The present results suggest that (i) the inflammatory process is intense in cutaneous ATL lesions and maintains a similar activity for several months; (ii) the dynamics of cell infiltration change during this period, with a gradual decrease in CD8+ T cells, probably correlated with a reduction in the parasite number; (iii) neutrophils may participate in the inflammatory process even during later stages of infection; (iv) the relative increase in the number of CD4+ T cells associated with the onset of fibrosis may suggest a participation of these cells in the control of the inflammatory process; and (v) late lesions with tendency for healing usually show focal inflammation. The study of healing lesions might contribute to the understanding of the late steps of the control of the inflammatory process in ATL lesions.

Abstract. We evaluated the effectiveness and safety of intralesional meglumine antimoniate (MA) in 24 not submitted to previous treatment patients with cutaneous leishmaniasis (CL) and with contraindication to systemic therapy. Each treatment consisted of one to four intralesional applications of MA at 15-day intervals. Patients' age ranged from 3 to 90 years; fourteen were females. Intralesional treatment in the absence of any relevant toxicity was successful in 20 (83.3%) patients. Three patients required additional treatment with amphotericin B and one required systemic MA. None of the patients developed mucosal lesions when followed up to 60 months. Intralesional MA is an effective and less toxic alternative treatment of patients with CL and contraindication to systemic therapy.American tegumentary leishmaniasis (ATL) affects the skin (cutaneous leishmaniasis, CL) and/or mucous membranes, and is caused by protozoa of the genus Leishmania, transmitted through the bite of sandflies. Research of IPEC; all patients signed a free informed consent form. All patients had a confirmed parasitological diagnosis of CL, had not been previously submitted to TTM, and had contraindication to systemic use of MA. A scale adapted from the Aids Table for Grading the Severity of Adverse Events 7 was used for the evaluation of AE and baseline clinical alterations, where G1 = mild, G2 = moderate, G3 = severe, and G4 = life-threatening. Contraindications to systemic antimonial therapy were 1) presence of baseline clinical alterations corresponding to G3; 2) presence of baseline laboratory alterations corresponding to G2; 3) presence of baseline electrocardiographic alterations corresponding to G3 or G4 (baseline adjusted QT interval [QT adj ] 0.46 ms was considered G3); 4) psychiatric disorders or high probability of low compliance with systemic TTM.AE were monitored by clinical examination, electrocardiogram (EKG), complete blood count and blood biochemistry, before, during, and soon after the end of TTM.The MA was supplied by the Brazilian Ministry of Health (Aventis Pharma, Sã o Paulo, Brazil). Each TTM consisted of 1-4 IL applications of MA, at 15-day intervals. The IL MA was injected subcutaneously until completely infiltrating the base of the lesion. Immediate cure was defined as epithelization up to 90 days after IL TTM. Lesion progression until complete healing was monitored through absence of crusts up to 1 month after epithelization, desquamation up to 3 months, infiltration up to 6 months, and erythema up to 9-12 months, as well as the absence of mucosal lesions. 8 Patients who presented lesion reactivation after TTM were retreated using the same or an alternative regimen; additional IL TTM or other medications were applied according to the presence or absence of EKG changes at the occasion of retreatment and/or therapeutic failure.The nonparametric Mann-Whitney test was used to compare the distribution of continuous variables (lesion area, volume of infiltrated medication per lesion area, etc.) between two groups (pres...

BackgroundAlthough high dose of antimony is the mainstay for treatment of American cutaneous leishmaniasis (ACL), ongoing major concerns remain over its toxicity. Whether or not low dose antimony regimens provide non-inferior effectiveness and lower toxicity has long been a question of dispute.MethodsA single-blind, non-inferiority, randomized controlled trial was conducted comparing high dose with low dose of antimony in subjects with ACL treated at a referral center in Rio de Janeiro, an endemic area of Leishmania (Viannia) braziliensis transmission. The primary outcome was clinical cure at 360 days of follow-up in the modified-intention-to-treat (mITT) and per-protocol (PP) populations. Non-inferiority margin was 15%. Secondary objectives included occurrence of epithelialization, adverse events and drug discontinuations. This study was registered in ClinicalTrials.gov: NCT01301924.ResultsOverall, 72 patients were randomly assigned to one of the two treatment arms during October 2008 to July 2014. In mITT, clinical cure was observed in 77.8% of subjects in the low dose antimony group and 94.4% in the high dose antimony group after one series of treatment (risk difference 16.7%; 90% CI, 3.7–29.7). The results were confirmed in PP analysis, with 77.8% of subjects with clinical cure in the low dose antimony group and 97.1% in the high dose antimony group (risk difference 19.4%; 90% CI, 7.1–31.7). The upper limit of the confidence interval exceeded the 15% threshold and was also above zero supporting the hypothesis that low dose is inferior to high dose of antimony after one series of treatment. Nevertheless, more major adverse events, a greater number of adverse events and major adverse events per subject, and more drug discontinuations were observed in the high dose antimony group (all p<0.05). Interestingly, of all the subjects who were originally allocated to the low dose antimony group and were followed up after clinical failure, 85.7% achieved cure after a further treatment with local therapy or low dose of antimony.ConclusionsCompared with high dose, low dose of antimony was inferior at the pre-specified margin after one series of treatment of ACL, but was associated with a significantly lower toxicity. While high dose of antimony should remain the standard treatment for ACL, low dose antimony treatment might be preferred when toxicity is a primary concern.

Skin inflammation plays an important role during the healing of American tegumentary leishmaniasis (ATL), the distribution of cells in active lesions may vary according to disease outcome and parasite antigens in ATL scars have already been shown. We evaluated by immunohistochemistry, 18 patients with 1- or 3-year-old scars and the corresponding active lesions and compared them with healthy skin. Small cell clusters in scars organized as in the active lesions spreaded over the fibrotic tissue were detected, as well as close to vessels and cutaneous glands, despite a reduction in the inflammatory process. Analysis of 1-year-old scar tissue showed reduction of NOS2, E-selectin, Ki67, Bcl-2 and Fas expression. However, similar percentages of lymphocytes and macrophages were detected when compared to active lesions. Only 3-year-old scars showed reduction of CD3(+), CD4(+) and CD8(+)T cells, in addition to reduced expression of NOS2, E-selectin, Ki67 and BCl-2. These results suggest that the pattern of cellularity of the inflammatory reaction observed in active lesions changes slowly even after clinical healing. Analysis of 3-year-old scars showed reduction of the inflammatory reaction as demonstrated by decrease in inflammatory cells and in the expression of cell-activity markers, suggesting that the host-parasite balance was only established after that period.