Tick-borne diseases, including Lyme disease caused by Borrelia burgdorferi and babesiosis caused by Babesia microti, are increasingly reported in the northeastern United States, with New York and Pennsylvania being high-incidence states ^[4,5]. Pennsylvania reported an age-adjusted Lyme disease incidence of 67.8 cases per 100,000 in 2022, while New York has seen rising cases of babesiosis, surpassing other tick-borne illnesses except Lyme ^[6,7]. Co-infections with Babesia and Borrelia are common due to shared Ixodes scapularis vectors, occurring in up to one-fifth of Lyme cases and often leading to more severe symptoms and prolonged illness ^[1,8]. Typical babesiosis presents with flu-like symptoms, hemolytic anemia, and elevated liver enzymes, but severe cases can involve multi-organ failure, particularly in older or comorbid patients ^[3,9]. Neurological manifestations, such as depressive mood, are rare and more commonly associated with Lyme disease, making this co-presentation unique ^[2,10]. We describe a case from Middletown, New York, highlighting rapid progression to hemolytic anemia with hepatobiliary involvement and neuropsychiatric symptoms, adding to the literature on atypical co-infections^[11].

A 65-year-old male from Middletown, New York, with a past medical history of chronic hypertension, overweight (BMI 28.5), prediabetes, and osteoarthritis of the lumbar spine, presented on August 8, 2025, with symptoms of upper respiratory infection including headache, fatigue, burning eyes, body aches, fever (102.3°F), and posterior pharyngeal erythema with bilateral cervical lymphadenopathy. Rapid tests for streptococcus, influenza, and COVID-19 were negative. No tick bite was recalled, but the patient reported travel to Pennsylvania two weeks prior, with symptom onset shortly after return.

On August 13, 2025, after one week of illness, empirical doxycycline was initiated for suspected tick-borne disease. On August 14, 2025, the patient returned with worsening symptoms: abdominal pain, bloating, fever, chills, night sweats, clear nasal discharge, sneezing, myalgias (right knee and lower back pain), headache, and depressed mood. Physical examination revealed unspecified leukocytosis from prior records. Urinalysis showed hematuria (blood +++) and icterus. Glycated hemoglobin (HbA1c) was 6.5%, confirming prediabetes, and triglycerides were elevated at 321 mg/dL. Electrocardiogram demonstrated sinus rhythm with a heart rate of 94 bpm and a PR interval 128 ms.

A tick-borne disease acute molecular panel confirmed Babesia microti DNA detection via real-time PCR, while Anaplasma phagocytophilum, Ehrlichia chaffeensis, Borrelia miyamotoi, and Borrelia species were not detected. Lyme serology showed elevated IgM (0.91, reference 0.00-0.80) and normal IgG (0.22, reference 0.00-0.80). Western blot revealed IgG bands present for p83/93, p66, p41, and p39 kDa, but absent for others, with overall interpretation negative. IgM showed p41 present, others absent, and also negative.

Laboratory findings indicated hemolytic anemia, hepatobiliary dysfunction, and mild renal involvement, as summarized in Tables 1-3. Unique features included rapid hemolytic anemia with significant bilirubin elevation and LDH surge, suggestive of intraerythrocytic hemolysis, alongside prominent depressive mood—potentially indicating early neurological involvement from co-infection—and abdominal pain possibly due to splenic congestion or micro-infarcts, a rare complication in babesiosis ^[12,13]. The patient was switched to atovaquone plus azithromycin for babesiosis, with continued doxycycline for early Lyme, leading to symptom resolution over two weeks.

Table 1: Liver Function Tests and Lipid Profile

NR: Not Reported

Table 2: Renal Function Tests

Table 3: Complete Blood Count and Differential

Table 4: Tick-Borne Testing

This case illustrates a co-infection of Babesia microti and early Lyme disease in an endemic region, with travel history to Pennsylvania aligning with high tick activity areas ^[4,14]. Co-infections exacerbate symptoms, as seen in prior reports where babesiosis with Lyme leads to severe hemolytic anemia and prolonged fatigue ^[1,11,15]. The patient’s rapid drop in hemoglobin (from 13.7 to 10.1 g/dL) and elevated LDH (607 U/L) reflect hemolytic processes typical of babesiosis, but the degree of hepatobiliary involvement (alkaline phosphatase 163 U/L, GGT 78 U/L, bilirubin 2.3 mg/dL) is notable, potentially amplified by co-infection ^[3,16].

Unique to this case is the prominent depressive mood alongside headache, suggesting neurological involvement rarely reported in babesiosis, more akin to Lyme neuroborreliosis or co-infection effects^[2,10]. Abdominal pain and bloating may indicate splenic involvement, a rare complication including infarction or rupture, reported in severe cases ^[12,13]. Initial doxycycline treatment, effective for Lyme but not babesiosis, likely contributed to delayed resolution, highlighting diagnostic pitfalls [17]. Comorbidities like prediabetes and hypertriglyceridemia may have predisposed to severity, though not directly linked in the literature ^[18]. The rarity of this case—co-infection with neuropsychiatric and possible splenic features—adds to the spectrum of presentations, urging prompt PCR testing in suspicious cases ^[19,20].

This rare case of Babesia-Lyme co-infection demonstrates the potential for atypical manifestations, including depressive mood and hepatobiliary prominence, in older patients from endemic areas. Early recognition and targeted therapy are crucial to prevent complications. Further studies on neuropsychiatric features in babesiosis are warranted.

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