Heartland virus: An emerging tick-borne threat

Heartland virus (HRTV) is a tick-borne phlebovirus in the family Bunyaviridae.

HRTV is closely related to the severe fever with thrombocytopenia syndrome virus, (SFTSV), that causes a similar disease in Asia.

The lone star tick (Amblyomma americanum) is the likely vector. When field studies were conducted at the original site, researchers found that the collected ticks contained both HRTV RNA and infectious virus.

Further cases and surveillance showed that HRTV had been infecting people in multiple states in the US (for example, Tennessee, Oklahoma, Kansas, Arkansas, Kentucky, Indiana, Illinois, Georgia, and South Carolina), essentially wherever lone star ticks occur.

This viral infection happen mainly during the warm months when ticks are alive (spring through early fall).

Heartland virus causes a nonspecific flu-like illness.

The symptoms are:

• Fever
• Severe fatigue or weakness
• Generalized muscle aches (myalgia)
• Headache
• Loss of appetite

Some people also experience gastrointestinal symptoms:

• Nausea
• Vomiting
• Diarrhea

Rash is absent or very mild, unlike in many other tick-borne diseases.

Key laboratory findings often include:

• Low neutrophils and platelets
• Mildly elevated liver enzymes
• Sometimes reduced sodium levels (hyponatremia)

Severe symptoms can be seen in some cases:

• Confusion or altered mental status (about one-third of cases)
• Shock or organ failure (rare)

No unique clinical features distinguish HRTV from other tick-borne illnesses. Overall presentation is similar to other tick fevers: Fever, headache, fatigue, muscle aches, sometimes stomach upset.

Infection with HRTV is often mistaken for ehrlichiosis; the first Missouri cases were initially treated with doxycycline.

Clinicians should suspect HRTV in someone who has fever, leukopenia and thrombocytopenia in the spring or summer. Especially if there is a possibility of tick bites. When routine testing for other tick diseases (ehrlichiosis, anaplasmosis, Rocky Mountain spotted fever, Lyme disease) is negative, HRTV must be considered.

Currently, there is no commercially available test for detecting HRTV. Confirmation requires sending specimens to a reference laboratory (CDC or state public health labs). Healthcare providers should contact local health departments or the CDC for coordination if HRTV is suspected.

Testing at the reference laboratory will include:

• PCR (reverse-transcriptase PCR): detects HRTV RNA in blood during the acute phase (up to ~2 weeks after symptom onset).
• Serologic tests (neutralizing antibody or immunoassay): confirm past infection later in the course.

In essence, a Heartland virus diagnosis is done through exclusion: after ruling out common tick diseases.

No specific antiviral therapy or vaccine exists for the Heartland virus. All management is supportive.

• Usual hospital care includes:
  • Fluids
  • Management of complications (e.g., platelet transfusion for very low counts)
• Antibiotics such as doxycycline may be given at first, since illness can resemble ehrlichiosis, but they do not act against the virus.
• Favipiravir has shown activity against related phleboviruses in lab studies, but has not been tested in humans with HRTV.
• Supportive intensive care remains the mainstay; most infected people recover as the immune system clears the virus.

Severe disease management

• Intensive care unit (ICU) support is required for organ failure or shock.
• Supportive measures may include:
  • Intravenous fluids
  • Blood pressure support
  • Mechanical ventilation for respiratory failure
  • Dialysis for kidney failure
• Some severe cases have been treated with high-dose steroids or other immunosuppressives (based on experience with the related SFTSV), though evidence is anecdotal.

Key point: No targeted therapy exists; the most effective “treatment” is preventing tick bites.

Preventing Heartland virus infection means avoiding lone star tick bites. There is currently no vaccine, so personal protective measures are critical. Outdoor workers and hikers in endemic areas should use tick-avoidance strategies.

These include:

• Wearing long pants and long sleeves
• Tucking pants into socks
• Treating clothing with permethrin
• Applying repellents to exposed skin
• Removing ticks quickly if attached

Heartland virus disease is a rare but serious emerging tick-borne infection in the United States. First identified in 2009 in Missouri, it has since been documented in multiple states within the range of the lone star tick.

Clinicians in endemic areas should recognize the symptoms of fever, cytopenia, and tick exposure,  and include HRTV in the differential when common diagnoses have been ruled out. As with other tick-related diseases, the focus remains on awareness and prevention.

Although most patients recover, severe cases can lead to multiorgan failure or even death, especially in the elderly. Until a specific therapy is developed, protecting oneself from tick bites is the best defense.

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