In September 2016, a 60-year-old male Austrian patient presented at the Department of Internal Medicine, Medical University of Graz, Graz, Austria, with a three-week history of fever of unknown origin, fatigue, and unintentional weight loss of 6 kg. Initial physical examination was inconspicuous. Concomitant diseases were adequately treated diabetes mellitus type 2 and hypothyroidism. Travel history revealed a two-week trip to the south of Crete in September 2015 and a two-week trip the south of Spain in May 2016.
Laboratory parameters showed elevated C-reactive protein (CRP) ranging between 94.2 and 188.9 mg/L (normal range 0-5 mg/L), slight hypochromic, normocytic anemia without signs of hemolysis (hemoglobin 12.5 g/dL), mild thrombopenia (127,000/muL; normal range 140,000-440,000/muL) and a discreetly elevated gamma-glutamyltransferase (GGT) but were otherwise inconspicuous. The soluble interleukin 2-receptor (IL-2R) was elevated (5156.1 pg/mL, reference range 458.0-1997.0). Chest X-ray, urine analysis, abdominal sonography, transthoracic as well as transoesophageal echocardiography showed no focus of infection but revealed splenomegaly (7.2 x 16.4 cm). Serial blood cultures were negative, as were tests for influenza (negative PCR), other viral infections (negative IgM antibody test for Puumala, Dobrava, and Hantaan virus, negative PCR for cytomegalovirus and Epstein-Barr virus), leptospirosis (negative antibody test), malaria (negative blood smear), tuberculosis (negative interferon-gamma release assay), and human immunodeficiency virus (HIV) (negative antibody).
Empiric antibiotic therapy with initially ampicillin/sulbactam and later piperacillin/tazobactam plus vancomycin did not lead to improvement. Interestingly, in the course of the following 3 weeks, discrete bicytopenia turned into severe pancytopenia requiring blood transfusions. Lactate dehydrogenase (LDH), initially normal, increased to 1107 U/L (reference range 120-240). Liver enzymes including GGT, alkaline phosphatase (AP), aspartate transaminase (AST) also increased. Fever persisted with levels up to 40 C.
Positron emission tomography-computed tomography (see Fig. 1A and B) showed tracer enhancement in the central and peripheral bone marrow. Bone marrow biopsy revealed microorganisms within macrophages (Fig. 2). PCR from peripheral blood and bone marrow confirmed infection with Leishmania donovani. Therapy with liposomal amphotericin B was initiated, causing rapid cessation of fever and a significant drop in CRP levels within days. Blood count ameliorated rapidly, and transfusions were no longer required. After release from hospital, regular follow-up visits at the outpatient clinic ensued. Until today, VL has not recurred.