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.

In India, visceral leishmaniasis (VL) caused by Leishmania donovani has been successfully treated with miltefosine with a cure rate of > 90%. To assess the efficacy and safety of oral miltefosine against Brazilian VL, which is caused by Leishmania infantum, a phase II, open-label, dose-escalation study of oral miltefosine was conducted in children (aged 2–12 years) and adolescent-adults (aged 13–60 years). Definitive cure was assessed at a 6-month follow-up visit. The cure rate was only 42% (6 of 14 patients) with a recommended treatment of 28 days and 68% (19 of 28 patients) with an extended treatment of 42 days. The in vitro miltefosine susceptibility profile of intracellular amastigote stages of the pretreatment isolates, from cured and relapsed patients, showed a positive correlation with the clinical outcome. The IC₅₀ mean (SEM) of eventual cures was 5.1 (0.4) µM, whereas that of eventual failures was 12.8 (1.9) µM (P = 0.0002). An IC₅₀ above 8.0 µM predicts failure with 82% sensitivity and 100% specificity. The finding of L. infantum amastigotes resistant to miltefosine in isolates from patients who eventually failed treatment strongly suggests natural resistance to this drug, as miltefosine had never been used in Brazil before this trial was carried out.

Keywords: Kala-azar; Visceral leishmaniasis; Prediction; Mortality; Software

Visceral leishmaniasis (VL) caused by Leishmania infantum is a lethal disease transmitted by sand flies. Although, considered a zoonosis with dogs held as the main reservoirs, humans are also sources of infection. Therefore, control policies currently focused on dog culling may need to consider that VL and human immunodeficiency virus (HIV)/VL patients may also be infectious, contributing to transmission. Reservoir competence of patients with VL without and with HIV infection and of persons asymptomatically infected with Leishmania was assessed by xenodiagnosis with the vector Lutzomyia longipalpis. Parasites in sand fly’s guts were identified by using optical microscopy and by conventional polymerase chain reaction (PCR). Leishmania infantum blood parasite burden was determined by quantitative PCR. Among the 61 participants, 27 (44%) infected sand flies as seen by microscopy or PCR. When infectiousness was assessed by microscopy, xenodiagnosis was positive in five (25%) patients not infected with HIV, whereas nine (45%) of those harboring HIV were positive. Among the 19 asymptomatic patients four (21%) infected sand flies only demonstrated by PCR. One (50%) asymptomatic patient with HIV had a positive xenodiagnosis by microscopy. 9/372 (2.4%) and 37/398 (9.2%) sand flies were infected when feeding in patients without and with HIV, respectively. Infectiousness was poorly correlated with quantitative PCR. The study shows that asymptomatic humans are capable of transmitting L. infantum, that ill persons with HIV infection are more infectious to sand flies, and that humans are more important reservoirs than previously thought. This fact may be considered when designing control policies for zoonotic VL.

Visceral leishmaniasis (VL), a fatal parasitic infection, is categorized as being neglected among tropical diseases. The use of conventional tissue aspiration for diagnosis is not possible in every setting. The immunochromatography-based lateral flow assay (LFA) has attracted attention for a long time due to its ability to give results within a few minutes, mainly in resource-poor settings. In the present study, we optimized and developed the LFA to detect anti-Leishmania antibodies for VL diagnosis. The performance of the developed test was evaluated with serum and urine samples of Indian VL patients and Brazilian sera. The new test exploits well-studied and highly-sensitive purified antigens, LAg isolated from Leishmania donovani promastigotes and protein G conjugated colloidal-gold as a signal reporter. The intensity of the bands depicting the antigen–antibody complex was optimized under different experimental conditions and quantitatively analyzed by the ImageJ software. For the diagnosis of human VL in India, LFA was found to be 96.49% sensitive and 95% specific with serum, and 95.12% sensitive and 96.36% specific with urine samples, respectively. The sensitivity and specificity of LFA were 88.57% and 94.73%, respectively, for the diagnosis of Brazilian VL using patients’ sera infected with Leishmania infantum. LFA is rapid and simple to apply, suitable for field usage where results can be interpreted visually and particularly sensitive and specific in the diagnosis of human VL. Serum and urine LFA may improve diagnostic outcomes and could be an alternative for VL diagnosis in settings where tissue aspiration is difficult to perform.