Glucantime-resistant Leishmania tropica isolated from Iranian patients with cutaneous leishmaniasis are sensitive to alternative antileishmania drugs

Hadighi, Ramtin; Boucher, P.; Khamesipour, Ali; Meamar, Ahmad Reza; Roy, Gaétan; Ouellette, Marc; Mohebali, Mehdi

doi:10.1007/s00436-007-0638-0

Cited by 64 publications

(46 citation statements)

References 23 publications

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“…MA is the treatment of leishmaniasis for nearly 65 years. In addition to the low response recently reported against various forms of leishmaniasis due to resistance Hadighi et al 2006Hadighi et al , 2007Pour et al 2011) treatment with antimonials is long, painful, and associated with toxicity (Alvar et al 2006). In Iran, ACL due to L. tropica is a chronic disease and at present combination of treatment such as MA with cryotherapy or along with other drugs are used (Khatami et al 2007;Layegh et al 2009;Modabber et al 2007).…”

Section: Discussionmentioning

confidence: 93%

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The effect of verapamil on in vitro susceptibility of promastigote and amastigote stages of Leishmania tropica to meglumine antimoniate

et al. 2011

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Pentavalent antimonials are the standard treatment for cutaneous leishmaniasis (CL) with low efficacy and resistance is emerging. CL is increased significantly in respect to incidence rate and expanding to new foci. In the present study, the effect of verapamil on in vitro susceptibility of promastigote and amastigote stages of Leishmania tropica to meglumine antimoniate (MA, Glucantime) was evaluated using colorimetric assay (MTT) and in a macrophage model, respectively. Verapamil, as a calcium channel blocker, affects drug uptake by preventing of drug efflux from the cells. In promastigote form, several concentrations of MA with or without verapamil showed significant decrease (P < 0.05) in optical density. The overall mean IC₅₀ value with combination of MA plus verapamil (IC50 = 116.03 μg/ml) was significantly less than MA (IC50 = 225.14 μg/ml) alone (P < 0.05) for promastigote stage. Similarly, the amastigote stage was more susceptible to treatment with MA plus verapamil to that of MA alone (P < 0.05). Analysis of overall effect of different concentrations of MA alone, compared with combination of MA plus verapamil by mean infection rate of amastigotes in each macrophage showed a significant difference (P < 0.05).These findings indicated some degree of synergistic effects between MA and verapamil on in vitro susceptibility of L. tropica to MA. Further works are required to evaluate this synergistic effect on animal model or volunteer human subjects.

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Section: Discussionmentioning

confidence: 93%

“…Treatment failure is common in many endemic areas (Firooz et al 2006;Khatami et al 2007;Modabber et al 2007). In Iran, CL is increased significantly and resistance is reported (Hadighi et al 2006(Hadighi et al , 2007Pour et al 2011). There is urgent need for development of new treatment.…”

Section: Introductionmentioning

confidence: 87%

The effect of verapamil on in vitro susceptibility of promastigote and amastigote stages of Leishmania tropica to meglumine antimoniate

et al. 2011

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“…For Leishmania tropica from Iran, the mean effective dose (ED50) for parasites from 165 lesions that responded to systemic or ILSb was 4.6 μg/mL, whereas the mean ED50 for parasites from 16 lesions that did not respond was 19 μg/mL. 23 The authors concluded that primary Glucantime-resistant L. tropica field isolates were now frequent in Iran. On the other hand, for L. braziliensis from Peru, in vitro resistance was found for eight patients who failed systemic Sb but also for 11 patients who cured.…”

Section: 15mentioning

confidence: 99%

Intralesional Pentamidine: A Novel Therapy for Single Lesions of Bolivian Cutaneous Leishmaniasis

Soto¹,

Paz²,

Rivero³

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. A novel therapy, intralesional (IL) pentamidine, was compared to intralesional therapy with antimony (ILSb), a World Health Organization-recommended therapy, for single Bolivian Leishmania braziliensis lesions. In Study 1, 90 patients were randomized equally between three injections of ILSb over 5 days, five injections of ILSb over 11 days, and three injections of IL pentamidine (120 μg/mm 2 lesion area [ILPenta-120-3]) over 5 days. Cure rates at 6 months were 57% for ILSb-3 injections, 73% for ILSb-5 injections, and 72% for ILPenta-120-3 injections. Adverse effects were local irritation and injection-site pain-ILSb (60 patients): mild (25), moderate (4); IL pentamidine (30 patients): mild (4), moderate (3). In Study 2, 60 patients were randomized equally between five injections of ILSb and three injections of a double dose of IL pentamidine (240 μg/mm 2 ). In Study 2, cure rates were 67% for ILSb-5 injections and 73% for ILPenta-240-3. For three IL injections of pentamidine, efficacy was optimized at a dose of 120 μg/mm 2 lesion area. The cure rate of that regimen was similar to that for ILSb-5 injections and nonstatistically larger than that of ILSb-3 injections. IL pentamidine is an attractive alternative to ILSb on the basis of efficacy for Bolivian L. braziliensis, the threat of Sb-resistant parasites, tolerance, and patient convenience of three visits over 5 days.

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“…Pentavalent antimonials require daily injections and treatment duration is rather long. Resistance to pentavalent antimonials is increasing (5,6). Due to the antimonial resistance issue, amphotericin B (AMB) has been introduced as a first-line treatment.…”

Section: Introductionmentioning

confidence: 99%

Drug Targeting to Macrophages With Solid Lipid Nanoparticles Harboring Paromomycin: an In Vitro Evaluation Against L. major and L. tropica

et al. 2015

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Abstract. Leishmaniasis is a worldwide disease that leads to high mortality and morbidity in human populations. Today, leishmaniasis is managed via drug therapy. The drugs that are already in clinical use are limited to a number of toxic chemical compounds and their parasite drug resistance is increasing. It is therefore essential, in order to circumvent the current difficulties, to design a new anti-leishmanial drug treatment strategy. Besides producing new, active anti-leishmanial entities, another promising strategy could be developing novel delivery systems and formulations of the existing pharmaceutical ingredients to improve drug efficacy. In the present study, paromomycin sulfate (PM), as one of the promising antileishmanial drugs, was formulated in solid lipid nanoparticles (SLN), and its in vitro efficacy was investigated against different strains of Leishmania using a MTT test, Parasite-Rescue-Transformation-Assay, SYTO Green staining, and fluorescent microscope imaging. The results show that PM-loaded SLN is significantly more effective than PM in inhibiting parasite propagation (P<0.05) and that cytotoxicity of PM-SLN formulations is size dependent. According to our results, delivery of the drugs to the macrophages via nanoparticle utilization seems to be an accessible and practical approach.KEY WORDS: cutaneous leishmaniasis; drug delivery system; paromomycin sulfate; solid lipid nanoparticle.

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Glucantime-resistant Leishmania tropica isolated from Iranian patients with cutaneous leishmaniasis are sensitive to alternative antileishmania drugs

Cited by 64 publications

References 23 publications

The effect of verapamil on in vitro susceptibility of promastigote and amastigote stages of Leishmania tropica to meglumine antimoniate

The effect of verapamil on in vitro susceptibility of promastigote and amastigote stages of Leishmania tropica to meglumine antimoniate

Intralesional Pentamidine: A Novel Therapy for Single Lesions of Bolivian Cutaneous Leishmaniasis

Drug Targeting to Macrophages With Solid Lipid Nanoparticles Harboring Paromomycin: an In Vitro Evaluation Against L. major and L. tropica

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