Emerging tick-borne viruses that can infect humans and animals have attracted a lot of attention due to the increasing occurrence of tick-borne viral diseases and their considerable influence on human health. Among these, the Heartland virus was recently identified as a novel tick-borne phlebovirus in the United States, and its link to severe human disease with recognizable clinical manifestations was established.

The virus has been isolated from Amblyomma americanum tick (also known as the Lone Star Tick), and the potential infectious reservoirs are white-tailed deer, northern raccoons and certain breeds of horses. Serologic surveillance of North American wildlife has shown wide-ranging prevalence of antibodies to Heartland virus.

First Cases of Heartland Virus Infection

In June 2009, two middle-aged farmers living approximately 100 kilometers (60 miles) apart in northwestern Missouri independently presented with symptoms of fever, fatigue, anorexia, diarrhea, headache and nausea. Both of them spent most of their time working in fields of a wooded area where they were exposed to plenty of tick bites. Nonetheless, there was no itching or rashes at any body site from which embedded ticks had been removed.

Approximately one week after their symptoms began, both men were hospitalized. Laboratory testing revealed thrombocytopenia and leukopenia. The farmers were immediately treated with antibiotics, on the suspicion of ehrlichiosis (a bacterial flulike disease transmitted by ticks).

The illness failed to respond to the antibiotics, although a significant improvement was seen in both farmers approximately 4-6 weeks after initial symptoms. It was later established that these man had contracted an arthropod virus carried by Amblyomma americanum tick, now known as the Heartland virus.

How Does Heartland Virus Disease Present?

As additional cases followed the initial two, a set of clinical case criteria was devised in order to ease the identification and tracking of new cases. This set of criteria depends on the diagnosis of a clinically compatible illness associated with laboratory evidence of a recent infection with Heartland virus. The criteria are as follows:

• Fever greater than 38 °C (or 100.4 °F)
• Thrombocytopenia or platelet count lower than 150,000 per mm3
• Leukopenia or white blood cell count lower than 4,500 cells per mm3
• Evidence of a recent infection with Heartland virus (detection of viral RNA in the blood or tissues by reverse transcription polymerase chain reaction, or by viral neutralization assays using convalescent serum from the patient)

Subsequent Cases of Heartland Virus Infection

Since the initial description in 2009, approximately ten cases of Heartland virus infection have been described in the United States. All of them occurred among men older than 50 years of age, of which three-quarters required hospitalization, and most of them reported a history of tick bite. Mortality was less than 10%.

It has to be emphasized that Heartland virus can cause a fatal, and rapidly disseminated infection with multisystem organ failure and severe shock – even in patients without any significant comorbidities. Likewise, some unusual manifestations of the disease may also occur, such as very high levels of ferritin (protein that stores iron), as was described in 2018.

Infection with this virus has also recently been linked to the condition known as hemophagocytic lymphohistiocytosis, which represents a syndrome of macrophage and T-cell hyperactivation that leads to elevated cytokine levels and end-organ malfunction.

Hence, even though there is no routine testing or treatment options available, public health implications from potential new cases have to be considered. When confronted with a patient presenting with acute disease compatible with Heartland virus infection, health personnel should contact  the relevant health departments.

Further Reading

• All Heartland Virus Content
• Heartland Virus Diagnosis and Treatment
• Heartland Virus Biology and Transmission Patterns

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university – University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.