Dataset Information

Effectiveness of miltefosine in cutaneous leishmaniasis caused by Leishmania tropica in Pakistan after antimonial treatment failure or contraindications to first line therapy-A retrospective analysis.

ABSTRACT:

Background

Cutaneous 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.

Methods

A 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.

Results

Of 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%).

Conclusion

Results 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.

SUBMITTER: Kamink S

PROVIDER: S-EPMC7872246 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Effectiveness of miltefosine in cutaneous leishmaniasis caused by Leishmania tropica in Pakistan after antimonial treatment failure or contraindications to first line therapy-A retrospective analysis.

Kämink Suzette S Masih Boota B Ali Noor N Ullah Aman A Khan Syed Juma SJ Ashraf Shakil S Pylypenko Tetyana T Grobusch Martin P MP Fernhout Jena J den Boer Margriet M Ritmeijer Koert K

PLoS neglected tropical diseases 20210128 1

<h4>Background</h4>Cutaneous 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 tolera ...[more]

PMID: 33507944

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Project description:Cutaneous Leishmaniasis (CL) is a parasitic infection classified by the WHO as one of the most uncontrolled spreading neglected diseases. Syria is endemic for Leishmania tropica and Leishmania major, causing CL in the Eastern Mediterranean. The large-scale displacement of Syrian refugees exacerbated the spread of CL into neighboring countries. Therapeutic interventions against CL include local, systemic and physical treatments. The high risk for drug-resistance to current treatments stresses the need for new therapies. Imiquimod is an immunomodulatory drug with a tested efficacy against L. major species. Yet, Imiquimod efficacy against L. tropica and the molecular mechanisms dictating its potency are still underexplored. In this study, we characterized the effect of Imiquimod against L. tropica and L. major, and characterized the molecular mechanisms dictating its anti-leishmanial efficacy against both strains. We also investigated the potency and molecular mechanisms of an Imiquimod analog, EAPB0503, against these two strains. We have tested the effect of Imiquimod and EAPB0503 on macrophages infected with either L. major, L. tropica strains, or patient-derived freshly isolated L. tropica parasites. The anti-amastigote activity of either drugs was assessed by quantitative real time PCR (RT-PCR) using kinetoplast specific primers, confocal microscopy using the Glycoprotein 63 (Gp63) Leishmania amastigote antibody or by histology staining. The mechanism of action of either drugs on the canonical nuclear factor kappa- B (NF-?B) pathway was determined by western blot, and confocal microscopy. The immune production of cytokines upon treatment of infected macrophages with either drugs was assessed by ELISA. Both drugs reduced amastigote replication. EAPB0503 proved more potent, particularly on the wild type L. tropica amastigotes. Toll-Like Receptor-7 was upregulated, mainly by Imiquimod, and to a lesser extent by EAPB0503. Both drugs activated the NF-?B canonical pathway triggering an immune response and i-NOS upregulation in infected macrophages. Our findings establish Imiquimod as a strong candidate for treating L. tropica and show the higher potency of its analog EAPB0503 against CL.

Dataset Information

Effectiveness of miltefosine in cutaneous leishmaniasis caused by Leishmania tropica in Pakistan after antimonial treatment failure or contraindications to first line therapy-A retrospective analysis.

Background

Methods

Results

Conclusion

Publications

Effectiveness of miltefosine in cutaneous leishmaniasis caused by Leishmania tropica in Pakistan after antimonial treatment failure or contraindications to first line therapy-A retrospective analysis.

Similar Datasets

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