Visceral Leishmaniasis in Liver Transplant Recipients From an Endemic Area

Visceral leishmaniasis (VL) is a parasitic infection generally caused by the Leishmania donovani complex, and in Brazil by Leishmania chagasi. Every year, half a million new cases are diagnosed worldwide, and five countries—Nepal, Bangladesh, Brazil, India, and Sudan—account for up to 90% of cases (1, 2). Although considered a rare disease among transplant recipients, the number of reported cases has increased over the last two decades (3). VL diagnosis should also be considered in transplant recipients from nonendemic areas, in view of increasing migration and the globalized world. We report three cases of VL in liver transplantation (LT) recipients in a single center from Brazil. Hospital records of 595 patients who underwent LT from September 1994 to December 2009 at the Federal University Hospital of Minas Gerais, Brazil, were reviewed. Three of the 595 liver transplanted patients were diagnosed with VL. Their detailed clinical characteristics are shown in Table 1.TABLE 1: Clinical features of three patients with VL diagnosed after liver transplantationA case is defined as the presence of Leishmania amastigotes in bone marrow aspirate or specimens of other reticuloendothelial system organs in patients with symptoms consistent with VL. The typical clinical picture is characterized by fever, splenomegaly, weight loss, blood cytopenia, and hypergammaglobulinemia (2, 4). All patients presented with fatigue, pancytopenia, and hypergammaglobulinemia, and two patients had fever and splenomegaly. Diagnosis was established by the presence of Leishmania amastigotes in bone marrow aspirate (Fig. 1) in all cases. Initial therapy was amphotericin B deoxycholate, which caused nephrotoxicity in all three patients and was replaced by liposomal amphotericin B. Immunosuppression was reduced once the VL diagnosis was established, and maintained at the lowest possible level for a few months. Two patients are alive and free of disease. The other patient is alive but experienced a VL relapse; he was retreated with liposomal amphotericin B and has continued on monthly secondary prophylaxis (3 mg/kg/monthly).FIGURE 1.: (A) Leishmania amastigotes within reticular cell (magnification ×400). (B) Free Leishmania amastigotes and amastigotes within cells in bone marrow aspiration (magnification ×100), immersion (hematoxylin-eosin).VL infection in transplant recipients may occur in four ways: (1) the recipient may be infected by the graft; (2) by transfusion; (3) a previously infected recipient may reactivate a latent infection; and (4) immunosuppressed patients may develop de novo infections (3, 5). Because specific antibody responses are not protective (6), suppression of the T-cell host response after organ transplantation may reactivate a latent VL infection. In the present series, it was not possible to identify the way of transmission. The rising number of transplants, including in VL-endemic regions, justifies the increasing interest in such a neglected disease. Timely diagnosis followed by prompt treatment can have an impact on the high lethality rates (3). Until now, only 10 cases of VL in LT recipients have been described, one of them by our group (7–14). Cases are probably underestimated by misdiagnosis. Given that the liver is a reticuloendothelial organ preferentially affected by the protozoan, the risk of transmission through the graft may be greater than in other transplants. Transplanted patients should benefit from lipid formulations as of the beginning of treatment, because immunosuppressive drugs are also nephrotoxic and renal dysfunction is frequent. Cure is generally defined by clinical and hematological criteria (resolution of fever, hepatosplenomegaly, and pancitopenia). Follow-up is recommended for 6 months after treatment (15, 16). Although some authors also consider negative bone marrow biopsies or aspirate cultures after treatment (17), these are invasive procedures and absence of parasites does not define resolution or exclude relapse (18). VL cure rates after amphotericin treatment in transplanted patients are approximately 80%. However, relapse may occur in up to 35% of the cases, associated to poor prognosis (13). One described patient, despite adequate treatment, presented a relapse 5 months after amphotericin discontinuation. He was then retreated and remains on secondary prophylaxis with monthly liposomal amphotericin. Some studies have shown that secondary prophylaxis may prevent a VL relapse, but they were carried out in HIV patients (18, 19). The evidence of this recommendation in transplanted patients is not yet established, but it should be considered in those who relapse. Asymptomatic infection (from donors or recipients) in the pretransplant phase could facilitate the suspicion of VL after LT in the presence of certain symptoms (19). We do not perform VL serology routinely for screening liver donors and recipients before transplant, but this is the matter of an ongoing research project. At present, if recipients or donors have a positive result, we perform a stricter follow-up with a lower threshold of suspicion for VL. In conclusion, VL is a potential infectious complication in liver transplanted patients, mainly in endemic areas, and probably remains underestimated and underdiagnosed in these patients. Prompt diagnosis and treatment are essential to reduce lethality. Wanessa T. Clemente1,2,3,4 Luciana C. Faria4,5 Roberta M. C. Romanelli2,6 Stella S. S. Lima1,2 Juliane Raquel G. Cortes2 Ana Paula P. Oliveira2 Andréa L. Carvalho6,7 Alexandre R. Ferreira4,6 Agnaldo S. Lima4,8 1 Infection Control Committee Hospital das Clínicas/UFMG 2 Study and Research Group on Health Care and Hospital Epidemiology- Associated Infections (GREPI) 3 Laboratory Medicine Department Medical School UFMG 4 Alpha Institute of Gastroenterology – Liver Transplant Unit Hospital das Clínicas/UFMG 5 Department of Internal Medicine Medical School UFMG 6 Department of Pediatrics Medical School UFMG 7 Orestes Diniz Training and Referral Infectious Diseases Center 8 Department of Surgery Medical School UFMG UFMG – Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

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