scholarly journals Investigation of susceptibility to paromomycin in isolates from dogs of Leishmania (Leishmania) infantum

2019 ◽  
Author(s):  
Viviane da Luz Oliveira ◽  
Adriano Cappellazzo Coelho ◽  
Edite H. Y. Kanashiro ◽  
Mussya C. Rocha ◽  
Paulo C. Cotrim
Keyword(s):  
Side Effects ◽  
Visceral Leishmaniasis ◽  
Amphotericin B ◽  
Leishmania Infantum ◽  
Sao Paulo ◽  
Parasitic Disease ◽  
Effectiveness Rate ◽  
Alternative Drug ◽  
The City

In Brazil, visceral leishmaniasis (VL) is a parasitic disease caused by the protozoan Leishmania (Leishmania) infantum. This disease is serious and may be lethal if not treated. The treatment of leishmaniasis in Brazil consists in the use of pentavalent antimonials and/or amphotericin B. These drugs are toxic, have several side effects and the effectiveness of treatment has decreased in the last years. Paromomycin is an alternative drug already used in the treatment of VL in Asia with effectiveness rate higher than 90%. In this project, we aimed to evaluate the susceptibility in vitro to paromomycin of isolates of L. (L.) infantum from dogs of the city of Embu-Guaçu, State of São Paulo.

scholarly journals Miltefosine susceptibility of isolates of Leishmania (Leishmania) infantum from dogs of the municipality of Embu-Guaçu, Brazil

2018 ◽  
Author(s):  
Bianca Alves Ferreira ◽  
Adriano Cappellazzo Coelho ◽  
Paulo César Cotrim ◽  
Edite Hatsumi Yamashiro Kanashiro ◽  
Mussya Cisotto Rocha
Keyword(s):  
Visceral Leishmaniasis ◽  
Amphotericin B ◽  
Leishmania Infantum ◽  
Sao Paulo ◽  
Metropolitan Region ◽  
Parasitic Disease ◽  
Canine Visceral Leishmaniasis ◽  
Highly Effective ◽  
The City

Visceral leishmaniasis (VL) is a parasitic disease caused by the protozoan Leishmania (L.) infantum. In Brazil, the number of cases of the disease has increased in the last years. The treatment of leishmaniasis in Brazil consists of the use of pentavalent antimonials and amphotericin B. Recently, miltefosine has been shown to be highly effective against VL in Asia. Although, this drug is not used in the treatment of VL in Brazil, miltefosine is approved for use in the treatment of canine visceral leishmaniasis (CVL). In this study, we evaluate the susceptibility to miltefosine in vitro of isolates of L. (L.) infantum from dogs of municipality of Embu-Guaçu, located in the metropolitan region of the city of São Paulo.

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 In vitro and in vivo resistance of Leishmania infantum to meglumine antimoniate: a study of 37 strains collected from patients with visceral leishmaniasis.

1997 ◽  
Vol 41 (4) ◽  
pp. 827-830 ◽  
Author(s):  
F Faraut-Gambarelli ◽  
R Piarroux ◽  
M Deniau ◽  
B Giusiano ◽  
P Marty ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Infantum ◽  
Strongly Correlated ◽  
Duration Of Treatment ◽  
In Vitro Sensitivity ◽  
Sensitivity Tests ◽  
Leishmania Parasites ◽  
Immunocompetent Patients

Primary and secondary unresponsiveness to meglumine has long been described in human visceral leishmaniasis. However, no studies have been performed to elucidate if these therapeutic failures were due to strain variability in meglumine sensitivity or were related to host factors. We have studied the in vitro sensitivity of 37 strains of Leishmania infantum isolated from 23 patients (11 human immunodeficiency virus-infected and 12 immunocompetent patients) with visceral leishmaniasis. Sensitivity tests were performed by infecting murine macrophages with Leishmania parasites and culturing them in medium containing different concentrations of meglumine. For each test we calculated a 50% effective dose (ED50) corresponding to the meglumine concentration at which 50% of the Leishmania parasites survived. In vitro results were strongly correlated to immediate clinical outcome. All strains requiring an ED50 of >70 microg/ml were related to therapeutic failures, whereas all strains requiring an ED50 of <40 microg/ml corresponded to an initial efficiency of meglumine. Among those patients who were initially improved, relapses occurred in all immunocompromised patients and in most immunocompetent patients who had a short duration of treatment (15 days). Finally, we found that in vitro sensitivity of strains decreased progressively in relapsing patients treated with meglumine. Consequently, the physician may be encouraged to alternate meglumine with other treatments such as amphotericin B or pentamidine, especially in the case of relapsing patients.

scholarly journals Space-time cluster analysis of American visceral leishmaniasis in Bauru, São Paulo State, Brazil

2012 ◽  
Vol 28 (10) ◽  
pp. 1949-1964 ◽  
Author(s):  
Vanessa Aparecida Feijó de Souza ◽  
Luiz Ricardo Paes de Barros Cortez ◽  
Ricardo Augusto Dias ◽  
Marcos Amaku ◽  
José Soares Ferreira Neto ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Urban Areas ◽  
Sao Paulo ◽  
Space Time ◽  
São Paulo ◽  
Prevention Measures ◽  
Paulo State ◽  
Positive Tendency ◽  
São Paulo State ◽  
The City

A space-time analysis of American visceral leishmaniasis (AVL) in humans in the city of Bauru, São Paulo State, Brazil was carried out based on 239 cases diagnosed between June 2003 and October 2008. Spatial analysis of the disease showed that cases occurred especially in the city's urban areas. AVL annual incidence rates were calculated, demonstrating that the highest rate occurred in 2006 (19.55/100,000 inhabitants). This finding was confirmed by the time series analysis, which also showed a positive tendency over the period analyzed. The present study allows us to conclude that the disease was clustered in the Southwest side of the city in 2006, suggesting that this area may require special attention with regard to control and prevention measures.

scholarly journals Resistance to Experimental Visceral Leishmaniasis in Mice Infected With Leishmania infantum Requires Batf3

2020 ◽  
Vol 11 ◽  
Author(s):  
Manuel Soto ◽  
Laura Ramírez ◽  
José Carlos Solana ◽  
Emma C. L. Cook ◽  
Elena Hernández-García ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Infantum ◽  
Rational Design ◽  
Leucine Zipper ◽  
Basic Leucine Zipper ◽  
Vector Borne ◽  
The Impact ◽  
Deficient Mice

Unveiling the protective immune response to visceral leishmaniasis is critical for a rational design of vaccines aimed at reducing the impact caused by this fatal, if left untreated, vector-borne disease. In this study we sought to determine the role of the basic leucine zipper transcription factor ATF-like 3 (Batf3) in the evolution of infection with Leishmania infantum, the causative agent of human visceral leishmaniasis in the Mediterranean Basin and Latin America. For that, Batf3-deficient mice in C57BL/6 background were infected with an L. infantum strain expressing the luciferase gene. Bioluminescent imaging, as well as in vitro parasite titration, demonstrated that Batf3-deficient mice were unable to control hepatic parasitosis as opposed to wild-type C57BL/6 mice. The impaired microbicide capacities of L. infantum-infected macrophages from Batf3-deficient mice mainly correlated with a reduction of parasite-specific IFN-γ production. Our results reinforce the implication of Batf3 in the generation of type 1 immunity against infectious diseases.

scholarly journals Amphotericin B-loaded mannose modified poly(d,l-lactide-co-glycolide) polymeric nanoparticles for the treatment of visceral leishmaniasis: in vitro and in vivo approaches

RSC Advances ◽  
2017 ◽  
Vol 7 (47) ◽  
pp. 29575-29590 ◽  
Author(s):  
Santanu Ghosh ◽  
Suman Das ◽  
Asit Kumar De ◽  
Nabanita Kar ◽  
Tanmoy Bera
Keyword(s):  
Visceral Leishmaniasis ◽  
Amphotericin B ◽  
Polymeric Nanoparticles ◽  
Plga Nanoparticles

Amphotericin B-loaded mannose modified PLGA nanoparticles are more efficacious in the treatment of visceral leishmaniasis in bothin vitroandin vivomodels than unmodified nanoformulations.

scholarly journals Seroepidemiology of Leishmania infantum in dogs in the city of Porto Alegre, Rio Grande do Sul, Brazil

2016 ◽  
Vol 37 (6) ◽  
pp. 4077 ◽  
Author(s):  
Mariana Caetano Teixeira ◽  
Neusa Saltiel Stobbe ◽  
Verônica Schmidt ◽  
Valéria Marçal Felix de Lima ◽  
Ana Luisa Tartarotti ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Infantum ◽  
Clinical Manifestations ◽  
Rio Grande ◽  
The State ◽  
Canine Leishmaniasis ◽  
Insect Vector ◽  
Rio Grande Do Sul ◽  
Porto Alegre ◽  
The City

Leishmaniosis are zoonoses that present several clinical manifestations in humans and have dogs as their main reservoir in the urban environment. Visceral leishmaniasis (VL) is the most severe form of the parasitosis and has been increasing in Brazil, despite the actions of public health agencies. Until 2002, the State of Rio Grande do Sul (RS) was considered free of human and canine leishmaniasis. The first human case of cutaneous leishmaniasis in RS was recorded in 2003. In 2009, the first autochthonous cases of human VL and canine visceral leishmaniasis (CVL) were confirmed in São Borja, RS, and the occurrence of the insect vector was recorded for the first time in the state. In 2010, the first confirmed case of CVL was reported and seropositive dogs were identified in the city of Porto Alegre, RS. Given the importance of this zoonosis and the difficulties of a reliable diagnosis in dogs, this study aimed to identify epidemiological aspects of CVL in dogs in an area of Porto Alegre where cases of the disease have been reported. A total of 300 blood samples were collected from dogs in this area, which were then tested by the methods of RT-DPP® and ELISA for diagnosis of Leishmania infantum. An epidemiological questionnaire was completed by dog owners, containing aspects related to care of the animals, characteristics of their environment, and their living conditions. We observed that 83% (250/300) of the studied dogs were of mixed breed, 58% (175/300) were female, 78% (238/300) slept outdoors, and 61% (183/300) shared their living quarters with other species. Clinically, we observed that 90% (270/300) of the animals were infested by ectoparasites, 70% (210/300) had dermatopathies, 24% (72/300) presented weight loss and anorexia, and 22% (65/300) had ocular disorders. The results of the two serological tests were 100% concordant for the three seropositive samples (1%), and the remaining 297 (99%) were negative for both tests. We conclude that despite the low prevalence of L. infantum seropositive dogs, conditions in the region are favorable for CVL transmission, creating a risk of VL for the human population in the city of Porto Alegre.

scholarly journals Nanoliposomal Buparvaquone Immunomodulates Leishmania infantum-Infected Macrophages and Is Highly Effective in a Murine Model

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Thais Alves da Costa-Silva ◽  
Andrés Jimenez Galisteo ◽  
José Angelo Lauletta Lindoso ◽  
Leandro R. S. Barbosa ◽  
Andre Gustavo Tempone
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Infantum ◽  
Drug Repositioning ◽  
Interleukin 10 ◽  
Pcr Analysis ◽  
Hydrodynamic Diameter ◽  
Content Type ◽  
Highly Effective

ABSTRACT Visceral leishmaniasis is a fatal parasitic neglected disease affecting 1.5 million people worldwide. Based on a drug repositioning approach, the aim of this work was to investigate the in vitro immunomodulatory potential of buparvaquone (BPQ) and to establish a safe regimen to evaluate the in vivo efficacy of BPQ entrapped by negatively charged nanoliposomes (BPQ-LP) in Leishmania infantum-infected hamsters. Small-angle X-ray scattering, dynamic light scattering, and the ζ-potential were applied in order to study the influence of BPQ on the liposome structure. Our data revealed that BPQ was located in the polar-apolar interface, snorkeling the polar region, and protected against aggregation inside the lipophilic region. The presence of BPQ also decreased the Z-average hydrodynamic diameter and increased the surface charge. Compared to intravenous and intramuscular administration, a subcutaneous route was a more effective route for BPQ-LP; at 0.4 mg/kg, BPQ-LP reduced infection in the spleen and liver by 98 and 96%, respectively. Treatment for 5 days resulted in limited efficacy, but 10 days of treatment resulted in an efficacy similar to that of a 15-day regimen. The nanoliposomal drug was highly effective, with a mean 50% effective dose of 0.25 mg/kg, reducing the parasite load in bone marrow by 80%, as detected using quantitative PCR analysis. In addition, flow cytometry studies showed that BPQ upregulated cytokines as tumor necrosis factor, monocyte chemoattractant protein 1, interleukin-10 (IL-10), and IL-6 in Leishmania-infected macrophages, eliminating the parasites via a nitric oxide-independent mechanism. This new formulation proved to be a safe and effective treatment for murine leishmaniasis that could be a useful candidate against visceral leishmaniasis.

In vitro effect of new formulations of amphotericin B on amastigote and promastigote forms of Leishmania infantum

2007 ◽  
Vol 30 (4) ◽  
pp. 325-329 ◽  
Author(s):  
Lara Ordóñez-Gutiérrez ◽  
Raquel Espada-Fernández ◽  
María Auxiliadora Dea-Ayuela ◽  
Juan José Torrado ◽  
Francisco Bolás-Fernandez ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Leishmania Infantum ◽  
Vitro Effect
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