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Figure. Tick collection sites associated with 2 cases of Heartland virus infection in humans, Kankakee and Williamson Counties, Illinois, USA, 2019. Locations of the counties are indicated by red dots on the Illinois map.
Source publication
In 2018, Heartland disease virus infected 2 persons in Illinois, USA. In 2019, ticks were collected at potential tick bite exposure locations and tested for Heartland and Bourbon viruses. A Heartland virus–positive pool of adult male Amblyomma americanum ticks was found at 2 locations, 439 km apart, suggesting widespread distribution in Illinois.
Citations
... Amblyomma americanum is a multi-host tick with an ever-expanding distribution that strongly overlaps the geographical presentation of human cases of HRTV, and surveillance studies have identified HRTV-infected ticks in areas proximal to known human cases and across the range of A. americanum occurrence. Virus or viral nucleic acids have been recovered from both nymph and adult stages of A. americanum [18,[44][45][46][47][48][49], though to date, the virus has not been recovered from tick larvae collected in the field. Experimental studies have found larvae to be susceptible, however, with both transovarial and transstadial viral transmission reported [50]. ...
... The typical signalment for HRTV cases is an adult male over the age of 40-though most cases are over the age of 60, often with preexisting comorbidities-an outdoor lifestyle including farming, camping, or hunting, and very likely a history of tick exposure [1,19,44,[60][61][62][63][64][65][66][67]. Clinical presentations are those which may mimic other regional tick-borne diseases most commonly seen in the summer months, such as Ehrlichia, Rickettsia, and Babesia, and include a short history of fever (≥38 • C), headache, fatigue, myalgia, nausea, anorexia, and non-bloody diarrhea. ...
... Clinical presentations are those which may mimic other regional tick-borne diseases most commonly seen in the summer months, such as Ehrlichia, Rickettsia, and Babesia, and include a short history of fever (≥38 • C), headache, fatigue, myalgia, nausea, anorexia, and non-bloody diarrhea. A localized rash, as may be seen with some other tick-borne diseases, has been reported in just a subset of cases, though a patient with a more diffuse maculopapular rash has also been reported [19,44,62]. Purpura has been reported on occasion as well [60]. ...
Heartland virus (HRTV) is an emerging tick-borne bandavirus that is capable of causing severe disease characterized by acute thrombocytopenia and lymphopenia. The virus is endemic to the eastern United States and is carried by the Lone Star tick (Amblyomma americanum). Since its discovery in 2009, at least 60 human infections have been recorded across this area, with an overall 5–10% estimated mortality rate. All infections reported thus far have occurred following a known tick bite or exposure to tick-infested areas, but the possibility of nosocomial transmission has not been ruled out. Despite relatively high rates of seroprevalence among certain wildlife species such as white-tailed deer, the reservoir species for HRTV remains unknown, as the virus has never been isolated from any mammalian wildlife species. Furthermore, how the virus is transmitted to its vector species in nature remains unknown, though laboratory studies have confirmed both horizontal and vertical transmission of HRTV in A. americanum. In addition, the recent 2017 introduction of the Asian longhorned tick (Haemaphysalis longicornis) to the US has raised concerns about possible spillover of HRTV into a new tick species that has been confirmed to be a competent vector for HRTV in the laboratory. Thus, an increased awareness of its clinical presentation is needed, and further research is urgently required to establish the natural transmission cycle and develop new countermeasures for this novel zoonotic pathogen.
Background: The tick-borne pathogens, Bourbon virus (BRBV) and Heartland virus (HRTV) are the cause of febrile illnesses that may progress to severe and fatal diseases. Materials and Methods: As a preliminary effort to determine if these viruses were enzootic in Texas, ticks and blood samples were collected from feral swine (Sus scrofa) and white-tailed deer (Odocoileus virginianus) (WTD) killed by gunning as part of an abatement program during 2019-2021 in Travis County, Texas. Ticks were collected from these animals by hand and blood samples were obtained by cardiac puncture using 22-gauge needles and 5 mL syringes. Information was recorded for each animal, including date, sex, and location. The species of ticks were identified morphologically using a taxonomic key, and serum samples were tested for neutralizing antibodies to BRBV and HRTV. Results: A total of 83 Ixodes scapularis and 58 Amblyomma americanum ticks were collected from feral swine, and 196 I. scapularis and 11 Dermacentor albipictus from WTD. Although A. americanum, the implicated vector of both viruses was collected from feral swine, neutralizing antibody was not detected to BRBV, but 12% (9/75) had antibody to HRTV as evidence of a previous infection. Of the serum samples obtained from WTD, all were negative for BRBV neutralizing antibody, but 6.6%% (5/75) were positive for HRTV antibody. Conclusion: These preliminary results indicated that HRTV was enzootic in Travis, County, Texas and further studies are warranted to determine the specific tick vectors and the possible role of WTD and feral swine in the maintenance and transmission cycle of this virus.
Wprowadzenie
Kleszczowe zapalenie mózgu ( tick-borne encephalitis – TBE) jest chorobą wywoływaną przez wirusa kleszczowego zapalenia mózgu, który jest przenoszony przez ukąszenia kleszczy. Rozpowszechnienie TBE ocenia się na 10,000–15,000 przypadków rocznie i jest porównywalne dla krajów europejskich i azjatyckich. Około 10–20% wszystkich zainfekowanych osób jest w wieku dziecięcym. Znaczna większość, bo aż 70–98% z nich, przechodzi tę chorobę bezobjawowo lub jest niezdiagnozowana. Do głównych objawów klinicznych zalicza się zapalenie opon mózgowo-rdzeniowych (obecne w 69% przypadków) i mózgu (30%) oraz rdzenia kręgowego (1%). U około 2,1% pacjentów rozwijają się długotrwałe następstwa neurologiczne.
Metodyka
Artykuły do pracy zostały wybrane z trzech ogólnodostępnych baz danych. Wykorzystano w tym celu następujące hasła: „infection/epidemiology” + „tick bites/tick-borne encephalitis” + „clinical manifestation/pathogenesis/treatment” oraz „aseptic/viral/bacterial” + „encephalitis/meningitis”. Ostatecznie wybrano 71 prac naukowych i 8 witryn internetowych opublikowanych w latach 1995–2023.
Stan wiedzy
TBE, ze względu na wektor kleszczowy, może być różnicowane z takimi jednostkami chorobowymi jak: babeszjoza, borelioza, południowa wysypka związana z kleszczami ( southern tick-associated rash illness – STARI), chlamydioza, erlichioza, gorączka kleszczowa Kolorado ( Colorado tick fever – CTF), wirus Heartland (HRTV), wirus Powassan (POWV), anaplazmoza granulocytarna, dur powrotny ( tick-borne relapsing fever – TBRF), toksoplazmoza, tularemia, riketsjozy; lub z jednostkami o podobnej symptomatologii, takimi jak: udar mózgu, bruceloza, mononukleoza zakaźna ( infectious mononucleosis – IM), żółta febra ( yellow fever – YF), japońskie zapalenie mózgu ( Japanese encephalitis – JE), inne wirusowe zapalenie opon mózgowo-rdzeniowych, mózgu, rdzenia kręgowego oraz aseptyczne zapalenie opon mózgowo-rdzeniowych.
Wnioski
Diagnostyka różnicowa TBE jest obszerna i powinna obejmować szeroki zakres zakażeń ośrodkowego układu nerwowego wywołanych zarówno przez inne czynniki zakaźne, jak i choroby niezakaźne.
Heartland virus (HRTV), an emerging tick-borne pathogenic bunyavirus, has been a concern since 2012, with an increasing incidence, expanding geographical distribution, and high pathogenicity in the United States. Infection from HRTV results in fever, thrombocytopenia, and leucopenia in humans, and in some cases, symptoms can progress to severe outcomes, including haemorrhagic disease, multi-organ failure, and even death. Currently, no vaccines or antiviral drugs are available for treatment of the HRTV disease. Moreover, little is known about HRTV-host interactions, viral replication mechanisms, pathogenesis and virulence, further hampering the development of vaccines and antiviral interventions. Here, we aimed to provide a brief review of HRTV epidemiology, molecular biology, pathogenesis and virulence on the basis of published article data to better understand this virus and provide clues for further study.
Simple Summary
Heartland virus is an underrecognized emerging viral disease with potentially serious sequelae. The tick vector that transmits this disease, A. americanum, continues to expand to states and regions in the US where it was previously undocumented. This geographic expansion is stimulated by increasingly favorable climatic conditions and increasing numbers of host animal populations upon which the tick can feed. More work needs to be conducted to identify all aspects of the natural transmission cycle for HRTV. The true human population burden of Heartland virus is unknown, as comprehensive state, regional and national serosurveys have not been conducted. Expanded HRTV disease surveillance is needed. The absence of commercially available rapid and accurate HRTV tests dictates that the burden of testing remains with the CDC. Given the absence of antiviral treatment for Heartland virus disease, rest, fluids and OTC medications are most often used to treat patients, with hospital-provided IV fluids and supportive care for serious cases. Potential but unused treatments for HRTV infections include favipiravir, tanshinone I and IIa, anidulafungin and the NF-κB inhibitor SC75741, with anidulafungin potentially available for ‘off-label’ use for serious illness. Developmental research to create vaccines for SFTSV and HRTV suggests that vaccines might one day become available for prevention against HRTV infections.
Abstract
First recognized 15 years ago, Heartland virus disease (Heartland) is a tickborne infection contracted from the transmission of Heartland virus (HRTV) through tick bites from the lone star tick (Amblyomma americanum) and potentially other tick species. Heartland symptoms include a fever <100.4 °F, lethargy, fatigue, headaches, myalgia, a loss of appetite, nausea, diarrhea, weight loss, arthralgia, leukopenia and thrombocytopenia. We reviewed the existing peer-reviewed literature for HRTV and Heartland to more completely characterize this rarely reported, recently discovered illness. The absence of ongoing serosurveys and targeted clinical and tickborne virus investigations specific to HRTV presence and Heartland likely contributes to infection underestimation. While HRTV transmission occurs in southern and midwestern states, the true range of this infection is likely larger than now understood. The disease’s proliferation benefits from an expanded tick range due to rising climate temperatures favoring habitat expansion. We recommend HRTV disease be considered in the differential diagnosis for patients with a reported exposure to ticks in areas where HRTV has been previously identified. HRTV testing should be considered early for those matching the Heartland disease profile and nonresponsive to initial broad-spectrum antimicrobial treatment. Despite aggressive supportive therapy, patients deteriorating to sepsis early in the course of the disease have a very grim prognosis.
Co-infections are a poorly understood aspect of tick-borne diseases. In the United States alone, nineteen different tick-borne pathogens have been identified. The majority of these agents are transmitted by only two tick species, Ixodes scapularis and Amblyomma americanum. Surveillance studies have demonstrated the presence of multiple pathogens in individual ticks suggesting a risk of polymicrobial transmission to humans. However, relatively few studies have explored this relationship and its impact on human disease. One of the key factors for this deficiency are the intrinsic limitations associated with molecular and serologic assays employed for the diagnosis of tick-borne diseases. Limitations in the sensitivity, specificity and most importantly, the capacity for inclusion of multiple agents within a single assay represent the primary challenges for the accurate detection of polymicrobial tick-borne infections. This review will focus on outlining these limitations and discuss potential solutions for the enhanced diagnosis of tick-borne co-infections.
Heartland (HRTV) and Bourbon (BRBV) viruses are newly identified tick-borne viruses, isolated from serious clinical cases in 2009 and 2014, respectively. Both viruses originated in the lower Midwest United States near the border of Missouri and Kansas, cause similar disease manifestations, and are presumably vectored by the same tick species, Amblyomma americanum Linnaeus (Ixodida: Ixodidae). In this article, we provide a current review of HRTV and BRBV, including the virology, epidemiology, and ecology of the viruses with an emphasis on the tick vector. We touch on current challenges of vector control and surveillance, and we discuss future directions in the study of these emergent pathogens.
Heartland virus was first isolated in 2009 from two patients in Missouri and is transmitted by the Lone Star tick, Amblyomma americanum. To understand disease transmission and pathogenesis, it is necessary to develop an animal model which utilizes the natural route of transmission and manifests in a manner similar to documented human cases. Herein we describe our investigations on identifying A129 mice as the most appropriate small animal model for HRTV pathogenesis that mimics human clinical outcomes. We further investigated the impact of tick saliva in enhancing pathogen transmission and clinical outcomes. Our investigations revealed an increase in viral load in the groups of mice that received both virus and tick salivary gland extract (SGE). Spleens of all infected mice showed extramedullary hematopoiesis (EH), depleted white pulp, and absence of germinal centers. This observation mimics the splenomegaly observed in natural human cases. In the group that received both HRTV and tick SGE, the clinical outcome of HRTV infection was exacerbated compared to HRTV only infection. EH scores and the presence of viral antigens in spleen were higher in mice that received both HRTV and tick SGE. In conclusion, we have developed a small animal model that mimics natural human infection and also demonstrated the impact of tick salivary factors in exacerbating the HRTV infection.
