scholarly journals Experimental Evaluation of Second-Line Oral Treatments of Visceral Leishmaniasis Caused by Leishmania infantum

1999 ◽  
Vol 43 (1) ◽  
pp. 172-174 ◽  
Author(s):  
Jean-Pierre Gangneux ◽  
Michael Dullin ◽  
Annie Sulahian ◽  
Yves Jean-Francois Garin ◽  
Francis Derouin
Keyword(s):  
Visceral Leishmaniasis ◽  
Murine Model ◽  
Experimental Evaluation ◽  
Leishmania Infantum ◽  
Parasite Load ◽  
Second Line ◽  
Meglumine Antimoniate ◽  
Marked Activity

ABSTRACT In a murine model of Leishmania infantum visceral leishmaniasis, metronidazole, ketoconazole, fluconazole, itraconazole, and terbinafine were less effective than antimonial agents in reducing hepatic parasite load. Ketoconazole potentiated the effect of meglumine antimoniate reference therapy through its marked activity against spleen infection.

scholarly journals Efficacy of Spironolactone Treatment in Murine Models of Cutaneous and Visceral Leishmaniasis

2021 ◽  
Vol 12 ◽  
Author(s):  
Valter Viana Andrade-Neto ◽  
Juliana da Silva Pacheco ◽  
Job Domingos Inácio ◽  
Elmo Eduardo Almeida-Amaral ◽  
Eduardo Caio Torres-Santos ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Cutaneous Lesion ◽  
Parasite Burden ◽  
Parasite Load ◽  
New Drugs ◽  
Drug Candidate ◽  
Success Rates ◽  
Meglumine Antimoniate ◽  
Future Possibility

Translational studies involving the reuse and association of drugs are approaches that can result in higher success rates in the discovery and development of drugs for serious public health problems, including leishmaniasis. If we consider the number of pathogenic species in relation to therapeutic options, this arsenal is still small, and each drug possesses a disadvantage in terms of toxicity, efficacy, price, or treatment regimen. In the search for new drugs, we performed a drug screening of L. amazonensis promastigotes and intracellular amastigotes of fifty available drugs belonging to several classes according to their pharmacophoric group. Spironolactone, a potassium-sparing diuretic, proved to be the most promising drug candidate. After demonstrating the in vitro antileishmanial activity, we evaluated the efficacy on a murine experimental model with L. amazonensis and L. infantum. The treatment controlled the cutaneous lesion and reduced the parasite burden of L. amazonensis significantly, as effectively as meglumine antimoniate. The treatment of experimental visceral leishmaniasis was effective in reducing the parasite load on the main affected organs (spleen and liver) via high doses of spironolactone. The association between spironolactone and meglumine antimoniate promoted better control of the parasite load in the spleen and liver compared to the group treated with meglumine antimoniate alone. These results reveal a possible benefit of the concomitant use of spironolactone and meglumine antimoniate that should be studied more in depth for the future possibility of repositioning for leishmaniasis co-therapy.

scholarly journals Efficacy of Combined Therapy with Liposome-Encapsulated Meglumine Antimoniate and Allopurinol in Treatment of Canine Visceral Leishmaniasis

2012 ◽  
Vol 56 (6) ◽  
pp. 2858-2867 ◽  
Author(s):  
Sydnei M. da Silva ◽  
Izabela F. G. Amorim ◽  
Raul R. Ribeiro ◽  
Erly G. Azevedo ◽  
Cynthia Demicheli ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Visceral Leishmaniasis ◽  
Drug Combination ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Parasite Load ◽  
The Other ◽  
Sand Flies ◽  
Content Type ◽  
Meglumine Antimoniate

ABSTRACTAn innovative liposomal formulation of meglumine antimoniate (LMA) was recently reported to promote both long-term parasite suppression and reduction of infectivity to sand flies in dogs with visceral leishmaniasis. However, 5 months after treatment, parasites were still found in the bone marrow of all treated dogs. In order to improve treatment with LMA, the present study aimed to evaluate its efficacy in combination with allopurinol. Mongrel dogs naturally infected withLeishmania infantumwere treated with six doses of LMA (6.5 mg Sb/kg of body weight/dose) given at 4-day intervals, plus allopurinol (20 mg/kg/24 hper os) for 140 days. Comparison was made with groups treated with LMA, allopurinol, empty liposomes plus allopurinol, empty liposomes, and saline. Dogs remained without treatment from day 140 to 200 after the start of treatment. The drug combination promoted both clinical improvement of dogs and significant reduction in the parasitic load in bone marrow and spleen on days 140 and 200 compared to these parameters in the pretreatment period. This is in contrast with the other protocols, which did not result in significant reduction of the bone marrow parasite load on day 200. Strikingly, the combined treatment, in contrast to the other regimens, induced negative quantitative PCR (qPCR) results in the liver of 100% of the dogs. Both xenodiagnosis and skin parasite determination by qPCR indicated that the drug combination was effective in blocking the transmission of skin parasites to sand flies. Based on all of the parasitological tests performed on day 200, 50% of the animals that received the combined treatment were considered cured.

scholarly journals Quantification of Leishmania infantum Kinetoplast DNA for Monitoring the Response to Meglumine Antimoniate Therapy in Visceral Leishmaniasis

2013 ◽  
Vol 88 (5) ◽  
pp. 868-871 ◽  
Author(s):  
Bahman Pourabbas ◽  
Zahra Rezaee ◽  
Abdolkarim Ghadimi Moghadam ◽  
Abdolvahab Alborzi ◽  
Gholamreza Pouladfar
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Infantum ◽  
Kinetoplast Dna ◽  
Meglumine Antimoniate

scholarly journals Hemostatic assessment of dogs associated with hepatic parasite load of Leishmania infantum chagasi

2016 ◽  
Vol 25 (2) ◽  
pp. 244-247
Author(s):  
Mariana de Medeiros Torres ◽  
Arleana do Bom Parto Ferreira de Almeida ◽  
Daphine Ariadne Jesus de Paula ◽  
Adriane Jorge Mendonça ◽  
Luciano Nakazato ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Infantum ◽  
Rank Correlation ◽  
Immunological Response ◽  
Parasite Load ◽  
Serum Biochemistry ◽  
Screening Tests ◽  
Hemorrhagic Diathesis ◽  
Spearman’S Rank Correlation ◽  
Leishmania Infantum Chagasi

Abstract Leishmania infantum chagasi liver parasite load was compared to hemostatic abnormalities, as well as to clinical, laboratorial, and histopathological findings in dogs with visceral leishmaniasis. The liver parasite load of 30 dogs L. infantum chagasi naturally-infected was evaluated by quantitative real- time PCR and the results were compared with serum biochemistry and primary and secondary hemostasis findings. Moreover, hepatic histological lesions were described in these dogs. Prolonged bleeding time, prothrombin time (PT), and activated partial thromboplastin time (APTT), were observed in the group with visceral leishmaniasis. Eleven dogs presented inflammatory liver lesions, with predominance of mild multifocal mononuclear periportal hepatitis. No association between the presence of parasites and abnormalities in screening tests was observed by Spearman’s rank correlation coefficient. The clinical progression in leishmaniasis is associated with the occurrence of hemorrhagic diathesis, which depends not only on the presence of the parasite but also the inflammatory process, compromised immunological response, hepatic and renal failure in symptomatic dogs.

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 A clioquinol-containing Pluronic® F127 polymeric micelle system is effective in the treatment of visceral leishmaniasis in a murine model

Parasite ◽  
2020 ◽  
Vol 27 ◽  
pp. 29 ◽  
Author(s):  
Grasiele S.V. Tavares ◽  
Débora V.C. Mendonça ◽  
Isabela A.G. Pereira ◽  
João A. Oliveira-da-Silva ◽  
Fernanda F. Ramos ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Murine Model ◽  
Parasite Load ◽  
Polymeric Micelle ◽  
Oral Route ◽  
Immunological Parameters ◽  
Gm Csf ◽  
Ifn Γ ◽  
Antibody Levels ◽  
Micelle System

A clioquinol (ICHQ)-containing Pluronic® F127 polymeric micelle system (ICHQ/Mic) was recently shown to be effective against Leishmania amazonensis infection in a murine model. In the present study, ICHQ/Mic was tested against L. infantum infection. BALB/c mice (n = 12 per group) were infected with L. infantum stationary promastigotes through subcutaneous injection and, 45 days after challenge, received saline or were treated via the subcutaneous route with empty micelles, ICHQ or ICHQ/Mic. In addition, animals were treated with miltefosine by the oral route, as a drug control. Half of the animals were euthanized 1 and 15 days after treatment, aiming to evaluate two endpoints after therapy, when parasitological and immunological parameters were investigated. Results showed that the treatment using miltefosine, ICHQ or ICHQ/Mic induced significantly higher anti-parasite IFN-γ, IL-12, GM-CSF, nitrite and IgG2a isotype antibody levels, which were associated with low IL-4 and IL-10 production. In addition, a higher frequency of IFN-γ and TNF-α-producing CD4+ and CD8+ T-cells was found in these animals. The parasite load was evaluated in distinct organs, and results showed that the treatment using miltefosine, ICHQ or ICHQ/Mic induced significant reductions in organic parasitism in the treated and infected mice. A comparison between the treatments suggested that ICHQ/Mic was the most effective in inducing a highly polarized Th1-type response, as well as reducing the parasite load in significant levels in the treated and infected animals. Data obtained 15 days after treatment suggested maintenance of the immunological and parasitological responses. In conclusion, ICHQ/Mic could be considered in future studies for the treatment of visceral leishmaniasis.

scholarly journals Frequency of detection and load of amastigotes in the pancreas of Leishmania infantum-seropositive dogs: clinical signs and histological changes

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
William de Oliveira Kost ◽  
Sandro Antonio Pereira ◽  
Fabiano Borges Figueiredo ◽  
Artur Augusto Velho Mendes Junior ◽  
Maria de Fátima Madeira ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Visceral Leishmaniasis ◽  
Body Condition ◽  
Leishmania Infantum ◽  
Clinical Signs ◽  
Low Frequency ◽  
Parasite Load ◽  
Cell Degeneration ◽  
Histological Changes ◽  
Etiological Agents

Abstract Background Zoonotic visceral leishmaniasis is caused by the protozoan Leishmania infantum and is highly lethal in humans and dogs if left untreated. The frequency of this parasite and associated histological changes in the pancreas of dogs are poorly studied. Therefore, the objectives of this study were to evaluate the frequency of detection and load of amastigotes in the pancreas of L. infantum-seropositive dogs and to identify the clinical signs and histological changes associated with parasitism of this organ. Methods One hundred forty-three dogs from an endemic area in Brazil that tested seropositive for L. infantum were studied. The dogs were clinically examined, killed, and necropsied between 2013 and 2014. One fragment of the pancreas was randomly collected for histopathology and immunohistochemistry, and spleen and bone marrow were collected for culture. Results Leishmania amastigotes were detected in the pancreas of 22 dogs (15.4%) by immunohistochemistry, all exhibiting L. infantum parasitism in the spleen and/or bone marrow. Poor body condition and cachexia were only associated with infection of the pancreas with Leishmania spp. (p = 0.021) and were found in 40.9% of dogs with pancreatic infection. Anorexia, vomiting, and/or diarrhea were observed in 9.2% of dogs with pancreatitis. The median parasite load in the pancreas was 1.4 infected macrophages/mm2. Pancreatic histological changes and their frequencies were: granulomatous pancreatitis (28.0%), lymphoplasmacytic pancreatitis (23.8%), acinar cell degeneration (6.3%), fibrosis (5.6%), hemorrhage (2.1%), eosinophilic pancreatitis (0.7%), suppurative pancreatitis (0.7%), and necrosis (0.7%). Conclusions The present results demonstrate that L. infantum is one of the etiological agents of chronic pancreatitis in dogs; however, the frequency of detection and parasite load are low in this organ. The lack of an association of poor body condition and cachexia with pancreatitis and the low frequency of clinical signs commonly associated with pancreatitis suggest that a significant portion of the organ is not affected by this parasite. On the other hand, the association of poor body condition and cachexia with concomitant infection of the pancreas, spleen, and/or bone marrow with this parasite suggests that these manifestations are the result of a more advanced stage of canine visceral leishmaniasis. Graphic abstract

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