ABSTRACT
BACKGROUND Leishmania parasites cause leishmaniasis that range from self-limiting cutaneous lesions to more serious forms of the disease. The search for potential drug targets focusing on biochemical and metabolic pathways revealed the sterol biosynthesis inhibitors (SBIs) as a promising approach. In this class of inhibitors is found ketoconazole, a classical inhibitor of 14α-methysterol 14-demethylase. OBJECTIVE The present study aimed to better understand the biological response of Leishmania (Leishmania) amazonensis promastigotes at the cellular level after ketoconazole treatment. METHODS Herein, techniques, such as fluorimetry, flow cytometry, fluorescence microscopy, electron and scanning microscopy were used to investigate the cellular structures and to identify organelles affected by ketoconazole treatment. FINDINGS The study demonstrated, for the first time, the effect of ketoconazole on mitochondrion functioning and its probable relationship to cell cycle and death on L. (L.) amazonensis promastigotes (IFLA/BR/67/PH8 strain). MAIN CONCLUSIONS Ketoconazole-induced mitochondrial damages led to hyperpolarisation of this single organelle and autophagic vacuoles formation, as a parasite survival strategy. These damages did not reflect directly on the parasite cell cycle, but drove the parasites to death, making them susceptible to ketoconazole treatment in in vitro models.
ABSTRACT
Leishmaniasis is a disease that can affect visceral organs (visceral leishmaniasis; VL) or mucous membranes and skin, causing lesions of different forms and levels of severities (tegumentary leishmaniasis; TL). Like several others, leishmaniasis is a neglected disease, as the pharmaceutical industry seems to show little to no interest in developing new drugs targeting the disease. This study aims to trace the epidemiological profile of leishmaniasis in the Municipality of Patrocínio, State of Minas Gerais, over a period of time. Secondary data of reported cases from 2000 to 2017 were analyzed as provided by the Patrocinio Health Department. As no literature was found on the status of such a disease in Patrocinio, it is important to trace the epidemiological profile of leishmaniasis in the area. The findings pointed out that the disease affected predominantly male in the economically active population, mainly from the urban area, and that it had no relationship with professional activity. Twenty-two cases of leishmaniasis (15 of TL and 7 of VL) were reported, all of which were treated and cured. Five cases of TL and 1 case of VL were autochthonous, and confirmed cases of canine infection took place in 2011, 2016 and 2017.KEYWORDS: Alto Paranaíba. Autochthonous. Human leishmaniasis. Triângulo Mineiro. INTRODUCTION Leishmaniasis is a parasitic disease caused by protozoa of the Leishmania genus, which are transmitted from one host to another by phlebotomine sandflies (NAGLE et al., 2014). It may affect both visceral organs and skin surfaces (HANDLER et al., 2015) and lead to four major clinical syndromes: cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), visceral leishmaniasis or kala-azar (VL) and post-kala-azar dermal leishmaniasis (PKDL) (ANVERSA et al., 2018). Leishmaniasis is treated as a public health problem due to its high incidence and the disorders it can cause to the affected individuals. TL is characterized by ulcers on the face and/or extremities and nasal/oral/pharyngeal mucous (HANDLER et al, 2015), which can cause deformities such as disfiguring and permanent scars with partial or total mutilation of the nasopharyngeal mucosa, with further social, economic and psychological implications (ANVERSA et al., 2018, SUNYOTO; BOELAERT; MEHEUS, 2019). The mortality rate for VL, a more severe form, is 10%, making it the second most deadly tropical parasitic infection in the world after malaria (HANDLER et al., 2015). Updated regional information on the disease is important for epidemiological surveillance. However, the actual number of leishmaniasis cases is unknown due to underreporting, lack of epidemiological surveillance system or adequate diagnostic methods. Most data on incidence rates are based on estimates (PACE, 2014). Around 1.5 to 2 million new cases of leishmaniasis are estimated to occur annually worldwide: 500,000 are VL; 1 to 1.5 million cases are related to cutaneous or mucocutaneous leishmaniasis. Both forms commonly occur in Brazil (ANVERSA et al., 2018; WHO, 2020). Silva (2017) reported that the highest incidence rates of VL in the State of Minas Gerais, Brazil, from 2002 to 2013 were concentrated in the mesoregions in the North (Noroeste de Minas, Norte de Minas, and Jequitinhonha), in the East (Vale do Rio Doce) and in the center of the state (Central Mineira and Metropolitana de Belo Horizonte). The other mesoregions (Campo das Verentes, Oeste de Minas, Sul/Sudoeste de Minas, Triângulo Received: 08/04/19 Accepted: 20/12/19
A leishmaniose é uma doença que pode afetar órgãos viscerais (leishmaniose visceral; LV) ou as mucosas e a pele, provocando lesões de diferentes formas e gravidades (leishmaniose tegumentar; LT). Como várias outras moléstias, a leishmaniose é uma doença negligenciada, já que a indústria farmacêutica parece mostrar pouco ou nenhum interesse em desenvolver novos medicamentos direcionados à enfermidade. O estudo teve como objetivo traçar o perfil epidemiológico da leishmaniose no município de Patrocínio, estado de Minas Gerais, ao longo de um período de tempo. Dados secundários de casos registrados no período de 2000 a 2017 foram analisados, conforme fornecido pelo Departamento de Saúde de Patrocínio. Como não foi encontrada literatura sobre a situação dessa doença em Patrocínio, é importante traçar o perfil epidemiológico da leishmaniose na região. Os achados apontaram que a doença afetou predominantemente o sexo masculino da população economicamente ativa, principalmente da área urbana, e que não tinha relação com a atividade profissional. Foram notificados 22 casos de leishmaniose (15 de LT e 7 de LV), todos tratados e curados. Cinco casos de LT e 1 de LV foram considerados autóctones, e houve casos confirmados de infecção canina nos anos de 2011, 2016 e 2017.