Therapy For Cutaneous Leishmaniasis Research Articles

Local amphotericin B therapy for Cutaneous Leishmaniasis: A systematic review.

Cutaneous leishmaniasis (CL) is characterized by potentially disfiguring skin ulcers carrying significant social stigma. To mitigate systemic drug exposure and reduce the toxicity from available treatments, studies addressing new local therapeutic strategies using available medications are coming up. This review systematically compiles preclinical and clinical data on the efficacy of amphotericin B (AmB) administered locally for cutaneous leishmaniasis. Structured searches were conducted in major databases. Clinical studies reporting cure rates and preclinical studies presenting any efficacy outcome were included. Exclusion criteria comprised nonoriginal studies, in vitro investigations, studies with fewer than 10 treated patients, and those evaluating AmB in combination with other antileishmanial drug components. A total of 21 studies were identified, encompassing 16 preclinical and five clinical studies. Preclinical assessments generally involved the topical use of commercial AmB formulations, often in conjunction with carriers or controlled release systems. However, the variation in the treatment schedules hindered direct comparisons. In clinical studies, topical AmB achieved a pooled cure rate of 45.6% [CI: 27.5-64.8%; I2 = 79.7; p = 0.002), while intralesional (IL) administration resulted in a 69.8% cure rate [CI: 52.3-82.9%; I2 = 63.9; p = 0.06). In the direct comparison available, no significant difference was noted between AmB-IL and meglumine antimoniate-IL administration (OR:1.7; CI:0.34-9.15, I2 = 79.1; p = 0.00), however a very low certainty of evidence was verified. Different AmB formulations and administration routes have been explored in preclinical and clinical studies. Developing therapeutic technologies is evident. Current findings might be interpreted as a favorable proof of concept for the local AmB administration which makes this intervention eligible to be explored in future well-designed studies towards less toxic treatments for leishmaniasis.

Serum Zinc Level and Efficacy of Zinc Therapy in Cutaneous Leishmaniasis: a Systematic Review and Meta-analysis.

Cutaneous leishmaniasis is a parasitic skin disease prevalent in many parts of the world. Zinc has been investigated for its potential role in the immune response against Leishmania parasites. This study aimed to systematically review the literature and conduct meta-analyses to evaluate the serum zinc level and efficacy of zinc therapy in cutaneous leishmaniasis. A comprehensive search of electronic databases was performed to find studies reporting serum zinc levels and the efficacy of zinc therapy in cutaneous leishmaniasis. Meta-analyses were conducted using RevMan software (version 5.4), calculating the mean difference for serum zinc levels and risk ratio for the efficacy of zinc therapy. A total of 11 studies with 1009 participants were evaluated. Five of these studies, comprising 637 participants, examined serum zinc levels; the remaining six, involving 372 individuals, examined the effectiveness of zinc therapy in treating cutaneous leishmaniasis. The results showed that the serum zinc level was significantly lower in cutaneous leishmaniasis patients compared to controls (MD: - 26.65; 95% CI: [- 42.74, - 10.57]; p = 0.001). However, zinc therapy did not demonstrate a significant clinical improvement compared to standard treatment (RR: 0.96; 95% CI: [0.74, 1.23], p = 0.73).

Organic and Inorganic Light Emitting Diodes for Photodynamic Therapy of Cutaneous Leishmaniasis

Organic and Inorganic Light Emitting Diodes for Photodynamic Therapy of Cutaneous Leishmaniasis

Anti-Leishmanial Effect of Oral Zinc Sulfate in Acute Cutaneous Leishmaniasis: A Mini-review

Cutaneous Leishmaniasis (CL) is an endemic parasitic infection caused by various Leishmania species, with a specific predisposition of each species into a particular geographical area. Cutaneous lesions can either be a single, limited skin lesion or multiple, large, locally destructions skin lesions. Several therapies are proposed for CL, but severe side effects, high costs, and incomplete efficacy make researchers find replaceable therapies. Since the usage of zinc sulfate as a therapeutic agent has a long history in treating of various dermatological diseases, Zinc plays an essential role in the development and function of innate immunity cells (neutrophils and natural killer cells), which play significant roles in killing parasites. It also has a significant inhibitory effect on key enzymes involved in the carbohydrate metabolism and virulence of L. major and L.tropica. Therefore, its use as an oral therapy for CL might represent a significant addition to the armamentarium of anti-leishmanial medications. This review summarizes and discusses previous and recent findings regarding the therapeutic roles of oral zinc sulfate in cutaneous leishmaniasis therapy.

Influence of Obesity on Clinical Manifestations and Response to Therapy in Cutaneous Leishmaniasis Caused by Leishmania braziliensis.

Cutaneous leishmaniasis (CL) caused by Leishmania braziliensis is characterized by a single ulcer or multiple cutaneous lesions with raised borders. Cure rates <60% are observed in response to meglumine antimoniate therapy. We investigated the impact of obesity on CL clinical presentation and therapeutic response. A total of 90 age-matched patients with CL were included (30 obese, 30 overweight, and 30 with normal body mass index [BMI]). CL was diagnosed through documentation of L. braziliensis DNA by polymerase chain reaction or identification of amastigotes in biopsied skin-lesion samples. Serum cytokine levels were determined by chemiluminescence. Antimony therapy with Glucantime (Sanofi-Aventis; 20 mg/kg/day) was administered for 20 days. Obese CL patients may present hypertrophic ulcers rather than typical oval, ulcerated lesions. A direct correlation between BMI and healing time was noted. After 1 course of antimony, cure was achieved in 73% of patients with normal BMI, 37% of overweight subjects, yet just 18% of obese CL patients (P < .01). Obese CL cases additionally presented higher leptin levels than overweight patients or those with normal BMI (P < .05). Obesity modifies the clinical presentation of CL and host immune response and is associated with greater failure to therapy.

Efficacy of amiodarone and voriconazole combination therapy in cutaneous leishmaniasis in the mice experimentally infected with Leishmania major

IntroductionThe aim of the present study was to evaluate in vitro and in vivo efficacy of combination therapy of amiodarone and voriconazole against Leishmania major and investigating immune and wound healing responses of cutaneous leishmaniasis to this combination therapy. Methods: For in vitro study, replication of L. major promastigotes and intracellular amastigotes were investigated in the presence and absence of amiodarone and voriconazole. Isobologram construction and calculation of the Fractional Inhibitory Concentration (FIC) were performed. After the appearance of ulcers on the base of tails of BALB/c mice, treatment was initiated by a combination of amiodarone at 40 mg/kg plus voriconazole at 30 mg/kg orally and glucantime at 60 mg/kg intraperitoneally for 28 consecutive days. Results: According to the concave isobologram and fractional inhibitory concentration <1, combination of amiodarone plus voriconazole had synergistic effects against L. major promastigotes and intracellular amastigotes. There were less inflammatory cells, more fibroblasts and more collagen deposition in tissue sections in the mice treated with combined drugs compared to the vehicle and untreated mice. Increased glutathione peroxidase activity and decreased malondialdehyde, Interleukin-6, and Tumor necrosis factor-α levels were detected in the combination therapy group in comparison to the vehicle and untreated groups. Conclusions: It seems a combination of amiodarone plus voriconazole can be a rational and promising therapeutic approach in the treatment of cutaneous leishmaniasis.

درمان‌های موضعی در لیشمانیوز پوستی (سالک): یک مطالعه مروری

درمان‌های موضعی در لیشمانیوز پوستی (سالک): یک مطالعه مروری

Safety and efficacy of miltefosine in cutaneous leishmaniasis: An open label, non-comparative study from Balochistan.

Background & Objective:Cutaneous Leishmaniasis (CL) is endemic in Baluchistan and treated traditionally with Meglumine antimoniate. Miltefosine appears appealing therapy in cutaneous Leishmaniasis. Our objective was to evaluate safety and efficacy of Miltifossine in treatment of cutaneous Leishmaniasis.Methods:This experimental study was conducted from 10 September 2017 to 10 May 2018 at Combined Military Hospital Quetta. Total of 42 patients were recruited by purposive sampling technique. Lesional skin smears were stained with giemsa for Leishmania amastigotes under magnification (100 x).Complete blood count, serum urea, creatinine, bilirubin, aspartate aminotransferases (AST), alanine aminotransferase (ALT) were done at the beginning of treatment and then weekly, thereafter. Cap Miltefosine 50 mg (2.5mg/kg) were given as directly observed therapy .Daily observation during treatment phase was done for clinical side effects of therapy. Clinical response was documented at two weeks then at eight weeks. Photographs were taken before and after the therapy. Data was analyzed by SPSS 16.Results:Complete clinical response was observed in 39 (92.9%) patients and partial clinical response in 1(2.4%) patient. Two patients were lost to follow up at eight weeks. No significant derangements in laboratory profile were noted before and after treatment. Mean duration of treatment was 23.47+SD 4.44 days. Sixteen patients (38.1%) took Miltefosine for 28 days, 12 (28.6%) for 21 days and 9 (25%) for 25 days.Conclusion:Miltefosine is safe and cost effective treatment for cutaneous Leishmaniasis. It is effective in CL cases not susceptible to antimony compounds.

Topical tamoxifen in the therapy of cutaneous leishmaniasis.

The aims of the present work were to test the effect of tamoxifen administered topically and the therapeutic efficacy of tamoxifen and pentavalent antimonial combinations in an experimental model of cutaneous leishmaniasis. BALB/c mice infected with a luciferase expressing line of Leishmania amazonensis were treated with topical tamoxifen in two different formulations (ethanol or oil-free cream) as monotherapy or in co-administration with pentavalent antimonial. Treatment efficacy was evaluated by lesion size and parasite burden, quantified through luminescence, at the end of treatment and 4 weeks later. Topical tamoxifen, formulated in ethanol or as a cream, was shown to be effective. The interaction between tamoxifen and pentavalent antimonial was additive in vitro. Treatment with combined schemes containing tamoxifen and pentavalent antimonial was effective in reducing lesion size and parasite burden. Co-administration of tamoxifen and pentavalent antimonial was superior to monotherapy with antimonial.

A Comparison between the Effects of Glucantime, Topical Trichloroacetic Acid 50% plus Glucantime, and Fractional Carbon Dioxide Laser plus Glucantime on Cutaneous Leishmaniasis Lesions.

Background. Cutaneous leishmaniasis is an endemic disease in Iran. Pentavalent antimonial drugs have been the first line of therapy in cutaneous leishmaniasis for many years. However, the cure rate of these agents is still not favorable. This study was carried out to compare the efficacies of intralesional glucantime with topical trichloroacetic acid 50% (TCA 50%) + glucantime and fractional carbon dioxide laser + glucantime in the treatment of cutaneous leishmaniasis. Methods. A total of 90 patients were randomly divided into three groups of 30 to be treated with intralesional injection of glucantime, a combination of topical TCA 50% and glucantime, or a combination of fractional laser and glucantime. The overall clinical improvement and changes in sizes of lesions and scars were assessed and compared among three groups. Results. The mean duration of treatment was 6.1 ± 2.1 weeks in all patients (range: 2–12 weeks) and 6.8 ± 1.7, 5.2 ± 1.0, and 6.3 ± 3.0 weeks in glucantime, topical TCA plus glucantime, and fractional laser plus glucantime groups, respectively (P = 0.011). Complete improvement was observed in 10 (38.5%), 27 (90%), and 20 (87%) patients of glucantime, glucantime + TCA, and glucantime + laser groups, respectively (P < 0.001). Conclusion. Compared to glucantime alone, the combination of intralesional glucantime and TCA 50% or fractional CO2 laser had significantly higher and faster cure rate in patients with cutaneous leishmaniasis.

Microwave thermotherapy: New treatment for cutaneous leishmaniasis

Introduction: Cutaneous leishmaniasis(CL) is an endemic disease with variable therapeutic agents. Microwave radiation has been used in many medical disciplines as therapeutic and diagnostic tools. Objective: To evaluate the efficacy of microwave radiofrequency in the treatment of cutaneous leishmaniasis. Patients and methods: This is a case, controlled, therapeutic, clinical trial. Thirty five patients completed the study, 18 (51.43%) females and 17 (48.57%) males, with female to male ratio 1.1:1, their ages ranged from 6–60 (26.98±15.22) years and the duration of lesions ranged between 1–6 (2.17±1.44) months. The size of lesions ranged from 1-6.5 (2.87±1.60) cm. Eleven (31.43%) patients had single lesion and 24 (68.57%) patients had multiple lesions. Classical cases of CL were studied and diagnosis was confirmed by histopathological examination. Lesions had been divided in 2 groups, Group A: lesions were exposed to a microwave radiation once every two weeks for a maximum of 8 weeks, while Group B lesions, received no treatment and left as a control group. Patients were seen every 2 weeks for 8 weeks to reassess the therapeutic effect and to record any side effects. Follow up after cure was carried out for 2-6 months to watch any sign of relapse. Results: The total number of lesions were 99;52 (52.53%) ulcerated lesions and 47 (47.47%) dry lesions. In Group A, 64 (85.33%) lesions out of 75 showed clinical cure with 1-4 (2.77±0.91) sessions while in Group B, 5 (20.83%) lesions out of 24 lesions showed slight healing during the treatment period. No side effects appear in all patients. Conclusion: Microwave thermotherapy is highly effective, new therapy for cutaneous leishmaniasis with no harmful side effects.

Effect of Amphotericin B Nanodisks on Leishmania major Infected Mice.

ObjectiveTo assess the efficacy of a novel formulation of the polyene antibiotic, amphotericin B (AMB), as therapy for cutaneous leishmaniasis in different mouse strains.Methods(AMB), was formulated into water-soluble transport particles, termed nanodisks (ND). Balb/c and CH3 mice infected with Leishmania major on Day 0 were administered vehicle alone, empty ND or AMB-ND on Day 1 and day 7, via the tail vein. Mice were sacrificed 25 or 50 days post inoculation and tissue histology evaluated. Balb/c mice treated with vehicle or empty ND showed signs of severe infection while CH3 mice had less inflammation and fewer parasites. AMB-ND treatment (2 mg/kg) had a marked therapeutic effect on L. major infected Balb/c mice and a discernable therapeutic benefit on CH3 mice.ConclusionsAMB-ND is efficacious in the treatment of cutaneous leishmaniasis in both susceptible and resistant mouse strains. It may be inferred that AMB-ND may be useful for prophylactic and/or treatment of early stage Leishmania spp. infection.

New therapy for cutaneous leishmaniasis

New therapy for cutaneous leishmaniasis

Topical Treatment Modalities for Old World Cutaneous Leishmaniasis: A Review

Diagnosis and therapy of cutaneous leishmaniasis (CL) can be difficult due to the variability of the clinical pictures and resistance to therapy. There is no vaccine currently available for CL. The aim of the present review is to describe different topical treatment modalities for old world CL. The mainstays of treatment for old world CL are pentavalent antimony compounds which are administered parenterally or intralesionally. New topical treatment alternatives have been available within the past few years. Amongst several treatments used topically, physical therapies including cryotherapy, heat therapy and CO2 laser are promising for the treatment of old world CL. Along with that, other randomized placebo controlled trials should be designed to find new effective therapeutic regimens.

Monitoring the efficacy of antimicrobial photodynamic therapy in a murine model of cutaneous leishmaniasis using L. major expressing GFP.

A murine model of cutaneous leishmaniasis with green fluorescent protein positive (GFP+) L. major enables the monitoring of parasitic load via measurements of GFP fluorescence intensity, allowing for a faster and more efficient way of monitoring the clinical outcome of photodynamic therapy (PDT). This model may provide new insights on the phototoxic aspects in PDT. Although PDT regimens may be somewhat different in humans, it is expected that the developed model will facilitate the optimization and clinical translation of PDT as a therapy for cutaneous leishmaniasis and the eventual development of topical PDT treatments for other granulomatous infections.

A review of photodynamic therapy in cutaneous leishmaniasis

We present a review of six clinical studies investigating the use of photodynamic therapy (PDT) using porphyrin precursors for the treatment of Old World cutaneous leishmaniasis (CL). Thirty-nine patients with a total of 77 lesions received PDT using a range of treatment schedules following topical application of aminolevulinic acid (ALA) or methyl-aminolevulinate (MAL). The tissue response to PDT is accompanied by a mild burning sensation, erythema and reversible hypo- and hyperpigmentation. Few mechanistic studies have addressed the principles underlying the use of PDT for CL. All six reviewed papers suggest that PDT with porphyrin precursors is relatively effective in treating CL. Data are still limited, and PDT cannot at this point be recommended in routine clinical practice. The mechanism of action of this promising therapeutic modality needs to investigated further and additional controlled trials need to be performed.

Selective heat therapy in cutaneous leishmaniasis: a preliminary experience using the 585 nm pulsed dye laser

Aim The purpose of this paper is to examine the effect of the yellow pulsed dye laser on the natural history of cutaneous leishmaniasis (CL).Materials and methods A 31 year old Saudi patient suffered from CL due to L. tropica. He was treated with 585 nm, 450 μs flashlamp pulsed dye (FLPD) laser. The patient received two laser sessions, 2 weeks apart using 5 mm spot size with a fleunce range of 8–8.5 J/cm2.Results The lesion healed completely within 6 weeks with hyperpigmentation. At 16 weeks, the skin exhibited excellent texture with no scarring or recurrence.Discussion The ability to achieve a high temperature at structures or individual cells with minimal injury in healthy tissue and/or selective destruction of superficial dermal capillaries may in theory explain the possible efficacy of FLPD laser in CL. However, the exact mechanism(s) remains unknown.Conclusion The use of FLPD laser may promise local, practical, and a safe alternative form of heat therapy in CL. It has a unique advantage of possible scar improvement. Further extensive well-controlled studies are indicated.

Selective heat therapy in cutaneous leishmaniasis: a preliminary experience using the 585 nm pulsed dye laser

AbstractAim The purpose of this paper is to examine the effect of the yellow pulsed dye laser on the natural history of cutaneous leishmaniasis (CL).Materials and methods A 31 year old Saudi patient suffered from CL due to L. tropica. He was treated with 585 nm. 450 μs flashlamp pulsed dye (FLPD) laser. The patient received two laser sessions, 2 weeks apart using 5 mm spot size with a fleunce range of 8–8.5 J/cm2.Results The lesion healed completely within 6 weeks with hyperpigmentation. At 16 weeks, the skin exhibited excellent texture with no scarring or recurrence.Discussion The ability to achieve a high temperature at structures or individual cells with minimal injury in healthy tissue and/or selective destruction of superficial dermal capillaries may in theory explain the possible efficacy of FLPD laser in CL. However, the exact mechanism(s) remains unknown.Conclusion The use of FLPD laser may promise local, practical, and a safe alternative form of heat therapy in CL. It has a unique advantage of possible scar improvement. Further extensive well‐controlled studies are indicated.

Efficacy of a Short Course (10 Days) of High-Dose Meglumine Antimonate With or Without Interferon- in Treating Cutaneous Leishmaniasis in Guatemala

Sixty-six Guatemalan men with parasitologically confirmed cutaneous leishmaniasis, due most commonly to Leishmania braziliensis, were randomly assigned to receive one of three treatment regimens: meglumine antimonate (meglumine) for 20 days; meglumine for 10 days; and meglumine for 10 days plus alternate-day injections of interferon-gamma. In each group, meglumine was given intravenously as 20 mg of antimony/(kg of body weight.d). All treatment regimens were associated with similar response rates: the lesions of 19 (90%) of 21 patients who received meglumine for 20 days, 18 (90%) of 20 patients who received meglumine for 10 days, and all 22 patients who received meglumine plus interferon-gamma were completely reepithelialized by 13 weeks. In addition, for patients receiving all treatment regimens, test-of-cure cultures for Leishmania were negative and reactivation of lesions did not occur during 12 months of follow-up. The high efficacy of our 10-day course of meglumine indicates that the currently recommended duration of 20 days may be unnecessary for infections caused by L. braziliensis and suggests that a 10-day course of high-dose antimony should be tested as therapy for cutaneous leishmaniasis in other geographic areas.

Cutaneous Leishmaniasis In India

Fifteen patients with cutaneous leishmaniasis were randomly selected for clinical trials with itraconazole. A single daily itraconazole dose of approximately 4 mg per 1 kg of body weight was administered to each patient with breakfast for 6 weeks. Five patients served as controls. On completion of therapy, ten cases in the study group (66.6%) were considered to be cured. No major adverse effects were reported. No significant changes were seen in the controls at the end of the study. The possibility of spontaneous recovery will be discussed in this report even though it is considered to be unlikely. Itraconazole has promising potential in cutaneous leishmaniasis therapy.