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Novel Heartland Virus Responsible for Two Deaths in the US

By Amesh A. Adalja, MD, FACP, FACEP, May 30, 2014

In 2009, 2 patients presented to healthcare facilities in Missouri with signs and symptoms that included fever, fatigue, diarrhea, thrombocytopenia, and leukopenia subsequent to tick bites received 5 to 7 days prior. Both patients recovered, but laboratory test results for usual pathogens were negative. To determine the etiology of the illness, further investigation was undertaken. After cytopathic effects in cell culture were observed, electron microscopy revealed particles of a virus found to be a novel member of the phlebovirus family; it was named Heartland virus.1 Two people infected with Heartland virus have died, with the most recent reported on May 27.2

Tick-borne Transmission

Phleboviruses are RNA viruses whose members include Rift Valley Fever (RVF) and Severe Fever with Thrombocytopenia Syndrome (SFTS). They are transmitted via bites from ticks, sand flies, and mosquitoes. Given the case histories of patients and the subsequent isolation of the virus from Lone Star ticks, Heartland virus is likely transmitted through the bite of that tick.3

Patient Characteristics

Since its discovery, Heartland virus has been found in 7 people in 3 states—Missouri, Tennessee, and Oklahoma. All cases have been in males over age 50, most of whom reported tick bites and that they engaged in a lot of outdoor activities (hunting, biking, etc.). Fever, thrombocytopenia, and leukopenia were present in all, and most patients were hospitalized.3

While most recovered, 2 patients died. The first was an elderly man with multiple comorbidities and the second was an Oklahoma man over the age of 65.2,3

Familiar Spillover Pattern

As of this writing, this disease appears to be rare and affects only a selected segment of the population in a restricted geographic area. This pattern is similar to other emerging infectious diseases that first spill into sentinel human populations who interface with the virus and its vector in unique ways. It is difficult to determine the true spectrum of illness with such a small number of patients and no systematic serosurvey. However, the experience with SFTS (case fatality rate 17.4%) and RVF indicate that phleboviruses can produce severe disease. There is currently no vaccine or antiviral treatment for Heartland virus.

Physicians are encouraged to send samples to reference laboratories for testing on those patients who have compatible symptoms and test negative for Ehrlichia or Anaplasma species and do not respond to doxycycline.3


  1. McMullan LK, Folk SM, Kelly AJ, et al. A new phlebovirus associated with severe febrile illness in Missouri. N Engl J Med 2012;367:834–41.
  2. Oklahoma: Man dies after acquiring Heartland virus. Washington Post. May 27, 2014. . Accessed May 28, 2014.
  3. Pastula DM, Turabelidze G, Yates KF, et al. Heartland virus disease — United States, 2012–2013. MMWR 2014;63:270-71.
  4. Liu W, Lu QB, Cui N, et al. Case-fatality ratio and effectiveness of ribavirin therapy among hospitalized patients in china who had severe fever with thrombocytopenia syndrome. Clin Infect Dis 2013;57:1292-9.