Thursday, December 06, 2018

EID Journal: Seroprevalence Of Heartland Virus Antibodies In Northwestern Missouri


One of the surest bets in epidemiology is that that whenever a pathogen is detected in the human population, there are more cases out there than can be  picked up by normal surveillance.  
The numbers detected and reported - even under the best of circumstances - are inevitably only a subset of the total number of cases in the community.
We see this with infections as common and ubiquitous as seasonal flu (see CDC: The Estimated Burden Of Last Year's Flu Season), and as rare and exotic as MERS-CoV (see EID Journal: Estimation of Severe MERS Cases in the Middle East, 2012–2016).

In August of 2012, in a New Phlebovirus Discovered In Missouri, I wrote about the CDC’s announcement of a new tick-borne virus phlebovirus detected in two Missouri farmers with no epidemiological links and living 60 miles apart.
Dubbed `The Heartland Virus’ (HLV),  the virus was  named after the Heartland Regional Medical Center in St. Joseph, Mo which alerted the CDC back in 2009 about these cases.
Phleboviruses are part of the large family Bunyaviridae - which includes such infamous pathogens as Crimean-Congo hemorrhagic fever and Rift Valley FeverBunyaviruses -  are mostly spread via arthropod vectors (ticks, mosquitoes & sand flies).

This newly described `Heartland virus’  is genetically similar to another tickborne disease identified in China in 2011 called the SFTS virus (see EID Journal  dispatch Severe Fever with Thrombocytopenia Syndrome Virus, Shandong Province, China Jun 2012).  Since then, SFTS-like viruses have been found in ticks in Japan, Korea, and Australia.

According to the CDC
Heartland virus is likely spread by the Lone Star tick. As of September 2018, more than 40 cases of Heartland virus disease have been reported from states in the Midwestern and southern United States. Most people diagnosed with the disease became sick during May through September. Heartland virus is not currently a notifiable disease, but CDC asks that states report possible cases of Heartland virus on a voluntary basis.

While 40 cases across 10 states over six years makes this a very rare diagnosis, the actual incidence of infection is unknown, as is the range of symptoms.  Some cases may see only mild illness, others may prove asymptomatic, and some may experience severe illness, but be diagnosed with something else.
Despite certain limitations (sensitivity and selectivity of lab tests, persistence of detectable antigens post infection, etc.), the best way to estimate the number of cases is through serological testing for virus-specific antigens in representative blood samples. 
Which is what is presented in the following EID Journal dispatch, which found evidence of prior Heartland virus infection in just under 1% of 486 blood samples tested across 10 Northwestern Missouri counties.

While a low incidence overall, this certainly suggests a sizable number of cases go undetected each year.

Volume 25, Number 2—February 2019
Seroprevalence of Heartland Virus Antibodies in Blood Donors, Northwestern Missouri, USA

Nicole P. Lindsey , Jay E. Menitove, Brad J. Biggerstaff, George Turabelidze, Pat Parton, Kim Peck, Alison J. Basile, Olga I. Kosoy, Marc Fischer, and J. Erin Staples
Author affiliations: Centers for Disease Control and Prevention, Fort Collins, Colorado, USA (N.P. Lindsey, B.J. Biggerstaff, A.J. Basile, O.I. Kosoy, M. Fischer, J.E. Staples); Community Blood Center of Greater Kansas City, Kansas City, Missouri, USA (J.E. Menitove, P. Parton, K. Peck); Missouri Department of Health and Senior Services, St. Louis, Missouri, USA (G. Turabelidze)

We estimated the seroprevalence of Heartland virus antibodies to be 0.9% (95% CI 0.4%–4.2%) in a convenience sample of blood donors from northwestern Missouri, USA, where human cases and infected ticks have been identified. Although these findings suggest that some past human infections were undetected, the estimated prevalence is low.

In 2012, Heartland virus, a novel virus in the family Phenuiviridae, genus Phlebovirus was identified in blood specimens obtained from 2 residents (men) of northwestern Missouri, USA (1). Given the clinical manifestations of illness and history of tick bites of the patients, both men were initially believed to have ehrlichiosis but they failed to improve after being given doxycycline.

Before identification of Heartland virus in these 2 patients, to our knowledge, there were no known phleboviruses that caused human disease in the United States (1,2). Subsequent field work identified Amblyomma americanum ticks, which are widely distributed across the eastern and central United States, as the likely vector for the virus (3,4). Wild animals in Florida, Georgia, Illinois, Indiana, Kansas, Kentucky, Maine, Missouri, New Hampshire, North Carolina, Tennessee, Texas, and Vermont have been found to be seropositive for Heartland virus antibodies (5).
Investigations are underway to identify more disease cases, but little is known about the incidence of Heartland virus infection in humans. The objective of this study was to estimate the seroprevalence of antibodies against Heartland virus in a convenience sample of blood donors who reside in northwestern Missouri where human cases and infected ticks have been identified (1,3,6).


We estimated a prevalence of 0.9% for Heartland virus infection in northwestern Missouri, where the virus is known to have circulated. These results suggest that several infections have gone unidentified because they were asymptomatic or the infected persons did not seek care, were not tested, or were ill before the identification of Heartland virus as a cause of human disease. The finding that most identified infections were in 1 county could be a chance occurrence but also might suggest that the virus is geographically focally distributed.

On the basis of available data for >30 reported cases of Heartland virus disease, healthcare providers should consider testing for patients who have an acute febrile illness and leukopenia or thrombocytopenia not explained by another condition or who were suspected to have another tickborne disease but did not improve after appropriate treatment (e.g., doxycycline) (6,11). Testing should be limited to patients who resided in or traveled to an area with previous evidence of Heartland virus or had a known tick exposure (5,6).

Because Heartland virus is transmitted by infected ticks, prevention depends on using insect repellents, wearing long sleeves and pants, avoiding bushy and wooded areas, and performing tick checks after spending time outdoors. The clinical spectrum of Heartland virus disease remains to be described, including determination of whether asymptomatic infections can occur. In addition, research is needed to determine whether there are other modes of transmission for Heartland virus, including bloodborne transmission.


Ms. Lindsey is an epidemiologist at the Centers for Disease Control and Prevention, Fort Collins. Her primary research interests are arbovirus disease surveillance and epidemiology.
Over the past 6 years we've seen several other newly identified tickborne illnesses isolated in the United States, including:
CDC: New Lyme-Disease-Causing Bacteria Species Discovered

CDC & EID Journal On The Recently Discovered Bourbon Virus
EID Journal: Novel Bunyavirus In Livestock – Minnesota

And less than a month ago, in  CDC: Record Number Of Tickborne Infections Reported In 2017, we looked at this growing trend. As impressive as these latest numbers are, the CDC acknowledges that the actual numbers are likely far higher.

The latest numbers on Tickborne diseases (for 2017) can be found at:
Tickborne Disease Surveillance Data Summary

The CDC offers the following advice on avoiding the Heartland Virus, and other tickborne diseases:


Protect yourself and your family by preventing tick bites. It only takes one bite from an infected tick to make you sick. There is no vaccine to prevent or medicine to treat infection with Heartland virus. Reduce your risk of getting sick by:
Preventing tick bites
Preventing ticks on your pets
Preventing ticks in your yard

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