Cutaneous <i>Leishmania tropica</i> in children: report of three imported cases successfully treated with liposomal amphotericin B

Knöpfel, Nicole; Noguera‐Morel, Lucero; Azorín, Daniel; Sanz, Francisco Javier Sanz; Torrelo, Antonio; Hernández‐Martín, Ángela

doi:10.1111/jdv.14434

Cited by 10 publications

(11 citation statements)

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“…Due to the toxicity of the current anti-leishmanial drugs, including the antimonials (first-line medication), amphotericin B (AmB) (2nd line medication), imidazoles, miltefosine, paromomycin and liposomal amphotericin B, as well as the emerging resistance, high cost of medications and long duration of the treatment regimen, there have been calls for the development of novel, effective drugs [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

The leishmanicidal effect of Lucilia sericata larval saliva and hemolymph on in vitro Leishmania tropica

et al. 2021

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Background Leishmaniasis is a major parasitic disease worldwide, except in Australia and Antarctica, and it poses a significant public health problem. Due to the absence of safe and effective vaccines and drugs, researchers have begun an extensive search for new drugs. The aim of the current study was to investigate the in vitro leishmanicidal activity of larval saliva and hemolymph of Lucilia sericata on Leishmania tropica. Methods The effects of different concentrations of larval products on promastigotes and intracellular amastigotes of L. tropica were investigated using the mouse cell line J774A.1 and peritoneal macrophages as host cells. The 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and direct observation and counting method were used to assess the inhibitory effects and cell cytotoxicity of the larval products. The effects of larval products on the amastigote form of L. tropica were quantitatively estimated by calculating the rate of macrophage infection, number of amastigotes per infected macrophage cell, parasite load and survival index. Results The 50% cytotoxicity concentration (CC50) value of both larval saliva and hemolymph was 750 µg/ml, and the 50% inhibitory concentration (IC50) values were 134 µg/ml and 60 µg/ml for larval saliva and larval hemolymph, respectively. The IC50 for Glucantime, used a positive control, was (11.65 µg/ml). Statistically significant differences in viability percentages of promastigotes were observed for different doses of both larval saliva and hemolymph when compared with the negative control (p ≤ 0.0001). Microscopic evaluation of the amastigote forms revealed that treatment with 150 µg/ml larval hemolymph and 450 µg/ml larval saliva significantly decreased the rate of macrophage infection and the number of amastigotes per infected macrophage cell. Conclusion Larval saliva and hemolymph of L. sericata have acceptable leishmanicidal properties against L. tropica.

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Section: Introductionmentioning

confidence: 99%

The leishmanicidal effect of Lucilia sericata larval saliva and hemolymph on in vitro Leishmania tropica

et al. 2021

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“…Using AmBisome® for the treatment of CL may not be as successful as VL due to poor infrastructure and number of patients in the endemic areas (Bhattacharya and Ali, 2016; Knöpfel et al, 2018; Wortmann et al, 2010). Search for new treatment modalities for CL is needed (Butsch et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Development of a topical liposomal formulation of Amphotericin B for the treatment of cutaneous leishmaniasis

Jaafari

Hatamipour

Alavizadeh

et al. 2019

International Journal for Parasitology: Drugs and Drug Resistan

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BackgroundCurrently, there is no topical treatment available for any form of cutaneous leishmaniasis (CL) in most of the endemic areas. The aim of the current study was to develop a topical nano-liposomal Amphotericin B (AmB) for the treatment of CL.Methodology/principal findingsLiposomes containing 0.1, 0.2 and 0.4% AmB (Lip-AmB) were formulated and characterized for the size, entrapment efficiency, long term stability, and skin penetration properties using Franz diffusion cells. Liposomes diameters were around 100 nm with no change during more than 20 months’ storage either at 4 °C or at room temperature. Franz diffusion cells studies showed that almost 4% of the applied formulations penetrated across the skin and the highest skin retention (73.92%) observed with Lip-AmB 0.4%. The median effective doses (ED50), the doses of AmB required to kill 50% of L. major amastigotes were 0.151, 0.151, and 0.0856 (μg/mL) in Lip-AmB 0.1, 0.2, 0.4%, respectively. Lip-AmB 0.4% caused 80% reduction in fluorescence intensity of GFP+ L. tropica infected macrophages at 5 μg/mL of AmB concentration. Topical Lip-AmB was applied twice a day for 4 weeks to the skin of BALB/c mice to treat lesions caused by L. major. Results showed the superiority of Lip-AmB 0.4% compared to Lip-AmB 0.2 and 0.1%. The parasite was completely cleared from the skin site of infection and spleens at week 8 and 12 post-infection in mice treated with Lip-AmB 0.4%. The results suggest that topical Lip-AmB 0.4% may be a useful tool in the treatment of CL and merits further investigation.

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“…16 By binding to ergosterol in the cell membranes of parasites, amphotericin B causes changes in cell membrane permeability, induction of metabolic shock and increased cell death. 11,16,17 Amphotericin B triggers the release of inflammatory molecules such as interleukin 1B, leading to fever, arthralgia, headache, and infusion-related gastrointestinal symptoms. [18][19][20] In addition, vasoconstriction of the afferent arteriole and its uptake by renal tubular cells trigger hypokalemia, hypomagnesemia, renal tubular acidosis, polyuria, and hyperazotemia.…”

Section: Discussionmentioning

confidence: 99%

“…9,[12][13][14][15] It has been stated that the difference in success rates in these treatments depends on the type of causative parasite, the dose, and duration of use of the drug. 12,[14][15][16][17] There are few data on the efficacy and safety of IV L-AmB in pediatric CL patients. 10,17 It has been reported that Leishmania tropica is associated with a low treatment response rate in pediatric patients.…”

Section: Introductionmentioning

confidence: 99%

“…12,[14][15][16][17] There are few data on the efficacy and safety of IV L-AmB in pediatric CL patients. 10,17 It has been reported that Leishmania tropica is associated with a low treatment response rate in pediatric patients. 10 In one study, the efficacy of IV L-AmB was found to be 43% in 24 pediatric patients with CL, and 42% of the patients experienced an infusionrelated adverse event that led to treatment discontinuation.…”

Section: Introductionmentioning

confidence: 99%

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Treatment of pediatric cutaneous leishmaniasis with liposomal amphotericin B

Erat

2022

Dermatologic Therapy

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The use of liposomal amphotericin B (L-AmB) in the treatment of cutaneous leishmaniasis (CL) is increasing. However, few data are available regarding the efficacy and safety of L-AmB in pediatric CL patients. Our aim in this study is to evaluate the efficacy and safety of L-AmB in pediatric CL patients. Pediatric patients admitted to a tertiary training and research hospital in a hyperendemic region for CL between January 2019 and May 2021 and receiving L-AmB therapy for CL were included in this retrospective study. L-AmB treatment was administered as 3 mg/kg for 5 consecutive days and on the 10th day, in a total of 6 doses (18 mg/kg total dose). A total of 52 pediatric patients who received L-AmB therapy for CL were included in the study.

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Cutaneous Leishmania tropica in children: report of three imported cases successfully treated with liposomal amphotericin B

Cited by 10 publications

References 10 publications

The leishmanicidal effect of Lucilia sericata larval saliva and hemolymph on in vitro Leishmania tropica

The leishmanicidal effect of Lucilia sericata larval saliva and hemolymph on in vitro Leishmania tropica

Development of a topical liposomal formulation of Amphotericin B for the treatment of cutaneous leishmaniasis

Treatment of pediatric cutaneous leishmaniasis with liposomal amphotericin B

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