Dear Editor,

Babesiosis is a tick-borne zoonosis caused by intra-erythrocytic protozoa. In Europe, it is probably underdiagnosed [1,2,3,4]. Symptoms can range from a mild flu-like disease to rapid death in immunocompromised patients.

We report here on a 52-year-old splenectomized male, with a medical history including T cell large granular lymphocytic leukemia (T-LGL), cyclic neutropenia, idiopathic trombocytopenic purpura, hypogammaglobulinemia, bouts of hemolytic anemia, and treatment with rituximab 2 years earlier. The patient was admitted to the Department of Hematology in March 2015 due to fever, muscle pain, and dark urine (not unusual as his hemolytic anemia often exacerbated during unspecific infections). His medication consisted of cyclosporine 150 mg/day, prednisolone 10 mg/day, human immunoglobulin 25 g i.v./4th week, fluconazole 100 mg/day, co-trimoxazole 1600 mg/320 mg twice weekly, and valaciclovir 100 mg/day. A bone marrow examination showed a few phagocytosing macrophages and monocytosis. A tentative diagnosis of hemophagocytic syndrome was entertained with supporting laboratory evidence including elevated triglycerides, ferritin, and soluble interleukin-2-receptor (Table 1). The patient was given cefotaxime i.v., became afebrile and was discharged. In April, he was readmitted with fever and became spontaneously afebrile within a few days without any specific treatment. In May, he was admitted again because of fever with rigors, this time to the Department of Infectious Diseases. Laboratory investigations revealed a similar picture as on the admission in March. A laboratory technician in the Department of Clinical Chemistry reviewed the white blood cell smear microscopically at 4th of May since the instrument gave an automatic alarm concerning the shape of some of the white cells. She noticed piriform inclusions in the erythrocytes (Fig. 1) and we found 4% Babesia parasites. Serology [2] was negative for B. microti IgG/IgM and B. divergens IgM and positive for B. divergens IgG (1:128). Molecular characterization [2, 5] with PCR and sequencing (18S rRNA) identified B. venatorum.

Table 1 Laboratory investigations in relation to admissions and treatments (reference values in parenthesis)
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Fig. 1
figure 1

A blood smear (×100 magnification under oil) from 4th of May showing red blood cells infected with Babesia parasites. Arrow (1) indicates a red blood cell containing both pear-shaped and round forms; (2), (3), and (5) show typical paired pear-shaped forms; (4) shows a round form of parasite. The solid, black arrow indicates a Howell Jolly body

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The patient was put on quinine and clindamycin for 1 week and quickly became afebrile. He was discharged with azithromycine and atovaquone for a further 5 weeks. He has been well since then.

Retrospectively, saved thin blood films and a bone marrow smear were re-evaluated. Although parasites were found on all blood slides, and in the bone marrow smears made 2 months earlier, he did not develop severe disease, perhaps due to the prophylactic administration of co-trimoxazole. This drug is not a first line agent but has been used anecdotally in severe Babesia infections [6]. The hemolysis and thrombocytopenia resolved at the first admission in March during treatment with cefotaxim. However, in April, there was a similar resolution without any new therapy. This fluctuation in parasitemia for several months may partly represent the natural course of a Babesia infection but could also be due to the injections with human immunoglobulin (for dates, see Table 1). As up to 50% of tick-infested individuals, the patient could not recall a recent tick-bite. We assume, however, that the infection originated from such a bite that went unnoted. More than 2 years had passed since his last blood transfusion, and in the meantime he recalled no history of recurrent fever.

A tentative diagnosis of hemophagocytic syndrome was first entertained as the patient fulfilled the criteria. Babesia infection with a reactive hemophagocytosis has been reported earlier but only in B. microti infection [7,8,9] and not in B. venatorum infection.

In Sweden, this is the first PCR-confirmed case of B. venatorum, although in ticks, all three Babesia spp. known to be pathogenic for humans (B. divergens, B. venatorum, B. microti) are present [10].