Transgenic T cell-specific expression of CXCR3 enhances splenic and hepatic T cell accumulation but does not affect the outcome of visceral leishmaniasis.

The outcome of visceral leishmaniasis, caused by parasite Leishmania donovani, depends on the recruitment of leishmanicidal Th1 cells. Chemokine receptor CXCR3, preferentially expressed by Th1 cells, is critical for migration of these T cells during infection. During chronic VL, there is a decrease in the presence of CXCR3-expressing CD4+ T cells in the spleen, which is associated with high parasitic burden in this organ. We therefore examined whether T cell-specific expression of CXCR3 in mice (CXCR3Tg) would promote resistance to VL. L. donovani infected CXCR3Tg mice showed increased accumulation of T cells in the spleens compared to WT littermates (CXCR3+/+). However, CXCR3+ T cells from CXCR3Tg mice showed low CD69 expression and these mice developed fewer granulomas. Additionally, both groups of mice showed similar cytokine profiles and parasitic burdens during the course of infection. In summary, although T cell-specific expression of CXCR3 promoted the accumulation of CXCR3-expressing T cells during L. donovani infection, this did not enhance resistance to VL.

Oral Efficacy of a Diselenide Compound Loaded in Nanostructured Lipid Carriers in a Murine Model of Visceral Leishmaniasis.

Leishmaniasis urgently needs new oral treatments, as it is one of the most important neglected tropical diseases that affects people with poor resources. The drug discovery pipeline for oral administration currently discards entities with poor aqueous solubility and permeability (class IV compounds in the Biopharmaceutical Classification System, BCS) such as the diselenide 2m, a trypanothione reductase (TR) inhibitor. This work was assisted by glyceryl palmitostearate and diethylene glycol monoethyl ether-based nanostructured lipid carriers (NLC) to render 2m bioavailable and effective after its oral administration. The loading of 2m in NLC drastically enhanced its intestinal permeability and provided plasmatic levels higher than its effective concentration (IC50). In L. infantum-infected BALB/c mice, 2m-NLC reduced the parasite burden in the spleen, liver, and bone marrow by at least 95% after 5 doses, demonstrating similar efficacy as intravenous Fungizone. Overall, compound 2m and its formulation merit further investigation as an oral treatment for visceral leishmaniasis.

Clinical and laboratory alterations in dogs naturally infected by Leishmania chagasi / Alterações clínicas e laboratoriais em cães naturalmente infectados por Leishmania chagasi

INTRODUCTION: Canine visceral leishmaniasis (CVL) is a zoonotic disease with different clinical manifestations. Parasitism often occurs in bone marrow, but changes have been observed in peripheral blood and serum biochemical parameters. The aim of this study was to evaluate the hematological and biochemical parameters in dogs naturally infected by Leishmania chagasi. METHODS: Eighty-five adult dogs of both sexes and various weights and ages from the Zoonosis Control Center of Fortaleza (CCZ) were used, selected by immunofluorescence assay (IFA) and considered positive with IFA titers greater than 1:40 and by visualizing amastigotes of Leishmania chagasi in smears obtained by bone marrow aspiration. The dogs (n = 85) were grouped according to clinical signs: negative (CN = 7), subclinical (CS = 10), and clinical (CC = 68). Blood samples were collected for determination of hematological and biochemical serum values. The experimental protocol was approved by the CEUA/UECE. RESULTS: The most frequent clinical signs were cachexia (77.9 percent), keratitis (61.8 percent), and lymphadenopathy (55.9 percent), and 86.8 percent of the animals showed more than one clinical sign characteristic of CVL. In CC were observed reductions in red blood cells (63 percent), hematocrit (72 percent), and hemoglobin (62 percent), as well as leukocytosis (33 percent), neutropenia (28 percent), thrombocytopenia (50 percent), uremia (45 percent), hyperproteinemia (53 percent, p<0.05), hypergammaglobulinemia (62 percent, p<0.01), and hypoalbuminemia (58 percent). CONCLUSIONS: Animals with the clinical form of the disease demonstrate hematological and biochemical changes consistent with anemia, uremia, hyperproteinemia, and hyperglobulinemia, which present themselves as strong clinical markers of visceral leishmaniasis associated with the signs previously reported.

INTRODUÇÃO: A leishmaniose visceral canina (LVC) é uma zoonose com diferentes manifestações clínicas. O parasitismo ocorre frequentemente na medula óssea e têm sido relatadas alterações hematológicas e bioquímicas. Objetivou-se avaliar os parâmetros clínicos, hematológicos e bioquímicos de cães naturalmente infectados por Leishmania chagasi. MÉTODOS: Utilizaram-se 85 cães adultos, ambos os sexos, peso e idade variados, oriundos do Centro de Controle de Zoonoses de Fortaleza, selecionados pela reação de imunofluorescência indireta (RIFI), sendo considerados positivos os animais com títulos de RIFI > 1:40 e pelo exame parasitológico das formas amastigotas de Leishmania chagasi em esfregaços de medula óssea. Os cães foram agrupados conforme os sinais clínicos associados à doença: negativos (CN=7); subclínicos (CS=10) e clínicos (CC=68). Amostras de sangue foram coletadas para determinação dos parâmetros hematológicos e bioquímicos séricos. O protocolo experimental foi aprovado pelo CEUA/UECE, protocolo n° 08622833-1. RESULTADOS: Os sinais clínicos mais frequentes foram caquexia (77,9 por cento), ceratoconjuntivite (61,8 por cento) e linfadenopatia (55,9 por cento), sendo que 86, 8 por cento dos animais apresentaram mais de um sinal clínico característico de LVC. Em CC foram observadas reduções nas hemácias (63 por cento), hematócrito (72 por cento) e hemoglobina (62 por cento), leucocitose (33 por cento), neutropenia (28 por cento), trombocitopenia (50 por cento), uremia (45 por cento), hiperproteinemia (53 por cento, p<0,05), hiperglobulinemia (62 por cento, p<0,01) e hipoalbuminemia (58 por cento). CONCLUSÕES: Concluiu-se que os animais com a forma clínica da doença apresentam alterações condizentes com anemia, uremia, hiperproteinemia e hiperglobulinemia, as quais se apresentam como marcadores clínicos da leishmaniose visceral, associados aos sinais previamente relatados.