Be Aware of the Risk of Phlebotominae.

Abstract

To the Editors: We read the retrospective analysis about visceral leishmaniasis (VL) and secondary hemophagocytic lymphohistiocytosis (HLH) described by López et al.1 In our hospital (Meyer Children’s Hospital in Florence, Italy) a cluster of 5 patients in 5 months (November 2021–March 2022) with VL and secondary HLH was recently recorded. Patients’ characteristics are reported in Table 1. TABLE 1. - Patient’ s Characteristics. Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Age (mo) 10 12 18 11 16 Sex (M, F) M M M F F BT (°C) at admission 38.7 38.6 39.4 39.9 40 Splenomegaly + + + + + Blood tests at admission Hb (g/dL) 7.6 7.8 8.3 9.1 10.5 PLTs (×109/L) 66 96 131 229 108 WBC (% N) (×109/L) 3 (10.2) 5.21 (15.1) 4.77 (17.7) 5.36 (6.8) 4.74 (37.4) Ferritin (ng/mL) 1195 1806 6945 7084 4962 Triglycerides (mg/dL) 234 438 269 299 165 ALT (UI/L) 49 71 132 76 59 AST (UI/L) 68 107 253 90 89 CRP (mg/dL) 2.98 6.84 2.63 2.37 4.19 Fibrinogen (mg/dl) 153 204 152 259 219 Timing lat BMA (days after admission; days after onset) (1; 9) (1; 13) (3; 20) (3; 12) NA Leishmania DNA on BMA + NA + + NA Morphology on BMA Hemophagocytosis Hemophagocytosis Hemophagocytosis Hemophagocytosis NA Real-time PCR on blood − + + + + Serological assay for L. + Dubious + + + Fever remission (days after first dose of Lip-Ampho-B; days after admission) 2; 9 4; 7 1; 7 1; 5 3; 5 Length of hospitalization (d) 22 17 8 10 12 Blood tests at discharge Hb (g/dL) 10.1 9.8 9.9 8.1 9 PLTs (×109/L) 363 389 308 404 115 WBC (%N)(x109/L) 8.24 (26.9) 15.88 (38.7) 10.24 (28.8) 13.46 (13.6) 5.48 (28.7%) Ferritin (ng/mL) 15 90 700 832 3812 Triglycerides (mg/dL) 242 137 416 384 310 ALT (UI/L) 34 53 330 50 47 AST (UI/L) 30 41 127 43 94 CRP (mg/dL) <0.29 0.16 0.16 0.15 0.52 Fibrinogen (mg/dL) 136 236 299 242 257 ALT indicates alanine aminotransferase; AST, aspartate aminotransferase; BMA, bone marrow aspiration; BT, body temperature; CRP, C reactive protein; Hb, hemoglobin; NA, not applicable; PLT, platelets; WBC, white blood cells. They were admitted with suspected HLH; meanwhile, infectious tests were ongoing, due to life-threatening clinical conditions, immunosuppressive therapy was started to achieve the control of the fast-evolving HLH. Leishmania was detected by molecular methods in the blood in all patients and in the bone marrow in 3 of them. In addition, 4 of them had a positive serology for Leishmania infantum (determined by chemiluminescence immunoassay). After these positive results, liposomal amphotericin B was started with clinical improvement. VL is endemic in Southern Europe,2 with 50,000–90,000 new cases estimated annually worldwide by the World Health Organization (WHO),2 and nearly, half of the VL cases occur in children.3 The fatality rate of this condition is about 100% within 2 years, if not treated.2 Actually, L. infantum is the one most often associated with VL,4 and it is transmitted through infected phlebotomine sandflies bites.3 VL should be suspected in children with prolonged fever of unknown origin, hepatosplenomegaly and/or pancytopenia.2 Immune response to Leishmania is associated with an interaction of T helper 1-2 cytokines, interferon-gamma, interleukin 4 and 105: this could be explained why leishmaniasis is a cause, although rare in childhood,3 of HLH. The presence of Leishman bodies in the bone marrow or tissue sections as splenic smears of lymph node samples is theoretically the gold standard,5 but to achieve the correct diagnosis also the molecular testing on bone marrow aspiration and/or the blood, along to the detection of antileishmanial antibodies, are recommended.4 To our knowledge, our case series represented the only cluster (5 cases in 5 months) in these last 10 years in Italy, except for another cases series in 20136 in Bologna within a 6-month period (14 patients with VL but only 4 of them presenting HLH), a case report described in Rome3 and other 2 cases described in twins from Germany-Switzerland border, after traveling to Tuscany in 2018.7 Interestingly, a higher prevalence of Leishmania in dogs was recorded in 2021 in Tuscany8 (our patients had reported previously contact with dogs), and an increased number of leishmaniasis (both in adults and in children) was reported to the Tuscany Public Health Services in 2021 (personal communication). This epidemiologic link suggests that close monitoring of Leishmaniasis cases is necessary to understand the epidemiologic situation of each country, with the aim to implement prevention strategies. Moreover, considering the risk of VL in travelers to Southern Europe is pivotal to increase awareness not only among local physicians but also globally to avoid misdiagnosis in nonendemic countries. In conclusion, due to its high fatality rate, prompt diagnosis and early appropriate treatment has crucial importance and a multidisciplinary approach is pivotal to obtaining a full recovery.