Intraerythrocytic rings in a patient who has not traveled
A 66-year-old man from coastal Rhode Island presents in July with 5 days of fever to 39.4 °C, profound fatigue, and dark urine. He has not traveled outside New England in 20 years and has an intact spleen. He removed an engorged tick from his calf 3 weeks earlier. Laboratory results: hemoglobin 10.2 g/dL, platelets 88,000/µL, LDH 640 U/L, haptoglobin low, total bilirubin 2.1 mg/dL, creatinine 1.4 mg/dL. A Giemsa-stained thin film shows intraerythrocytic ring forms involving about 1.5% of erythrocytes, with several rings lying outside cells and no pigment visible. A malaria rapid antigen test (HRP2/pLDH) is negative. The requisition did not include a travel history.
1. How do you distinguish the organism on the smear from Plasmodium falciparum, and why is the rapid antigen test negative?
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Morphologic clues favoring Babesia:
- No hemozoin pigment in the rings or in any other stage - Plasmodium trophozoites accumulate pigment.
- Pleomorphic rings of varying size, some very small and delicate.
- Extracellular ring forms are common in babesiosis and uncommon in malaria.
- Absence of any of the P. falciparum-defining forms: no banana-shaped gametocytes, no appliqué forms, no Maurer clefts, no schizonts in a heavy infection.
- Rare tetrad ('Maltese cross') forms, though their absence proves nothing.
Why the antigen test is negative: the device detects Plasmodium HRP2 and pLDH and has no cross-reactivity with Babesia. A negative result in a patient with visible intraerythrocytic parasites and no travel history is a strong hint that the organism is not Plasmodium. It cannot be used to exclude malaria, however, because HRP2-deleted P. falciparum also gives a negative HRP2 line.
The travel history on the requisition is the trap: without it, a laboratorian may report 'ring forms, rule out P. falciparum' and trigger inappropriate therapy.
2. What should the preliminary report say and what confirmatory and clinical steps follow?
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Preliminary report: describe the finding and the differential honestly - 'intraerythrocytic ring forms, approximately 1.5% parasitemia; no pigment seen; morphology suggests Babesia species; malaria cannot be excluded on morphology alone.' Call the provider rather than letting a descriptive report sit in the chart, and state that the malaria rapid antigen test was negative.
Confirmation:
- PCR for Babesia microti/B. duncani (and Plasmodium species) at a reference or public health laboratory; PCR is the most reliable species-level test.
- Serology (IgM and IgG by IFA) supports the diagnosis, though IgG can persist for months and IgM may lag.
- Repeat thin film to follow parasitemia if the patient is treated or deteriorating.
Clinical steps:
- Assess severity: the low platelets, hemolysis, and creatinine of 1.4 raise concern; severe babesiosis is treated with clindamycin plus quinine (or an alternative such as atovaquone plus azithromycin for mild disease).
- If the patient has been transfused, notify the blood center - babesiosis is transfusion-transmissible.
- Counsel that asplenia, older age, and immunosuppression predispose to fulminant disease, and that coinfection with other tick-borne agents (e.g., Borrelia burgdorferi, Anaplasma) should be considered in this exposure setting.