Topical treatment of experimental cutaneous leishmaniasis in golden hamster (Mesocricetus auratus) with formulations containing pentamidine

Current treatment of cutaneous leishmaniasis (CL) relies mainly on pentavalent antimonials salts and second-line drugs include pentamidine and amphotericin B, but these therapies have side effects and require parenteral administration. The aim of this work was to evaluate the topical formulations containing pentamidine isethionate (PI) in the experimental treatment of cutaneous leishmaniasis (CL). Golden hamsters (Mesocricetus auratus) were infected in the nose with Leishmania (Leishmania) amazonensis. Six treatment groups received different topical treatments of anhydrous or hydrating emulsions, for a maximum of 10 days, with an application of 50 mg day(-1). After treatment tissue samples of lesions were evaluated by histology, transmission electron microscopy and biopsy cultivation. Compared with untreated group, topical treatment with hydrating emulsion with 10% PI and usnic acid (ACE5AU) showed significantly decrease in volume lesion (P= 0.028) on 20th day after the end of the treatment with reduction of 27.37%. Topical treatment with anhydrous emulsion with 10% PI and usnic acid (ACPU) reduces parasite burden in Golden hamsters. This study demonstrated the potential of topical treatment to reduce the number of parasites that could be combined with others drugs and to have a faster and more effective treatment of cutaneous leishmaniasis.Peer reviewe

The Role of Inflammatory, Anti-Inflammatory, and Regulatory Cytokines in Patients Infected with Cutaneous Leishmaniasis in Amazonas State, Brazil

The authors discuss in this paper the role of inflammatory, anti-inflammatory, and regulatory cytokines in patients infected with different species of Leishmania in Amazonas State, Brazil. A comparative analysis was made of serum concentrations of these cytokines in the peripheral blood of 33 patients infected with cutaneous leishmaniasis. The isolates were identified as Leishmania guyanensis, L. naiffi, and L. amazonensis. Most (64%) of the patients were male ranging in age from 18 to 58 years. Protein expression profiles of IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, and IL-17 cytokines were shown to vary significantly between infected and noninfected (control group) individuals and according to the Leishmania species. Infection caused by L. guyanensis accounted for 73% of the cases and patients with this parasite also showed higher concentrations of IL-2, IFN-γ, IL-4, and IL-17 when compared to infection by L. amazonensis. Patients with infection caused by L. naiffi showed higher concentration of the cytokines analyzed when compared to uninfected patients; however, there was no statistically significant difference with the other species analyzed

Avaliação in vitro da atividade antileishmania de complexos de cobre (I)

In the research for the development of new drugs for the therapy of American tegumentary leishmaniasis, copper has been studied for its antileishmania activity. This study aims to report the activity of three copper(I) complexes on parasites of the species L. amazonensis and L. guyanensis. The metal complexes were tested according to in vitro antileishmanial assays, against promastigote and amastigote forms of the most prevalent species in the state of Amazonas, Brazil. Cytotoxicity of the complexes was evaluated in murine macrophage-like cell line (MJ774). The results of the in vitro assays indicated that, among the copper complexes tested, the homoleptic phosphine complex [Cu(thp)4][PF6](thp=tris-hydroxymethylphosphine) presented promising activity against the evolutionary forms of L. amazonensis, and obtained a IC50 of  26.45 and 24.61 µM in a period of 48 and 72 h, respectively. The results for copper complex at concentration 160 µM in amastigote forms showed a decrease in the infection index (32% of infected cells) and, in the cytotoxicity assay with MJ774, 52.43% of cell viability was observed. The results showed that the complex [Cu(thp)4][PF6] presented significant biological activity, indicating a need for future in vivo studies.Na busca do desenvolvimento de novos fármacos para a terapia da leishmaniose tegumentar americana, o cobre tem sido estudado quanto a sua atividade antileishmania. Esse estudo tem como objetivo relatar a atividade de três complexos de cobre (I) sobre parasitas das espécies L. amazonensis e L. guyanensis. Os complexos metálicos foram testados por meio de ensaios antileishmania in vitro contra as formas promastigota e amastigota das espécies mais prevalentes no estado do Amazonas, Brasil. A citotoxicidade dos complexos foi avaliada em linhagem de células semelhantes a macrófagos murinos (MJ774). Os resultados dos ensaios in vitro indicaram que, entre os complexos de cobre testados, o complexo homoléptico de fosfina [Cu(thp)4][PF6](thp=tris-hidroximetilfosfina) apresentou atividade promissora contra as formas evolutivas de L. amazonensis, e obtiveram IC50 de 26,45 e 24,61 µM em um período de 48 e 72 h, respectivamente. Os resultados para o complexo de cobre na concentração de 160 µM nas formas amastigotas reportaram diminuição no índice de infecção (32% das células infectadas) e, no ensaio de citotoxicidade com MJ774, observou-se 52,43% de viabilidade celular. Os resultados evidenciaram que o complexo [Cu(thp)4][PF6] apresentou atividade biológica significativa, indicando a necessidade de futuros estudos in vivo

The Role of Inflammatory, Anti-Inflammatory, and Regulatory Cytokines in Patients Infected with Cutaneous Leishmaniasis in Amazonas State, Brazil

The authors discuss in this paper the role of inflammatory, anti-inflammatory, and regulatory cytokines in patients infected with different species of Leishmania in Amazonas State, Brazil. A comparative analysis was made of serum concentrations of these cytokines in the peripheral blood of 33 patients infected with cutaneous leishmaniasis. The isolates were identified as Leishmania guyanensis, L. naiffi, and L. amazonensis. Most (64%) of the patients were male ranging in age from 18 to 58 years. Protein expression profiles of IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, and IL-17 cytokines were shown to vary significantly between infected and noninfected (control group) individuals and according to the Leishmania species. Infection caused by L. guyanensis accounted for 73% of the cases and patients with this parasite also showed higher concentrations of IL-2, IFN-γ, IL-4, and IL-17 when compared to infection by L. amazonensis. Patients with infection caused by L. naiffi showed higher concentration of the cytokines analyzed when compared to uninfected patients; however, there was no statistically significant difference with the other species analyzed. © 2014 Thaís Tibery Espir et al

The Role of Inflammatory, Anti-Inflammatory, and Regulatory Cytokines in Patients Infected with Cutaneous Leishmaniasis in Amazonas State, Brazil

The authors discuss in this paper the role of inflammatory, anti-inflammatory, and regulatory cytokines in patients infected with different species of Leishmania in Amazonas State, Brazil. A comparative analysis was made of serum concentrations of these cytokines in the peripheral blood of 33 patients infected with cutaneous leishmaniasis. The isolates were identified as Leishmania guyanensis, L. naiffi, and L. amazonensis. Most (64%) of the patients were male ranging in age from 18 to 58 years. Protein expression profiles of IL-2, IL-4, IL-6, IL-10, IFN-, TNF-, and IL-17 cytokines were shown to vary significantly between infected and noninfected (control group) individuals and according to the Leishmania species. Infection caused by L. guyanensis accounted for 73% of the cases and patients with this parasite also showed higher concentrations of IL-2, IFN-, IL-4, and IL-17 when compared to infection by L. amazonensis. Patients with infection caused by L. naiffi showed higher concentration of the cytokines analyzed when compared to uninfected patients; however, there was no statistically significant difference with the other species analyzed

Evaluation of different diagnostic methods of American Cutaneous Leishmaniasis in the Brazilian Amazon

Epidemiological studies have been conducted to better understand the dynamics of American Cutaneous Leishmaniasis (ACL) in the Amazon region where distinct species of Leishmania circulate. In endemic areas, the optimal diagnosis must be made in the earlier clinical presentation to avoid the complications of chronic disease. The scarcity of financial support, laboratory infrastructure and trained persons are the major obstacles in this reality. This paper describes the result of performing different diagnostic methods for ACL in Amazonas State between the years 2010 and 2011. The tests used were the intradermal skin test (Montenegro's skin test), ELISA (Enzyme-Linked Immunosorbent Assay), direct examination, culture isolation and identification of Leishmania species. A total of 38 suspected human cases of ACL were diagnosed by different methods, of which 71.0% (n = 27) were positive by direct examination, 75.6% (n = 28) had positivity in the culture isolates and, of these, 54.0% (n = 19) had infection with Leishmania (Viannia) guyanensis. The positivity of the intradermal skin test with the leishmanin solution was observed in 77.0% of cases analyzed and the serology with detection of IgG and IgM showed the presence of antibodies in 100% of exams realized results, showing variation in the titles of antibodies. The success of Leishmaniasis treatment depends on an effective and early diagnosis. Parasitological diagnosis is highly specific, but sensitivity is subject to variation because the tissue distribution of parasites generally is not homogeneous and depends on the specie of parasite. Moreover, parasitological tests require invasive procedures and depend on restrictive conditions for the collection of biological sample, which limit their use in large-scale for epidemiological studies. ELISA has been the most widely used serological method for the diagnosis of Visceral Leishmaniasis (VL) as it is easy to perform and has a low cost. However, flaws in specificity are observed in the diagnosis of cutaneous leishmaniasis. Actually the diagnosis needs to be done as an associated methods depending on the question to be solved. © 2016 Elsevier Inc

New human case reports of cutaneous leishmaniasis by Leishmania (Viannia) naiffi in the Amazon region, Brazil

ABSTRACT Few cases of human cutaneous leishmaniasis (CL) caused by Leishmania naiffi were described in the medical literature. The aim of this study was to report and analyze new cases of L. naiffi in the period between the years 1992 to 2011. The strains were characterized by isoenzyme analysis. All patients assisted had small lesions; ranging from 1.0x1.0 mm and 13.5x11.5 mm. The lesions observed were widely distributed: 55.5% on the lower limb, 5.5% in the abdominal area, 16.6% on upper limb and 22.2% in upper limb and back. Seventy-two percent of patients had ulcerated lesions. Clinical course of the disease varied from 1 to 10 months. According to gender, most infected individuals were men (83.3%). The patients came from Amazonas (10), Par