scholarly journals Investigation of Drug Resistance in Leishmania tropica as Causative Agent of Canine Leishmaniasis

2020 ◽  
Author(s):  
Nami Ege Perk ◽  
İbrahim Çavuş ◽  
Ahmet Özbilgin
Keyword(s):  
Drug Resistance ◽  
Amphotericin B ◽  
Treatment Method ◽  
Polymerase Chain Reaction Method ◽  
Canine Leishmaniasis ◽  
Leishmania Tropica ◽  
Sodium Stibogluconate ◽  
Meglumine Antimoniate ◽  
Leishmania Spp ◽  
Ic50 Values

Objective: Leishmaniasis is endemic in 98 countries, and poses risk to 1 billion people in the world. The infection caused by obligatory intracellular parasite Leishmania spp. in dogs is called Canine Leishmaniasis (CanL). In this study, it was aimed to detect the resistance status of Leishmania tropica strains isolated from dogs in our country against amphotericin B, meglumine antimoniate and sodium stibogluconate applied in leishmaniasis treatment. Method: Leishmania spp. promastigotes, taken out from the liquid nitrogen were first cultured in NNN media, then the growing isolates were transferred to RPMI-1640 medium and abundant amount of promastigotes were obtained. Isolates were genotyped using real-time polymerase chain reaction method with primers and probes specific to the ITS-1 region of Leishmania spp. and in five isolates that were found to be L. tropica causing CanL, resistance status against amphotericin B, meglumine antimoniate and sodium stibogluconate was investigated by hemocytometer and XTT methods. Results: The mean IC50 values were determined as 10.60 mg/ml for meglumine antimoniate, 0.1471 mg/ml for sodium stibogluconate, 0.0328 μM/ml for amphotericin B by hemocytometer method. Average IC50 values determined by XTT method were 10.48 mg/ml for meglumine antimoniate, 0.1470 mg/ml for sodium stibogluconate, 0.0326 μM/ml for amphotericin B. Conclusion: According to our data, while L. tropica strains which were isolated from CanL cases which are very rarely found causative agents in dogs, were not found to be resistant to amphoreticin B and sodium stibogluconate, parasite developed drug resistance against meglumine antimoniate. In future, this situation is thought to be a problem during treatment in human cutaneous leishmaniasis cases.

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 Failure of Miltefosine Treatment in Two Dogs with NaturalLeishmania infantumInfection

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Daniela Proverbio ◽  
Eva Spada ◽  
Giada Bagnagatti De Giorgi ◽  
Roberta Perego
Keyword(s):  
Drug Resistance ◽  
Veterinary Medicine ◽  
Initial Treatment ◽  
Clinical Signs ◽  
Initial Response ◽  
Response To Therapy ◽  
The Other ◽  
Canine Leishmaniasis ◽  
Early Relapse ◽  
Meglumine Antimoniate

Two dogs, with naturally acquired canine leishmaniasis, were treated orally with miltefosine (2 mg/kg q 24 hr) and allopurinol (10 mg/kg q 12 hr) for 28 days. Both dogs showed good initial response to therapy, with reduction in clinical signs and improvement of clinicopathological changes. However, in both dogs, clinical and clinicopathological abnormalities recurred 150 days after initial treatment and a second course of miltefosine and allopurinol was administered. One dog failed to respond to the 2nd cycle of miltefosine treatment and the other dog responded initially but suffered an early relapse. Treatment with meglumine antimoniate (100 mg/kg q 24 hr for a minimum of 4 weeks) was then started in both dogs. Both dogs showed rapid clinical and clinicopathological improvement and to date they have not received further treatment for 420 and 270 days, respectively. In view of the low number of antileishmanial drugs available and the fact that some of these are used in human as well as veterinary medicine, it is of paramount importance that drug resistance is monitored and documented.

scholarly journals Diversity and Drug Resistance of Filamentous Fungi Isolated from the Fresh Raspberries

2021 ◽  
Author(s):  
Ewelina Farian ◽  
Angelina Wójcik-Fatla
Keyword(s):  
Drug Resistance ◽  
Food Safety ◽  
Human Health ◽  
Amphotericin B ◽  
Filamentous Fungi ◽  
Rubus Idaeus ◽  
Disc Diffusion ◽  
Potential Threat ◽  
Fungal Strains ◽  
Strip Method

AbstractFungi are one of the most widely distributed microorganisms in the environment, including food such as fruits, vegetables and other crops, posing a potential threat to food safety and human health. The aim of this study was to determine the diversity, intensity and drug resistance of potentially pathogenic filamentous fungi isolated from the fresh raspberries (Rubus idaeus L.). A total of 50 strains belonging to genera Fusarium, Cladosporium, Alternaria, Penicillium, Mucor, Rhizopus, Aspergillus and Acremonium were tested for drug resistance against 11 antifungals by disc diffusion and gradient strips methods. The average mycological contamination in the examined samples of raspberries amounted to 4.34 log CFU/g. The Cladosporium was isolated from all tested samples, followed by Alternaria and Fusarium with a frequency of 61% and 34%, respectively. The highest level of drug resistance was observed for Acremonium genera and Fusarium strains recorded a wide variation in drug resistance as revealed by susceptibility with amphotericin B and voriconzole with MICs ranged from 0.5–4 µg/ml and posaconazole with MICs ranging from 3–8 µg/ml. All fungal strains showed 100% resistance to caspofungin, fluconazole and flucytosine with both the methods, and 100% resistance to micafungin and anidulafungin in the gradient strip method.

New amphotericin B-gamma cyclodextrin formulation for topical use with synergistic activity against diverse fungal species and Leishmania spp

2014 ◽  
Vol 473 (1-2) ◽  
pp. 148-157 ◽  
Author(s):  
Helga K. Ruiz ◽  
Dolores R. Serrano ◽  
María Auxiliadora Dea-Ayuela ◽  
Pablo E. Bilbao-Ramos ◽  
Francisco Bolás-Fernández ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Fungal Species ◽  
Synergistic Activity ◽  
Leishmania Spp ◽  
Gamma Cyclodextrin

scholarly journals Canine Leishmaniasis: Serological Results in Private and Kennel Dogs Tested over a Six-Year Period (2009–2014) in Abruzzo and Molise Regions, Italy

2020 ◽  
Vol 8 (12) ◽  
pp. 1915
Author(s):  
Fabrizio De Massis ◽  
Carla Ippoliti ◽  
Simona Iannetti ◽  
Manuela Tittarelli ◽  
Sandro Pelini ◽  
...  
Keyword(s):  
Fluorescent Antibody ◽  
Antibody Test ◽  
Information Management System ◽  
Canine Leishmaniasis ◽  
Serological Tests ◽  
Leishmania Spp ◽  
Molise Region ◽  
Favorable Conditions ◽  
Laboratory Information Management

This paper reports the results of serological tests for the detection of antibodies against Leishmania spp. in Abruzzo and Molise regions from 2009 to 2014, with the aim of evaluating the presence and distribution of canine leishmaniasis. Data were extracted from the Laboratory Information Management System (LIMS) of the Istituto Zooprofilattico Sperimentale of Abruzzo and Molise, and then the dog identification numbers were matched with those stored in the Canine Registries of the two regions to get information about the age of dogs at time of testing. Dogs were considered positive when having an IFAT (Indirect Fluorescent Antibody Test) titer ≥1:80. In total, 41,631 dogs were tested, 85.3% from Abruzzo and 14.7% from Molise. At the provincial level, the percentage of positive dogs ranged from 5.2% (L’Aquila, Abruzzo region) to 21.8% (Campobasso, Molise region). Findings are consistent with the hypothesis that in the coastal areas, the relationships between the host, the vector, and the agent are more favorable for the spreading of CanL, and it seems that densely populated urban internal areas have less favorable conditions. Being a dog hosted in a kennel seems not to be a factor increasing the probability that dogs show positivity, even in long-term sheltering conditions.

Comparative mitochondrial proteomics of Leishmania tropica clinical isolates resistant and sensitive to meglumine antimoniate

2020 ◽  
Vol 119 (6) ◽  
pp. 1857-1871 ◽  
Author(s):  
Minoo Tasbihi ◽  
Faezeh Shekari ◽  
Homa Hajjaran ◽  
Majid Khanmohammadi ◽  
Ramtin Hadighi
Keyword(s):  
Clinical Isolates ◽  
Leishmania Tropica ◽  
Meglumine Antimoniate

scholarly journals In Vitro Susceptibilities of Leishmania donovani Promastigote and Amastigote Stages to Antileishmanial Reference Drugs: Practical Relevance of Stage-Specific Differences

2009 ◽  
Vol 53 (9) ◽  
pp. 3855-3859 ◽  
Author(s):  
Marieke Vermeersch ◽  
Raquel Inocêncio da Luz ◽  
Kim Toté ◽  
Jean-Pierre Timmermans ◽  
Paul Cos ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Leishmania Donovani ◽  
Crystalline Substance ◽  
Sodium Stibogluconate ◽  
Cellular Mechanisms ◽  
Intracellular Amastigotes ◽  
Discovery Research ◽  
Drug Discovery Research ◽  
Primary Mouse

ABSTRACT The in vitro susceptibilities of the reference strain Leishmania donovani MHOM/ET/67/L82 to sodium stibogluconate, amphotericin B, miltefosine, and the experimental compound PX-6518 were determined for extracellular log-phase promastigotes, established axenic amastigotes, fresh spleen-derived amastigotes, and intracellular amastigotes in primary mouse peritoneal macrophages. Susceptibility to amphotericin B did not differ across the various axenic models (50% inhibitory concentrations [IC50], 0.6 to 0.7 μM), and amphotericin B showed slightly higher potency against intracellular amastigotes (IC50, 0.1 to 0.4 μM). A similar trend was observed for miltefosine, with comparable efficacies against the extracellular (IC50, 0.4 to 3.8 μM) and intracellular (IC50, 0.9 to 4.3 μM) stages. Sodium stibogluconate, used either as Pentostam or as a crystalline substance, was inactive against all axenic stages (IC50, >64 μg SbV/ml) but showed good efficacy against intracellular amastigotes (IC50, 22 to 28 μg SbV/ml); the crystalline substance was about two to three times more potent (IC50, 9 to 11 μg SbV/ml). The activity profile of PX-6518 was comparable to that of sodium stibogluconate, but at a much higher potency (IC50, 0.1 μg/ml). In conclusion, the differential susceptibility determines which in vitro models are appropriate for either drug screening or resistance monitoring of clinical field isolates. Despite the more complex and labor-intensive protocol, the current results support the intracellular amastigote model as the gold standard for in vitro Leishmania drug discovery research and for evaluation of the resistance of field strains, since it also includes host cell-mediated effects. Axenic systems can be recommended only for compounds for which no cellular mechanisms are involved, for example, amphotericin B and miltefosine.

Relationship between the As2O3 Induced Expression of NF-κB and Drug Resistance in K562/ADR Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4414-4414
Author(s):  
Xiao-hong Zhang ◽  
Li-da Su ◽  
Xiao-ying Zhao ◽  
Qing-hua Lv
Keyword(s):  
Flow Cytometry ◽  
Drug Resistance ◽  
K562 Cells ◽  
Suppressive Effect ◽  
Resistance Mechanisms ◽  
Leukemic Cells ◽  
Ic50 Values ◽  
Induced Apoptosis ◽  
The Relationship ◽  
Cells Cultured

Abstract Summery: Anti-apoptosis is one of drug resistance mechanisms in leukemic cells. It was found in our early study that As2O3 can induce apoptosis of K562 cells, and this effect involve the degradation of IκB-αand consequently the activation of NF-κB. The relationship between drug resistance of leukemic cells and the expression of both IκB-αand NF-κB associated with apoptosis induced by arsenic trioxide(As2O3) was studied in K562 and K562/ADR cells. Methods: Apoptosis was induced in K562 and K562/ADR cells cultured with As2O3 in different concentrations. Western blot was used to analyze the expression of NF-κB in nuclear and IκB-α in cytoplasm of these cells. Apoptosis and degradation of IκB-αprotein were also observed by flow cytometry. Results: The suppressive effect of As2O3 on proliferation of K562/ADR was lower than that in K562 cell, IC50 values were 19.07μmol/L and 5.26μmol/L, respectively. After exposure to As2O3, the ratio of apoptosis cells increased with the concentration of As2O3 in K562 cells, from(13.25±1.83)% to (50.56±8.62)% with variation of As2O3 from 1μmol/L to 4μmol/L(P<0.05). The ratio of apoptosis cells in K562/ADR cultured with 4μmol/L As2O3 was significantly lower than that in K562 cells, (8.00±1.47)% vs. (50.56±8.62)%, (P<0.05). The level of IκB-α in K562 cytoplasm was down-regulated from (88.07±0.99)% to (49.21±0.95)%, (P<0.01) after As2O3 stimulation, while NF-κB in nuclear was up-regulated, that was not found in K562/ADR cells. Conclusion: As2O3 could induce apoptosis of K562 cells, associated with the degradation of IκB-αand the activation of NF-κB. There were resistance to As2O3 induced apoptosis and an abnormal regulation of NF-κB expression by As2O3 in K562/ADR cells.

scholarly journals Imported leishmaniasis in a dog in a sandfly-populated area in northeastern Romania

2017 ◽  
Vol 29 (5) ◽  
pp. 683-685 ◽  
Author(s):  
Geta Pavel ◽  
Dorina Timofte ◽  
Diana Mocanu ◽  
Razvan Malancus ◽  
Carmen Solcan
Keyword(s):  
Clinical Case ◽  
Canine Leishmaniasis ◽  
Populated Area ◽  
Cytologic Examination ◽  
Fine Needle ◽  
Clinical Symptomatology ◽  
Fine Needle Aspirates ◽  
Public Health Threat ◽  
Significant Public Health ◽  
Leishmania Spp

We report the importation of a clinical case of canine leishmaniasis (CanL) in Romania, a country where several types of sandflies are present with the potential to develop a new focus of CanL. The Staffordshire Bull Terrier dog was imported into Romania from Spain 1.5 y before he developed clinical symptomatology that included proliferative dermatitis, lymphadenomegaly, and bilateral uveitis. Hematologic analyses showed regenerative anemia and subacute inflammation. Cytologic examination of lymph node fine-needle aspirates revealed Leishmania spp. amastigotes that were confirmed as L. infantum by PCR. The importation of canine leishmania cases into nonendemic areas in which the vector exists could potentially lead to the silent spread of a disease posing a significant public health threat.

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