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Heartland virus disease
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Heartland virus disease

Contributors: Mukesh Patel MD, Paritosh Prasad MD
Other Resources UpToDate PubMed


Heartland virus infection is due to a Phlebovirus (family Bunyaviridae), with cases reported (as of September 2018) from Arkansas, Georgia, Kansas, Illinois, Indiana, Kentucky, Missouri, North Carolina, Oklahoma, and Tennessee in the United States. The virus has been isolated in deer, raccoons, coyotes, and moose in at least 13 states in the United States (from Texas to North Carolina and Florida to Maine). Infection with Heartland virus is believed to occur after a bite from an infected Amblyomma americanum tick (lone star tick). As of 2017, more than 30 cases of Heartland virus infection have been reported. Typical patients are males older than 50 years, and deaths have occurred. All patients describe outdoor exposures, and most recalled prior tick bites. Symptom onset has occurred during May to September, coinciding with the time when ticks are active.

While the transmission of Heartland virus from ticks to humans has yet to be confirmed, detection of Heartland virus in field-collected ticks supports the role of ticks and subsequent bites in the development of disease in humans.

Fever is universally present in reported cases. The most common symptoms include fatigue and anorexia. Other symptoms include headache, nausea, myalgia, arthralgia, and diarrhea. Thrombocytopenia and leukopenia are commonly noted at presentation. Leukopenia can be progressive, and mild neutropenia has occurred. Progressive transaminitis without coagulopathy appears to be common. Mild anemia and hyponatremia have also been noted.

Complications of Heartland virus infection that may have contributed to death in one elderly patient include hypoxia and respiratory failure, hypotension, progressive cytopenia, acute kidney injury, gastrointestinal bleeding from gastric ulcers, and persistent encephalopathy.


A93.8 – Other specified arthropod-borne viral fevers

35620001 – Disease caused by Phlebovirus

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Differential Diagnosis & Pitfalls

Numerous arboviral infections may have a similar clinical presentation to Heartland virus infection. Differentiation may be difficult on clinical grounds alone. In addition, several important noninfectious disorders should be considered.
  • Ehrlichiosis – Look for the presence of morulae on blood smear.
  • Rocky Mountain spotted fever – Morbilliform rash often present.
  • Anaplasmosis – Look for the presence of morulae on blood smear.
  • Severe fever and thrombocytopenia syndrome virus – A related and clinically similar infection that occurs in China.
  • West Nile fever – Cytopenia and transaminitis are less common.
  • Malaria – Elicit a careful travel history; labs may suggest evidence of hemolysis. Thick and thin Giemsa stains and rapid malaria tests can verify the diagnosis of malaria.
  • Hemophagocytic lymphohistiocytosis (HLH) – Fever, cytopenia, and transaminitis are typical. HLH may be genetic or acquired, usually secondary to infection (Epstein-Barr virus most commonly), malignancy, or autoimmune disease. Hyperferritinemia is suggestive of HLH.
  • Adult-onset Still disease – An autoimmune disease that shares many common features with many infections including sepsis. Ferritin is usually very elevated.

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Last Updated:07/01/2019
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Heartland virus disease
A medical illustration showing key findings of Heartland virus disease : Fatigue, Fever, Headache, Nausea, Tick bite, Anorexia, Arthralgia, Myalgia, WBC decreased, PLT decreased, AST/ALT elevated
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