ATIVIDADE ANTIPARASITÁRIA DA Artemisia annua CONTRA ESPÉCIES DE Leishmania

Introdução: A Artemisia annua é uma planta natural da Ásia e foi introduzida em diversos países ao redor do mundo(1). Conhecida há séculos por suas características medicinais, essa planta pode ser utilizada, por exemplo, na forma de óleo essencial ou pó para auxiliar contra diversas patologias, desde uma simples inflamação até mesmo infecção viral e bacteriana, diabetes e cânceres(1,3,4). O amplo espectro de ação da A. annua se deve ao fato de haver em sua composição metabólitos como artemisinina, flavonóides, terpenóides, cumarinas e saponinas(4). A Artemisia annua possui também ação contra a leishmaniose, uma doença causada por mais de 20 agentes etiológicos intracelulares(4). Transmitida por insetos dos gêneros Phlebotomus e Lutzomyia spp, a leishmaniose é considerada uma doença de preocupação global e se divide em três formas, sendo elas a cutânea, mucocutânea e visceral(2,4). Uma vez que os medicamentos que existem atualmente no mercado possuem graves efeitos colaterais, fez-se necessário o melhor entendimento acerca da ação da Artemisia annua sobre as espécies de Leishmania(4). Objetivos: Este resumo tem como objetivo analisar a ação anti-leishmania da Artemisia annua e em quais formas do parasita essa planta é capaz de atuar. Métodos: Foi realizada uma busca nas plataformas de dados PubMed e Google Acadêmico, e os artigos científicos foram encontrados por meio do descritor “artemisia annua AND leishmania”. Resultados: As folhas da Artemisia annua apresentaram ação contra as amastigotas da Leishmania panamensis, agente etiológico da leishmaniose cutânea, e não foi observada cito e genotoxicidade(4). Além disso, as sementes e folhas da A. annua mostraram atividade contra promastigotas e amastigotas de Leishmania donovani, agente causador da leishmaniose visceral. A ação anti-leishmania ocorreu por meio da ativação da morte celular programada, onde foi possível observar a exteriorização de fosfatidilserina e fragmentos de DNA. Os componentes da A. annua identificados na pesquisa foram a cânfora, n-hexano, acetato de alfa-amirina, β-cariofileno e derivados da artemisinina. Ademais, não foi encontrada citotoxicidade nas células de mamíferos(2,3). Conclusões: Em decorrência do que foi exposto, conclui-se que a Artemisia annua possui componentes com ação anti-leishmania, provocando a morte de amastigotas e promastigotas. Com isso, é necessário que pesquisas continuem sendo realizadas com a A. annua para que mais compostos com potencial contra espécies de Leishmania possam ser identificados e, assim, abordagens terapêuticas mais baratas e seguras possam ser aplicadas em indivíduos infectados por esse parasita.

Imported leishmaniasis in travelers: a 7-year retrospective from a Parisian hospital in France

Background Leishmaniases are regularly seen in non-endemic areas due to the increase of international travels. They include cutaneous leishmaniases (CL) and mucocutaneous (MC) caused by different Leishmania species, and visceral leishmaniases (VL) which present with non-specific symptoms. Methods We reviewed all consecutive leishmaniasis cases seen between September 2012 and May 2020. The diagnostic strategy included microscopy after May-Grünwald-Giemsa staining, a diagnostic quantitative PCR (qPCR) assay, and species identification based on sequencing of the cytochrome b gene. Results Eighty-nine patients had a definitive leishmaniasis diagnosis. Nine patients had VL with Leishmania infantum. Eighty patients had CL. Twelve patients acquired CL after trips in Latin America (7 Leishmania guyanensis, 2 Leishmania braziliensis, 2 Leishmania mexicana, and 1 Leishmania panamensis). Species could be identified in 63 of the 68 CLs mainly after travel in North Africa (59%) with Leishmania major (65%), Leishmania tropica/killicki (24%), and L. infantum (11%), or in West Sub-Saharan Africa (32%), all due to L. major. The median day between appearance of the lesions and diagnosis was 90 [range 60–127]. Conclusions Our diagnostic strategy allows both positive diagnoses and species identifications. Travelers in West Sub-Saharan Africa and North Africa should be better aware of the risk of contracting leishmananiasis.

Gene expression patterns associated with Leishmania panamensis infection in macrophages from BALB/c and C57BL/6 mice

Leishmania parasites can trigger different host immune responses that result in varying levels of disease severity. The C57BL/6 and BALB/c mouse strains are among the host models commonly used for characterizing the immunopathogenesis of Leishmania species and the possible antileishmanial effect of novel drug candidates. C57BL/6 mice tend to be resistant to Leishmania infections, whereas BALB/c mice display a susceptible phenotype. Studying species-specific interactions between Leishmania parasites and different host systems is a key step to characterize and validate these models for in vivo studies. Here, we use RNA-Seq and differential expression analysis to characterize the transcriptomic profiles of C57BL/6 and BALB/c peritoneal-derived macrophages in response to Leishmania panamensis infection. We observed differences between BALB/c and C57BL/6 macrophages regarding pathways associated with lysosomal degradation, arginine metabolism and the regulation of cell cycle. We also observed differences in the expression of chemokine and cytokine genes associated with regulation of immune responses. In conclusion, infection with L. panamensis induced an inflammatory gene expression pattern in C57BL/6 macrophages that is more consistently associated with a classic macrophage M1 activation, whereas in BALB/c macrophages a gene expression pattern consistent with an intermediate inflammatory response was observed.

Colombian Contributions Fighting Leishmaniasis: A Systematic Review on Antileishmanials Combined with Chemoinformatics Analysis

Leishmaniasis is a parasitic morbid/fatal disease caused by Leishmania protozoa. Twelve million people worldwide are appraised to be currently infected, including ca. two million infections each year, and 350 million people in 88 countries are at risk of becoming infected. In Colombia, cutaneous leishmaniasis (CL) is a public health problem in some tropical areas. Therapeutics is based on traditional antileishmanial drugs, but this practice has several drawbacks for patients. Thus, the search for new antileishmanial agents is a serious need, but the lack of adequately funded research programs on drug discovery has hampered its progress. Some Colombian researchers have conducted different research projects focused on the assessment of the antileishmanial activity of naturally occurring and synthetic compounds against promastigotes and/or amastigotes. Results of such studies have separately demonstrated important hits and reasonable potential, but a holistic view of them is lacking. Hence, we present the outcome from a systematic review of the literature (under PRISMA guidelines) on those Colombian studies investigating antileishmanials during the last thirty-two years. In order to combine the general efforts aiming at finding a lead against Leishmania panamensis (one of the most studied and incident parasites in Colombia causing CL) and to recognize structural features of representative compounds, fingerprint-based analyses using conventional machine learning algorithms and clustering methods are shown. Abstraction from such a meta-description led to describe some function-determining molecular features and simplify the clustering of plausible isofunctional hits. This systematic review indicated that the Colombian efforts for the antileishmanials discovery are increasingly intensified, though improvements in the followed pathways must be definitively pursued. In this context, a brief discussion about scope, strengths and limitations of such advances and relationships is addressed.

Efficacy and Tolerability of Miltefosine in the Treatment of Cutaneous Leishmaniasis

Background Cutaneous leishmaniasis (CL) is a neglected tropical disease causing an estimated 1 million new cases annually. While antimonial compounds are the standard of care worldwide, they are associated with significant adverse effects. Miltefosine, an oral medication, is United States (US) Food and Drug Administration approved to treat CL caused by Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis. Evidence of efficacy in other species and side-effect profiles in CL has been limited. Methods Twenty-six patients with CL were treated with miltefosine at the US National Institutes of Health. Species included L. braziliensis (n = 7), L. panamensis (n = 5), Leishmania mexicana (n = 1), Leishmania infantum (n = 3), Leishmania aethiopica (n = 4), Leishmania tropica (n = 2), Leishmania major (n = 1), and unspeciated (n = 3). Demographic and clinic characteristics of the participants, response to treatment, and associated adverse events were analyzed. Results Treatment with miltefosine resulted in cure in 77 % (20/26) of cases, with cures among all species. Common adverse events included nausea/vomiting (97%) and lack of appetite (54%). Clinical management or dose reduction was required in a third of cases. Gout occurred in 3 individuals with a prior history of gout. Most laboratory abnormalities, including elevated creatinine and aminotransferases, were mild and normalized after treatment. Conclusions Our data suggest that miltefosine has good but imperfect efficacy to a wide variety of Leishmania species. While side effects were common and mostly mild to moderate, some resulted in discontinuation of therapy. Due to oral administration, broad efficacy, and manageable toxicities, miltefosine is a viable alternative treatment option for CL, though cost and lack of local availability may limit its widespread use.

In Vitro Anti-Leishmanial Effect of Metallic Meso-Substituted Porphyrin Derivatives against Leishmania braziliensis and Leishmania panamensis Promastigotes Properties

In this study, a family of porphyrins based on 5,10,15,20-Tetrakis(4-ethylphenyl)porphyrin (1, Ph) and six metallo-derivatives (Zn2+(2, Ph-Zn), Sn4+(3, Ph-Sn), Mn2+ (4, Ph-Mn), Ni2+ (5, Ph-Ni), Al3+ (6, Ph-Al), and V3+ (7, Ph-V)) were tested as photosensitizers for photodynamic therapy against Leishmania braziliensis and panamensis. The singlet oxygen quantum yield value (ΦΔ) for (1–7) was measured using 1,3-diphenylisobenzofuran (DPBF) as a singlet oxygen trapping agent and 5,10,15,20-(tetraphenyl)-porphyrin (H2TPP) as a reference standard; besides, parasite viability was estimated by the MTT assay. After metal insertion into the porphyrin core, the ΦΔ increased from 0.76–0.90 and cell viability changed considerably. The ΦΔ and metal type changed the cytotoxic activity. Finally, (2) showed both the highest ΦΔ (0.90) and the best photodynamic activity against the parasites studied (IC50 of 1.2 μM).