Tacaribe Virus in Florida: An Example of Bottom-Up Discovery of Potential Human and Animal Pathogens

Tacaribe Virus in Florida: An Example of Bottom-Up Discovery of Potential Human and Animal Pathogens

Tick-borne diseases (TBDs) are becoming increasingly recognized for their public health relevance, as ticks are surpassed only by mosquitoes as arthropod vectors of human and animal disease. Emerging tick-borne agents capable of causing human disease are being discovered at a rapid pace although TBDs have a long, documented history in veterinary medicine. In fact, establishment of tick vectored Babesia bigemina as the causative agent of Texas cattle fever in 1893 predates discovery of the vectors of malaria and yellow fever, as well as the insight that fleas transmit plague-causing bacillus Since that early discovery, a new disease-causing agent transmitted by a tick vector has been discovered globally every 5-7 years, on average. Thanks in part to the advent and widespread use of molecular tools, the pace of TBD discovery has changed expeditiously over the past 30 years and the number of epidemiologically important and distinct diseases has rapidly increased or exponentially increased. For example, in 1990 only two tick-associated diseases were reportable in the United States: Rocky Mountain spotted and tularemia (2). Today at least ten TBDs are recognized in the United States including tick-borne bacterial infections such as anaplasmosis, babesiosis (3), ehrlichiosis (caused by Ehrlichia chaffeensis and E. ewingii, which are responsible for the monocytotrophic and granulocytotrophic forms of human ehrlichiosis, respectively); Lyme borreliosis caused by several genospecies of Borrelia (most notably Borrelia burgdorferi in the U.S.);Borrelia hermsii and other Borrelia spp. which cause tick-borne relapsing fever (4), and tick-borne viruses including Colorado tick fever (5), Powassan virus (6), and Heartland virus (7).

Since their discovery and recognition as agents of human disease, the reported case incidences have increased for many of these important tick-borne pathogens, often dramatically, including A. phagocytophilum and Ehrlichia chaffeensis (8), spotted fever group rickettsiae (9), and Borrelia burgdorferi(10). Some TBDs endemic to North America are associated with long-term morbidity or relatively high case fatality rates that generate considerable fear and public health concerns that outweigh actual disease burden. In particular, fear of Lyme disease in the southeastern United States where the disease is not considered to be endemic has captured public attention and led to debate among researchers and the public, alike. In contrast, other less recognized diseases, such as Ehrlichia spp. may cause disease that goes unrecognized by many medical practitioners, thereby underestimating the true impact on human or animal health levied by these agents (11). Furthermore, for the less recognized tick-borne pathogens, consistent surveillance efforts are entirely passive and reported disease incidence rates can vary widely from year to year. This is often because proactive surveillance at the level of the tick vector itself does not take place, which can act as an early warning system. Additional factors that can lead to fluctuations between years include changes in definitions of disease and alterations to reporting practices.

A number of factors which may be working synergistically, but are often poorly understood, are likely contributing to upward trends and yearly fluctuations in TBD incidence abroad and in the US. These factors include expanding ranges of tick vectors, better diagnostic assays, and improved awareness among physicians, against a backdrop of highly variable regional and local surveillance for tick-borne diseases. Additionally, climate change as a phenomenon affecting tick range, activity, reproduction, behavior, and the rate of human/vector contact has also been discussed as having an impact on TBD incidence globally (12–14). Other, more subtle trends, including land use and habitat fragmentation, suburbanization, increased outdoor recreation, and changes in wildlife populations may also influence disease incidence in people and in animals (11). For example, in the Czech Republic, researchers recently observed that counter-urbanization (movement from urban, densely populated areas to rural areas) correlated with residential exposure and extension of the seasonal case distribution of Lyme borreliosis (15). Complex interactions involving human land use, species richness and diversity of both the vector and wildlife reservoirs have the potential to affect the circulation of tick-borne diseases in a geographic area. In particular, the role of wildlife reservoirs in the maintenance of TBDs is important for making predictions about disease “hotspots” and likely locations of disease emergence (16-18). Therefore, a system-wide, bottom-up One Health approach is important for understanding human exposure risks to tick-borne pathogens.

This type of approach has led to our recent re-discovery of a lost arenavirus in highly prevalent, aggressive, human and animal biting tick species in Florida (19). The virus we found, the Tacaribe virus, was first discovered in the 1950s in Trinidad during a rabies surveillance survey (20).  The presence of the virus in ticks in the U.S. is of particular interest because Arenaviridae are known to cause severe hemorrhagic disease in humans, particularly in parts of sub-Saharan Africa, and in Central and South America. Humans typically become infected with an arenavirus through contact with excreta from infected rodents and it is highly unusual to find this type of virus associated with a tick vector. This is especially alarming because Tacaribe virus is closely related to the most highly pathogenic viruses that cause up to 30% mortality in infected patients, including Junin virus, and its wildlife reservoir has never been identified. We found that the tick-derived isolate is nearly identical to the only remaining isolate from Trinidad (TRVL-11573), with 99.6% nucleotide identity across the genome. We also developed a quantitative RT-PCR assay to test for viral RNA in host-seeking ticks collected from 3 Florida state parks. Virus RNA was detected in 56/500 (11.2%) of surveyed lone star ticks.  As this virus was isolated from ticks that readily parasitize humans, the ability of the tick to transmit the virus to people should be evaluated. Furthermore, reservoir hosts for the virus need to be identified in order to develop risk assessment models of human infection.

The benefit of using a bottom-up approach for tick-borne agents is early identification of the virus in the environment. Detection of the virus in an appropriate sentinel species (the tick) does not rely on waiting for human cases associated with severe disease to occur. Instead, this type of approach can be used to make a proactive and predictive rather than reactive response to potentially serious disease-causing agents. However, this can only be accomplished with support from funding sources and the development of successful, multidisciplinary teams. This is particularly true of viral pathogens of zoonotic origin where a vector species is implicated. The United States Agency for International Development (USAID) has applied this approach as part of its PREDICT initiative that is focused on risk determination, capacity building and pathogen discovery. Domestically, disease surveillance efforts in vectors and wildlife reservoirs remain largely reactive. Only when funding for active surveillance and interdisciplinary working groups increases can we expect to see further improvements in pathogen discovery and the use of vectors, rather than humans, as sentinels of emerging disease.

A multidisciplinary team including a virologist (Dr. John Lednicky), a pathologist and physician (Dr. William Clapp), a veterinarian (Dr. Rick Alleman), a biochemist (Dr. Anthony Barbet) and vector biologist (Dr. Katherine Sayler, author) worked together to isolate the Tacaribe virus from ticks and perform the experiments described above.

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This and other articles were published in Volume 8 Issue 1 of the One Health Newsletter.
Article written by: Katherine A. Sayler, PhD