Comparison of Three Different Therapies for Cutaneous Leishmaniasis and Identification of the Etiologic Isolates in Isfahan, Iran

Abdellahi, Latifeh; Hejazi‬, ‪Seyed Hossein; Amirmozafari, Nour; Sotoodehnejadnematalahi, Fattah

doi:10.34172/aim.2020.98

Cited by 4 publications

(8 citation statements)

References 33 publications

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“…For example, 42-168 days were used, when evaluating topical paromomycin, 4,35 and 30-180 days when evaluating meglumine antimoniate. 28 The negative PCR results evident in our study after 56 days provide further evidence to support the need for a long (2 months) treatment period with LAmB gel to achieve significant improvement from CL. We could not find in previous reports repeated PCR tests done in addition to the clinical follow-up, and this novel correlation further supports our findings.…”

Section: Discussionsupporting

confidence: 68%

“…Previous clinical studies designed to assess topical treatment for CL indeed set their endpoints timing to even more extended periods. For example, 42–168 days were used, when evaluating topical paromomycin, 4,35 and 30–180 days when evaluating meglumine antimoniate 28 . The negative PCR results evident in our study after 56 days provide further evidence to support the need for a long (2 months) treatment period with LAmB gel to achieve significant improvement from CL.…”

Section: Discussionmentioning

confidence: 57%

“…A longer follow-up would be needed to observe changes in scarring and size, as set up in previous clinical trials for topical antileishmania treatments. 4,28,35 The 4-to 8-week treatment with LAmB gel was well tolerated in patients with L. major infection. Among patients treated with LAmB gel, all the AEs were mild in severity, and the vast majority of AEs were considered unrelated to the LAmB gel.…”

Section: Discussionmentioning

confidence: 99%

“…Our study had a limited follow‐up period, so the statistically significant clinical improvement was noted mainly in the inflammatory process. A longer follow‐up would be needed to observe changes in scarring and size, as set up in previous clinical trials for topical antileishmania treatments 4,28,35 …”

Section: Discussionmentioning

confidence: 99%

“…Amphotericin B (active pharmaceutical ingredient), dimethyl sulfoxide (solvent and skin penetrating enhancer [SPE] 28 ), oleic acid (SPE), isopropyl alcohol (co‐solvent and SPE), poloxamer 407 (gel‐forming agent), potassium sorbate (preservative of the aqueous phase), lecithin soy (liposome forming agent), isopropyl palmitate (lecithin soy solvent and SPE), sorbic acid (preservative of the lipophilic phase), purified water (gel‐forming agent), citric acid (pH adjustment), potassium hydroxide (pH adjustment). All the chemicals except Lecithin Soy were pharma grade (United States pharmacopeia or the European pharmacopeia).…”

Section: Methodsmentioning

confidence: 99%

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Topical liposomal amphotericin B gel treatment for cutaneous leishmaniasis caused by Leishmania major: a double‐blind, randomized, placebo‐controlled, pilot study

Horev

Sagi

Zur³

et al. 2022

Int J Dermatology

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Background Cutaneous leishmaniasis (CL) topical treatments may have low efficacy, while systemic treatments have adverse effects (AEs) and high cost. Since treatment options for CL nowadays have numerous disadvantages, an alternative topical treatment is vastly needed. We assessed liposomal amphotericin B gel (LAmB gel) treatment efficacy and safety.Methods A randomized, double-blind, placebo-controlled trial. Adults with CL (PCR proven, ≤5 lesions) were randomized for 28 days with LAmB gel (cases) versus placebo gel (controls), followed by LAmB gel for 28 days (both groups). Lesion size, ulceration, induration, scarring, swelling, and AEs (pain, itch, erythema, discharge, fever, and urticaria) were assessed at days 1, 28, and 56. PCR was repeated at day 56.Results Thirteen patients (four cases, nine controls) with 39 lesions (11 cases, 28 controls) caused by Leishmania major (L. major) were randomized. Ulcer, induration, scarring, and swelling were noted in 18%, 91%, 0%, and 27% of cases, respectively, versus 86%, 89%, 7%, and 54% of controls, respectively. At day 28, improvement rates were low in both groups. Induration improved comparing LAmB gel treatment for 56 days versus 28 days. Ulceration, induration, and swelling improved comparing all patients at 56 days versus 28 days. PCR turned negative in three of four cases and eight of nine controls. Mild, only local, AEs were reported in <30% of the patients.Conclusions LAmB gel is safe and may be considered as an alternative topical treatment for CL caused by L. major. Further, larger-scale studies are warranted to evaluate the long-term impact of LAmB gel on the management of CL. Cases groupAll four patients were males, with mean age (AESD) of . Two (50%) patients had a single lesion, one (25%) had four lesions, and one (25%) had five lesions. The mean duration from lesion appearance to L. major diagnosis was 15.0 AE 8.2 weeks (range: 8-24 weeks) (Table 1).The mean maximal diameter of lesions was 1.7 AE 1.3 cm (range: 0.5-4.5 cm).Ulcer, induration, scarring, and swelling were noted in 18%, 91%, 0%, and 27% of all 11 lesions. In one lesion (9%), pain and discharge were noted. Control groupOf the nine patients, six (67%) were males, with a mean age (AESD) of 34.1 AE 13.1 years (range: 19-60 years). Two (22%) patients had a single lesion, two (22%) had two lesions, one (11%) had three lesions, one (11%) had four lesions, and three (33%) had five lesions. The mean duration from lesion appearance to L. major diagnosis was 8.6 AE 4.6 weeks (range: 3-18 weeks) (Table 2).The mean maximal diameter of lesions was 1.7 AE 1.0 cm (range: 0.7-5.0 cm).Ulcer, induration, scarring, and swelling were noted in 86%, 89%, 7%, and 54% of all 28 lesions. In four lesions (14%), itching, pain, redness, or discharge were noted.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Topical liposomal amphotericin B gel treatment for cutaneous leishmaniasis caused by Leishmania major: a double‐blind, randomized, placebo‐controlled, pilot study

Horev

Sagi

Zur³

et al. 2022

Int J Dermatology

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CRISPR/Cas9-mediated deletion of a kinetoplast-associated gene attenuates virulence inLeishmania majorparasites

Darzi,

Khamesipour,

Bahrami

et al. 2024

Preprint

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The CRISPR/Cas9 system has emerged as a powerful tool for precise genome editing, allowing for the deletion of genes, generation of point mutations, and addition of tags to endogenous genes. We employed an efficient CRISPR/Cas9 technique in Leishmania major to assess its efficiency in editing a kDNA-associated gene, universal minicircle sequence binding protein (UMSBP), which is involved in mitochondrial respiration and kinetoplast division. We generated UMSBP C-tagged and UMSBP single knockout L. major (LmUMSBP+/−) parasites using the CRISPR/Cas9 toolkit. C-tagged parasite were confirmed by PCR, flow cytometry and Western blot analyses. Gene expression of mitochondrial redox regulating enzymes, tryparedoxin peroxidase (TXNPx) and trypanothione synthetase (TryS), were analysed by real-time RT-PCR. Growth rate of promastigotes in culture and infectivity rate in macrophages were analysed in vitro. Mice were immunized by LmUMSBP+/− mutant strain and lesion size and parasite burden were measured upon challenge with live wild type (WT) L. major. Cytokines were titrated on supernatant of lymph nodes cell culture by sandwich ELISA. Complete UMSBP deletion (LmUMSBP-/- null mutant) impaired promastigote survival, suggesting its essential role in parasite fitness. Despite this, we were able to produce attenuated LmUMSBP+/- parasites, which showed significant reduced growth in culture (P<0.05), increase in apoptosis (P<0.05) and downregulation of TXNPx and TryS gene expressions during growth of promastigotes compared to WT L. major. LmUMSBP+/- mutant strains did not cause ulcerative lesions in susceptible BALB/c mouse model. Furthermore, immunization of mice with LmUMSBP+/- parasites elicited a Th1 immune response with significantly high IFN-γ and low IL4 production in cell culture (P<0.001) associated with partial protection against L. major WT challenge, as evidenced by reduced parasite burden and lesion development in BALB/c mice. Our findings demonstrate the potential of CRISPR/Cas9-edited LmUMSBP+/- parasites as live attenuated vaccine candidate against Leishmania infection.

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Vaccinomics-based next-generation multi-epitope chimeric vaccine models prediction against Leishmania tropica - a hierarchical subtractive proteomics and immunoinformatics approach

Aiman,

Ahmad,

Khan

et al. 2023

Front. Immunol.

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Leishmania tropica is a vector-borne parasitic protozoa that is the leading cause of leishmaniasis throughout the global tropics and subtropics. L. tropica is a multidrug-resistant parasite with a diverse set of serological, biochemical, and genomic features. There are currently no particular vaccines available to combat leishmaniasis. The present study prioritized potential vaccine candidate proteins of L. tropica using subtractive proteomics and vaccinomics approaches. These vaccine candidate proteins were downstream analyzed to predict B- and T-cell epitopes based on high antigenicity, non-allergenic, and non-toxic characteristics. The top-ranked overlapping MHC-I, MHC-II, and linear B-cell epitopes were prioritized for model vaccine designing. The lead epitopes were linked together by suitable linker sequences to design multi-epitope constructs. Immunogenic adjuvant sequences were incorporated at the N-terminus of the model vaccine constructs to enhance their immunological potential. Among different combinations of constructs, four vaccine designs were selected based on their physicochemical and immunological features. The tertiary structure models of the designed vaccine constructs were predicted and verified. The molecular docking and molecular dynamic (MD) simulation analyses indicated that the vaccine design V1 demonstrated robust and stable molecular interactions with toll-like receptor 4 (TLR4). The top-ranked vaccine construct model-IV demonstrated significant expressive capability in the E. coli expression system during in-silico restriction cloning analysis. The results of the present study are intriguing; nevertheless, experimental bioassays are required to validate the efficacy of the predicted model chimeric vaccine.

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Comparison of Three Different Therapies for Cutaneous Leishmaniasis and Identification of the Etiologic Isolates in Isfahan, Iran

Cited by 4 publications

References 33 publications

Topical liposomal amphotericin B gel treatment for cutaneous leishmaniasis caused by Leishmania major: a double‐blind, randomized, placebo‐controlled, pilot study

Topical liposomal amphotericin B gel treatment for cutaneous leishmaniasis caused by Leishmania major: a double‐blind, randomized, placebo‐controlled, pilot study

CRISPR/Cas9-mediated deletion of a kinetoplast-associated gene attenuates virulence inLeishmania majorparasites

Vaccinomics-based next-generation multi-epitope chimeric vaccine models prediction against Leishmania tropica - a hierarchical subtractive proteomics and immunoinformatics approach

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