Intellectual Merit: Human babesiosis is a rapidly emerging tick-borne zoonosis in the United States caused by the protozoan Babesia microti and transmitted by Ixodes scapularis, the Lyme disease vector. Unlike Lyme disease, babesiosis is a potentially fatal disease and poses a threat to blood transfusion recipients. In the Northeast, both Lyme disease and babesiosis were originally restricted to coastal New England. While Lyme disease has expanded dramatically over the past thirty years and now is endemic from Maine to Virginia, babesiosis cases appears to be expanding at a slower rate for reasons that are not understood. This differential spread provides a unique opportunity to examine factors driving pathogen emergence by comparing these species'natural history and transmission dynamics. Furthermore, because B. microti encounters a large proportion of host populations already infected with 6. /jurgdor/er/throughout its geographic expansion, the goal ofthis study is to investigate how pathogen interactions at the individual, population, and community levels influence B. microti invasion patterns and enzootic prevalence. Evidence for a mutualistic effect of B. burgdorferi infection on B. m/crof/transmission are based on recent findings by .Diuk- Wasser and collaborators that coinfected hosts produce more S. m/crof/-infected ticks than 6. /77/crof/-only infected hosts in laboratory studies and that tick infection prevalence and human disease can be as high for 6. microti than B. burgdorferi at long-established sites. This project will directly compare transmission rates of both B. microti and B. burgdorferi in the laboratory by employing established colonies of /. scapularis and white-footed mice {Peromyscus leucopus) and will explore how host coinfection with both pathogens enhances B. m/crof/transmission (Aim 1). Scaling up from this system, Ro will be estimated for populations of infected and non-infected hosts to determine the extent to which coinfection drives invasion of B. microti into previously uninfected areas (Aim 2). A dynamic multi-host, multi-pathogen model will be developed to identify key factors determining B. microti infection prevalence in host-seeking nymphs once B. microti has become established (Aim 3). The proposed project is innovative because it investigates the drivers of an active invasion process for an emerging human pathogen;uses a comparative approach to identify key determinants ofthe invasion and persistence of two /. scapularls-borne pathogens;and examines the role of mutualistic interactions among vector-borne pathogens in invasion and persistence. Expected outcomes include elucidation ofthe mechanisms determining human exposure risk to a rapidly emerging, potentially lethal tick-borne pathogen, and the development of a transmission model including the effect of pathogen interactions. A long-term goal of this study is to develop optimal prevention and control strategies that can synergistically target 6. microti and 6. burgdorferi, as well as other known, or new, tick-borne pathogens. ? Broader Impacts: This project will employ one postdoctoral researcher, one PhD student researcher and three field assistants, as well as two high-school students from the Yale University Peabody Museum of Natural History Evolutions school program through an after school program for underserved populations with a demonstrated interest in the natural and environmental sciences. Yale undergraduate and Master's of Public Health students will be exposed to the findings ofthe research through Dr. Diuk-Wasser's Eco-Epidemiology course and will be encouraged to pursue undergraduate/MPH theses on different aspects of the project, providing a unique opportunity for bridging ecological and epidemiological concepts. This project will make an important and novel contribution to public health by elucidating the ecological mechanisms of spread and persistence of the human babesiosis and Lyme disease agents. The results from our studies will be disseminated among a wide variety of scientific journals, and will be presented at scientific meetings that target ecologists, evolutionary biologists, mathematical modelers, and public health scientists. The results will also be disseminated widely to popular media outlets through press releases and interviews upon the publication of important findings, as well as through independent organizations, such as the American Lyme Disease Foundation and through the Lyme disease iPhone App. This project will make an important and novel contribution to public health by elucidating ecological mechanisms of persistence and spread of the agents of human babesiosis and Lyme disease. It will help increase public and physician's awareness ofthe emerging risk of babesiosis and the probability of coinfection causing more serious symptoms than either disease alone. Development of a study design and modeling framework for the study of interactions among multiple pathogens will also inform studies of a range of pathogens typically studied in isolation.

Public Health Relevance

Human babesiosis is an emerging tick-borne disease that is potentially fatal and a threat to blood transfusion recipients. Transmitted by the same tick vector as Lyme disease, it follows a similar expansion trajectory from focal areas in the US Northeast and Midwest. We seek to understand the biological processes influencing its expansion to develop more effective'intervention strategies for both diseases.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-IDM-U (55))
Program Officer
Eckstrand, Irene A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Columbia University (N.Y.)
Other Domestic Higher Education
New York
United States
Zip Code
McClure, Max; Diuk-Wasser, Maria A (2018) Climate impacts on blacklegged tick host-seeking behavior. Int J Parasitol :
McClure, Max; Diuk-Wasser, Maria (2018) Reconciling the Entomological Hazard and Disease Risk in the Lyme Disease System. Int J Environ Res Public Health 15:
Tufts, Danielle M; Diuk-Wasser, Maria A (2018) Transplacental transmission of tick-borne Babesia microti in its natural host Peromyscus leucopus. Parasit Vectors 11:286
Rynkiewicz, Evelyn C; Brown, Julia; Tufts, Danielle M et al. (2017) Closely-related Borrelia burgdorferi (sensu stricto) strains exhibit similar fitness in single infections and asymmetric competition in multiple infections. Parasit Vectors 10:64
States, S L; Huang, C I; Davis, S et al. (2017) Co-feeding transmission facilitates strain coexistence in Borrelia burgdorferi, the Lyme disease agent. Epidemics 19:33-42
Walter, Katharine S; Carpi, Giovanna; Caccone, Adalgisa et al. (2017) Genomic insights into the ancient spread of Lyme disease across North America. Nat Ecol Evol 1:1569-1576
Diuk-Wasser, Maria A; Vannier, Edouard; Krause, Peter J (2016) Coinfection by Ixodes Tick-Borne Pathogens: Ecological, Epidemiological, and Clinical Consequences. Trends Parasitol 32:30-42
Walter, Katharine S; Carpi, Giovanna; Evans, Benjamin R et al. (2016) Vectors as Epidemiological Sentinels: Patterns of Within-Tick Borrelia burgdorferi Diversity. PLoS Pathog 12:e1005759
Walter, Katharine S; Pepin, Kim M; Webb, Colleen T et al. (2016) Invasion of two tick-borne diseases across New England: harnessing human surveillance data to capture underlying ecological invasion processes. Proc Biol Sci 283:
Vannier, Edouard G; Diuk-Wasser, Maria A; Ben Mamoun, Choukri et al. (2015) Babesiosis. Infect Dis Clin North Am 29:357-70

Showing the most recent 10 out of 16 publications