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Study of factors associated with therapeutic failure to multidrug therapy in Brazilian leprosy patients

Grant number: 19/17833-1
Support type:Regular Research Grants
Duration: April 01, 2020 - March 31, 2023
Field of knowledge:Health Sciences - Collective Health - Public Health
Principal researcher:Ana Carla Pereira Latini
Grantee:Ana Carla Pereira Latini
Home Institution: Instituto Lauro de Souza Lima (ILSL). Coordenadoria de Controle de Doenças (CCD). Secretaria da Saúde (São Paulo - Estado). Bauru , SP, Brazil
Assoc. researchers: Andrea de Faria Fernandes Belone ; Daniele Ferreira de Faria Bertoluci ; Dejair Caitano do Nascimento ; Emmanuelle Cambau ; Gisele Medeiros Bastos ; Luciana Raquel Vincenzi Fachin ; Luiza Hubinger ; Miguel Viveiros Bettencourt ; Patrícia Sammarco Rosa ; Renata Bilion Ruiz Prado ; Suzana Madeira Diorio ; Victor Fernandes de Oliveira

Abstract

Leprosy is an infectious disease, caused by Mycobacterium leprae, and with dermato-neurological manifestations. About 200,000 new cases of the disease are detected worldwide per year, with Brazil accounting for 28,000 cases. The treatment for the disease, since the 90's, is the multidrug therapy scheme composed of dapsone, rifampicin and clofazimine. However, the retreatment of leprosy patients is of great concern, since It impacts on epidemiological, social and economic aspects. So far, the only investigated cause of leprosy retreatment is the molecular evidence of relapse associated with resistance to drugs. Despite the effectiveness of MDT in reducing the epidemiological indexes of the disease, cases of relapse and therapeutic failure have been a concern of WHO and Brazilian Ministry of Health. These agencies have recommended for these cases the investigation of factors related to the drug resistance of the pathogen to the MDT drugs. Lauro de Souza Lima Institute (ILSL) is a reference for the Leprosy Drug Resistance Surveillance Committees of OMS and MS and receives samples for research from several Brazil states and Latin American countries. Only 1.8% of the patients tested in ILSL present this cause as an explanation for relapse or therapeutic failure. However, only three loci in the pathogen genome are systematically investigated, which may underestimate the magnitude of this cause. No mechanism related to the host genetics has been focus of investigation. However, data show ten-fold inter-individual variability in the pharmacokinetic parameters of rifampicin, which should have an effect on the success of leprosy therapy. Thus, we propose a broad investigation of factors related to the human and M. leprae genomes, with potential to explain the therapeutic failure in leprosy. In addition, the Bardin content analysis approach will be used to measure patient adherence to treatment. The data obtained should help in the elaboration of criteria for the adequate therapeutic decision in leprosy, and to provide subsidies for the programs of leprosy control. (AU)

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