Reservoir Host Population Genetics And Its Influence On Tick-Borne Relapsing Fever Maintenance

Spending time outdoors is an important component of the lifestyle valued so highly by many of the residents of Nevada. The image of squirrels hopping by a cabin or a chipmunk begging for food in a picnic area is common, and relaxing. Although these forest denizens belong in the natural landscape, they also serve to maintain diseases that are transmitted to humans and domestic animals that share these habitats.

Recent closures of state parks due to bubonic plague outbreaks serve as good examples of potential risks posed to human health and the loss to rural economies due to decreased tourism. Increased numbers of rodents often lead to higher rates of infection with zoonotic diseases such as hantavirus and plague. Chipmunks are commonly found in close association with humans in campgrounds and around rural cabins.

Research conducted by University of Nevada, Reno indicates that in the Sierra Nevada ecosystem, chipmunks are commonly infected by relapsing fever spirochetes and that chipmunks serve as an important link in disease transmission to humans.

The disease, relapsing fever, has affected citizens of Nevada and California alike and is transmitted to individuals through the bite of an infected tick. Wild rodents, especially chipmunks serve both to maintain tick populations and as reservoirs for the bacteria, Borrelia hermsii, which causes relapsing fever in humans.

Human induced changes to the natural environment, such as woodpiles, trash cans and homes uninhabited during the winter may serve to benefit wild rodents resulting in higher rodent survival and reproduction. Further research conducted by University of Nevada, Reno indicates that chipmunks serve as a reservoir for relapsing fever and appear to be in higher densities around rural/summer cabins than in areas without human habitation. The high rodent densities help to amplify the potential for disease transmission to humans.

In order to understand how rodent survival, reproduction and recruitment can affect the prevalence of disease around human habitations, this project will use chipmunks as model organisms to understand the transmission dynamics that occur to maintain relapsing fever in nature. Through the use of genetic techniques, investigator will test whether human habitation influences rodent dispersal by testing paired sites in Nevada and California that are endemic for relapsing fever. Chipmunk DNA from study sites where humans live for part of the year will be compared to chipmunk DNA collected from endemic sites in which humans recreate but do not live. We plan to test whether chipmunk dispersal is altered by human habitation and whether this influences the ecological maintenance of relapsing fever.

Vector-borne relapsing fever is a zoonotic disease endemic in much of Africa and Asia, Europe, and throughout the Americas (Barbour 1986; Brouqui and Raoult 2006). In both Africa and North America, relapsing fever has been recognized as a cause of significant morbidity since the late 1800s and early 1900s (Ordman 1957; Fritz, Bronson et al. 2004). Worldwide the disease is caused by at least 17 species of bacteria in the spirochetes genus Borrelia (Cutler 2006).

Relapsing fever is an undulant febrile illness with many non-specific symptoms including headache, myalgia, arthralgia, and abdominal pain. In most cases, disease is resolved after up to six episodes that occur weeks to months apart. In east Africa, relapsing fever is a significant cause of infant mortality and perinatal death (Barclay and Coulter 1990). A case fatality rate of 10% has been reported in east Africa, but many other areas also maintain endemic disease that is often unreported or misdiagnosed as other febrile illnesses.

Misdiagnosis of human cases of relapsing fever is also common in western North America due to the disease’s non-specific clinical signs. Relapsing fever spirochetes in the western U.S., utilize a diverse range of soft tick vectors, (Ornithodoros spp. on mammals and Argas spp. on birds and reptiles) while the body louse (Pediculus humanus, utilized by B. recurrentis) serves to transmit the pathogen in Africa.

In the U.S., relapsing fever occurs throughout the mountainous west and southwestern deserts and involves one of at least seven different species of spirochetes, each closely associated with its own soft tick vector. Relapsing fever research from as early as the 1920s has focused on the distribution and prevalence of B. hermsii from high elevations in California and Nevada, including Lake Tahoe and Big Bear lakes (Longanecker 1951).

In the western U.S., cases occur mostly in summer months but beginning in the spring (Dworkin and al. 1998). Human infection often occurs in localized endemic spatial patches and is maintained between a specific soft tick vector and a rodent reservoir host. Humans become infected following a nocturnal bite by a tick and risk of infection is classically associated with rodent infestation of a home or cabin, especially following extended periods of vacancy (Fritz, Bronson et al. 2004).

Once in the host, the relapsing fever spirochete avoids host detection and destruction via hyper-variability in major surface antigens (what causes production of antibodies in host).

Host reservoir species composition vary greatly for relapsing fever spirochetes in the western U.S. pine squirrels, chipmunks, and meadow voles were able to become experimentally infected with the spirochetes, while ground squirrels, wood rats, flying squirrels, and deer mice may also play a role (Burgdorfer and Mavros 1970). In collaboration with members of the Vector-borne Diseases Program, Washoe County Health Department (NV) and the California Department of Public Health (Vector-borne Diseases Section) University of Nevada, Reno’s investigators have captured, ear tagged, bled and assayed wild rodents for relapsing fever spirochetes using a Taqman-PCR assay designed to detect B. hermsii since 2009.

1. Test whether dispersal in chipmunks (Tamias spp.) influences the prevalence of the bacteria Borrelia hermsii  infection at sites endemic for relapsing fever in Nevada and California, 
2. To genetically identify strains of B. hermsii obtained at these sites and 
3. Perform statistical comparisons of reservoir host population structure and migration with B. hermsii infection prevalence and potential risk to humans.