From Infection to Death: An Overview of the Pathogenesis of Visceral Leishmaniasis

Abstract

Kala-azar, also known as visceral leishmaniasis (VL), is a disease caused by Leishmania infantum and L. donovani. Patients experience symptoms such as fever, weight loss, paleness, and enlarged liver and spleen. The disease also affects immunosuppressed individuals and has an overall mortality rate of up to 10%. This overview explores the literature on the pathogenesis of preclinical and clinical stages, including studies in vitro and in animal models, as well as complications and death. Asymptomatic infection can result in long-lasting immunity. VL develops in a minority of infected individuals when parasites overcome host defenses and multiply in tissues such as the spleen, liver, and bone marrow. Hepatosplenomegaly occurs due to hyperplasia, resulting from parasite proliferation. A systemic inflammation mediated by cytokines develops, triggering acute phase reactants from the liver. These cytokines can reach the brain, causing fever, cachexia and vomiting. Similar to sepsis, disseminated intravascular coagulation (DIC) occurs due to tissue factor overexpression. Anemia, hypergammaglobulinemia, and edema result from the acute phase response. A regulatory response and lymphocyte depletion increase the risk of bacterial superinfections, which, combined with DIC, are thought to cause death. Our understanding of VL’s pathogenesis is limited, and further research is needed to elucidate the preclinical events and clinical manifestations in humans.

Prevalence of hepatitis B and C virus infections among visceral leishmaniasis patients: a systematic review and meta-analysis

“…The risk of HBV and HCV infections in VL is an emerging problem in hepatic tissue that elevates the liver enzymes such as alanine aminotransferase and aspartate aminotransferase and increases the level of bilirubin (Werneck et al, 2003;Endale et al, 2021). A comparable mechanism to explain the liver involvement in viral hepatitis has been suggested by the recognized relationship between hepatic inflammation and the rise of IL-1β, TNF-α, and IL-6 (Costa et al, 2023). This systematic review and meta-analysis was the first to determine the pooled prevalence of HBV and HCV infections in VL patients.…”

Targeting Trypanothione Metabolism in Trypanosomatids

“…These insects typically feed on blood during the night and defecate near the bite wound, enabling the parasite's entry into the body through mucous membranes or breaks in the skin [9]. Once inside the body, the parasite can induce acute symptoms, such as fever, causes systemic symptoms, such as fever, weight loss, anemia, and enlarged organs [42][43][44]. A dermatological complication of visceral leishmaniasis, known as post kala-azar dermal leishmaniasis, can occur in some patients after completion of the treatment [45].…”

Identification of Leishmania donovani PEX5-PTS1 Interaction Inhibitors through Fluorescence Polarization-Based High-Throughput Screening

“…The disease is transmitted through the bite of the female sand fly in the genera of Phlebotomus or Lutzomyia for the New World and the Old World, respectively [5]. The clinical forms depend on the species of Leishmania transmitted by the sand fly in which L. donovani and L. infantum are responsible for VL, and L. major and L. tropica are the main causes for CL [6,7]. Once infected, patients are treated with therapeutic agents such as pentavalent antimony and amphotericin B.…”