to humans is unknown. For this reason, experts recommend wearing long sleeves and pants, using an insect repellent that is effective against ticks, avoiding wooded or bushy areas, and checking for ticks after being outdoors.

“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,” the authors write.

Given the possibility that the Bourbon virus, similar to the recently described Heartland virus, is a tick-borne pathogen, the authors caution that “the public health burden of these pathogens has been underestimated. As nonselective molecular methods of pathogen identification (i.e., [next generation] sequencing) become more widely used, ideally in combination with classical microbiologic techniques, it is anticipated that similar discoveries will be made in the future.”