What is the most likely etiologic agent in a patient with a 2-week history of progressive weakness, shortness of breath, jaundice, and a recent tick bite, who also has a history of intravenous (IV) drug use and presents with intraerythrocytic organisms on blood smear, elevated liver enzymes, and lactate dehydrogenase levels?

Etiologic Agent: Babesia microti

The most likely etiologic agent is Babesia microti, an intraerythrocytic protozoan parasite transmitted by Ixodes scapularis ticks, which causes the clinical syndrome of babesiosis. 1

Clinical Reasoning

Key Diagnostic Features Present

The patient's presentation is pathognomonic for babesiosis based on the following constellation:

• Intraerythrocytic organisms on blood smear - This is the definitive diagnostic finding for babesiosis, as Babesia parasites invade and replicate within red blood cells 1
• Hemolytic anemia with jaundice (total bilirubin 10, scleral icterus) - Babesiosis causes hemolytic anemia with elevated bilirubin and reticulocyte counts 1
• Markedly elevated LDH (450) - Lactate dehydrogenase elevation reflects ongoing hemolysis, a hallmark of babesiosis 1
• Recent tick bite with erythema migrans-like rash (6 cm circular lesion with clear center on left calf) - Ixodes scapularis ticks transmit both Borrelia burgdorferi (Lyme disease) and Babesia microti, making coinfection common 1
• Progressive symptoms over 2 weeks - The viral infection-like prodrome (fever, weakness) followed by hemolytic complications matches the typical babesiosis timeline 1

Geographic and Epidemiologic Correlation

The fishing trip exposure is critical - babesiosis is endemic in the same geographic regions where Ixodes ticks transmit Lyme disease (New England, North Central states, and northern California) 1. The blacklegged tick (Ixodes scapularis) is the vector for both pathogens 1.

High-Risk Features for Severe Disease

This patient has two major risk factors for severe babesiosis:

• IV drug use history - Immunocompromised patients are at significantly increased risk for severe, potentially fatal babesiosis 1, 2
• Possible transfusion-transmitted infection - IV drug users may have received blood products; transfusion-transmitted babesiosis carries high fatality risk 2, 3

Patients with immune compromise can develop respiratory failure, disseminated intravascular coagulation, congestive heart failure, coma, and renal failure 1. This patient's shortness of breath on exertion suggests early respiratory compromise.

Why Not Other Tick-Borne Diseases?

Human Granulocytic Anaplasmosis (HGA)

• HGA causes intraleukocytic (not intraerythrocytic) organisms - morulae appear in granulocytes, not red blood cells 1
• HGA typically causes leukopenia and thrombocytopenia without significant hemolysis or jaundice 1
• The patient's hemoglobin of 7.5 with marked jaundice points to hemolytic anemia, not HGA 1

Rocky Mountain Spotted Fever (RMSF)

• RMSF does not cause intraerythrocytic organisms on blood smear 1
• RMSF rash appears 2-4 days after fever onset and progresses to involve palms and soles, not a single circular lesion 4, 5
• The 2-week progressive course is too prolonged for untreated RMSF, which causes acute illness 1

Human Monocytic Ehrlichiosis (HME)

• HME causes intramonocytic morulae, not intraerythrocytic organisms 1
• HME is transmitted by Amblyomma americanum (lone star tick), not Ixodes species 1

Critical Management Implications

Immediate Treatment Required

The presence of intraerythrocytic organisms with hemolytic anemia and respiratory symptoms in an immunocompromised patient constitutes severe babesiosis requiring urgent antimicrobial therapy 1:

• Atovaquone 750 mg PO twice daily PLUS azithromycin 500-1000 mg on day 1, then 250 mg daily for at least 7-10 days (standard regimen) 1
• Alternative: Clindamycin 600 mg IV three times daily PLUS quinine 650 mg PO three times daily for severe disease 1
• Immunocompromised patients may require prolonged treatment (weeks to months) until blood smears and PCR are negative 2

Consider Exchange Transfusion

Given the severe anemia (hemoglobin 7.5), high parasitemia (visible on smear), respiratory symptoms, and immunocompromised status, exchange transfusion should be strongly considered 1. This is indicated for patients with severe babesiosis, high parasitemia (>10%), or significant complications.

Evaluate for Coinfection

The circular rash with clear center suggests possible concurrent Lyme disease (Borrelia burgdorferi) 1. However, doxycycline (which treats Lyme disease) is not effective for babesiosis 1. The patient requires babesiosis-specific therapy with atovaquone-azithromycin or clindamycin-quinine, with consideration for adding doxycycline if Lyme disease serology is positive 1.

Common Pitfalls to Avoid

• Do not delay treatment waiting for confirmatory serology - babesiosis serology may be negative early in infection 1
• Do not use doxycycline alone - while it treats HGA and Lyme disease, it has no activity against Babesia 1
• Do not assume mild disease - immunocompromised patients can deteriorate rapidly despite initially appearing stable 1, 2
• Do not miss transfusion history - transfusion-transmitted babesiosis has increased over the past decade and carries high mortality 2, 3