Bourbon virus infection

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2], Usama Talib, BSc, MD [3], Syed Hassan A. Kazmi BSc, MD [4], Aravind Reddy Kothagadi M.B.B.S[5]

Bourbon virus infection is caused by Bourbon virus, a type of Thogotovirus, which belongs to Orthomyxoviridae family. A tick bite is usually responsible for Bourbon virus infection. The virus is transmitted by arthropods like tics and replicates in both arthropods and vertebrate hosts. Bourbon virus infection must be differentiated from other diseases that may cause arthralgia, fever, and skin manifestations with the history of exposure to ticks. Only 5 cases of Bourbon virus infection have been confirmed in the United States since its disovery in 2014. The most potent risk factor in the development of Bourbon virus infection is a tick bite. Other risk factors include traveling, residing or working in the endemic regions will increase chances of infection. If left untreated patients with Bourbon virus infection, may develop hemophagocytic lymphohistiocytosis and eventually death. Complications that can develop as a result of Bourbon virus infection are meningitis, encephalitis and multiorgan failure. A detailed history and physical exam is very helpful in the diagnosis of Bourbon virus infection. Infected individuals are treated with symptomatic therapy since a specific treatment has not yet been established. Preventing bites from ticks and other insects is the is helpful in the prevention of Bourbon virus infection.

In 2014, Olga Kosoy, from the Centers for Disease Control and Prevention isolated Bourbon virus for the first time from a blood sample of an infected person in Bourbon County, Kansas, United States.

Bourbon virus infection can be classified under tick-borne diseases.

Bourbon virus is a negative sense segmented RNA virus belonging to the genus Thogotovirus, family Orthomyxovirida. It is transmitted by insects and replicates in both arthropods and vertebrate hosts. The negative sense RNA virus replicates within the nuclei of the host cells. Thogoto virus Infection induces a sustained type 1 interferon response in the host until the adaptive immunity takes effect. Microscopically, bourbon viruses are 80-120nm in diameter with a genome size of approximately 10Kb.

Bourbon virus infection is caused by a type of thogotovirus, which belongs to Orthomyxoviridae family. It is a single-stranded, negative-sense RNA virus, which is segmented and exists in two different morphologies.^[1]

Bourbon virus infection must be differentiated from other diseases that may cause arthralgia, fever, and skin manifestations with the history of exposure to ticks. The differential diagnosis of Bourbon virus disease includes Lyme disease, ehrlichiosis, anaplasmosis, Rocky Mountain spotted fever, leptospirosis, and influenza.

Only 5 cases of Bourbon virus infection have been confirmed in the United States since its disovery in 2014. ^[2]

The most potent risk factor in the development of Bourbon virus infection is a tick bite. Other risk factors include traveling, residing or working in the endemic regions will increase chances of infection.

According to CDC, there is insufficient evidence to recommend routine screening for Bourbon virus infection.^[3]

If left untreated patients with Bourbon virus infection, may develop hemophagocytic lymphohistiocytosis and eventually death. Complications that can develop as a result of Bourbon virus infection are meningitis, encephalitis and multiorgan failure. From 2014 to 2017 only 5 cases of Bourbon virus infection have been reported and all have resulted in death.

The patient with bourbon virus infection has a typical history of exposure to ticks or travel to endemic areas. A history of multiple tick bites is also common in individuals suspected of Bourbon virus infection. The patient of Bourbon virus infection may present with nausea, weakness, and diarrhea. Furthermore, symptoms such as fever, anorexia, chills, headache, myalgia, and arthralgia may develop.

The physical examination findings of bourbon virus infection may present with several tick bites and maculopapular rash on the trunk. The patient may appear as very weak, hypertensive and dyspneic.

There are no specific laboratory findings associated with Bourbon virus infection. Laboratory findings in bourbon virus infection may reveal leukopenia and thrombocytopenia.

There are no specific X-ray findings associated with Bourbon virus infection. A chest X-ray may reveal findings of pulmonary venous congestion and interstitial edema.

There are no CT findings associated with bourbon virus infection. Contrast CT scan of the chest, abdomen, and pelvis may show trace pleural effusions, bibasilar atelectasis, and multiple prominent abdominal lymph nodes. ^[4]

There are no MRI findings associated with bourbon virus infection.

There are no ultrasound findings associated with Bourbon virus infection. Echocardiogram of bourbon virus infection, may show global hypokinesia. ^[4]

There are no other imaging findings for Bourbon virus infection.

There are no other diagnostic studies for Bourbon virus infection.

There is no specific treatment, cure, or vaccine for Bourbon virus infection. Early diagnosis, hospitalization, and supportive therapy are fundamentals of treatment.

Surgical intervention is not recommended for the management of Bourbon virus infection.

There is no vaccine or drug to prevent Bourbon virus disease. Therefore, preventing bites from ticks and other insects is the best way to prevent infection.^[5]

Secondary preventive measures for Bourbon virus infection are similar to primary prevention.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

In 2014, Olga Kosoy, from the Centers for Disease Control and Prevention isolated Bourbon virus for the first time from a blood sample of an infected person in Bourbon County, Kansas, United States.

• In 2014, Olga Kosoy, from the Centers for Disease Control and Prevention isolated Bourbon virus for the first time from a blood sample of an infected person in Bourbon County, Kansas, United States.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2] Usama Talib, BSc, MD [3]

Bourbon virus infection can be classified under tick-borne diseases.

Various tick-borne diseases van be classified as follows:

Disease	Organism	Vector	Endemic Regions
Bacterial Infection
Borreliosis (Lyme Disease) [1]	Borrelia burgdorferi sensu lato (bacterium) and B. mayonii	Wood Tick (Dermacentor Variabilis), D. andersoni	United States: Eastern Region Southwest Region
Relapsing Fever [2]	Borrelia Species; Borrelia hermsii, Borellia Parkeri, Borellia duttoni, Borrelia miyamotoi	Ornithodoros species	Widespread: Spain Saudi Arabia Asia Africa Canada Western United States
Typhus (Rickettsia)
Rocky Mountain Spotted Fever [3]	Rickettsia Rickettsii	Wood Tick (Dermacentor Variabilis), D. andersoni	United States: Eastern Region Southwest Region
Helvetica Spotted Fever[4]	Rickettsia Helvetica	Ixodes Ricinus (European)	Europe: Sweden Switzerland France Laos
Ehrlichiosis (Anaplasmosis) [5]	Ehrlichia Chaffeensis, E. Equi	Lone Star Tick (Amblyomma Americanum), Ixodes Scapularis	United States: South Atlantic Regions South-central Regions
Tularemia [6]	Francisella Tularensis	D. Andersoni, D. Variabilis	United States: Widespread throughout the region, including higher populations in the Southeast, South-central, and the West.
Human neoehrlichiosis [5] [4]	Neoehrlichia mikurensis	Lone Star Tick (Amblyomma Americanum)’	Widespread: Europe Asia
Rickettsiosis [4]	Rickettsia	No specific species identified	Widespread: South Africa Morocco Mediterranean
African tick-bite fever [4]	Rickettsia africae	Amblyomma, Dermacentor, and Rhipicephalus species	Africa: Sub-Saharan West Indies
Queensland tick typhus [7] [4]	Rickettsia austalis	Ixodes species	Widespread: Australia Tasmania
Q fever (Typhus-like infection) [7]	Coxiella burnetii (mimics the mechanisms of Rickettsia)	Ixodes holocyclus and Amblyomma triguttatum	Australia Widespread throughout Australia
Mediterranean spotted fever (Boutonneuse fever) [8] [4]	Rickettsia conorii	Brown Dog Tick (Rhipicephalus sanguineus)	Widespread: Southern Europe Southern and Western Asia Africa India
Far Eastern spotted fever [4]	Rickettsia heilong-jiangensis	Tick	Widespread: Far portions of Eastern Russia Northern portions of China Eastern Asia
Aneruptive fever [4] [9]	Rickettsia helvetica	Ixodes species	Widespread: Northern and Central portions of Europe Non-specific portions of Asia
Flinders Island spotted fever (Thai tick typhus) [4] [7]	Rickettsia honei	Tick	Widespread in Independent Regions Australia Thailand
Japanese spotted fever [4]	Rickettsia japonica	Tick	Japan Widespread yet isolated to portions of Japan
Mediterranean spotted fever-like disease [4]	Rickettsia massiliae and R. monacensis	Tick	Widespread: R.massiliae induced: France Greece Spain Portugal Switzerland Sicily Central Africa Mali R.monacensis induced: Europe North Africa
Maculatum infection	Rickettsia parkeri	Tick	Americas: United States Portions of Canada South America
Tick-borne necrosis and lymphadenopathy [10]	Rickettsia raoultii	Dermacentor marginatus	Widespread: Europe Asia
North Asian Tick Typhus [4]	Rickettsia sibirica	Tick	Widespread: Russia China Mongolia
Lymphangitis [4]	Rickettsia sibirica mogolotimonae	‘No specific species identified	Widespread: Southern France Portugal China Africa
TIBOLA [4] [10]	Rickettsia slovaca	Dermacentor species	Widespread: Southern and Eastern Europe Asia
Viral Infection
Tick-borne Meningoencephalitis [11]	TBEV virus	Ixodes Scapularis, I. Ricinus, I.persulcatus	Widespread: Europe Northern Asia
Colorado Tick Fever [12]	CTF virus	Dermacentor andersoni	United States: Western Region
Crimean-Congo Hemorrhagic Fever [13]	CCHF virus	Hyalomma marginatum, Rhipicephalus bursa	Widespread: South Asia North Africa Southern Europe
Severe Febrile Illness [13]	Heartland Virus	Lone Star Tick (amblyomma americanum)	United States: Missouri Tennessee
Bourbon virus infection	Bourbon virus infection	Lone Star Tick	United States: Midwest and southern States
Protozoan Infection
Babesiosis [14]	Babesia microti, B divergens, B.equi	Ixodes Scapularis, I. pacificus	Widespread: Northeastern United States Europe Asia

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

Bourbon virus is a negative sense segmented RNA virus belonging to the genus Thogotovirus, family Orthomyxovirida. It is transmitted by insects and replicates in both arthropods and vertebrate hosts. The negative sense RNA virus replicates within the nuclei of the host cells. Thogoto virus Infection induces a sustained type 1 interferon response in the host until the adaptive immunity takes effect. Microscopically, bourbon viruses are 80-120nm in diameter with a genome size of approximately 10Kb.

Bourbon virus is a negative sense segmented RNA virus which belongs to the genus Thogotovirus, family Orthomyxovirida.

• Bourbon virus is transmitted mainly by ticks, although other arthropods may also be involved in transmission.
• The virus is able to replicate in vertebrate and tick cells.

• Virus attaches to the N-acetylneuraminic acid component found in host cell membrane (sialic acid receptors).^[1]

• The virus gets endocytosed by clathrins into the host cell.
• Endosome acidification induces fusion of virus membrane with the vesicle membrane.

• Thogoto viruses differ from influenza virus in having capped viral mRNA without host messenger-derived heterogeneous sequences at the 5′ end of the genome.^[2][3]
• Five larger RNA segments each encode only one gene product, the sixth segment encodes two matrix proteins, M and ML.^[4]
• Viral RNA polymerases (PA, PB1 and PB2) transcribe one mRNA from each genome segment.
• Splicing of segment 6 mRNA gives rise to mRNA coding for the matrix protein M1.^[4]
• Transcription of genomic segments by the viral polymerase produces mRNAs that are capped and polyadenylated by the viral polymerase.
• The M1 protein is involved in export of genome from the nucleus.
• Assembly of the virus takes place in the cytoplasm from where new virions are released to infect other cells.

• Thogoto virus Infection induces a sustained type 1 interferon response in the host until the adaptive immunity takes effect.^[5]
• IFN expression is mediated by specialized plasmacytoid dendritic cells (pDC).
• The interferon-induced dynamin-like MxA protein is involved in host antiviral activity against thogoto viruses.^[6][7][8][9]
• MxA recognizes the nucleocapsids of invading viruses, causing an early block of the viral replication cycle.^[6][10]
• Cytokines involved in the pathogenesis of bourbon virus infection are interleukin-1, interleukin-6, interleukin-10, macrophage inflammatory protein 1, monocyte chemoattractant protein (MCP)–1, and interferon (IFN).^[11]

Few rare conditions associated with bourbon virus infection are: ^[12]

• Neuromyelitis optica
• Meningitis
• Hemophagocytic lymphohistiocytosis (HLH)

Rash may be the first sign of infection.

• The rash of Bourbon virus infection is usually circular and located at the site of the tick bite.

• Thogoto viruses are spherical, enveloped single stranded RNA viruses with a segmented genome.
• Virions are 80-120nm in diameter with a genome size of approximately 10Kb.
• The 6-7 segments of genome encodes for 7-9 proteins with each segment size ranging from a low of 0.9Kb to 2.3Kb.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Bourbon virus infection is caused by Bourbon virus, a type of Thogotovirus, which belongs to Orthomyxoviridae family. It is a single-stranded, negative-sense RNA virus, which is segmented and exists in two different morphologies.^[1]

Bourbon virus is a type of Thogotovirus, which is in the RNA virus family Orthomyxoviridae.

• The virus particles show different morphologies, including filamentous and roughly spherical forms, and have projections from the surface.
• The spherical virions have a range of diameters, with broadly 100–130 nm being common.
• Bourbon virus is present at high levels in the extracellular space, with occasional particles being observed in the process of endocytosis.
• Like other members of the Orthomyxoviridae, the Bourbon virus genome is single-stranded, negative-sense RNA, which is segmented, or divided into a number of separate pieces.
• Bourbon virus has at least six segments. Bourbon virus is most similar in RNA sequence to Dhori virus and the closely related Batken virus, both members of the genus Thogotovirus, but has diverged substantially from these viruses. Dhori and Batken viruses have only been reported in the Eastern hemisphere.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Bourbon virus infection must be differentiated from other diseases that may cause arthralgia, fever, and skin manifestations with the history of exposure to ticks. The differential diagnosis of Bourbon virus disease includes Lyme disease, ehrlichiosis, anaplasmosis, Rocky Mountain spotted fever, leptospirosis, and influenza.

Bourbon virus infection must be differentiated from other diseases that may cause arthralgia, fever, history of tick exposure, and skin manifestations. The differential diagnosis of Bourbon virus disease includes Lyme disease, ehrlichiosis, anaplasmosis, Rocky Mountain spotted fever, leptospirosis, and influenza.

Disease	Symptoms
Bacterial Infection
Borreliosis (Lyme Disease) [1]	Flu-like illness, fatigue, fever, arthritis, neuroborreliosis, cranial nerve palsy, carditis and erythema migrans.
Relapsing Fever [2]	Consistently documented highfevers, flu-like illness, headaches, muscular soreness or joint pain, altered mental state, painful urination, rash, and rigors.
Typhus (Rickettsia)
Rocky Mountain Spotted Fever	Fever, alterations in mental state, myalgia, rash, and headaches.
Helvetica Spotted Fever [3]	Rash: spotted, red dots. Respiratory symptoms (dyspnea, cough), muscle pain, and headaches.
Ehrlichiosis Anaplasmosis [4]	Fever, headache, chills, malaise, muscle pain, nausea, confusion, conjunctivitis, or rash(60% in children and 30% in adults).
Tularemia [5]	Ulceroglandular, Glandular, Oculoglandular, Oroglandular, Pneumonic, Typhoidal.
Viral Infection
Tick-borne meningoencephalitis [6]	Early Phase: Non-specific symptoms including fever, malaise, anorexia, muscle pains, headaches, nausea, and vomiting. Second Phase: Meningitis symptoms, headache, stiff neck, encephalitis, drowsiness, sensory disturbances, and potential paralysis.
Colorado Tick Fever [7]	Common symptoms include fever, chills, headache, body aches, and lethargy. Other symptoms associated with the disease include sore throat, abdominal pain, vomiting, and a skin rash. A biphasic fever is a hallmark of Colorado Tick Fever and presents itself in nearly 50% of infected patients.
Crimean-Congo Hemorrhagic Fever	Initially infected patients will likely feel a few of the following symptoms; headache, high fever, back and joint pain, stomach pain, vomiting, flushed face, red throat petechiae of the palate, and potentially changes in mood as well as sensory perception.
Heartland virus disease [8]	Fever, fatigue, anorexia, nausea, or diarrhea. Patients also have leukopenia, thrombocytopenia, and mildly to moderately elevated liver transaminases.
Bourbon virus disease [9]	Fever, fatigue, anorexia, nausea, vomiting, and maculopapular rash. Patients are also found to have thrombocytopenia and leukopenia.
Protozoan Infection
Babesiosis [10]	Non-specific flu like symptoms.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Only 5 cases of Bourbon virus infection have been confirmed in the United States since its disovery in 2014. ^[1]

Only 5 cases of Bourbon virus infection have been confirmed in the United States since its disovery in 2014. ^[1]

There is no racial predilection for Bourbon virus infection.

Men and women are affected equally by Bourbon virus infection.

The disease has been limited to the Midwest and southern parts of United States.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

The most potent risk factor in the development of Bourbon virus infection is a tick bite. Other risk factors include traveling, residing or working in the endemic regions will increase chances of infection.

The most common risk factor associated with Bourbon virus infection is being bitten by a tick. Other risk factors include:

• Traveling to endemic areas
• Residing in endemic areas
• Spending time outdoors
• Pets that go outdoors in endemic regions ^[1][2]
• Hiking
• Camping in the woods
• Forest adventures
• Working in the fields

Rare risk factors for bourbon virus infection include:

• Blood transfusion
• Organ transplantation

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

If left untreated patients with Bourbon virus infection, may develop hemophagocytic lymphohistiocytosis and eventually death. Complications that can develop as a result of Bourbon virus infection are meningitis, encephalitis and multiorgan failure. From 2014 to 2017 only 5 cases of Bourbon virus infection have been reported and all have resulted in death.

If left untreated patients with Bourbon virus infection, may develop hemophagocytic lymphohistiocytosis and eventually death.^[1]

Complications that can develop as a result of Bourbon virus infection are:

• Meningitis
• Encephalitis
• Multiorgan failure

From 2014-2017 only 5 cases have been reported with Bourbon virus infection and all resulted in death.

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