Characterization of a Leishmania amazonensis clinical isolate multiresistant to the drugs used in the treatment of leishmaniasis

• Grant number: 22/06176-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2022
• End date: August 31, 2024
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Adriano Cappellazzo Coelho
• Grantee: Stephane Soares Gomes Senhorinha
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 16/21171-6 - Paromomycin for the treatment of Tegumentary Leishmaniasis: investigation in vitro, in vivo and in the identification of molecular markers associated with susceptibility and resistance, AP.JP

Abstract

Leishmaniasis is a group of parasitic diseases caused by several species of the genus Leishmania, whose transmission occurs through the blood meal of sandfly vectors infected by the parasite. Among the endemic species in Brazil, Leishmania amazonensis is the most prevalent, and it is responsible for localized cutaneous and diffuse cutaneous leishmaniasis. Treatment options for cutaneous leishmaniasis are restricted to pentavalent antimony, amphotericin B, pentamidine; and miltefosine, the only oral drug, recently approved for use in Brazil. Treatment failure has been reported and may be associated with several factors such as the immune response of the infected patient, co-infection with other pathogens, such as the HIV virus, and factors directly related to the parasite, in which drug resistance is the main factor. In this research project, we propose to characterize a clinical isolate of L. amazonensis refractory to the treatment with two of the main drugs used in the treatment of leishmaniasis in Brazil: pentavalent antimony and liposomal amphotericin B. Preliminary results of the in vitro susceptibility of this isolate to both drugs confirmed the findings of the treatment failure. In this proposal, we will evaluate the in vivo experimental efficacy of two alternative drugs (miltefosine and paromomycin), in which this clinical isolate of L. amazonensis was not previously exposed, and identify the potential genes associated with the pentavalent antimony resistance phenotype. This project will provide data on the limitations and potential of use of miltefosine and paromomycin as an alternative treatment for infection with a multiresistant isolate of L. amazonensis and will identify potential molecular markers of clinical resistance to pentavalent antimony, still the main drug used in the treatment of leishmaniasis in Brazil.