Marise Mattos

T-Cell-Mediated Immune Responses in Patients with Cutaneous or Mucosal Leishmaniasis: Long-Term Evaluation after Therapy

ABSTRACT T-cell immune responses in patients with cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) were studied during the active disease, at the end of therapy, and 1 to 17 years posttherapy (long-term follow-up). Lymphocyte proliferative responses, phenotypic characterization of CD4+ and CD8+Leishmania-reactive T cells, and cytokine production were assayed. Patients with active ML and CL showed higher proportions of CD4+ than CD8+ T cells. In CL, the healing process was associated with a decrease of CD4+ and an increase of CD8+, leading to similar CD4+ and CD8+ proportions. This pattern was only seen in ML after long-term therapy. Long-term follow-up of patients with CL showed a positive CD4+/CD8+ ratio as observed during the active disease, although the percentages of these T cell subsets were significantly lower. Patients with CL did not show significant differences between gamma interferon (IFN-γ) and interleukin-5 (IL-5) production during the period of study. Patients with active ML presented higher IFN-γ and IL-5 levels compared to patients with active CL. IL-4 was only detected during active disease. Patients long term after cure from ML showed increasing production of IFN-γ, significant decrease of IL-5, and no IL-4 production. Two apparently beneficial immunological parameters were detected in tegumentary leishmaniasis: (i) decreasing proportions of CD4+Leishmania-reactive T cells in the absence of IL-4 production associated with cure of CL and ML and (ii) decreasing levels of IL-5 long after cure, better detected in patients with ML. The observed T-cell responses maintained for a long period in healed patients could be relevant for immunoprotection against reinfection and used as a parameter for determining the prognosis of patients and selecting future vaccine preparations.

Intralesional therapy of American cutaneous leishmaniasis with pentavalent antimony in Rio de Janeiro, Brazil – an area of Leishmania (V.) braziliensis transmission

Background The drug of choice for leishmaniasis is pentavalent antimony and different regimens are under continuous evaluation. The ideal therapy should be simple, effective, and with no or minor side‐effects, in this paper we have studied the efficacy of intralesionally applied antimony in New World cutaneous leishmaniasis.

American tegumentary leishmaniasis (ATL) in Rio de Janeiro State, Brazil: main clinical and epidemiologic characteristics

Background Rio de Janeiro State in Brazil is an endemic area of American tegumentary leishmaniasis (ATL) induced by Leishmania (Viannia) braziliensis.

Leishmaniasis recidiva cutis in New World cutaneous leishmaniasis

Background Leishmaniasis recidiva cutis (LRC) is rare in New World leishmaniasis. Only seven cases have been reported so far.

Blepharo-conjunctivitis due to leishmania (viannia) braziliensis cutaneous infection- Report of two cases in Rio de Janeiro, Brazil

are no current therapeutic options. The size and the scope of our article were limited by the nature of a retrospective chart review, which only allows analysis of followup that occurred within the defined time frame. Additional factors limiting the scope and length of the study included (1) the logistical and financial complexity involved in following up patients in two geographically separated states; (2) the differences in available equipment in the two institutions; and (3) the importance of sharing a potential new treatment with the ophthalmic community sooner rather than later. The retrospective chart review process was begun while the senior author was at the University of Florida, and because he moved from Florida to Massachusetts, the analysis was carried out in Massachusetts, and appropriate Institutional Review Board approval from the Massachusetts site was published in the article. The valproic acid treatment regimen analysed retrospectively in the charts of the seven patients is detailed in the article. Prospective follow-up was not carried out, nor is it allowed under the mandate of a retrospective chart review. To clarify, the treatment of patients with valproic acid has not been stopped for any of the patients who tolerated it well (most of the patients). Our retrospective chart review reported on in the BJO article captured a relatively short period for a slowly progressive condition such as RP, and we recognise that the most rigorous validation of a therapy will be a well-designed clinical trial. A prospective, multicentre, randomised, placebo-controlled clinical trial is in the final stages of preparation in the USA, and we will be registering this clinical trial very soon at the US clinical trials website, http://www.clinicaltrials.gov. On a separate note, as part of our current clinical practice in Massachusetts, several RP patients new to our practice have been treated with valproic acid; our clinical impressions of these new patients are similar to what was reported in our article. There is mounting evidence that valproic acid may have potent neuroprotective properties and have other beneficial effects, and we have an intensive programme of in vitro and in vivo experiments (including mice models of RP) under way. The results of our experiments in the context of retinal degenerative conditions have been reported at recent meetings. We are planning to submit these data as articles to peer-reviewed journals. Our work has been motivated by the spirit of translational research, with the goal of more quickly identifying a promising therapeutic approach and stimulating scientific interest and further research, based on preclinical data and unexpectedly positive vision function observed in a clinical setting. Repurposing drugs such as valproic acid, which have been shown to be safe, is an economical and time-efficient way to quickly bring new treatments to patients.The authors report two uncommon cases of chronic granulomatous blepharo-conjunctivitis as a recurrence of Leishmania (Viannia) braziliensis cutaneous leishmaniasis (CL). Patients were otherwise healthy immunocompetent adults, as revealed by a positive cutaneous delayed-type hypersensitivity (DTH) reaction to Leishmania-derived antigens and a typical cell-mediated immunity-induced granulomatous reaction that had effect on the control of parasite replication at the lesions. This rare cause of ocular involvement should be considered in areas where Leishmania is endemic.