Lyme disease, caused by tick-transmitted bacteria (Borrelia burgdorferi) affects more than 300,000 people annually in North America. Active-duty Service Members in endemic areas such as the northeastern United States and Europe have a high probability of tick exposure and Lyme disease incidence. Persistent musculoskeletal problems observed with some patients who remain undiagnosed and untreated remains a serious concern generally, and for military personnel specifically. An increasingly common tick-transmitted pathogen is Anaplasma phagocytophilum, which causes fever, headache, and aberrations in white blood cell, platelet, and chemistry parameters. In severe cases, infection requires hospitalization and can even result in death. How co-infection with these intracellular bacteria and B. burgdorferi affects the immune response and development of disease is an important and unanswered question. Studies which have been conducted in humans show that co-infected patients experience more symptoms for a longer duration. However, the studies on the impact of co-infection on immune responses (which affect the accuracy of diagnostic tests) and quantifiable measures of disease has not been conducted.

In vitro and animal studies testing co-infection with these two pathogens have shown that the presence of the Lyme disease spirochete can inhibit the host from making antibodies to A. phagocytophilum and that these bacteria, which cause Anaplasmosis, can enhance the permeability of brain blood vessels, potentially allowing more Borrelia spirochetes to enter the central nervous system.

Rationale

Preliminary studies in mice indicate that this co-infection changes the immune response typically induced by each pathogen alone. Given that both infections alone can cause severe disease, the dual infection can have very serious consequences if not diagnosed and treated properly. This proposal addresses a key Focus Areas of the research program, namely (1) Pathogenesis: Tick-borne infections and co-infections (simultaneous or sequential) and their effects on human disease severity, the local and systemic immune response, or pathogen synergy and competition. Our goal is to improve diagnosis, prevention, and treatment by deciphering the specific effects of co-infection in a novel animal model. To achieve this, we will use nonhuman primates as a representative model for humans, comparing immune responses and disease between animals infected with B. burgdorferi, A. phagocytophilum, or both. Thus, we propose the following Aims:

Aim 1: Evaluate differences in the acquired pathogen-specific immune responses in co-infected nonhuman primates versus animals infected with each pathogen individually.

Aim 2: Determine the specific impact of co-infection on levels of B. burgdorferi and A. phagocytophilum in blood and affected tissues, and evaluate subsequent differences in clinical disease and pathology.

These results and this model system can then be utilized for identifying better diagnostic modalities and evaluating new treatments for both the disease and the pathogen. Our findings will inform the medical community and help to guide patient-centered treatment for military Service Members and the American public as a whole.