scholarly journals In vitro susceptibility of Leishmania infantum to meglumine antimoniate in isolates from repeated leishmaniasis episodes in HIV-coinfected patients

2001 ◽  
Vol 47 (1) ◽  
pp. 120-121 ◽  
Author(s):  
J. Carrio
Keyword(s):  
Leishmania Infantum ◽  
In Vitro Susceptibility ◽  
Meglumine Antimoniate

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 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

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

2011 ◽  
Vol 110 (3) ◽  
pp. 1113-1117 ◽  
Author(s):  
Azar Shokri ◽  
Iraj Sharifi ◽  
Ali Khamesipour ◽  
Nozar Nakhaee ◽  
Majid Fasihi Harandi ◽  
...  
Keyword(s):  
Leishmania Tropica ◽  
In Vitro Susceptibility ◽  
Meglumine Antimoniate

scholarly journals In Vitro Susceptibility to Miltefosine of Leishmania infantum (syn. L. chagasi) Isolates from Different Geographical Areas in Brazil

2021 ◽  
Vol 9 (6) ◽  
pp. 1228
Author(s):  
Caroline Ricce Espada ◽  
Erica V. de Castro Levatti ◽  
Mariana Côrtes Boité ◽  
Dorcas Lamounier ◽  
Jorge Alvar ◽  
...  
Keyword(s):  
Leishmania Infantum ◽  
Oral Drug ◽  
Efficacy And Safety ◽  
In Vitro Susceptibility ◽  
Intracellular Amastigotes ◽  
Geographic Regions ◽  
Therapeutic Tools ◽  
Cure Rates ◽  
Intracellular Amastigote

Treatment of visceral leishmaniasis in Brazil still relies on meglumine antimoniate, with less than ideal efficacy and safety, making new therapeutic tools an urgent need. The oral drug miltefosine was assayed in a phase II clinical trial in Brazil with cure rates lower than previously demonstrated in India. The present study investigated the susceptibility to miltefosine in 73 Brazilian strains of Leishmania infantum from different geographic regions, using intracellular amastigote and promastigote assays. The EC50 for miltefosine of 13 of these strains evaluated in intracellular amastigotes varied between 1.41 and 4.57 μM. The EC50 of the 73 strains determined in promastigotes varied between 5.89 and 23.7 μM. No correlation between in vitro miltefosine susceptibility and the presence of the miltefosine sensitive locus was detected among the tested strains. The relatively low heterogeneity in miltefosine susceptibility observed for the 73 strains tested in this study suggests the absence of decreased susceptibility to miltefosine in Brazilian L. infantum and does not exclude future clinical evaluation of miltefosine for VL treatment in Brazil.

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 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 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.

Sign in / Sign up

Export Citation Format

Share Document