Genetically Engineering Wild Mice to Combat Lyme Disease: An Ecological Perspective

Abstract Genetic engineering of wild populations has been proposed for reducing human diseases by altering pathogens’ hosts. For example, CRISPR-based genome editing may be used to create white-footed mice (Peromyscus leucopus) that are resistant to the Lyme disease spirochete vectored by blacklegged ticks (Ixodes scapularis). Toward this goal, academic researchers are developing Lyme-resistant and tick-resistant white-footed mice, which are a primary pathogen reservoir for Lyme disease in the United States. If field trials on small, experimental islands are successful, the project would scale up to the larger islands of Nantucket and Martha's Vineyard, Massachusetts, and possibly to the mainland, most likely with a local gene drive to speed the traits’ proliferation, pending approvals from relevant constituents. Despite considerable publicity, this project has yet to be evaluated by independent professional ecologists. In the present article, I discuss key ecological and evolutionary questions that should be considered before such genetically engineered mice are released into natural habitats.

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Human Coinfection withBorrelia burgdorferiandBabesia microtiin the United States

Journal of Parasitology Research ◽

10.1155/2015/587131 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 21

Author(s):

Kristen L. Knapp ◽

Nancy A. Rice

Keyword(s):

United States ◽

Lyme Disease ◽

Causative Agent ◽

Ixodes Scapularis ◽

Immunological Response ◽

The United States ◽

Babesia Microti ◽

Current State ◽

Tick Borne Disease ◽

Multiple Pathogens

Borrelia burgdorferi, the causative agent of Lyme disease, andBabesia microti, a causative agent of babesiosis, are increasingly implicated in the growing tick-borne disease burden in the northeastern United States. These pathogens are transmitted via the bite of an infected tick vector,Ixodes scapularis, which is capable of harboring and inoculating a host with multiple pathogens simultaneously. Clinical presentation of the diseases is heterogeneous and ranges from mild flu-like symptoms to near-fatal cardiac arrhythmias. While the reason for the variability is not known, the possibility exists that concomitant infection with bothB. burgdorferiandB. microtimay synergistically increase disease severity. In an effort to clarify the current state of understanding regarding coinfection withB. burgdorferiandB. microti, in this review, we discuss the geographical distribution and pathogenesis of Lyme disease and babesiosis in the United States, the immunological response of humans toB. burgdorferiorB. microtiinfection, the existing knowledge regarding coinfection disease pathology, and critical factors that have led to ambiguity in the literature regarding coinfection, in order to eliminate confusion in future experimental design and investigation.

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A climate-based model predicts the spatial distribution of the Lyme disease vector Ixodes scapularis in the United States.

Environmental Health Perspectives ◽

10.1289/ehp.6052 ◽

2003 ◽

Vol 111 (9) ◽

pp. 1152-1157 ◽

Cited By ~ 164

Author(s):

John S Brownstein ◽

Theodore R Holford ◽

Durland Fish

Keyword(s):

United States ◽

Spatial Distribution ◽

Lyme Disease ◽

Ixodes Scapularis ◽

The United States ◽

Disease Vector

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Borrelia burgdorferi (Spirochaetales: Spirochaetaceae) Infection Prevalence and Host Associations of Ticks Found on Peromyscus spp. in Maryland

Journal of Medical Entomology ◽

10.1093/jme/tjab206 ◽

2021 ◽

Author(s):

Julia E Poje ◽

Jose F Azevedo ◽

Nisha Nair ◽

Kurayi Mahachi ◽

Lexi E Frank ◽

...

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Disease Risk ◽

Ixodes Scapularis ◽

Sensu Stricto ◽

Infection Prevalence ◽

Private Land ◽

Tissue Samples ◽

Wild Mice ◽

Significant Difference

Abstract Lyme disease, caused by Borrelia burgdorferi sensu stricto and most commonly transmitted by Ixodes scapularis Say (Ixodida: Ixodidae), is the most common tick-borne disease in Maryland. Because B. burgdorferi s.s. is maintained in enzootic cycles among wild mice (Peromyscus spp) and Ixodes spp ticks, differing patterns of parasitism of ticks on mice could impact the infection prevalence with B. burgdorferi. We determined the infection prevalence of Peromyscus spp as well as questing and partially engorged nymphal ticks collected at six sites on private land in five counties in Maryland from May to August 2020. Questing nymph infection prevalence (NIP) was 14%. We trapped 1258 mice and collected 554 ticks and 413 ear tissue samples. The prevalence of infested Peromyscus spp varied based on host age and sex, with older and male mice more likely to be infested. We detected a significant difference amongst the proportion of attached Ixodes and the location of trapping. Similarly, the prevalence of B. burgdorferi infected Peromyscus spp mice varied between locations (average mouse infection prevalence was 40%), with the highest prevalence in locations where Ixodes were the most commonly found ticks. The B. burgdorferi infection prevalence in partially engorged I. scapularis nymphs retrieved from Peromyscus spp was ~36% which lends further support to the host infection prevalence. Local differences in distribution of infected vectors and reservoirs are important factors to consider when planning interventions to reduce Lyme disease risk.

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Variation in the Microbiota of Ixodes Ticks with Regard to Geography, Species, and Sex

Applied and Environmental Microbiology ◽

10.1128/aem.01562-15 ◽

2015 ◽

Vol 81 (18) ◽

pp. 6200-6209 ◽

Cited By ~ 76

Author(s):

Will Van Treuren ◽

Loganathan Ponnusamy ◽

R. Jory Brinkerhoff ◽

Antonio Gonzalez ◽

Christian M. Parobek ◽

...

Keyword(s):

New York ◽

North Carolina ◽

South Carolina ◽

Lyme Disease ◽

Ixodes Scapularis ◽

Illumina Miseq ◽

The United States ◽

Upper Midwest ◽

Content Type ◽

Ixodes Ticks

ABSTRACTIxodes scapularisis the principal vector of Lyme disease on the East Coast and in the upper Midwest regions of the United States, yet the tick is also present in the Southeast, where Lyme disease is absent or rare. A closely related species,I. affinis, also carries the pathogen in the South but does not seem to transmit it to humans. In order to better understand the geographic diversity of the tick, we analyzed the microbiota of 104 adultI. scapularisand 13 adultI. affinisticks captured in 19 locations in South Carolina, North Carolina, Virginia, Connecticut, and New York. Initially, ticks from 4 sites were analyzed by 454 pyrosequencing. Subsequently, ticks from these sites plus 15 others were analyzed by sequencing with an Illumina MiSeq machine. By both analyses, the microbiomes of female ticks were significantly less diverse than those of male ticks. The dissimilarity between tick microbiomes increased with distance between sites, and the state in which a tick was collected could be inferred from its microbiota. The genusRickettsiawas prominent in all locations.Borreliawas also present in most locations and was present at especially high levels in one site in western Virginia. In contrast, members of the familyEnterobacteriaceaewere very common in North CarolinaI. scapularisticks but uncommon inI. scapularisticks from other sites and in North CarolinaI. affinisticks. These data suggest substantial variations in theIxodesmicrobiota in association with geography, species, and sex.

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Assessing Recognition of the Vector of Lyme Disease Using Resin-Embedded Specimens in a Lyme Endemic Area

Journal of Medical Entomology ◽

10.1093/jme/tjaa234 ◽

2020 ◽

Author(s):

Gebbiena M Bron ◽

Hannah Fenelon ◽

Susan M Paskewitz

Keyword(s):

United States ◽

Lyme Disease ◽

Adult Female ◽

Endemic Area ◽

Ixodes Scapularis ◽

The United States ◽

Convenience Sample ◽

Potential Benefits ◽

Vector Borne ◽

Tick Check

Abstract Lyme disease (LD) is the most common vector-borne disease in the United States. To assess whether a tick bite puts someone at risk for LD, adequate tick identification skills are needed. We surveyed residents of a high LD-incidence state, Wisconsin, on their ability to distinguish ticks from insects and to identify the specimens that could transmit the LD causative agent. Surveys were conducted using resin blocks with four insects and four tick specimens embedded. About half of the participants (64 of 130) recognized all of the ticks, and 60% of those individuals chose only ticks and no insects. Younger participants (18- to 44-yr old) were more likely to identify ticks correctly compared with those 45 yr and older. Participants who agreed strongly with the statement ‘I know a lot about ticks` were also likelier to correctly identify ticks. When asked to identify which specimens could transmit LD, less than 25% of participants chose both the Ixodes scapularis Say adult female and nymph and about half of those (15% of participants) picked only those two and no other specimens. Although the relatively small convenience sample was biased toward younger participants who consider themselves ‘outdoorsy’, results showed that further assessments of tick recognition skills are needed to understand what determines whether people can recognize medically important ticks and to evaluate the potential benefits of enhanced education. In addition to the value of the resin blocks as research tools, the blocks may be useful as training tools to improve tick check efficacy.

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Passage through Ixodes scapularis Ticks Enhances the Virulence of a Weakly Pathogenic Isolate of Borrelia burgdorferi

Infection and Immunity ◽

10.1128/iai.00470-09 ◽

2009 ◽

Vol 78 (1) ◽

pp. 138-144 ◽

Cited By ~ 4

Author(s):

Sarojini Adusumilli ◽

Carmen J. Booth ◽

Juan Anguita ◽

Erol Fikrig

Keyword(s):

United States ◽

Lyme Disease ◽

Borrelia Burgdorferi ◽

Ixodes Scapularis ◽

The United States ◽

Sensu Stricto ◽

Array Analysis ◽

C3h Mice ◽

Attenuated Isolate

ABSTRACT Lyme disease is the most common tick-borne illness in the United States. In this paper we explore the contribution of Ixodes scapularis ticks to the pathogenicity of Borrelia burgdorferi in mice. Previously we demonstrated that an isolate of B. burgdorferi sensu stricto (designated N40), passaged 75 times in vitro (N40-75), was infectious but was no longer able to cause arthritis and carditis in C3H mice. We now show that N40-75 spirochetes can readily colonize I. scapularis and multiply during tick engorgement. Remarkably, tick-transmitted N40-75 spirochetes cause disease in mice. N40-75 spirochetes isolated from these animals also retained their pathogenicity when subsequently administered to mice via syringe inoculation. Array analysis revealed that several genes associated with virulence, including bba25, bba65, bba66, bbj09, and bbk32, had higher expression levels in the tick-passaged N40-75 spirochete. These data suggest that transmission of a high-passage attenuated isolate of B. burgdorferi by the arthropod vector results in the generation of spirochetes that have enhanced pathogenesis in mice.

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Modeling the Sensitivity of Blacklegged Ticks (Ixodes scapularis) to Temperature and Land Cover in the Northeastern United States

Journal of Medical Entomology ◽

10.1093/jme/tjaa179 ◽

2020 ◽

Author(s):

Jonathan M Winter ◽

Trevor F Partridge ◽

Dorothy Wallace ◽

Jonathan W Chipman ◽

Matthew P Ayres ◽

...

Keyword(s):

United States ◽

Lyme Disease ◽

Land Cover ◽

New Hampshire ◽

Ixodes Scapularis ◽

Compartment Model ◽

The United States ◽

Growth Stages ◽

Eastern United States ◽

Northeastern United States

Abstract The prevalence of Lyme disease and other tick-borne diseases is dramatically increasing across the United States. While the rapid rise in Lyme disease is clear, the causes of it are not. Modeling Ixodes scapularis Say (Acari: Ixodidae), the primary Lyme disease vector in the eastern United States, presents an opportunity to disentangle the drivers of increasing Lyme disease, including climate, land cover, and host populations. We improved upon a recently developed compartment model of ordinary differential equations that simulates I. scapularis growth, abundance, and infection with Borrelia burgdorferi (Spirochaetales: Spirochaetaceae) by adding land cover effects on host populations, refining the representation of growth stages, and evaluating output against observed data. We then applied this model to analyze the sensitivity of simulated I. scapularis dynamics across temperature and land cover in the northeastern United States. Specifically, we ran an ensemble of 232 simulations with temperature from Hanover, New Hampshire and Storrs, Connecticut, and land cover from Hanover and Cardigan in New Hampshire, and Windsor and Danielson in Connecticut. Consistent with observations, simulations of I. scapularis abundance are sensitive to temperature, with the warmer Storrs climate significantly increasing the number of questing I. scapularis at all growth stages. While there is some variation in modeled populations of I. scapularis infected with B. burgdorferi among land cover distributions, our analysis of I. scapularis response to land cover is limited by a lack of observations describing host populations, the proportion of hosts competent to serve as B. burgdorferi reservoirs, and I. scapularis abundance.

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Do-It-Yourself Tick Control: Granular Gamma-Cyhalothrin Reduces Ixodes scapularis (Acari: Ixodidae) Nymphs in Residential Backyards

Journal of Medical Entomology ◽

10.1093/jme/tjaa212 ◽

2020 ◽

Author(s):

Gebbiena M Bron ◽

Xia Lee ◽

Susan M Paskewitz

Keyword(s):

United States ◽

Lyme Disease ◽

Ixodes Scapularis ◽

Low Cost ◽

The United States ◽

Tick Control ◽

Eastern United States ◽

Individual Level ◽

Nymphal Tick ◽

Do It Yourself

Abstract Lyme disease is the most common vector-borne disease in the United States with hotspots in the Northeast and Midwest. Integrated vector control for mosquito-borne disease prevention is often organized at the community level, but tick control is primarily coordinated at the household and individual level. Management of the blacklegged tick, Ixodes scapularis (Say), the vector of the causative agent of Lyme disease in the Midwest and eastern United States in peridomestic environments may be critical as many tick encounters are reported to occur in the yard. Therefore, we assessed the effectiveness of a widely available and low-cost pesticide that targets common lawn pests and is labeled for use against ticks. In June 2019, we evaluated a granular form of gamma-cyhalothrin in a placebo-controlled residential backyard study (n = 90) in two communities in Wisconsin. The product applied by the research team reduced nymphal blacklegged ticks in plots established in the lawn part of the ecotone by 97% one week after application at both communities and by 89–97% three to four weeks postapplication. The proportion of homes with at least one nymphal tick postapplication was significantly lower at acaricide-treated homes and ranged from 4.2 to 29.2% compared with placebo homes where at least one nymphal tick was found at 50–81.5% of homes. These results support the efficacy of a low-cost do-it-yourself strategy for homeowners seeking to reduce blacklegged ticks in the yard.

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