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Paromomycin for the treatment of Tegumentary Leishmaniasis: investigation in vitro, in vivo and in the identification of molecular markers associated with susceptibility and resistance

Grant number: 16/21171-6
Support type:Research Grants - Young Investigators Grants
Duration: December 01, 2017 - November 30, 2021
Field of knowledge:Biological Sciences - Parasitology
Principal Investigator:Adriano Cappellazzo Coelho
Grantee:Adriano Cappellazzo Coelho
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas, SP, Brazil
Assoc. researchers:Danilo Ciccone Miguel ; João Marcelo Pereira Alves ; José Angelo Lauletta Lindoso ; Paulo Cesar Cotrim ; Silvia Reni Bortolin Uliana

Abstract

Leishmaniasis is a parasitic disease with wide geographic distribution in Brazil with an increased number of cases in urban areas in recent years. The current state of treatment of different clinical forms of Leishmaniasis is one of the critical areas in the management of this disease, since the drugs used require parenteral use, are costly and induce side effects. The available drugs used in Brazil are limited to pentavalent antimony, amphotericin B and pentamidine. In the last years, two drugs have been approved as alternatives to the treatment of Visceral Leishmaniasis in Asia: miltefosine and paromomycin. In this scenario, we propose to evaluate in this study the susceptibility in vitro to paromomycin in clinical isolates of Leishmania spp. from patients of the State of São Paulo and dogs from the city of Embu-Guaçu, as well as its efficacy in vivo in experimental models of infection with species responsible for Tegumentary Leishmaniasis in Brazil. We also propose to characterize molecularly parasites resistant to paromomycin selected in vitro, in order to identify potential genes linked to susceptibility and resistance to paromomycin. Once identified, genes will be functionally validated using strategies of genetic manipulation of the parasite. This study will assess the potential use of paromomycin for the treatment of Leishmaniasis in Brazil and contribute to a better understanding of the mechanism of action and resistance to paromomycin that are not completely understood, despite its high clinical efficacy against Visceral Leishmaniasis. (AU)