ABSTRACT

Objective

Visceral leishmaniasis (VL), kala-azar, is a zoonotic parasitic infection caused by particular Leishmania species, which is transmitted to humans by infected female sandflies of the genus Phlebotomus. Infected sandflies spread it, and it is commonly observed in tropical and subtropical regions such as North Africa, South America, and East Asia (1). The onset of symptoms is generally subacute, insidious, and slowly progressive, rarely acute. Clinical findings include fever, weight loss, splenomegaly, hepatomegaly, pancytopenia (more frequently anemia and thrombocytopenia), elevated liver enzymes, and hypoalbuminemia. The most serious, potentially fatal complications of VL are disseminated intravascular coagulation and hemophagocytic lymphohistiocytosis (HLH). Diagnosis in a child clinically suspected of VL (fever with splenomegaly, hepatomegaly, weight loss, pancytopenia, and hypergammaglobulinemia or laboratory findings such as hemophagocytic syndrome) is confirmed by direct demonstration of Leishmania in tissue samples or cultures, or through serological tests (2). Migration, wars, economic difficulties, long journeys, and social or cultural influences facilitate the emergence and spread of infectious diseases (3). VL treatment is challenging due to factors including drug toxicity, resistance, epidemiological variability, and, importantly, a lack of evidence-based data for the pediatric population (4). Our case series underscores the need for further research to improve the understanding and management of VL in pediatric patients.

Materials and Methods

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Results

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Conclusion

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KEYWORDS

Hemophagocytic lymphohistiocytosis, pediatric, visceral leishmaniasis

INTRODUCTION

Visceral leishmaniasis (VL), kala-azar, is a zoonotic parasitic infection caused by particular Leishmania species, which is transmitted to humans by infected female sandflies of the genus Phlebotomus. Infected sandflies spread it, and it is commonly observed in tropical and subtropical regions such as North Africa, South America, and East Asia (1). The onset of symptoms is generally subacute, insidious, and slowly progressive, rarely acute. Clinical findings include fever, weight loss, splenomegaly, hepatomegaly, pancytopenia (more frequently anemia and thrombocytopenia), elevated liver enzymes, and hypoalbuminemia. The most serious, potentially fatal complications of VL are disseminated intravascular coagulation and hemophagocytic lymphohistiocytosis (HLH). Diagnosis in a child clinically suspected of VL (fever with splenomegaly, hepatomegaly, weight loss, pancytopenia, and hypergammaglobulinemia or laboratory findings such as hemophagocytic syndrome) is confirmed by direct demonstration of Leishmania in tissue samples or cultures, or through serological tests (2). Migration, wars, economic difficulties, long journeys, and social or cultural influences facilitate the emergence and spread of infectious diseases (3). VL treatment is challenging due to factors including drug toxicity, resistance, epidemiological variability, and, importantly, a lack of evidence-based data for the pediatric population (4). Our case series underscores the need for further research to improve the understanding and management of VL in pediatric patients.

MATERIALS AND METHODS

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RESULTS

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DISCUSSION

Leishmania infection can present in three forms: Cutaneous, mucocutaneous, and visceral. VL has the highest mortality rate, especially in Southeast Asia, where the visceral form is endemic. While the cutaneous and mucocutaneous forms are more common in the Mediterranean region, VL cases have also been reported(1). It may be asymptomatic or may lead to different clinical conditions that may lead to mortality. Initial symptoms usually include fever, weight loss, and splenomegaly (5). The reticuloendothelial system is most frequently affected. The parasite proliferates in the reticuloendothelial system, leading to bone marrow suppression, hemolysis, splenic sequestration, and liver dysfunction. This situation may cause patients to receive different diagnoses, such as aplastic anemia, as in our fourth case. The clinic is mostly similar to hematological malignancies as in our cases. Diagnosis may be delayed due to lack of specific findings. HLH is a life-threatening syndrome caused by excessive activation of the macrophage-monocyte-histiocyte system or failure to down-regulate cytokine-secreting immune cells. Secondary HLH due to VL is a rare complication in the literature that presents diagnostic and therapeutic challenges. The clinical picture of VL overlaps with HLH. Early diagnosis and prompt treatment are essential in children to reduce severe complications, such as secondary HLH and the need for blood transfusions(6). Diagnosis requires clinical suspicion and pathogen isolation, commonly from bone marrow aspiration material, using histopathological, molecular methods or culture. In the review published by Scalzone et al., it was noted that six of the 50 cases of HLH secondary to Leishmaniasis reported died due to late diagnosis and hemorrhagic-infectious complications, which is similar to our patient. In some cases reported in the publication, diagnosis was delayed due to negative bone marrow and Leishmania antibodies in early stages(7). Therefore, repeating the tests in endemic areas and in patients with clinical suspicion may help prevent mortality. In addition to bone marrow, samples from other affected tissues can be used for diagnosis (8). While paramomycin, miltefosine, and sodium stibogluconate can be used in treatment, liposomal amphotericin B is the most effective agent(9). The commonly used regimen involves administering liposomal amphotericin B intravenously on days 1 and 5 and on days 14 and 21 to reach a total dose of 20-21 mg/kg. In the United States, liposomal amphotericin B is used for seven days (10,11). All our patients were treated with liposomal amphotericin B. In line with the literature, fever subsided within one to two weeks, weight gain was achieved within a month, and spleen size decreased in three patients(12). However, one patient, initially treated at a local hospital for HLH without success, was diagnosed with VL and subsequently developed VL-associated HLH. Liposomal amphotericin B treatment was started, but the patient passed away. Another patient, previously diagnosed with aplastic anemia in their country, was diagnosed with VL, and hematological parameters were normalized after treatment.

CONCLUSION

Due to the geographical location of our country, VL should be considered in patients presenting with fever, hepatosplenomegaly, and cytopenia or pancytopenia. Delays in diagnosis and treatment may lead to mortality. Since the disease can present with various clinical manifestations, it is essential to thoroughly evaluate the patient’s history and to include Leishmaniasis in the differential diagnosis.

REFERENCES