Treatment of visceral leishmaniasis with Alopurinol associated to the recombinant cysteine proteinase from Leishmania (Leishmania) infantum chagasi (rLdccys1).

• Grant number: 17/06350-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2017
• End date: June 30, 2020
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Clara Lúcia Barbiéri Mestriner
• Grantee: Fabiana Rodrigues de Santana
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Allopurinol is the main drug used for treatment of canine visceral leishmaniasis (CVL), resulting in reduction of the clinical signs of the disease as well as the decrease of parasite burden in treated dogs. However, cases of disease relapse following terminus of allopurinol treatment have been recorded which forces the extension of treatment indefinitely. Previous data from our laboratory showed that the treatment of CVL with the recombinant cysteine proteinase from L. (L.) infantum chagasi, rLdccys1, and Propionibacterium acnes as adjuvant led to protective immune responses and a significant reduction of the parasite burden, control of disease development and increase of survival in treated dogs. These findings led us to propose the present project whose aim is to evaluate the efficacy of the treatment of visceral leishmaniasis with Allopurinol associated to rLdccys1 plus P. acnes as adjuvant. The project will be performed in hamster as the animal model since it mimics the disease in humans and dogs. The weight and survival of animals will be weekly monitored. After the end of treatment the parasite load will be quantified by limiting dilution assay and the gene expression profile of IFN-g and IL-10 will be determined by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) The perspective is that the protective immune response induced by rLdccys1 plus P. acnes exerts a synergistic effect on the leishmanicidal action of Allopurinol, enhancing the efficacy of the drug for the treatment of visceral leishmaniasis.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DA SILVA, DANIELLE A. M.; SANTANA, FABIANA R.; KATZ, SIMONE; GARCIA, DANIEL M.; TEIXEIRA, DANIELA; LONGO-MAUGERI, IEDA M.; BARBIERI, CLARA L.. Protective Cellular Immune Response Induction for Cutaneous Leishmaniasis by a New Immunochemotherapy Schedule. FRONTIERS IN IMMUNOLOGY, v. 11, MAR 3 2020. (17/06350-4)

DE SANTANA, FABIANA RODRIGUES; MARINO DA SILVA, DANIELLE APARECIDA; KATZ, SIMONE; ORIKAZA, CRISTINA MARY; OLIVEIRA, KATIA CRISTINA; BARBIERI, CLARA LUCIA. A new immunochemotherapy schedule for visceral leishmaniasis in a hamster model. Parasitology Research, v. 121, n. 10, p. 12-pg., 2022-08-23. (17/06350-4)