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The Immunology of a Healing Response in Cutaneous Leishmaniasis Treated with Localized Heat or Systemic Antimonial Therapy.

ABSTRACT: BACKGROUND:The effectiveness of systemic antimonial (sodium stibogluconate, Pentostam, SSG) treatment versus local heat therapy (Thermomed) for cutaneous leishmaniasis was studied previously and showed similar healing rates. We hypothesized that different curative immune responses might develop with systemic and local treatment modalities. METHODS:We studied the peripheral blood immune cells in a cohort of 54 cutaneous Leishmania major subjects treated with SSG or TM. Multiparameter flow cytometry, lymphoproliferative assays and cytokine production were analyzed in order to investigate the differences in the immune responses of subjects before, on and after treatment. RESULTS:Healing cutaneous leishmaniasis lead to a significant decline in circulating T cells and NKT-like cells, accompanied by an expansion in NK cells, regardless of treatment modality. Functional changes involved decreased antigen specific CD4+ T cell proliferation (hyporesponsiveness) seen with CD8+ T cell depletion. Moreover, the healing (or healed) state was characterized by fewer circulating regulatory T cells, reduced IFN-? production and an overall contraction in polyfunctional CD4+ T cells. CONCLUSION:Healing from cutaneous Leishmaniasis is a dynamic process that alters circulating lymphocyte populations and subsets of T, NK and NKT-like cells. Immunology of healing, through local or systemic treatments, culminated in similar changes in frequency, quality, and antigen specific responsiveness with immunomodulation possibly via a CD8+ T cell dependent mechanism. Understanding the evolving immunologic changes during healing of human leishmaniasis informs protective immune mechanisms.

SUBMITTER: Lakhal-Naouar I

PROVIDER: S-EPMC4618688 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The Immunology of a Healing Response in Cutaneous Leishmaniasis Treated with Localized Heat or Systemic Antimonial Therapy.

Lakhal-Naouar Ines I Slike Bonnie M BM Aronson Naomi E NE Marovich Mary A MA

PLoS neglected tropical diseases 20151020 10

<h4>Background</h4>The effectiveness of systemic antimonial (sodium stibogluconate, Pentostam, SSG) treatment versus local heat therapy (Thermomed) for cutaneous leishmaniasis was studied previously and showed similar healing rates. We hypothesized that different curative immune responses might develop with systemic and local treatment modalities.<h4>Methods</h4>We studied the peripheral blood immune cells in a cohort of 54 cutaneous Leishmania major subjects treated with SSG or TM. Multiparamet ...[more]

PMID: 26485398

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Project description:BackgroundCutaneous leishmaniasis (CL) is a neglected tropical skin disease, caused by Leishmania protozoa. In Pakistan, where CL caused by L. tropica is highly endemic, therapy with pentavalent antimonials is the standard of care, but has significant toxicity when used in systemic therapy, while are no evidence-based safer alternative treatment options for L. tropica. The efficacy of oral miltefosine has not been studied in CL caused by L. tropica. We evaluated effectiveness and tolerability of miltefosine in patients with previous treatment failure or with contraindications to systemic antimonial treatment.MethodsA retrospective review was conducted of a cohort of CL patients who were treated with a 28-day course of miltefosine between December 2017 and August 2019, in urban Quetta, Pakistan, an area endemic for L. tropica. Descriptive analyses were performed, and effectiveness was assessed by initial response after treatment, and final cure at routine follow up visits, six weeks to three months post-treatment. Tolerability was assessed by routinely reported adverse events.ResultsOf the 76 CL patients in the cohort, 42 (55%) had contraindications to systemic antimonial treatment, and 34 (45%) had failure or relapse after antimonial treatment. Twelve patients defaulted during treatment and 12 patients were lost to follow up. In the remaining 52 patients, final cure rate was 77% (40/52). In those with contraindications to systemic antimonial treatment the final cure rate was 83% (24/29) and in the failure and relapse group 70% (16/23). Twenty-eight patients (40.0%) reported 39 mild to moderate adverse events with the main complaints being nausea (41.0%), general malaise (25.6%), and stomach pain (12.8%).ConclusionResults indicate that miltefosine is an effective second line treatment in CL in areas endemic for L. tropica. Prospective studies with systematic follow up are needed to obtain definitive evidence of effectiveness and tolerability, including identification of risk factors for miltefosine treatment failure.

Dataset Information

The Immunology of a Healing Response in Cutaneous Leishmaniasis Treated with Localized Heat or Systemic Antimonial Therapy.

Publications

The Immunology of a Healing Response in Cutaneous Leishmaniasis Treated with Localized Heat or Systemic Antimonial Therapy.

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