Cohabitating in the City: A Case of Hemolytic Anemia in a Patient Coinfected With Babesiosis, Lyme Disease, and Mononucleosis

In the past decades, the number of tick-borne illnesses reported in the United States has increased exponentially, leading to significant human morbidity and mortality. Among tick-borne illnesses, the most frequent in the United States is Lyme, a disease caused by the spirochetal bacteria <i>Borrelia burgdorferi</i>. Coinfection with Lyme disease and <i>Babesia spp. </i>is common among ticks, rodent reservoirs, and human hosts. At an early stage, both Lyme disease and babesiosis present with flu-like symptoms, such as fever, myalgias, fatigue, headache, and malaise. Due to the nonspecific presentation of these diseases and Lyme's cross-reactivity with other viral and bacterial illnesses, there is a broad spectrum of infectious, rheumatologic, and autoimmune differential diagnoses, including Epstein-Barr virus (EBV) infection. Herein, we present the case of a 60-year-old male New Yorker who came to the hospital for nine days of watery diarrhea and recurrent fever. No rash, enthesitis, or joint abnormalities were noted on arrival. Initial lab results and imaging were remarkable for non-autoimmune hemolytic anemia, monocytosis, atypical lymphocytosis, and splenomegaly. Stool cultures and ova-parasites were negative. Treatment with doxycycline and valganciclovir was started, as IgM antibodies were positive for Lyme disease and cytomegalovirus (CMV). Due to worsening symptoms and clinical deterioration, the treatment was broadened with azithromycin and atovaquone, after which the patient experienced significant clinical and paraclinical improvement. Further studies revealed active babesiosis and EBV infection, besides a negative CMV viral load, indicating a false-positive initial result. After finishing treatment for babesiosis and Lyme disease, the patient recovered completely and remains asymptomatic to this day. Diagnosing active babesiosis, Lyme, and EBV coinfection was challenging because of the absence of erythema migrans, lack of apparent tick exposure history, and concerns for cross-reactivity. To the best of our knowledge, this is one of the first cases of coinfection among these three pathogens reported in medical literature.