Background: Parasites of theLeishmaniagenus alternate between the flagellated extracellular promastigote stage and intracellular amastigotes. Here we report the characterization of aLeishmaniaisolate, obtained from a cutaneous leishmaniasis patient, which presents peculiar morphological features.Methods: The parasite was culturedin vitroand characterized morphologically using optical and electron microscopy. Identification was performed based on monoclonal antibodies and internal ribosomal spacer typing.In vitromacrophage cultures, murine experimental models and sand fly infections were used to evaluate infectivityin vitroandin vivo.Results: The isolate was identified asLeishmania(Viannia)braziliensis. In the atypical promastigotes grown in culture, a short flagellum surrounded or interrupted by a protuberance of disorganized material was observed. A normal axoneme was present close to the basal body but without elongation much further outside the flagellar pocket. A disorganized swelling at the precocious end of the axoneme coincided with the lack of a paraflagellar rod structure. The isolate was able to infect macrophagesin vitro, induce lesions in BALB/c mice and infectLutzomyia longipalpis.Conclusions: Notwithstanding the lack of an extracellular flagellum, this isolate infects macrophagesin vitroand produces lesions when inoculated into mice. Moreover, it is able to colonize phlebotomine sand flies. Considering the importance attributed to the flagellum in the successful infection and survival ofLeishmaniain the insect midgut and in the invasion of macrophages, these findings may bring new light into the infectious mechanisms ofL. (V.)braziliensis.

Infection with Leishmania amazonensis and L. mexicana may lead to diffuse cutaneous leishmaniasis. The cure is exceptional, especially for the strange case of this lady. Case report: The patient acquired the disease in childhood and remained with lesions for over 30 years, albeit several treatments. She worsened after a pregnancy, developing disseminated lesions. Miltefosine with amphotericin B and pentamidine resulted in remission. Lesions reappeared after one year, accompanied by intra-nasal infiltration of the disease. The nasal spraying of a single ampoule of pentavalent antimoniate resulted in the sustained disappearance of the nasal symptoms and all the cutaneous lesions. After over eight years, she remains disease-free, albeit under renal replacement therapy. The high nasal mucosal antimonial concentration may explain the long-lasting cure via new MHC class I epitope-specific CD8+ cell clones against L. amazonensis present in the nasal mucosa.

Background: Leishmania amazonensis, one of the causative agents of cutaneous leishmaniasis, is responsible for a neglected tropical disease affecting nearly one million individuals worldwide. Although clinical treatments are available, their effectiveness is often compromised by high toxicity and limited selectivity. Methods: From a database, 64 chalcone derivatives were studied using Comparative Molecular Similarity Indices Analysis (CoMSIA) and Hansch analysis (2D-QSAR) to construct predictive computational models. Internal and external validation criteria were applied to identify structural determinants associated with antileishmanial activity. Based on these insights, twelve novel quinoline–chalcone hybrids were designed, synthesized, and biologically evaluated against L. amazonensis. Results: The most robust CoMSIA model combined steric and hydrogen-bond acceptor fields (CoMSIA-SA), while Hansch analysis highlighted electronic descriptors—specifically LUMO energy and the global electrophilicity index—as critical for parasite growth inhibition. Guided by these computational findings, a new series of 12 hybrid quinoline–chalcone derivatives (E001–E012) was synthesized through a two-step procedure, achieving overall yields of 43–71%. Biological assays demonstrated that four compounds displayed inhibitory activity comparable to amphotericin B. Furthermore, physicochemical profiling and in silico pharmacokinetic predictions for the most active compounds (E003, E005, E006, and E011) indicated favorable biocompatibility and drug-like properties. Conclusions: These results underscore the value of an integrative computational–experimental approach in the rational design of next-generation L. amazonensis inhibitors, reinforcing chalcone-based scaffolds as promising pharmacophoric frameworks for antileishmanial drug discovery.

Visceral leishmaniasis (VL) results from protozoa Leishmania infantum and L. donovani infection. This study investigated whether host factors would explain the relapses. First, susceptibility to amphotericin B of L. infantum isolates was evaluated in vitro. Then, clinical data and the lipid profile of patients with relapsing and non-relapsing VL were assessed. Susceptibility to amphotericin B was similar between the isolates. CD4+ lymphocytes were reduced in both groups of patients in the first episode and with relapsing VL. Still, the strongest blood cell indicator associated with relapses was low total lymphocyte counts. Total plasma cholesterol, high-density lipoprotein, low-density lipoprotein, and, uniquely, triglycerides of the six individuals in the first episode and twenty-three with relapsing VL were lower in relapsing patients than those in the first episode. Deceased patients had extremely low low-density lipoprotein. After CD4+ decreases, lymphocyte CD8+ reduction is the final stage of immunological failure. The lower lipid concentrations appear to be secondary to the depletion of fat stores by inflammation-induced cachexia and fat exhaustion provoked by the co-occurrence of both diseases, which can finally lead to death.

Visceral leishmaniasis (VL) results from infection by the protozoa Leishmania infantum and L. donovani. HIV-coinfected patients may have a relapsing course of VL, even after secondary prophylaxis with amphotericin B. This study investigated whether host factors would explain the relapses. First, susceptibility to amphotericin B of L. infantum isolates was evaluated in vitro. Then, clinical data and the lipid profile of patients with relapsing and non-relapsing VL were assessed. Susceptibility to amphotericin B was similar between the isolates. CD4+ lymphocytes were reduced in both patients in the first episode and with relapsing VL. Still, the strongest blood cell associated with relapses was low total lymphocyte counts. Total plasma cholesterol, high-density lipoprotein, low-density lipoprotein, and, uniquely, triglycerides of the six individuals in the first episode and 23 with relapsing VL were lower in relapsing patients than those in the first episode. Deceased patients had extremely low, low-density lipoprotein. After CD4+ decrease, lymphocyte CD8+ reduction seem to be the final stage of the immunological failure. The lower lipid concentrations appear to be secondary to the depletion of fat stores by inflammation-induced cachexia provoked by the co-occurrence of both diseases, which can finally lead to death.