scholarly journals In Vitro Reduced Susceptibility to Pentavalent Antimonials of a Leishmania infantum Isolate from a Human Cutaneous Leishmaniasis Case in Central Italy

2021 ◽  
Vol 9 (6) ◽  
pp. 1147
Author(s):  
Aurora Diotallevi ◽  
Gloria Buffi ◽  
Giovanni Corbelli ◽  
Marcello Ceccarelli ◽  
Margherita Ortalli ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Infantum ◽  
Histopathological Examination ◽  
Central Italy ◽  
Complete Healing ◽  
Response To Treatment ◽  
Meglumine Antimoniate ◽  
Parasitological Diagnosis ◽  
New Treatment

Cutaneous leishmaniasis (CL) caused by Leishmania (Leishmania) infantum is endemic in the Mediterranean basin. Here we report an autochthonous case of CL in a patient living in central Italy with an unsatisfactory response to treatment with intralesional Meglumine Antimoniate and in vitro demonstration of reduced susceptibility to SbIII. Parasitological diagnosis was first achieved by histopathology on tissue biopsy and the patient was treated with a local infiltration of Meglumine Antimoniate. Since the clinical response at 12 weeks from the treatment’s onset was deemed unsatisfactory, two further skin biopsies were taken for histopathological examination, DNA extraction and parasite isolation. L. (L.) infantum was identified by molecular typing. The low susceptibility to Meglumine Antimoniate was confirmed in vitro: the promastigotes from the patient strain showed significantly lower susceptibility to SbIII (the active trivalent form of antimonial) compared to the reference strain MHOM/TN/80/IPT1. The patient underwent a new treatment course with intravenous liposomal Amphotericin B, reaching complete healing of the lesion. Additional studies are needed to confirm the epidemiological and clinical relevance of reduced susceptibility to SbIII of human L. (L.) infantum isolate in Italy.

scholarly journals Depot Subcutaneous Injection with Chalcone CH8-Loaded Poly(Lactic-Co-Glycolic Acid) Microspheres as a Single-Dose Treatment of Cutaneous Leishmaniasis

2017 ◽  
Vol 62 (3) ◽  
Author(s):  
Ariane de Jesus Sousa-Batista ◽  
Wallace Pacienza-Lima ◽  
Natalia Arruda-Costa ◽  
Camila Alves Bandeira Falcão ◽  
Maria Ines Ré ◽  
...  
Keyword(s):  
Single Dose ◽  
Cutaneous Leishmaniasis ◽  
Glycolic Acid ◽  
Content Type ◽  
Dose Treatment ◽  
Meglumine Antimoniate ◽  
Plga Microparticles ◽  
Single Dose Treatment

ABSTRACTConventional chemotherapy of cutaneous leishmaniasis (CL) is based on multiple parenteral or intralesional injections with systemically toxic drugs. Aiming at a single-dose localized therapy, biodegradable poly(lactic-co-glycolic acid) (PLGA) microparticles loaded with 7.8% of an antileishmanial nitrochalcone named CH8 (CH8/PLGA) were constructed to promote sustained subcutaneous release.In vitro, murine macrophages avidly phagocytosed CH8/PLGA smaller than 6 μm without triggering oxidative mechanisms. Upon 48 h of incubation, both CH8 and CH8/PLGA were 40 times more toxic to intracellularLeishmania amazonensisthan to macrophages.In vivo, BALB/c were given one or three subcutaneous injections in the infected ear with 1.2 mg/kg of CH8 in free or CH8/PLGA forms, whereas controls received three CH8-equivalent doses of naked PLGA microparticles or meglumine antimoniate (Glucantime; Sanofi-Aventis). Although a single injection with CH8/PLGA reduced the parasite loads by 91%, triple injections with free CH8 or CH8/PLGA caused 80 and 97% reductions, respectively, in relation to saline controls. Meglumine antimoniate treatment was the least effective (only 36% reduction) and the most toxic, as indicated by elevated alanine aminotransferase serum levels. Together, these findings show that CH8/PLGA microparticles can be effectively and safely used for single-dose treatment of CL.

In vitro evaluation of the effectiveness and cytotoxicity of meglumine antimoniate microspheres produced by spray drying against Leishmania infantum

2008 ◽  
Vol 102 (6) ◽  
pp. 1243-1247 ◽  
Author(s):  
G. Pujals ◽  
J. M. Suñé-Negre ◽  
P. Pérez ◽  
E. García ◽  
M. Portus ◽  
...  
Keyword(s):  
Spray Drying ◽  
Leishmania Infantum ◽  
In Vitro Evaluation ◽  
Meglumine Antimoniate

scholarly journals Granulomatous rhinitis secondary to feline leishmaniosis: report of an unusual presentation and therapeutic complications

2018 ◽  
Vol 4 (2) ◽  
pp. 205511691881137 ◽  
Author(s):  
Rodolfo Oliveira Leal ◽  
Hugo Pereira ◽  
Clara Cartaxeiro ◽  
Esmeralda Delgado ◽  
Maria da Conceição Peleteiro ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Fluid Therapy ◽  
Leishmania Infantum ◽  
Histopathological Examination ◽  
Kidney Injury ◽  
Needle Aspiration ◽  
Cutaneous Lesions ◽  
Meglumine Antimoniate ◽  
Nasal Tissue ◽  
Leishmania Amastigotes

Case summary A 12-year-old male neutered domestic shorthair cat underwent rhinoscopy due to inspiratory dyspnoea and stertor. Rhinoscopy showed signs of chronic rhinitis and a multinodular nasopharyngeal mucosa. A marked infiltrate of macrophages that contained intracellular parasitic forms morphologically compatible with Leishmania amastigotes were observed on histopathological examination of nasal and nasopharyngeal biopsies. PCR from nasal tissue was positive for Leishmania infantum DNA, confirming the diagnosis of granulomatous rhinitis secondary to this parasite. Two eyelid nodules were identified 2 weeks later. Fine-needle aspiration revealed Leishmania amastigotes within macrophages and in the background. Allopurinol therapy was started, but 5 days later the cat developed dermatological signs compatible with a cutaneous adverse drug reaction. The drug was discontinued and meglumine antimoniate prescribed. Twenty-five days later, the cat presented with acute kidney injury and meglumine antimoniate was discontinued. Despite clinical improvement after fluid therapy, mild azotaemia persisted. The cat was subsequently treated with nucleotides and active hexose correlated compounds (N-AHCC). Four months later upper respiratory signs were exacerbated. A relapse of granulomatous rhinitis was suspected and miltefosine therapy started. Chronic kidney disease (CKD) worsened during miltefosine treatment, having improved under fluid therapy. Since then, the cat has been treated with N-AHCC and renal diet and at the time of writing shows stable CKD with no recurrence of respiratory signs. Relevance and novel information This case describes Leishmania infantum as a cause of granulomatous rhinitis in a cat without cutaneous lesions, reporting the alternative use of N-AHCC and miltefosine when allopurinol seemed to have induced a cutaneous rash and there was acute kidney injury (AKI) after meglumine antimoniate therapy.

scholarly journals In VitroSensitivity of PairedLeishmania(Viannia)braziliensisSamples Isolated before Meglumine Antimoniate Treatment and after Treatment Failure or Reactivation of Cutaneous Leishmaniasis

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Cibele Baptista ◽  
Luciana de Freitas Campos Miranda ◽  
Maria de Fátima Madeira ◽  
Leonor Laura Pinto Leon ◽  
Fátima Conceição-Silva ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Cutaneous Leishmaniasis ◽  
Drug Exposure ◽  
Lethal Dose ◽  
Poor Response ◽  
Leishmania Braziliensis ◽  
Meglumine Antimoniate ◽  
Intralesional Administration ◽  
The Difference

This study evaluated thein vitrosensitivity of pairedLeishmania braziliensissamples isolated from the same patient before pentavalent antimonial treatment (Sample A) and after treatment failure or cutaneous leishmaniasis reactivation (Sample B) in patients undergoing intralesional administration or injections (5 mgSbV/kg/d) of meglumine antimoniate. Fourteen samples from 7 patients were studied. After 24 h of drug exposure, 50% lethal dose (LD50) values for promastigotes ranged from 0.37 mg/mL to 5.86 mg/mL for samples obtained before treatment (A) and 0.89 mg/mL to 7.80 mg/mL for samples obtained after treatment (B). After 48 h, LD50values ranged from 0.37 mg/mL to 5.75 mg/mL and 0.70 mg/mL to 7.68 mg/mL for A and B samples, respectively. After 48 h, LD50values for amastigotes ranged from 11.7 to 44.3 μg/mL for A samples and 13.7 to 52.7 μg/mL for B samples. Of 7 patients, 1 discontinued treatment and 6 were cured after retreatment with amphotericin B (4 cases) or meglumine antimoniate (2 cases). Overall the B samples had higher LD50values than A samples; however the difference was not significant. These results do not support the hypothesis that low-dose and intralesional treatments induce selection of resistant parasitesin vitroand suggest that other factors may influence therapeutic outcome in patients with poor response to initial treatment.

scholarly journals Therapeutic Potential of Green Synthesized Copper Nanoparticles Alone or Combined with Meglumine Antimoniate (Glucantime®) in Cutaneous Leishmaniasis

Nanomaterials ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 891
Author(s):  
Aishah E. Albalawi ◽  
Sobhy Abdel-Shafy ◽  
Amal Khudair Khalaf ◽  
Abdullah D. Alanazi ◽  
Parastoo Baharvand ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Copper Nanoparticles ◽  
Leishmania Major ◽  
Therapeutic Potential ◽  
No Production ◽  
Dependent Manner ◽  
Meglumine Antimoniate ◽  
The Mean ◽  
Dose Dependent

Background: In recent years, the focus on nanotechnological methods in medicine, especially in the treatment of microbial infections, has increased rapidly. Aim: The present study aims to evaluate in vitro and in vivo antileishmanial effects of copper nanoparticles (CuNPs) green synthesized by Capparis spinosa fruit extract alone and combined with meglumine antimoniate (MA). Methods: CuNPs were green synthesized by C. spinosa methanolic extract. The in vitro antileishmanial activity of CuNPs (10–200 µg/mL) or MA alone (10–200 µg/mL), and various concentrations of MA (10–200 μg/mL) along with 20 μg/mL of CuNPs, was assessed against the Leishmania major (MRHO/IR/75/ER) amastigote forms and, then tested on cutaneous leishmaniasis induced in male BALB/c mice by L. major. Moreover, infectivity rate, nitric oxide (NO) production, and cytotoxic effects of CuNPs on J774-A1 cells were evaluated. Results: Scanning electron microscopy showed that the particle size of CuNPs was 17 to 41 nm. The results demonstrated that CuNPs, especially combined with MA, significantly (p < 0.001) inhibited the growth rate of L. major amastigotes and triggered the production of NO (p < 0.05) in a dose-dependent manner. CuNPs also had no significant cytotoxicity in J774 cells. The mean number of parasites was significantly (p < 0.05) reduced in the infected mice treated with CuNPs, especially combined with MA in a dose-dependent response. The mean diameter of the lesions decreased by 43 and 58 mm after the treatment with concentrations of 100 and 200 mg/mL of CuNPs, respectively. Conclusion: The findings of the present study demonstrated the high potency and synergistic effect of CuNPs alone and combined with MA in inhibiting the growth of amastigote forms of L. major, as well as recovery and improving cutaneous leishmaniasis (CL) induced by L. major in BALB/c mice. Additionally, supplementary studies, especially in clinical settings, are required.

scholarly journals An old drug and different ways to treat cutaneous leishmaniasis: Intralesional and intramuscular meglumine antimoniate in a reference center, Rio de Janeiro, Brazil

2021 ◽  
Vol 15 (9) ◽  
pp. e0009734
Author(s):  
Carla Oliveira-Ribeiro ◽  
Maria Inês Fernandes Pimentel ◽  
Liliane de Fátima Antonio Oliveira ◽  
Érica de Camargo Ferreira e Vasconcellos ◽  
Fatima Conceição-Silva ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Rio De Janeiro ◽  
Treatment Interruption ◽  
Complete Healing ◽  
Cutaneous Lesions ◽  
Chi Square ◽  
Standard Regimen ◽  
Historical Cohort ◽  
Reference Center ◽  
Meglumine Antimoniate

Background Treatment of cutaneous leishmaniasis (CL) remains challenging since the drugs currently used are quite toxic, thus contributing to lethality unrelated to the disease itself but to adverse events (AE). The main objective was to evaluate different treatment regimens with meglumine antimoniate (MA), in a reference center in Rio de Janeiro, Brazil. Methodology A historical cohort of 592 patients that underwent physical and laboratory examination were enrolled between 2000 and 2017. The outcome measures of effectiveness were epithelialization and complete healing of cutaneous lesions. AE were graded using a standardized scale. Three groups were evaluated: Standard regimen (SR): intramuscular (IM) MA 10–20 mg Sb5+/kg/day during 20 days (n = 46); Alternative regimen (AR): IM MA 5 mg Sb5+/kg/day during 30 days (n = 456); Intralesional route (IL): MA infiltration in the lesion(s) through subcutaneous injections (n = 90). Statistical analysis was performed through Fisher exact and Pearson Chi-square tests, Kruskal-Wallis, Kaplan-Meier and log-rank tests. Results SR, AR and IL showed efficacy of 95.3%, 84.3% and 75.9%, with abandonment rate of 6.5%, 2.4% and 3.4%, respectively. IL patients had more comorbidities (58.9%; p = 0.001), were mostly over 50 years of age (55.6%), and had an evolution time longer than 2 months (65.6%; p = 0.02). Time for epithelialization and complete healing were similar in IL and IM MA groups (p = 0.9 and p = 0.5; respectively). Total AE and moderate to severe AE that frequently led to treatment interruption were more common in SR group, while AR and IL showed less toxicity. Conclusions/Significance AR and IL showed less toxicity and may be good options especially in CL cases with comorbidities, although SR treatment was more effective. IL treatment was an effective and safe strategy, and it may be used as first therapy option as well as a rescue scheme in patients initially treated with other drugs.

scholarly journals Treatment of canine visceral leishmaniasis with Milteforan™ induces Leishmania infantum resistance to miltefosine and amphotericin B

2021 ◽  
Author(s):  
Gustavo Gonçalves ◽  
Monique Paiva Campos ◽  
Alessandra Silva Gonçalves ◽  
Lia Carolina Soares Medeiros ◽  
Fabiano Borges Figueiredo
Keyword(s):  
Visceral Leishmaniasis ◽  
Amphotericin B ◽  
Leishmania Infantum ◽  
Cross Resistance ◽  
Canine Visceral Leishmaniasis ◽  
In Vitro Susceptibility ◽  
Meglumine Antimoniate ◽  
Parasite Fitness ◽  
The Impact

Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is caused by Leishmania infantum in the Americas. Since the use of Milteforam™ was authorized to treat canine visceral leishmaniasis (CVL) in Brazil in 2017, there has also been fear of the emergence of parasites resistant to this drug and, through cross-resistance mechanisms, to meglumine antimoniate and amphotericin B. Additionally, the literature shows that acquisition of resistance is followed by increased parasite fitness, with higher rates of proliferation, infectivity and metacyclogenesis, which are determining factors for parasite virulence. In this context, this study aims to analyze the impact of treating a dog with Milteforan™ on the generation of parasites resistant to miltefosine, meglumine antimoniate, and amphotericin B. To this end, in vitro susceptibility tests were conducted against these drugs with T0 (parasites isolated from the dog before treatment with Milteforan™), T1 (after one course of treatment), and T2 (after two courses of treatment) isolates. The rates of cell proliferation, infectivity, and metacyclogenesis of the isolates were also evaluated. The results indicate a gradual increase in parasite resistance to miltefosine and amphotericin B with increasing the number of treatment courses. A trend increase in the metacyclogenesis rate of the parasites was also observed as drug resistance increased. Therefore, treatment of CVL with Milteforan™ induces resistance to miltefosine and amphotericin B as well as changes in parasite fitness, and may have an impact on animal and human public health.

scholarly journals Mixed Formulation of Conventional and Pegylated Meglumine Antimoniate-Containing Liposomes Reduces Inflammatory Process and Parasite Burden in Leishmania infantum-Infected BALB/c Mice

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Levi Eduardo Soares Reis ◽  
Rory Cristiane Fortes de Brito ◽  
Jamille Mirelle de Oliveira Cardoso ◽  
Fernando Augusto Siqueira Mathias ◽  
Rodrigo Dian Oliveira Aguiar Soares ◽  
...  
Keyword(s):  
T Cells ◽  
Leishmania Infantum ◽  
Inflammatory Process ◽  
Parasite Burden ◽  
T Cell Subsets ◽  
Content Type ◽  
Meglumine Antimoniate ◽  
First Choice ◽  
Ifn Γ

ABSTRACT Pentavalent antimonial has been the first choice treatment for visceral leishmaniasis; however, it has several side effects that leads to low adherence to treatment. Liposome-encapsulated meglumine antimoniate (MA) arises as an important strategy for chemotherapy enhancement. We evaluated the immunopathological changes using the mixture of conventional and pegylated liposomes with MA. The mice were infected with Leishmania infantum and a single-dose treatment regimen. Comparison was made with groups treated with saline, empty liposomes, free MA, and a liposomal formulation of MA (Lipo MA). Histopathological analyses demonstrated that animals treated with Lipo MA showed a significant decrease in the inflammatory process and the absence of granulomas. The in vitro stimulation of splenocytes showed a significant increase of gamma interferon (IFN-γ) produced by CD8+ T cells and a decrease in interleukin-10 (IL-10) produced by CD4+ and CD8+ T cells in the Lipo MA. Furthermore, the Lipo MA group showed an increase in the IFN-γ/IL-10 ratio in both CD4+ and CD8+ T cell subsets. According to the parasite load evaluation using quantitative PCR, the Lipo MA group showed no L. infantum DNA in the spleen (0.0%) and 41.4% in the liver. In addition, we detected a low positive correlation between parasitism and histopathology findings (inflammatory process and granuloma formation). Thus, our results confirmed that Lipo MA is a promising antileishmanial formulation able to reduce the inflammatory response and induce a type 1 immune response, accompanied by a significant reduction of the parasite burden into hepatic and splenic compartments in treated animals.

scholarly journals Increased Leishmania infantum resistance to miltefosine and amphotericin B after treatment of a dog with miltefosine and allopurinol

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Gustavo Gonçalves ◽  
Monique Paiva Campos ◽  
Alessandra Silva Gonçalves ◽  
Lia Carolina Soares Medeiros ◽  
Fabiano Borges Figueiredo
Keyword(s):  
Amphotericin B ◽  
Leishmania Infantum ◽  
Resistance Mechanisms ◽  
Canine Leishmaniasis ◽  
Cross Resistance ◽  
In Vitro Susceptibility ◽  
Meglumine Antimoniate ◽  
Number Of Treatment ◽  
The Impact

Abstract Background Leishmania infantum is the most important etiological agent of visceral leishmaniasis in the Americas and Mediterranean region, and the dog is the main host. Miltefosine was authorized to treat canine leishmaniasis (CanL) in Brazil in 2017, but there is a persistent fear of the emergence of parasites resistant not only to this drug but, through cross-resistance mechanisms, also to meglumine antimoniate and amphotericin B. Additionally, the literature shows that acquisition of resistance is followed by increased parasite fitness, with higher rates of proliferation, infectivity and metacyclogenesis, which are drivers of parasite virulence. In this context, the aim of this study was to analyze the impact of treating a dog with miltefosine and allopurinol on the generation of parasites resistant to miltefosine, amphotericin B and meglumine antimoniate. Methods In vitro susceptibility tests were conducted against miltefosine, amphotericin B and meglumine antimoniate with T0 (parasites isolated from a dog before treatment with miltefosine plus allopurinol), T1 (after 1 course of treatment) and T2 (after 2 courses of treatment) isolates. The rates of cell proliferation, infectivity and metacyclogenesis of the isolates were also evaluated. Results The results indicate a gradual increase in parasite resistance to miltefosine and amphotericin B with increasing the number of treatment courses. An increasing trend in the metacyclogenesis rate of the parasites was also observed as drug resistance increased. Conclusion The data indicates an increased L. infantum resistance to miltefosine and amphotericin B after the treatment of a dog with miltefosine plus allopurinol. Further studies with a larger number of L. infantum strains isolated from dogs with varied immune response profiles and undergoing different treatment regimes, are advocated. Graphical Abstract

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